CN120641095A - Treatment of mental disorders - Google Patents

Abstract

5-Methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use in the treatment of a mental or neurological disorder in a mother who has a child of 18 months or less of age, wherein the 5-MeO-DMT or a pharmaceutically acceptable salt thereof is administered via intravenous, intramuscular or subcutaneous route.

Description

Treatment of mental disorders

Technical Field

The present invention relates to 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use in the treatment of maternal patients diagnosed with a disorder of the mental or nervous system, in particular breast-fed maternal patients.

The psychotic disorder is suitable for treatment with 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The treatment also improves maternal function.

Furthermore, the present invention allows for the treatment of mental or neurological disorders of the breast-feeding mother without the need to interrupt the breast-feeding almost completely.

Background

A disorder of the breast-feeding mother's mental or nervous system may have a series of negative consequences for the affected mother, her infant and her family. For example, women suffering from mental or neurological disorders may develop the idea of self-injury or injury to children, and their risk of suicide may increase.

Mental or neurological disturbances may further lead to interruption of the interaction between mother and child, examples being a higher incidence of uncoupling behavior between mother and child and a lower incidence of visual and acoustic communication. Evidence also suggests that there is a correlation between the mental or neurological disorder suffered by the mother and the development of the child, as evidenced by the fact that the child of a patient suffering from a mental or neurological disorder may be at greater risk of impaired cognitive development.

Despite these problems, treatment options remain quite limited. In general, known methods of treatment of mental or neurological disorders generally have limited success rates of treatment, particularly for patients suffering from symptoms of diseases above mild.

In the case of a patient who is a breast-feeding mother, a complicating factor is that for many medications, it is recommended that the lactating woman stop breast-feeding during and for a period of time after the administration, as the medication may be expelled with milk, exposing the unweaned child to risk.

Furthermore, studies have shown that breast-fed mothers may be reluctant to initiate medication due to a range of concerns.

Thus, a breastfed patient suffering from a mental or neurological disorder may be faced with a situation in which it is necessary to decide whether to stop breastfeeding or stop/forego treatment.

In this context, there is a need for improved treatment of mental or neurological disorders, in particular not only to effectively solve the symptoms of the disorder and to rapidly produce clinical responses, but also to avoid interfering with the daily activities of the patient, in particular with respect to the care of the infant. The treatment should improve maternal function. Furthermore, there is a need for a treatment of mental or neurological disorders that does not require an almost complete interruption of breast feeding.

Although there has recently been great interest in the treatment of psychotic disorders using hallucinogens, breast-feeding mothers have not been treated to date based on such substances. This is due to the general lack of relevant clinical data, the inability to draw conclusions about the clinical utility of hallucinogens, and also due to the particular concern that administration of hallucinogens may not be suitable for breast-feeding mothers.

Hallucinogens (including hallucinogens) are chemical compounds, some of which are naturally occurring, and some of which are synthetic, defined as being capable of causing sensory distortions, such as changes in auditory and visual perception, and emotional and cognitive distortions, upon administration to humans. The term hallucinogen encompasses a fairly broad group of psychoactive molecules with different modes of action. Some psychotic disorders are in principle considered suitable for treatment with psychoactive molecules such as hallucinogens.

However, no hallucinogens have been approved by any regulatory authorities. In fact, the clinical experience of such molecules remains quite limited.

One compound that has been studied in clinical trials is 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT). WO 2020/169850 reports tests performed on healthy volunteers and clinical trials involving patients suffering from treatment-resistant depression (TRD), i.e. a form of major depressive disorder. Patients suffering from PPD were not included in the trial.

Against this background, it is an object of the present invention, inter alia, to provide a more effective therapy than previously described (i.e. a) a greater percentage of patients experience clinical response, b) a greater average clinical response, c) an earlier onset of clinical response, and/or d) a longer lasting clinical response).

It is a further object of the present invention to provide compounds and dosing regimens for improved psychoactive therapies with better safety and/or better tolerability than previously described therapies. It is a further object of the present invention to provide compounds and dosing regimens for improved psychoactive therapies which are more convenient than the previously described therapies. It is a further object of the present invention to provide compounds and dosing regimens for improved psychoactive therapies which are associated with higher patient compliance rates (including higher therapeutic initiation rates) than previously described therapies. It is yet a further object of the present invention to identify specific disease aspects and subgroups of specific disease aspects that benefit from such improved psychoactive therapies.

It is a still further object of the present invention to improve maternal function in patients suffering from mental or neurological disorders, in particular breast-feeding mothers diagnosed with mental disorders.

Disclosure of Invention

The present invention provides 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT), or a pharmaceutically acceptable salt thereof, for use in the treatment of a mother diagnosed with a disorder of the mental or nervous system, in particular a breast-feeding mother diagnosed with such a disorder. The disorders may be particularly disorders characterized by depressive episodes, such as Major Depressive Disorder (MDD), persistent depressive disorder, seasonal affective disorder and bipolar affective disorder (BD), such as bipolar affective disorder type I and bipolar affective disorder type II, anxiety disorders, such as separation anxiety disorder, agoraphobia, generalized Anxiety Disorder (GAD), social Anxiety Disorder (SAD), panic disorder, phobia and substance/drug induced anxiety disorder, somatic symptom disorder, obsessive compulsive disorder and related disorders, such as Obsessive Compulsive Disorder (OCD) and physical deformity disorder (BDD), post Traumatic Stress Disorder (PTSD), pain disorders, such as chronic pain, fibromyalgia and migraine, mental and behavioural disorders due to the use of psychoactive substances, such as Substance Use Disorder (SUD), psychotic disorders, such as schizophrenia, pedigree disorder, attention Deficit Hyperactivity Disorder (ADHD), eating disorder, such as split-phase personality disorder and borderline personality disorder, autism disorder, chronic fatigue syndrome, HIV, post-traumatic injury or nervous system disorder.

In one aspect, the patient may suffer from sleep disorders.

Treatment may improve maternal function.

The patient to be treated is in particular a breast-fed mother.

The invention also allows the treatment of breast-feeding mothers without having to interrupt breast-feeding almost completely.

The invention also provides dosage ranges and dosing regimens useful in the above treatments.

In the context of the present invention, 5-MeO-DMT or a pharmaceutically acceptable salt thereof is administered via intravenous, intramuscular or subcutaneous administration.

The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, is administered at a dose or dosage regimen that causes the patient to experience a peak fantasy experience. A dose of about 1 mg to about 10 mg of 5-MeO-DMT, or an equimolar amount of a pharmaceutically acceptable salt, may be administered.

Detailed Description

Definition of the definition

As used in the context of the present invention, the term "5-MeO-DMT" refers to the free base 5-MeO-DMT unless otherwise indicated. It is contemplated that pharmaceutically acceptable salts of 5-MeO-DMT may also be used. Such salts are in particular acid addition salts, wherein the acid may be selected from, for example, acetic acid, benzoic acid, citric acid, fumaric acid, hydrobromic acid, hydrochloric acid, hydrofluoric acid, hydroiodic acid, oxalic acid, succinic acid and trifluoromethanesulfonic acid. A preferred example is hydrobromide. Assuming that equimolar amounts are used, the appropriate weight of salt to be administered can be calculated from the weight of the free base.

As used in the context of the present invention, a "patient" to be treated is a mother who typically has 18 months or less, particularly 12 months or less, of children who is diagnosed by a practitioner as a mental or neurological disorder according to accepted medical practice.

For example, diagnosis of a psychotic disorder or neurological disorder may be made according to the mental disorder diagnosis and statistics manual, fifth edition (DSM-5) published by the American psychomedical Association. In some cases, as will be apparent from the following discussion of specific cases, the criteria may be modified or supplemented to better define a patient or patient population that would benefit particularly from treatment according to the present invention. In any event, the diagnosis will be made by a physician or psychologist. The human subject himself considers that it is not enough to suffer from the disorder.

As used in the context of the present invention, unless otherwise indicated, the terms "treatment" and "treatment" shall include the management and care of a patient for the purpose of combating a disease, condition or disorder, and include the administration of the compounds and methods according to the present invention to alleviate signs and/or symptoms of a disease or to eliminate a disease, condition or disorder.

Patients may suffer from treatment-resistant diseases. Treatment resistance means that the patient is not substantially improved after at least two substantial courses of treatment. Patients are not substantially improved, particularly after at least two substantial courses of therapy, wherein at least one of the two courses is drug therapy, e.g., patients are not substantially improved after at least two substantial courses of drug therapy. In particular, at least two previous courses of treatment are administered in the current episode of the disease, e.g., if the patient suffers from a disorder characterized by a depressive episode.

As used in the context of the present invention, "suicidal ideation" refers to thinking, considering or planning suicide. A doctor or psychologist will use the established protocol and method for diagnosing suicidal tendencies to diagnose whether a patient has suicidal ideation. In general, patients consider that they are not enough to suffer from suicidal ideation. In some cases, a patient experiencing suicidal ideation will be at risk of impending suicide, or be considered "suicidal ideation".

As used in the context of the present invention, unless otherwise indicated, the term "therapeutically effective amount" shall mean an amount of an active compound or pharmaceutical ingredient that elicits the biological or clinical response in a human that is being sought by a researcher, doctor or other clinician, which includes alleviation of the signs and/or symptoms of the disease, disorder or condition being treated.

"Clinical response" includes, but is not limited to, improvement of the rating scale.

The severity of the condition and the change in severity can be assessed by a Clinical Global Impression (CGI) rating scale, which is a measure of symptom severity, treatment response, and treatment efficacy.

CGI rating scales were developed to provide a concise, independent assessment of the clinician's opinion of overall function before and after patient treatment (Busner, j. And Tagrum, S. D., 2007. The Clinical Global Impressions Scale: Applying a Research Tool in Clinical Practice. Psychiatry 2007, 29-37).

CGI severity (CGI-S) is based on a question that the clinician must answer-given your general clinical experience with that particular population, how does the patient' S current level of psychosis? 2 = borderline psychosis, 3 = mild illness, 4 = moderate illness, 5 = severe illness, 6 = severe illness, 7 = patient with the most severe illness.

CGI-S can be used to assess treatment success by comparing scores before and after treatment.

Alternatively, CGI-improvement (CGI-I) may be used to assess treatment success, in the same simple format. After treatment, the clinician compares the overall clinical condition of the patient to the pre-treatment condition (the so-called baseline value). Also, only one query was rated in the seven-component table, "the patient's condition was 1 = very much improved since the start of treatment, 2 = very improved, 3 = slightly improved, 4 = no change from baseline (treatment start), 5 = slightly worsened, 6 = much worse, 7 = very much worsened since the start of treatment".

Patient Global Impression Scales (PGIs), also known as Subject Global Impressions (SGIs), are the corresponding parts of Clinical Global Impression Scales (CGIs). It consists of a CGI-based item that is suitable for the patient. It can measure disease severity (PGI-S) or disease improvement (PGI-I).

The severity of the disorder and the change in severity can be further assessed by a rating scale applicable to the particular mental or neurological disorder the patient is suffering from.

Individual items of the scale as described herein, and sub-combinations of individual items, may be used to evaluate specific disease aspects.

Maternal function can be assessed using Barkin maternal function index (BIMF).

When assessing clinical response at an early time point (e.g., 2 hours) after administration of a drug based on an endpoint developed for a longer recall period (e.g., typically 7 days for MADRS), such endpoint may be reasonably modified (e.g., change MADRS recall period to 2 hours and turn around sleep program recorded at pre-drug baseline).

The outlined considerations apply to early time points, since in one aspect, to assess clinical response, the effect of the pre-treatment patient's state on any score recorded after treatment should be as low as possible, while in another aspect, sleep projects cannot be assessed 2 hours after administration of the drug.

At a later point in time, for example at day 1 or later, all items of the relevant scale for assessing clinical response can typically be assessed using an appropriate recall period (if necessary) so that no pre-treatment scoring need be reversed. For example, if BIMF is evaluated at day 7, a seven day recall period (rather than a 2 week standard recall period) would be used.

As used in the context of the present invention, the term "administering" (or "application") shall mean introducing an amount (which may be a predetermined amount) of an active compound or pharmaceutical ingredient into a patient via any route, unless otherwise indicated. The active compounds are administered by intravenous, intramuscular or subcutaneous administration.

As used in the context of the present invention, the terms "dose" and "dose (dosage)" and "dose (dosage amount)" shall mean the amount of active compound or pharmaceutical ingredient administered to a patient in a single administration, unless otherwise indicated. The term "dosage regimen" (or "dosing regimen") shall mean a defined sequence of one or more individual administrations.

Mental and neurological disorders

The mental and neurological disorders to be treated according to the present invention have in common that they are associated with one or more of the group of symptoms discussed below, including sleep disorders, cognitive dysfunction, anxiety, bradykinesia, social/emotional withdrawal, and negative thinking.

In one aspect, the invention relates to 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use in the treatment of breast-fed mother patients diagnosed with a mental or neurological disorder.

The mental or neurological disorder is suitably treated with 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The mental or nervous system disorder is in particular major depressive disorder, persistent depressive disorder, bipolar disorder, anxiety disorder, post traumatic stress disorder, body deformity disorder, obsessive-compulsive disorder, eating disorder or substance abuse.

In a preferred embodiment, the psychotic disorder is major depressive disorder.

In another preferred embodiment, the mental disorder is post-partum depression (PPD), a complex physical, emotional, and behavioral change that occurs after delivery in some women. PPD is also known as major depressive disorder with perinatal onset. PPD is diagnosed when symptoms of Major Depressive Disorder (MDD) occur during pregnancy or within four weeks after delivery according to the DSM-5 (manual for diagnosis of mental disorders and statistics, 5 th edition).

In another preferred embodiment, the psychotic disorder is a bipolar disorder, such as bipolar disorder type II. Patients diagnosed with bipolar disorder are particularly afflicted with current major depressive episodes.

Bipolar disorders, such as sleep disorders, mental retardation (reduced energy and activity and reduced power), negative thinking (worthless; helplessness and presupposity; guilt), anxiety, cognitive dysfunction (impaired concentration and memory), and social/emotional withdrawal or distraction (absence of pleasure, emotional withdrawal and frigidity) may all be ameliorated. Other aspects of the disease that may be ameliorated include suicidal ideation and mixed symptoms (psychotic symptoms; irritability; instability; increased motor drive; increased speech; agitation). The improvement achieved is reflected in clinically relevant scales.

Meter for assessing mental and neurological disorders

Various scales have been proposed to assess the severity of mental or neurological disorders. Such scales are based on tests that may be self-administered or administered by a clinician.

The scales that may be used in accordance with the present invention for assessing mental or neurological disorders include scales known in the art for diagnosing and/or monitoring mental or neurological disorders discussed in more detail below.

The treatment outcome is assessed by using one or more indices or scales at one or more time points after completion of the treatment procedure.

The assessment may be performed after the acute illusion experience has subsided. Suitable time points for early evaluation are typically about 2 to 3 hours after the last administration. Early evaluation may generally be performed, for example, about 2 hours or about 3 hours after the last administration.

However, the assessment of the effects of sleep disorders or of the effects of mental or neurological disorders associated with sleep disorder can be made the earliest on the following day (i.e., on day 1) after treatment, so that the patient receiving treatment has an opportunity to sleep at least one night.

Thus, the evaluation on day 1 or on day 1 means the evaluation on the second day after administration. The evaluation will be performed no earlier than 12 hours after the last administration and in any case no earlier than one night after the last administration and no later than 36 hours after the last administration. The evaluation can be performed after about 24 hours.

The evaluation on day 7 or 7 means an evaluation performed on the seventh day after administration (day of administration is day 0). Similar definitions apply to other evaluation times for measurements made in days.

For example, when one of the scales is used to assess the severity of a mental disorder or neurological disorder, a clinical response is assessed based on an endpoint developed for a longer recall period (e.g., MADRS is typically 7 days) at an early point in time (e.g., 2 hours) after administration of the drug, such endpoint can be reasonably modified (e.g., the MADRS recall period is changed to 2 hours and the sleep program recorded at the pre-drug baseline is turned). The same applies to any other scale used herein for assessing the effect of a treatment of a mental or neurological disorder, unless a recall period is specifically indicated.

The outlined considerations apply to early time points, since in one aspect, to assess clinical response, the effect of the pre-treatment patient's state on any score recorded after treatment should be as low as possible, while in another aspect, sleep projects cannot be assessed 2 hours after administration of the drug.

At a later point in time, e.g., at day 1 or later, all items of the relevant scale for assessing clinical response can typically be evaluated using an appropriate recall period (if needed) so that no pre-treatment scoring need be reversed.

Active agent

Mental or neurological disorders are characterized in several ways and thus impose a severe disease burden and should be treated appropriately. Thus, there is a need not only for treatment, particularly by pharmaceutical intervention, to improve overall disease scores, but also to improve specific aspects of the disease.

The inventors contemplate that carefully selected hallucinogens may lead to improved treatment and may also lead to overall improvement in disease and maternal function.

The inventors also considered that if breast-feeding mothers suffering from mental or neurological disorders were treated, carefully selected hallucinogens could allow breast-feeding to continue without nearly complete disruption.

One group of hallucinogens comprises compounds that bind to 5-hydroxytryptamine (5-HT) receptors, also known as serotonin receptors (7 families 5-HT1 through 5-HT7 are described with several subtypes). Examples are lysergic acid diacetamide (LSD), ouabain (psilocybin), and N, N-Dimethyltryptamine (DMT). These serotonin agents are often referred to as "hallucinogens" which emphasize their primary ability to induce a qualitative change in the state of consciousness, such as euphoria, absentmindedness, time and space, mental experience, disappearance of self-limits, or even moribund experience, while other effects, such as sedation, anesthesia, or overstimulation, are minimal.

From a chemical point of view, serotonin hallucinogens are either phenylalkylamines or indoleamines, which in turn are divided into two subsets, ergolines and tryptamines, the latter derived from tryptamine.

Various serotonin hallucinogens have different binding affinities and activation potencies for various serotonin receptors (particularly 5-HT1A, 5-HT2A and 5-HT 2C), and their activities may also be modulated by interactions with other targets such as monoamine transporters and microamine-related receptors.

Recent published studies using serotonin hallucinogens such as LSD, galectin and DMT (using salmeterol containing DMT) in certain psychotic disorders have shown that these compounds can provide an alternative approach to the treatment of certain psychotic disorders currently available. However, these compounds have been reported to induce mania in patients suffering from depressive symptoms, and this may hamper their clinical use.

For example, lake et al (Lake, C. R., Stirba, A. L., Kinneman, R. E. Jr, Carlson, B., Holloway, H. C., 1981. Mania associated with LSD ingestion. American Journal of Psychiatry. 138(11):1508-9) report that a patient had a manic episode after taking LSD or LSD analogs. Patients develop symptoms of acute LSD intoxication that are alleviated, but typical psychotic manic episodes occur after about 3 weeks. Hendin and Penn (Hendin, H.M., Penn, A. D., 2021. An episode of mania following self-reported ingestion of psilocybin mushrooms in a woman previously not diagnosed with bipolar disorder: A case report. Bipolar Disorders 23(4):1-3) report manic episodes following the ingestion of the stropharia mushrooms from the time of said ingestion. Szmulewicz et al (Szmulewicz, a.g., valerio, m.p. and Jose M Smith, J. M., 2015. Switch to mania after ayahuasca consumption in a man with bipolar disorder: a case report. International Journal of Bipolar Disorders (2015) 3:4)) reported that a male suffering from bipolar disorder had changed to mania after drinking dead vine water (a DMT-containing beverage).

Another case report can be found in Brown, T., Shao, W., Ayub, S., Chong, D., & Cornelius, C. (2017). A Physician's attempt to self-medicate bipolar depression with N, N-dimethyltryptamine (DMT).Journal of Psychoactive Drugs, 49(4), 294-296.

The inventors believe that in order to avoid or at least reduce the risk of inducing mania or hypomania, the compound to be administered must be appropriately selected and preferably administered according to a specific dosing regimen.

The inventors determined that 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) is a hallucinogen of particular interest for therapy. 5-MeO-DMT has unique pharmacological properties that differ from other hallucinogenic compounds.

5-MeO-DMT is a potent, fast-acting, naturally-occurring serotonin (5-HT) agonist that acts on 5-HT1A and 5-HT2A receptors with a higher affinity for the 5-HT1A receptor subtype than other classical hallucinogens.

The inhibition constants (K _i values) of dephosphorylated ouabain (psilocin) (the dephosphorylated form of ouabain formed after ingestion of ouabain), DMT and 5-MeO-DMT at the 5-HT1A receptor located in the hippocampus of postmortem human brain were 48, 38 and 1.80 nM, respectively, as described in further detail in the examples section below. Thus, 5-MeO-DMT shows high affinity for 5-HT1A receptor, while dephosphorylated galectin and DMT show moderate affinity. The inhibition constants (K _i values) of nupharin dephosphorylation, DMT and 5-MeO-DMT at the 5-HT2A receptor located in the frontal cortex of postmortem human brain were 37, 117 and 122 nM, respectively. Thus, dephosphorylated galectins showed medium/strong affinity for 5-HT2A receptors, while DMT and 5-MeO-DMT showed relatively weak affinity.

The 5-MeO-DMT exhibits enhanced affinity for the 5-HT1A receptor relative to the other psychoactive compounds previously mentioned, in which case the 5-MeO-DMT acts as a potent agonist. The contribution of 5-HT2A binding was increased in the case of dephosphorylated nupharicin and DMT relative to 5-MeO-DMT, where 5-MeO-DMT showed the greatest differential affinity for 5-HT1A relative to 5-HT2A among the three compounds. Thus, 5-HT1A binding plays a much greater role in the overall effect of 5-MeO-DMT relative to 5-HT2A binding than the other two compounds.

It is reported that 5-HT1A agonists reduce impulse and aggressiveness, whereas 5-HT2A agonists lead to short term increases in these same properties. Furthermore, the dopamine system is associated with causing mania and an increase in dopamine driving force is associated with mania. LSD, galectin and DMT show increased affinity for various dopamine receptors relative to 5-MeO-DMT.

In contrast to other hallucinations (such as LSD, nupharin or DMT), 5-MeO-DMT may preferably be administered to a patient using a dosing regimen as described herein without creating a significant risk of inducing mania or hypomania in patients suffering from mental or neurological disorders including disorders characterized by depressive episodes, such as Major Depressive Disorder (MDD), post-partum depression (PPD), persistent depressive disorder, seasonal affective disorder and bipolar affective disorder (BD), such as bipolar affective disorder type I and II, psychotic disorder such as schizophrenia, or personality disorder such as split-phase personality disorder. Patients suffering from such mental or neurological disorders and treated according to the invention do not experience treatment-induced mania or hypomania.

It is also notable that reports of mania or hypomania caused by treatment with psychoactive substances appear to indicate the use of large amounts of the corresponding compounds (e.g., DMT/dead rattan water, galectin, LSD).

The inventors' 5-MeO-DMT sequential up-titration (up-titration) method significantly reduced the risk of overdosing and the possibility of concomitant adverse events.

Further, antidepressants have been reported to induce isolated hypomanic events in patients suffering from treatment-resistant depression (TRD) (barer, cynthia d. And David L. Dunner. "Antidepressant-induced hypomania in treatment-resistant depression." Journal of Psychiatric Practice 13.4 (2007): 233-237). whereas, the clinical trial of 5-MeO-DMT in recently completed TRD patients did not show evidence of hypomanic induction.

5-MeO-DMT can trigger a peak experience (i.e., an experience characterized by a shift in emotional perspective, which is described as "self-loss", often ending with an overwhelming "universe-like" sensation) faster than other hallucinations, and has a short duration of acute illusive effects (5 to 30 minutes after intravenous injection compared to, for example, hours of oral nupharin and oral LSD). These characteristics of 5-MeO-DMT are associated with improved treatment profiles, which can be explained by specific changes in Resting State Network (RSN) activity under 5-MeO-DMT treatment.

In addition, 5-MeO-DMT is a 5-HT7 receptor agonist, which has a high affinity for the receptor. The inventors estimated non-specific binding using recombinant human 5-HT7 receptor, [ ³ H ] LSD as a radioligand and serotonin and determined a Ki of 2.3 nM.

Thus, in addition to the 5-HT1A and 5-HT2A receptors discussed above, 5-MeO-DMT also interacts with 5-HT7 receptors. 5-MeO-DMT acts as an agonist of this receptor and exhibits high (nanomolar) binding affinity.

The 5-HT7 receptor plays a role in neurogenesis, synaptogenesis and dendritic spine formation. It is associated with, among other things, central processes such as learning and memory, sleep regulation and circadian rhythms, and nociception.

The 5-HT7 receptor is expressed in particular in the spinal cord, the middle suture nucleus, the thalamus, the hypothalamus (including the supravisual nucleus), the hippocampus, the prefrontal cortex, the striatal complex, the amygdala, and the Purkinje neurons of the cerebellum.

The supravisual nucleus is the central pacemaker of the circadian timing system. It coordinates the circadian rhythms of various areas of the brain. Disruption of this coordination will lead to disease states, particularly those involving sleep disorders. In patients suffering from sleep disorders, resting state functional connection analysis reveals a change in functional connection between the supraoptic nucleus and regions within the default mode network.

The expression of the 5-HT7 receptor in the nucleus of the visual junction corresponds to the role of said receptor in the regulation of the sleep/wake cycle. The inventors believe that this allows treatment of patients suffering from sleep disorders by acting on the receptor 5-MeO-DMT.

The inventors believe that the binding of 5-MeO-DMT to the 5-HT7 receptor, an mediator (mediator) of the pharmacological actions of 5-MeO-DMT, involves functional link "reset" of the network as well as neuroplastic effects, contributing to the beneficial effects of 5-MeO-DMT in treating patients suffering from sleep disorders.

The inventors further believe that the binding of 5-MeO-DMT to 5-HT7 receptor and 5-HT1A receptor (two mediators that function as 5-MeO-DMT) includes a network of functional link "reset" and neuroplastic effects, allowing beneficial effects to be achieved in patients suffering from other symptoms or disorders such as cognitive dysfunction, anxiety, bradykinesia, negative thinking, or social/emotional withdrawal. The clinical results shown in the studies mentioned herein support this.

Another feature of 5-MeO-DMT is its short half-life.

5-MeO-DMT is deactivated primarily by monoamine oxidase A mediated deamination and O-demethylation by cytochrome P450 2D6 (CYP 2D 6) enzymes.

The inventors studied the pharmacokinetic properties of 5-MeO-DMT and observed rapid absorption and distribution of inhaled 5-MeO-DMT, with maximum concentrations and pharmacological effects observed during and immediately after dosing.

Pharmacokinetic analysis of 5-MeO-DMT after inhalation showed a very rapid decrease in plasma concentration. 10 minutes after administration, the concentration was reduced to 10% or less of Cmax, after 2 hours, the concentration was 1% or less of Cmax, and after 3 hours, 5-MeO-DMT was no longer detected in the plasma. This applies to the full dose range tested (6 mg, 12 mg, 18 mg). No accumulation was observed after repeated administration over a period ranging from 1 to 4 hours. Upregulation as disclosed herein does not lead to accumulation and therefore does not lead to higher plasma concentrations, e.g. 10 minutes, 2 hours or 3 hours after administration.

The inventors have further determined that 5-MeO-DMT has a number of characteristics that make it an attractive treatment for PPD. In contrast to SSRI, 5-MeO-DMT is a fast-acting agent (in the 5-MeO-DMT-TRD trial, 5 of 8 TRD patients achieved relief within 2 hours after dosing, 8 patients achieved relief on day 1, and 7 patients maintained relief on day 7). Treatment of PPD patients with 5-MeO-DMT not only can rapidly improve depression symptoms, but also can rapidly improve maternal function. Furthermore, 5-MeO-DMT is administered during a single day of treatment, optionally with infrequent re-dosing, thus unlike SSRI which requires a long-term daily dosing regimen, compliance is low, while for cloth Lei Shanuo ketone (brexanolone) long-term infusion and hospitalization are required.

Thus, the present invention also addresses compliance and patient convenience issues.

Furthermore, the inventors have determined that PPD treatment with 5-MeO-DMT or a pharmaceutically acceptable salt thereof allows breast feeding to continue and only briefly discontinue treatment.

Isotopic variants of 5-MeO-DMT and pharmaceutically acceptable salts thereof can also be used according to the present invention. Isotopic variants are also contemplated when referring to the use of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

These variants are in particular deuterated forms of 5-MeO-DMT and pharmaceutically acceptable salts of such forms.

The deuterated form of 5-MeO-DMT is a form with deuterium content higher than would be expected from the natural abundance of the isotope.

The deuterated form of 5-MeO-DMT is a specific form that introduces deuterium at one or more defined hydrogen positions.

Examples of deuterated forms of 5-MeO-DMT include, but are not limited to, 1-deuterium-2- (5-methoxy-1H-indol-3-yl) -N, N-dimethylethylamine, 1-dideutero-2- (5-methoxy-1H-indol-3-yl) -N, N-dimethylethylamine, 1, 2-tetradeuterium-2- (5-methoxy-1H-indol-3-yl) -N, N-dimethylethylamine, and N, N-dimethyl-2- [5- (tridecylmethoxy) -1H-indol-3-yl ] ethylamine.

Further examples include forms of 5-MeO-DMT in which deuterium has been introduced at one or more hydrogen positions of the N-bound methyl group. Still further examples include forms of 5-MeO-DMT in which one or more deuterium atoms replace a hydrogen atom of the indole ring system. It is furthermore noted that combinations of the above substitution patterns are also contemplated.

Methods for preparing these compounds are known in the art.

Mixtures of deuterated forms of 5-MeO-DMT, one or more deuterated forms of non-deuterated 5-MeO-DMT, mixtures of pharmaceutically acceptable salts of deuterated forms of 5-MeO-DMT, mixtures of such salts, and mixtures of salts of deuterated 5-MeO-DMT and non-deuterated 5-MeO-DMT may also be used according to the invention.

Furthermore, according to the present invention, the amount of deuterated 5-MeO-DMT and deuterated 5-MeO-DMT salts used is equimolar with the amount of the corresponding non-deuterated form.

Prodrugs of 5-MeO-DMT and pharmaceutically acceptable salts of such prodrugs may also be used according to the present invention. Such prodrugs of 5-MeO-DMT can be converted to 5-MeO-DMT by metabolism. Thus, when reference is made to the use of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the 5-MeO-DMT prodrug or salt thereof may be substituted.

In suitable prodrugs, the hydrogen in position 1 of the indole moiety is replaced with an organic moiety that may be cleaved upon administration.

Examples of suitable organic moieties are -C(O)OR¹、-C(O)R²、-CH(R³)OR⁴、-C(O)OCH(R³)OC(O)R⁴、-C(O)OCH(R³)OC(O)OR⁴、-CH(R³)C(O)R⁴、-CH(R³)OC(O)R⁴、-CH(R³)OC(O)OR⁴, wherein each of R ¹、R²、R³ and R ⁴ is independently hydrogen, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein each alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are independently substituted or unsubstituted.

Preferred examples of organic moieties are-CH (R ³)OC(O)R⁴ and-C (O) OR ¹, wherein R ¹、R³ and R ⁴ are as defined above.

Prodrugs, particularly prodrugs of the above structures, may also be used in the form of pharmaceutically acceptable salts.

Specific examples of prodrugs are 5-MeO-DMT carboxyisopropyl valine ester, preferably in salt form, especially as bistrifluoroacetate (1- (((S) -2-amino-3-methylbutanoyl) oxy) -2-methylpropyl 3- (2- (dimethylamino) ethyl) -5-methoxy-1H-indole-1-carboxylic acid bistrifluoroacetate) and 5-MeO-DMT methyl pivalate (3- (2- (dimethylamino) ethyl) -5-methoxy-1H-indol-1-yl) methyl pivalate).

Methods of preparing prodrugs as discussed herein are known in the art.

According to the invention, the metabolite 5-MeO-DMT preferably has a T _max value of 1 hour or less, more preferably 0.7 hour or less, especially 0.5 hour or less, measured in male Sprague-Dawley (SD) rats after oral administration of the prodrug of 10 mg/kg.

Furthermore, according to the present invention, the amount of the prodrug of 5-MeO-DMT and the salt of the prodrug of 5-MeO-DMT used is equimolar with the amount of the corresponding non-prodrug form.

Mode of administration

A therapeutically effective amount of 5-MeO-DMT is administered by intravenous administration, intramuscular administration, or subcutaneous administration. Administration via these routes may ensure rapid onset of action. The most preferred route of administration is via the intravenous route, i.e. by intravenous injection.

The 5-MeO-DMT may be used in the form of a pharmaceutically acceptable salt, preferably hydrobromide, or in the form of a formulation for administration via injection, examples of such formulation excipients and vehicles being known in the art.

Dosing regimen

The invention also provides dosage ranges, specific dosages, dosing regimens (administration regimens) and appropriate routes of administration.

The present invention is based, in part, on the inventors' conclusion that upon administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, a peak fantasy experience occurs during the acute phase, which drives the therapeutic benefit of 5-MeO-DMT or a pharmaceutically acceptable salt thereof to a patient diagnosed as defined herein (including a therapeutically resistant form of this disorder, and including this disorder associated with suicidal ideation), particularly one or more aspects of the above defined, either causally or at least as an alternative behavioral marker of a potentially unknown therapeutic mechanism.

Thus, achieving a peak experience faster in a larger proportion of patients and with better repeatability in individual patients will result in a better treatment profile than previously tested hallucinogens, dosing regimens and routes of administration.

Furthermore, the present invention relies on the short duration of action of 5-MeO-DMT and the absence of associated tolerance (i.e., the absence of a diminution or disappearance of the fanciful effect after reapplication) as a basis for achieving frequent reapplication (such as more than once a day or once a day) dosing regimens designed to increase the incidence of peak experiences, thereby increasing therapeutic benefit. Such repeated administration over a short period of time also allows for in vivo dose optimization which reduces the risk of overdosing which might otherwise lead to somatic side effects such as serotonin syndrome, negative mental reactions such as a flashback experienced at a later point in time, evoked mania or hypomania, or a less meaningful fantasy experience (so-called "albinism") resulting in little or no memory to change state. Furthermore, starting from a low dose allows the patient to become familiar with the general fanciful experience and to be ready for more intense symptoms to occur at higher doses, which will have a positive impact on the experience at higher doses. Furthermore, the prospect of being able to begin treatment at low doses will increase patient acceptance of the treatment regimen and increase overall compliance at the patient population level.

Frequent re-administration of serotonin hallucinogens to increase the frequency of peak experiences and modulate the reproducibility of peak experiences, and to increase therapeutic effects, reduce side effects, and increase compliance rates, which may not be achieved when using other hallucinogens, due to the late onset and longer duration of the hallucinogens, and due to rapid development of tolerance (i.e., the attenuation or disappearance of the hallucinogens after re-administration), which may last for several days.

Patients diagnosed with a disorder as defined herein (including a therapeutically resistant form of the disorder and including the disorder associated with suicidal ideation) as defined herein are treated by administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

In a preferred embodiment, 5-MeO-DMT is administered as monotherapy, i.e., the patient does not receive any other treatment for the disorder diagnosed.

The dosage of 5-MeO-DMT administered to a patient diagnosed as defined herein, including a therapeutically resistant form of such disorder and including such disorder associated with suicidal ideation, is in the range of about 1 mg to about 10 mg, or any range therein, and is administered in the form of an administration formulation based on a pharmaceutically acceptable salt of 5-MeO-DMT, such as a hydrobromide salt, the weight of which can be calculated from the prescribed weight of 5-MeO-DMT free base, assuming that equimolar amounts are used. Useful specific amounts of 5-MeO-DMT are, for example, about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6mg, about 7 mg, about 8 mg, about 9mg, and about 10 mg. Note that in this specification, when a range is listed (such as "about 1 mg to about 10 mg"), the inventors contemplate that all discrete values within the range, some of which are explicitly mentioned, but not all of which are mentioned-this is for the sake of brevity only.

In a preferred embodiment, an improved method of treating a patient diagnosed with a disorder as defined herein (including a therapeutically resistant form of the disorder, and including the disorder associated with suicidal ideation) with a therapeutically effective amount of 5-MeO-DMT, as defined herein, comprises developing a clinical response no later than about 2 hours after administration of 5-MeO-DMT.

In a preferred embodiment, an improved method of treating a patient diagnosed with a disorder as defined herein (including a therapeutically resistant form of such disorder, and including such disorder associated with suicidal ideation) with a therapeutically effective amount of 5-MeO-DMT, as defined herein, comprises a sustained clinical response comprising a clinical response occurring no later than about 2 hours after administration of 5-MeO-DMT until at least about 6 days after the last administration of 5-MeO-DMT, preferably until at least about 14 days after the last administration of 5-MeO-DMT, more preferably until at least about 28 days after the last administration of 5-MeO-DMT.

In a preferred embodiment, an improved method of treating a patient diagnosed with a disorder as defined herein (including a therapeutically resistant form of such a disorder, and including such a disorder associated with suicidal ideation) with a therapeutically effective amount of 5-MeO-DMT, as defined herein, comprises administering more than a single dose of 5-MeO-DMT.

In a preferred embodiment, the more than a single dose of 5-MeO-DMT is administered to the patient in one or more treatment blocks, each block consisting of 2 to 7 administrations, the interval between each administration within each treatment block being no less than about 1 hour and no more than about 24 hours, and the interval between the end of one treatment block and the beginning of the next treatment block being no less than about 6 days.

In an even more preferred embodiment, the more than a single dose of 5-MeO-DMT is administered to the patient in one or more treatment blocks, each block consisting of 1 to 3 administrations, the interval between each administration within each treatment block being about 24 hours, and the interval between the end of one treatment block and the start of the next treatment block being no less than about 6 days.

In a most preferred embodiment, the more than a single dose of 5-MeO-DMT is administered to the patient in one or more treatment blocks, each block consisting of 1 to 3 administrations, the interval between each administration within each treatment block being about 1 to 4 hours, preferably 1 to 2 hours, and the interval between the end of one treatment block and the start of the next treatment block being no less than about 6 days.

In embodiments, the dose of 5-MeO-DMT administered to an individual patient in each administration and each treatment block is constant for that individual patient and is selected from about 1 mg to about 10 mg.

In a preferred embodiment, the dose of 5-MeO-DMT administered to an individual patient at the first administration within each treatment block is selected from about 1 mg to about 2 mg, and then increased with each subsequent administration within each treatment block until 10 mg is reached, or the earlier of all administrations within that treatment block are administered.

In an even more preferred embodiment, the dose of 5-MeO-DMT administered to an individual patient at the first administration within each treatment block is selected from about 1mg to about 2 mg and then increased with each subsequent administration within each treatment block until the earlier of 10 mg is reached, or all administration within that treatment block is administered, or the patient experiences a peak fantasy experience, or the attending physician decides that it is not appropriate to further increase the dose depending on the observed side effects.

For the subsequently administered dose-escalating embodiment, the next administered dose is determined by adding about 0.25 mg to about 3 mg, preferably about 0.5 mg to about 3 mg, to the previously administered dose. For example, if the first administered dose is 1 mg and the dose increase is 3 mg, the second administered dose is 4 mg unless one of the aforementioned stopping criteria has been met. Preferably, the dose for the third administration is 7 mg.

In a preferred embodiment, the dose of 5-MeO-DMT administered to an individual patient in each treatment block is selected from about 1mg to about 3 mg at the first administration, and then increased to a dose selected from about 4 mg to about 6 mg at the second administration and to a dose selected from about 7 mg to about 9 mg at the third administration unless the patient has experienced a peak-in-phantom experience within the treatment block or the attending physician decides that it is not appropriate to further increase the dose based on observed side effects. Specific amounts useful for the first, second, and third applications are, for example, about 2 mg, about 5 mg, and about 8 mg.

In another preferred embodiment, the dose of 5-MeO-DMT administered to an individual patient in each treatment block is selected from about 0.5 mg to about 1.5 mg at the first administration, and then increased to a dose selected from about 1.5 mg to about 2.5 mg at the second administration and to a dose selected from about 2.5 mg to about 3.5 mg at the third administration unless the patient has experienced a peak-in experience within the treatment block or the attending physician decides to be unfavorable to further increase the dose based on observed side effects. Specific amounts useful for the first, second, and third applications are, for example, about 1 mg, about 2 mg, and about 3 mg.

In another preferred embodiment, the dose of 5-MeO-DMT administered to an individual patient in each treatment block is selected from about 1.5 mg to about 2.5 mg at the first administration, and then increased to a dose selected from about 3.5 mg to about 4.5 mg at the second administration and to a dose selected from about 5.5 mg to about 6.5 mg at the third administration unless the patient has experienced a peak-in experience within the treatment block or the attending physician decides to be unfavorable to further increase the dose based on observed side effects. Specific amounts useful for the first, second, and third applications are, for example, about 2 mg, about 4mg, and about 6 mg.

In a further preferred embodiment, the dose of 5-MeO-DMT administered to an individual patient in each treatment block is selected from about 2.5 mg to about 3.5 mg at the first administration, and then increased to a dose selected from about 4.5 mg to about 5.5 mg at the second administration and to a dose selected from about 6.5 mg to about 7.5 mg at the third administration unless the patient has experienced a peak-in experience within the treatment block or the attending physician decides to be unfavorable to further increase the dose based on observed side effects. Specific amounts useful for the first, second, and third applications are, for example, about 3 mg, about 5mg, and about 7 mg.

In a further preferred embodiment, the dose of 5-MeO-DMT administered to an individual patient in each treatment block is selected from about 2 mg to about 3 mg at the first administration, and then increased to a dose selected from about 4.5 mg to about 5.5 mg at the second administration and to a dose selected from about 7 mg to about 8 mg at the third administration unless the patient has experienced a peak illusive experience within the treatment block or the attending physician decides that it is not appropriate to further increase the dose based on observed side effects. Specific amounts useful for the first, second, and third applications are, for example, about 2.5 mg, about 5 mg, and about 7.5 mg.

In a further preferred embodiment, the dose of 5-MeO-DMT administered to an individual patient at the first administration of a first treatment block is selected from about 1 mg to about 2 mg and then increased with each subsequent administration within the first treatment block until the earliest of reaching 10 mg, or all administrations within the treatment block have been administered, or the patient experiences a peak fantasy experience, or the attending physician decides that it is not appropriate to further increase the dose based on observed side effects, wherein the highest dose in the first treatment block will be used as the dose for all subsequent treatment blocks and administrations within those subsequent treatment blocks. For example, if the highest dose in the first treatment zone is 8 mg, because the patient experiences a peak illusion experience at that dose, then all subsequent treatment zones, and the doses administered within those subsequent treatment zones, are 8 mg.

In particularly preferred embodiments, the dose of 5-MeO-DMT administered to an individual patient at the first administration of the first treatment block is selected from about 1 mg to about 3 mg, then unless the patient has experienced a peak fantasy experience within the treatment block or the attending physician decides that it is not appropriate to further increase the dose based on observed side effects, the second administration of the first treatment block will be increased to a dose selected from about 4mg to about 6 mg, and the third administration of the first treatment block will be increased to a dose selected from about 7 mg to about 9 mg, wherein the highest dose in the first treatment block will be used as the dose for all subsequent treatment blocks and administration within those subsequent treatment blocks. Specific amounts useful for the first, second, and third administrations in the first treatment zone are, for example, about 2mg, about 5mg, and about 8 mg.

In particularly preferred embodiments, the dose of 5-MeO-DMT administered to an individual patient at the first administration of the first treatment block is selected from about 0.5 mg to about 1.5 mg, then unless the patient has experienced a peak fantasy experience within the treatment block or the attending physician decides that it is not appropriate to further increase the dose based on observed side effects, the second administration of the first treatment block will be increased to a dose selected from about 1.5 mg to about 2.5 mg, and the third administration of the first treatment block will be increased to a dose selected from about 2.5 mg to about 3.5 mg, wherein the highest dose in the first treatment block will be used as the dose for all subsequent treatment blocks and administrations within those subsequent treatment blocks. Specific amounts useful for the first, second, and third administrations in the first treatment zone are, for example, about 1 mg, about 2 mg, and about 3 mg.

In particularly preferred embodiments, the dose of 5-MeO-DMT administered to an individual patient at the first administration of the first treatment block is selected from about 1 mg to about 3 mg, then unless the patient has experienced a peak fantasy experience within the treatment block or the attending physician decides that it is not appropriate to further increase the dose based on observed side effects, the second administration of the first treatment block will be increased to a dose selected from about 3 mg to about 5mg, and the third administration of the first treatment block will be increased to a dose selected from about 5mg to about 7 mg, wherein the highest dose in the first treatment block will be used as the dose for all subsequent treatment blocks and administration within those subsequent treatment blocks. Specific amounts useful for the first, second, and third administrations in the first treatment zone are, for example, about 2mg, about 4mg, and about 6 mg.

In particularly preferred embodiments, the dose of 5-MeO-DMT administered to an individual patient at the first administration of the first treatment block is selected from about 2mg to about 4mg, then unless the patient has experienced a peak fantasy experience within the treatment block or the attending physician decides that it is not appropriate to further increase the dose based on observed side effects, the second administration of the first treatment block will be increased to a dose selected from about 4mg to about 6 mg, and the third administration of the first treatment block will be increased to a dose selected from about 6 mg to about 8 mg, wherein the highest dose in the first treatment block will be used as the dose for all subsequent treatment blocks and administration within those subsequent treatment blocks. Specific amounts useful for the first, second, and third administrations in the first treatment zone are, for example, about 3 mg, about 5mg, and about 7 mg.

In particularly preferred embodiments, the dose of 5-MeO-DMT administered to an individual patient at the first administration of the first treatment block is selected from about 1.5 mg to about 3.5 mg, then unless the patient has experienced a peak fantasy experience within the treatment block or the attending physician decides that it is not appropriate to further increase the dose based on observed side effects, the second administration of the first treatment block will be increased to a dose selected from about 4 mg to about 6 mg, and the third administration of the first treatment block will be increased to a dose selected from about 6.5 mg to about 8.5 mg, wherein the highest dose in the first treatment block will be used as the dose for all subsequent treatment blocks and administration within those subsequent treatment blocks. Specific amounts useful for the first, second, and third administrations in the first treatment zone are, for example, about 2.5 mg, about 5 mg, and about 7.5 mg. It will be appreciated that pharmaceutically acceptable salts of 5-MeO-DMT are preferred for all of the above dosing regimens, and that the appropriate weight of salt to be administered can be calculated from the specified weight of the free base assuming equimolar amounts are used.

According to the invention, 5-MeO-DMT is preferably not administered with MAO inhibitors.

Whether a patient has a "peak fantasy experience" can be identified by reaching at least 60% of the highest possible score in each of the four sub-scales (mystery, positive emotion, override time and space, and self-evident) of the 30 item revised mystery experience questionnaire (MEQ-30) (as described in Barrett FS, J psychacol. 2015;29 (11): 1182-90).

Whether a patient experiences a "peak fantasy experience" can also be identified by reaching at least 60% of the highest possible score for the marine-like borderless feeling (OBN) dimension in the state of consciousness (ASC) questionnaire (as described in Roseman L et al, front Pharmacol.2018; 8:974).

Whether a patient has a "peak fantasy experience" is preferably identified according to the present invention by reaching at least 75 in the Peak Experience Scale (PES) total score, also known as peak fantasy experience questionnaire (PPEQ), which calculates the average score of the patient's answers to three questions from 0 to 100 points, 1. How strong the experience is, 2. How much control is lost, 3. How significant (i.e., profound and important) the experience is?

Sleep disorders

There are two basic types of sleep, rapid Eye Movement (REM) sleep and non-REM sleep. non-REM sleep may be divided into four phases (I-IV). These non-REM phases correspond to an increase in sleep depth. non-REM and REM sleep alternate during four to five cycles of normal human sleep per night. During the early part of the night, the non-REM sleep is deeper and takes disproportionately much more time, especially during the first sleep period. Over the night, non-REM sleep becomes lighter and more time per cycle is allocated to REM sleep.

Normal healthy sleep consists of different phases as described above, which are carried out in a continuous, strictly controlled sequence throughout the night.

Such severe control disruption may lead to sleep disturbance.

Sleep disorders refer to conditions affecting sleep quality, time or duration, whether idiopathic or occurring in the context of a medical condition (e.g., a mental disorder or a neurological disorder). Sleep disorders can affect a person's ability to normally move while awake.

Common forms of sleep disorders encompass disorders that fall asleep and maintain sleep (insomnia), excessive somnolence disorders (hypersomnia), sleep-wake plan disorders (circadian rhythm disorders), dysfunction associated with sleep, sleep stages or partial arousals (abnormal sleep), disorders characterized by respiratory disorders during sleep (sleep-related respiratory disorders), and disorders characterized by abnormal movements during sleep (sleep-related movement disorders).

Insomnia is a sleep disorder in which it is difficult for a patient to fall asleep or to remain asleep. Insomnia patients have difficulty falling asleep, wake often at night and have difficulty falling asleep again, wake too early in the morning, poor sleep quality, and/or at least one daytime problem due to poor sleep quality, such as fatigue, somnolence, emotional problems, inattention, accidents while working or driving, etc.

Excessive sleep is characterized by excessive daytime sleepiness and/or prolonged night sleep time. Intoxication is also a symptom found in patients with excessive sleep. Transition from sleep to wakefulness is very difficult. Individuals experiencing intoxication with sleep report that they are confused, disoriented, slow to move, and repeatedly sleep after waking up.

Circadian rhythm disorders are characterized by chronic or recurrent sleep disorders due to changes in the individual's internal circadian rhythm or due to inconsistencies between its circadian rhythm and its desired or required work or social plan. Such an out-of-sync may be temporary or continuous. Subsequent clinical manifestations combine symptoms of insomnia and hypersomnia. Sleep time is typically shortened and interrupted, performance in the desired awake state is affected, and normal sleep planning is temporarily disabled.

Abnormal sleep refers to various forms of sleep disorders characterized by people experiencing abnormal behavior or physiological activity (such as dream or nightmare) before falling asleep, while sleeping, or during the awake period between sleep and awake. There are considerable differences in characteristics, severity and frequency. Abnormal sleep may impair sleep quality.

Sleep-related breathing disorders are characterized by abnormal breathing and difficulty during sleep. Respiration is a complex process that relies largely on the coordination of the respiratory muscles and the (central control in the) brain. One form of sleep-related breathing disorder is central sleep apnea. This may occur, for example, when the brain stops sending signals to control breathing based on potential health conditions. Central sleep apnea has a potentially serious impact on sleep and the balance of oxygen and carbon dioxide in the blood. The reduced airflow may result in intermittent hypoxia, resulting in disruption of sleep due to micro-arousal or wakefulness. The result may be excessive daytime sleepiness.

In sleep-related dyskinesias, repetitive, relatively simple, often primitive movements can interfere with sleep or the onset of sleep. Among the most common are Restless Leg Syndrome (RLS) and Periodic Limb Movement Disorder (PLMD).

Insufficient sleep time or quality may lead to personality changes and may not only exacerbate existing mental illness but also be a cause of mental illness development. Sleep disorders may also interfere with cognitive function and lead to memory impairment. Subjects lacking sleep may experience difficult decisions, irritability, poor performance, and may slow down the response time. Insufficient sleep can also lead to the development of obesity, diabetes and heart disease, which can adversely affect life.

Treatment of sleep disorders varies depending on the type and underlying cause. Maintaining good sleep hygiene, a healthy sleep environment, and a consistent sleep-wake plan are often considered first-line therapies. If unsuccessful, the treatment also involves drug therapy or psychotherapy.

The available treatments are unsuccessful in all patients, may be associated with side effects and/or require long-term treatment to achieve the associated therapeutic effects.

In patients suffering from sleep disorders associated with mental or neurological disorders, known treatments of mental or neurological disorders do not necessarily improve sleep disorders.

For example, sleep disorders are frequently associated with mental disorders such as depression. However, treatment of depression does not necessarily lead to an concomitant improvement in sleep disturbance. While most antidepressants have been shown to affect sleep architecture, some classes of antidepressants improve sleep, while other antidepressants may cause sleep impairment.

While sleep disorders may be considered to be a condition that should be treated, irrespective of any other condition, disorder or symptom an individual may suffer from, several mental disorders and neurological disorders are associated with sleep disorders. Notably, the relationship between sleep and mental or neurological disorders is often bi-directional. Not only does a mental or neurological disorder negatively affect a healthy sleep pattern, but sleep disorders may also be causative of the onset, progression and prognosis of a mental health or neurological disorder.

Treatment according to the present invention may reduce or eliminate sleep disorders and preferably may also ameliorate related mental or neurological disorders.

Measuring sleep disorders

Sleep may be assessed by measuring parameters such as sleep duration, sleep structure, sleep latency, frequency and duration of wakefulness throughout the night. Quantitative indicators may be measured using objective methods, including polysomnography, a wrist meter (actigraphy), and determination of sleep latency, or by self-reporting measurements (questionnaires).

Polysomnography is a technique that requires overnight monitoring of patients in a specialty clinic. Various functions were measured throughout the night, including eye movements, brain and muscle activity, respiratory effort and airflow, blood oxygen levels, body posture and movement, snoring and heart rate.

Another quantitative measurement is a wrist-watch. Wrist-watch sensors are worn to measure athletic activity, which is continuously recorded and used to evaluate sleep-wake cycles. This technique allows the patient to continue to live normally while recording the required data in a natural sleep environment.

Sleep latency may be measured by a Multiple Sleep Latency Test (MSLT). This test provides an objective measure to determine how long a person takes to fall asleep after multiple test sleeps. An average sleep latency of about 10 minutes is considered normal, and less than eight minutes indicates sleep disturbance (excessive daytime sleepiness). Accompanying brain activity analysis may help to further diagnose sleep disorders.

Sleep assessment questionnaires record the assessment of components of sleep quality, such as perception of sleep depth, difficulty of arousal, and post-sleep rest conditions, as well as other factors that may affect sleep quality, such as co-disorders and drug use. Evaluation of the qualitative aspects of the sleep experience is very important because sleep discomfort may often persist despite normal values of the quantitative measure of sleep.

The questionnaire not only helps to quickly and accurately assess complex clinical problems, but may also help to track patient progress.

A variety of sleep quality indices are known. The following indices include examples of questionnaires for assessing general sleep and examples of questionnaires for assessing, inter alia, insomnia, excessive sleep, circadian rhythm disorders, and abnormal sleep, respectively. However, the invention is not limited to the use of a particular index or questionnaire.

Some questionnaires rely on recall periods (recall windows) of days or even weeks. While this may be suitable for diagnosing sleep disorders, it is not always suitable for assessing the effect of a treatment, in particular the effect of a rapid onset of action after treatment. For several questionnaires, the recall period may be modified so that the score obtained reflects a period of time after treatment. In particular, a questionnaire for assessing the sleep effect of a treatment on patients suffering from a particular disorder is discussed herein, which questionnaire relies on a recall period whose onset is no earlier than the point in time at which the acute fantasy experience subsides after the last administration. To meet this criterion, the recall period of the normal application is modified, if necessary.

For example, a sleep-50 questionnaire may be used to assess general sleep quality.

Sleep-50 questionnaires consist of 50 items designed to screen the general population for various sleep disorders. The scales consist of nine sub-scales reflecting some of the most common disorders and discomforts associated with sleep and factors required for diagnosis, such as sleep apnea, insomnia, narcolepsy, restless legs/periodic leg movement disorders, circadian rhythm sleep disorders, dream, nightmare, factors affecting sleep, and the effects of sleep discomforts on daily functions. For each item, the answer is given a scale from 1 ("no at all") to 4 ("very many") and is asked to indicate how well the statement matches their last month or experience with another suitable recall window.

In order to diagnose sleep disorders, not only must a particular sub-scale (e.g., insomnia) exceed a certain cut-off point, but the answer must also reach at least 3 or 4 (respectively "quite many" or "very many") cut-off points (Spoormaker et al, initial validation of the SLEEP-50 questionnaire, behav Sleep Med. 2005;3 (4): 227-46) on the sub-scale that evaluates the effect of sleep discomfort on daily functioning.

Treatment success is expressed as a decrease in (i) score, preferably a decrease in (ii) score below a cutoff value.

A common questionnaire for assessing sleep disorders is the Pittsburgh sleep quality index (Pittsburgh Sleep Quality Index). Other tools are insomnia severity index, espie sleep disorder questionnaire, and patient report outcome information measurement information system (Patient Reported Outcomes Measurement Information System, proci ^®) sleep disorders.

The Pittsburgh Sleep Quality Index (PSQI) evaluates overall sleep quality and sleep disturbances. PSQI is a self-assessment questionnaire containing 19 questions. The person asking the answer indicates how often they have experienced certain sleep difficulties in the past month or another suitable recall window.

The 19 self-assessment questions evaluate a variety of factors related to sleep quality, including estimates of sleep duration and latency, and estimates of the frequency and severity of particular sleep-related questions. The 19 items are divided into 7 component scores, namely (1) subjective sleep quality, (2) sleep latency, (3) sleep duration, (4) habitual sleep efficiency, (5) sleep disorder, (6) hypnotic use and (7) daytime dysfunction.

Each ingredient was scored from 0 to 3. The higher the score, the more severe the sleep disturbance. A detailed scoring description of the pittsburgh sleep quality index can be found in the annex of Buysse et al The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213.

The seven component scores are then added to arrive at a total score ranging from 0 to 21 points, "0" indicating no difficulty and "21" indicating serious difficulty in all areas. A total score cutoff of 5 distinguishes people with poor sleep quality from people with good sleep quality. A total score of > 5 indicates that the patient has serious difficulties in at least two areas, or moderate difficulties in more than three areas.

If PSQI is used to evaluate the outcome of the treatment, treatment success is indicated by a decrease in (i) score, preferably a decrease in (ii) score of 5 or less.

The Insomnia Severity Index (ISI) is a brief questionnaire that relates to subjective sleep quality, severity of symptoms, subjective satisfaction with sleep, degree of disturbance of insomnia to daily functions, how pronounced an answer person feels his or her insomnia compared to others, and the overall level of confusion caused by sleep problems. The individual answers can be scored from 0 (=none) to 4 (=very), with higher total scores corresponding to more severe insomnia. A total score of 0-7 means "no clinically significant insomnia", 8-14 means "subthreshold insomnia", 15-21 means "clinical insomnia (moderate severity)", and 22-28 means "clinical insomnia (severe)" (a. Shahid et al (edit), STOP, THAT and One Hundred Other SLEEP SCALES, SPRINGER SCIENCE + Business Media, LLC 2012; recall window is two weeks, another suitable recall window may also be used.

Treatment success is expressed as (i) a decrease in score, e.g., a decrease of >7 points, particularly >8 points, and preferably (ii) a decrease in score below the cutoff value for clinically significant insomnia.

Espie Sleep Disorder Questionnaire (SDQ) evaluates the subjective experience of insomnia. SDQ assesses restlessness/agitation, overactive spirit, insomnia consequences and sleep preparation insufficiency, focusing on the belief of the root cause of sleep problems. The answer sheet person uses a five-component scale to indicate that certain statements about insomnia represent the frequency they experience. 1 means "never true", and 5 means "often true". The higher the score, the more unusual the belief that the cause and related factors of insomnia (a. Shahid et al, supra).

A decrease in score indicates successful treatment.

Patient report outcome information system (proci) ^® sleep disorder tools are a general method of assessing sleep disorders. The tool has one long table and 4 different short tables (e.g., 4, 6, and 8 items) and evaluates self-reported sleep quality, perception of sleep depth, and any perceived difficulties associated with falling asleep and staying asleep within 7 days.

Each item in the measurement is rated in a 5-component table. The raw scores of the items are added to obtain a total raw score. The total raw score is then converted to a normalized T score using a conversion table.

A decrease in T score indicates successful treatment.

Hypersomnia or excessive somnolence can be assessed by the epwoth somnolence scale (Epworth SLEEPINESS SCALE), the Stanford somnolence scale (Stanford SLEEPINESS SCALE) or the idiopathic hypersomnia severity scale (Idiopathic Hypersomnia SEVERITY SCALE).

The Eplerian Sleepiness Scale (ESS) evaluates the overall daytime sleepiness. Questionnaires require that the respondents assess their likelihood of falling asleep in eight different situations, representing moments of relative inactivity, such as sleeping at the afternoon or sitting in a car parked in traffic. The answer sheet persons rated their likelihood of falling asleep using a scale of 0-3 (0 means "never doze" and 3 means "likely doze"). The score ranges from 0 to 24, with higher scores having a higher severity of daytime sleepiness. A cut-off score of 10 indicates that daytime sleepiness may occur at the clinical level (a. Shahid et al, supra).

Treatment success is expressed as a decrease in (i) score, preferably a decrease in (ii) score of 10 or less.

The Stanford sleepiness scale is a subjective measure of sleepiness that evaluates the degree of sleepiness at a particular time. The scale consists of only one item, requiring the answer person to select one of the seven statements that is most representative of the level of somnolence they currently perceive. Sleepiness levels were assessed using a scale from 1 (=sensory active and active; alert; fully awake) to 7 (=almost in phantom; fast sleep state; inability to stay awake) (a. Shahid et al, supra).

A decrease in score indicates successful treatment.

Abnormal sleep may be assessed by the Paris wake disorder severity scale (PADSS).

The Paris wake disorder severity scale (PADSS) is a self-rating scale listing the abnormal sleep behavior, assessing the frequency of the abnormal sleep behavior, and including an assessment of the outcome (Arnulf et al, A scale for ASSESSING THE SEVERITY of arousal disorders, sleep, 2014, 1, 37 (1): 127-36).

Treatment success is expressed as a decrease in (i) score, preferably a decrease in (ii) score below a cutoff value.

A common questionnaire for assessing sleep-related respiratory disorders is the Berlin questionnaire (A. Shahid et al, supra). An appropriate recall period may also be selected.

A decrease in score indicates successful treatment.

A common questionnaire for assessing sleep-related dyskinesias is the International restless leg syndrome research group rating scale (International RESTLESS LEGS Syndrome Study Group RATING SCALE). The 10-item questionnaire requires the respondent to use the Liktet rating method to indicate how severe this disorder has affected them in the past week. Problems can be divided into two categories, symptoms of disorders (nature, intensity and frequency) and their effects (sleep problems, daily dysfunction and the resulting mood changes). Each of the ten questions required the respondents to rate their RLS experience on a scale of 0 to 4, with 4 representing the most severe and frequent symptoms and 0 representing the least symptoms. The total score range may be 0 to 40. As a concise scale with excellent psychological measurement quality, the tool may be suitable for a variety of research and clinical purposes, including screening and evaluating therapeutic results. (A. Shahid et al, supra).

Treatment response can be assessed by a decrease in score.

Resting state network and sleep disturbance

Brain processes can be studied by functional magnetic resonance imaging (fMRI). Brain activity is related to blood flow and the time dependence of spontaneous Blood Oxygen Level Dependent (BOLD) signal fluctuations between different brain regions can be measured.

Functional images of the brain are obtained in a few minutes. A low frequency BOLD signal oscillation mode is observed throughout the brain. The decomposition of the spontaneous signal reveals a distribution region with correlated fluctuations and negatively correlated fluctuations.

In this way, resting state fMRI can be used to characterize a large scale functional network, the so-called Resting State Network (RSN), which is a set of spatially diverse brain regions that exhibit coordinated activity in the absence of any explicit cognitive tasks (i.e., at rest). The observed pattern characterizes a brain area network with a coherent pattern of signal changes, which is called a Resting State Network (RSN).

Different resting state networks have been identified and named based primarily on the spatial similarity between the resting state network and the activation pattern observed in the task fMRI experiments.

Thus, resting state fMRI can be used to assess the intrinsic functional tissue of the brain. The resting state network is characterized by aspects of attention, memory, cognitive control, default mode, motor and sensory systems.

RSN has proven to be responsible for various aspects of complex brain functions, and these connected networks have been found to be compromised in various disease states. Such disease states are associated with changing functional connections within a particular resting state network and/or between one or more areas in one or more additional resting state networks.

Altered resting state networks can be found in insomnia, hypersomnia, circadian rhythm disorders, abnormal sleep, sleep-related breathing disorders, and sleep-related movement disorders.

One key network involved in sleep is the Default Mode Network (DMN). In general, DMN's are deactivated during tasks and activated at rest. It is involved in a variety of cognitive processes such as advanced cognition, emotion and internal perception. During sleep, its overall activity level may decrease. Given the importance of DMN to sleep physiology, altered DMN activity is particularly relevant to sleep disorders.

As discussed further herein, an impaired resting state network may also be found in a mental or neurological disorder.

The resting state network associated with sleep disorders may also be affected by mental or neurological disorders resulting from certain medical health disorders.

In insomnia patients, dysfunctional connectivity is observed within the Default Mode Network (DMN) and within the significance network, which is related to the detection and integration of emotional and sensory stimuli. Studies have shown that these networks contain critical areas of integrated affective and physical state, and that dysfunction of functional connections within and/or between these networks and other brain areas can be responsible for patient alertness, subjective confusion, and poor sleep continuity.

In hypersomnia patients, the default mode network is affected. For example, in idiopathic hypersomnia, the different DMN centers (prefrontal and medial prefrontal cortex) show significant changes, and functional links in DMN are associated with self-reported somnolence severity.

A study studying the differences between night shift nurses and day shift nurses revealed that circadian dysrhythms promote changes in resting state functions in the cerebellum, involving sleep regulation and cognitive functions (such as reactivity and alertness). Furthermore, the functional link of DMN is fundamentally different in early and late circadian phenotypes. As with other forms of sleep disturbance, circadian rhythm disorders result in changes in brain function connections. Changes in resting state brain function connections in various diseases with circadian rhythm disorders have been reported.

While performing functional brain imaging during an abnormal sleep event is technically difficult, differences in anterior wedge lobes have been observed in wake disorders that represent non-REM abnormal sleep.

The anterior wedge lobes are involved in the analysis and integration of visual, auditory and somatosensory information and in the monitoring of movement. The anterior wedge lobe is a sub-region of the DMN. Thus, in patients with abnormal sleep, the default mode network may be affected.

Resting fMRI studies on patients suffering from sleep-related respiratory disorders such as central sleep apnea indicate the presence of serious global and regional connectivity defects, particularly in Default Mode Networks (DMN) and in regions involving arousal and sensorimotor systems.

Sleep-related dyskinesias, such as periodic limb movements during sleep, are reflected by changes in the forehead lobe movement control pathway (a sub-region of the default mode network). In addition, activity in the cerebellum and thalamus, as well as additional activation in the red nucleus and brainstem, can be observed.

In many cases, abnormal functional connections of the resting state network associated with sleep disturbances are also associated with the above mentioned disorders. Thus, according to the invention, influencing these networks by means of the therapy according to the invention will lead to an improvement of sleep disorders and, if the treated patient suffers from a mental disorder or a neurological disorder, also to an improvement of said disorder.

Treatment of sleep disorders and disorders of the mental and nervous system

According to the present invention, idiopathic sleep disorders can be treated as well as sleep disorders in patients suffering from mental disorders or neurological disorders. In patients suffering from sleep disorders associated with mental or neurological disorders, the treatment of sleep disorders according to the invention results in an improvement of the disorders associated with sleep disorders.

In many cases, resting state networks associated with sleep disorders are also associated with the above mentioned disorders.

The 5-MeO-DMT can interrupt an established functional connection mode of the rest state network. When the network is reconnected, this disruption can lead to a reset of the ill-connected brain connection. A new, healthy functional connection is established and has a continuous impact.

The neuroplasticity-promoting characteristics of 5-MeO-DMT may explain the persistence of this effect. 5-MeO-DMT promotes in particular structural and functional plasticity of synapses (i.e., sites where neurons interconnect and communicate). 5-MeO-DMT regulates the morphogenesis and maturation of dendritic spines, thereby initiating the formation of new synaptic connections. These new connections will be strengthened or weakened or even eliminated depending on the activity.

The new synapses that eventually form can in turn affect the pattern of neuronal activity. The inventors concluded that such mutual structural and functional modifications contribute to the correct establishment of the network and the persistence of the effect after 5-MeO-DMT administration.

From a biochemical point of view, 5-MeO-DMT interacts with 5-HT receptors, among others.

The 5-HT receptor, the receptor for the neurotransmitter serotonin or 5-hydroxytryptamine (5-HT), is distributed throughout the central and peripheral nervous system. A variety of physiological and pathological functions are mediated through these receptors.

In the brain, seven types of 5-HT receptors are expressed, which can be further divided into several subtypes. Each type and subtype shows a different spatial distribution.

5-MeO-DMT interacts with several 5-HT receptors. These receptors are involved in mediating the effects of 5-MeO-DMT on resting state networks and neural plasticity.

In addition to the 5-HT1A and 5-HT2A discussed above, 5-MeO-DMT also interacts with 5-HT7 receptors. 5-MeO-DMT acts as an agonist of this receptor and exhibits high (nanomolar) binding affinity.

The 5-HT7 receptor plays a role in neurogenesis, synaptogenesis and dendritic spine formation. It is associated with, among other things, central processes such as learning and memory, sleep regulation and circadian rhythms, and nociception.

The 5-HT7 receptor is expressed in particular in the spinal cord, the middle suture nucleus, the thalamus, the hypothalamus (including the supravisual nucleus), the hippocampus, the prefrontal cortex, the striatal complex, the amygdala, and the Purkinje neurons of the cerebellum.

The supravisual nucleus is the central pacemaker of the circadian timing system. It coordinates the circadian rhythms of various areas of the brain. Disruption of this coordination will lead to disease states, particularly those involving sleep disorders. In patients suffering from sleep disorders, resting state functional connection analysis reveals a change in functional connection between the supraoptic nucleus and regions within the default mode network.

The expression of the 5-HT7 receptor in the nucleus of the visual junction corresponds to the role of said receptor in the regulation of the sleep/wake cycle. The inventors believe that this allows treatment of patients suffering from sleep disorders by acting on the receptor 5-MeO-DMT.

The inventors believe that the binding of 5-MeO-DMT to the 5-HT7 receptor (as an mediator of the pharmacological action of 5-MeO-DMT) involves a "reset" of the functional link of the network and a neuroplastic effect, contributing to the beneficial effect of 5-MeO-DMT in treating patients suffering from sleep disorders.

The inventors further believe that the binding of 5-MeO-DMT to 5-HT7 receptor and 5-HT1A receptor (two mediators that function as 5-MeO-DMT) includes a network of functional link "reset" and neuroplastic effects, allowing beneficial effects to be achieved in patients suffering from other symptoms or disorders such as cognitive dysfunction, anxiety, bradykinesia, negative thinking, or social/emotional withdrawal. The clinical results shown in the studies mentioned herein support this.

Treatment according to the invention will result in an improvement of sleep disorders and, if the treated patient suffers from a mental or neurological disorder, also in an improvement of said disorder.

Clinical data from studies in patients suffering from treatment-resistant depression (TRD) or post-partum depression (PPD) demonstrate that sleep disorders can be successfully treated by administration of 5-MeO-DMT.

In the TRD study described in more detail in the examples section below, the MADRS project "sleep reduction" reflecting insomnia was evaluated, among other things.

The MADRS project "sleep reduction" represents the experience of reduced sleep duration or depth compared to the normal mode when the subject is healthy itself. When the subject sleep normally, the score is 0. Score 2 reflects a slight difficulty in falling asleep, or a slight decrease, shallowness, or intermittent sleep time. Score 4 means sleep time is reduced or discontinued for at least two hours. A score of 6 means that the sleep time is less than two hours or three hours.

In the study group receiving the personalized dosing regimen, the total score for the MADRS project "sleep reduction" for all 8 patients was 25 at baseline. On day 1 post-treatment, the earliest time point at which the effect of treatment on sleep was assessed, the score was reduced to 12, which corresponds to a 13 point or 52% improvement. On day 7 post-treatment, the score dropped to 9, which corresponds to a 16 point or 64% improvement.

In the 12 mg group, the total score for the MADRS project "sleep reduction" for all 4 patients was 12 at baseline. On day 1 after treatment, the score decreased to 10, which corresponds to a2 score or 17% improvement. On day 7 post-treatment, the score decreased to 6, which corresponds to a 6 score or 50% improvement.

Thus, the scale item "sleep reduction" associated with sleep disorders is a significant improvement in scoring. The inventors concluded that 5-MeO-DMT can be used for the treatment of sleep disorders, in particular patients suffering from mental disorders or neurological disorders.

Cognitive dysfunction

Cognition includes the skills required to think, memorize, pay attention to and solve a problem. Loss or decline of these skills can lead to cognitive dysfunction, and the term as used herein refers to any deficit or impairment in the cognitive domain. Cognitive dysfunction may be one of the manifestations of a patient's underlying illness.

DSM-5 defines six key areas of cognitive function, namely complex attention, executive function, learning and memory, language, perceived motor function and social cognition.

Cognitive dysfunction can affect one or more of these areas. In fact, cognitive abilities are highly relevant, and it is not uncommon for more than one area to be affected.

For example, domain complex attention has sub-domain continuous attention (commonly referred to as "focus" or "concentration"), distraction, selective attention, and processing speed.

Thus, complex attention clearly covers aspects critical to various cognitive tasks, such as performing functions and learning and memory. Cognitive control or executive function is attention in nature. In addition, perception and decision making are also deeply affected by the ability to pay attention to.

Thus, attention can be tested not only alone, but also through cognitive control tasks/executive functions. If attention is impaired, other types of cognitive abilities may also be impaired. Before understanding language, perceiving visual space relationships, remembering information, or solving problems, care must be taken to stimulate.

Cognitive dysfunction (the term means herein an acquired disorder and thus represents a decline in functional levels from previously achieved) may be associated with a variety of processes.

In healthy individuals, certain cognitive abilities, such as accumulated knowledge and vocabulary, may be maintained during the aging process and may even increase over time. However, aging can lead to a decrease in the ability to abstract thinking, reasoning and decisions, even in the absence of any pathological conditions. These exacerbations are associated with potential age-related deficiencies in processing speed, attention, memory and executive function (which indicate cognitive aging).

In addition to normal aging, cognitive dysfunction may be associated with mental or neurological disorders or some other medical condition.

Mental or neurological disorders as discussed herein may lead to or be associated with cognitive dysfunction.

Furthermore, cognitive dysfunction occurs in disorders that exhibit symptoms characteristic of cognitive dysfunction that can lead to clinically significant distress or impairment in social, professional, or other important areas of function, but do not meet all of the criteria for any etiologically related disorder.

Cognitive dysfunction may take the form of neurocognitive dysfunction.

Mild neurocognitive impairment is also known as mild cognitive impairment and is characterized by a mild cognitive decline in one or more areas of cognition compared to previous performance levels. The affected patient can still remain independent and complete daily tasks. However, patient function is often at a suboptimal level. The daily task becomes more laborious as compensation strategies are employed to maintain independence.

In severe neurocognitive disorders, a significant decline in cognitive ability in one or more areas of cognition is observed over previous performance levels. Cognitive deficits can interfere with the independence of daily activities.

Measuring cognitive dysfunction

Cognitive dysfunction can be assessed by questionnaire or neuropsychological assessment.

The questionnaire evaluates the mental state of the patient based on observations of the patient himself, the caregiver, or the clinician filling the questionnaire. A questionnaire for assessing whether a patient suffers from a particular mental or neurological disorder may include items related to cognitive function.

Neuropsychological assessment is the process of comprehensively evaluating a person's cognitive, psychological/emotional and behavioral functions. One core component of neuropsychological assessment is the administration of neuropsychological tests for the formal assessment of cognitive function.

The performance of these tests was compared to criteria appropriate for the age, education level and cultural background of the patient. Testing typically uses a set of performance-based questions, also known as neuropsychological suites.

The capabilities tested included language processing, visual space processing, attention/concentration, speech learning and memory, visual learning and memory, executive function, processing speed, and sensory perception function.

Common tests that assess cognitive dysfunction are Montreal cognitive assessment (MoCA), simple mental state examination (MMSE), mini-CogTM, psychiatric cognitive impairment Screening (SCIP), and MATRICS consensus cognitive complete test (MCCB).

Montreal cognitive assessment (MoCA) is a screening assessment that is widely used to detect cognitive impairment. It evaluates different cognitive domains, short term memory, visual space ability, executive function, attention, concentration and working memory, language, time and spatial orientation. The total score possible was 30, 26 or more, 18-25 as mild cognitive impairment, 10-17 as moderate cognitive impairment, and less than 10 as severe cognitive impairment.

Simple mental state examination (MMSE) is a measurement tool for 11 questions that test five areas of cognitive function, targeting, recording, attention and computing, recall, and language. And is divided up to 30. The original score may also need to be modified according to education level and age.

The severity of cognitive impairment is classified herein using four cut-off levels, 24-30 means no cognitive impairment, 19-23 means mild cognitive impairment, 10-18 means moderate cognitive impairment, and +.9 means severe cognitive impairment.

Repeatedly, MMSE is suitable for measuring changes in cognitive state.

Mini-Cog ^TM is a short cognitive impairment screening questionnaire. It combines 3 word recall with a clock drawing test. The clocked drawing test evaluates many cognitive areas that may be affected, such as executive function, visual space ability, motor programming, and attention. After clock drawing test, a score can be obtained for each correct recall of three words, and a clock value is correctly drawn for two scores. Score <4 indicates cognitive impairment.

Psychiatric cognitive impairment Screening (SCIP) is a well-evaluated screening tool for examining cognitive performance in psychiatric patients.

SCIP consists of five sub-scales, speech learning test-immediate (VLT-I), working Memory Test (WMT), speech fluency test (VFT), speech learning test-delay (VLT-D), and Processing Speed Test (PST). There are three different test formats to facilitate repeated tests, thereby reducing learning effects. Each sub-scale score for the five tests is calculated and a total score is calculated from the sum of the sub-scale scores. A total score below 70 indicates cognitive dysfunction.

Cognitive dysfunction may also be assessed by MCCB (MATRICS consensus cognitive test) or one or more different sub-tests. These subtasks include the link test A section (test processing speed), the schizophrenic cognitive ability conciseness assessment, the symbol code subtest (processing speed), the Hopkins language learning test-revision, immediate recall, only three learning tests (language learning), west memory scale 3 rd edition, spatial breadth subtest (working memory (nonverbal)), the letter-number breadth test (working memory (speech)), the neuropsychological assessment kit, the maze subtest (reasoning and problem solving), the concise visual spatial memory test revision (visual learning), the category fluency test, the animal naming (processing speed), the Mayer-Salovey-Caruso lover test, managing emotion branches (social cognition), and the sustained performance test, the same paired version (attention/alertness).

The kit is suitable for measuring cognitive changes.

Further tests include a speech recognition memory (VRM) test, a rapid visual information processing (RVP) test, a Spatial Working Memory (SWM) test, and a digital symbol replacement test (DSST).

Potential mechanisms of cognitive dysfunction

Brain processes can be studied by functional magnetic resonance imaging (fMRI). Brain activity is related to blood flow and the time dependence of spontaneous Blood Oxygen Level Dependent (BOLD) signal fluctuations between different brain regions can be measured.

Functional images of the brain are obtained in a few minutes. A low frequency BOLD signal oscillation mode is observed throughout the brain. The decomposition of the spontaneous signal reveals a distribution region with correlated fluctuations and negatively correlated fluctuations.

In this way, resting state fMRI can be used to characterize a large scale functional network, the so-called Resting State Network (RSN), which is a set of spatially diverse brain regions that exhibit coordinated activity in the absence of any explicit cognitive tasks (i.e., at rest). The observed pattern characterizes a brain area network with a coherent pattern of signal changes, which is called a Resting State Network (RSN).

Different resting state networks have been identified and named based primarily on the spatial similarity between the resting state network and the activation pattern observed in the task fMRI experiments.

Thus, resting state fMRI can be used to assess the intrinsic functional tissue of the brain. The resting state network is characterized by aspects of attention, memory, cognitive control, default mode, motor and sensory systems.

RSN has proven to be responsible for various aspects of complex brain functions, and these connected networks have been found to be compromised in various disease states. Such disease states (including some forms of cognitive dysfunction) are associated with altered functional connections within a particular resting state network and/or between one or more areas in one or more additional resting state networks.

Resting state fMRI is particularly advantageous when studying populations affected by cognitive dysfunction, as it is able to examine functional connectivity while removing task requirements that may be confused by potential cognitive or motor impairment.

The cognitive processes are reflected by the functional connections of certain brain regions located within and/or between regions of different networks.

In particular, certain core networks, also known as "higher order cognitive networks," appear to be critical to most mental activities.

A frontal control network (FPCN) (also referred to as a frontal network (FPN)), a Central Executive Network (CEN), or an Executive Network (EN), typically associated with executive functions. These functions include saving and updating relevant information in working memory, suppressing impulse responses, and guiding decision and goal-directed actions using flexible problem-solving strategies.

The other core network is a Default Mode Network (DMN). DMN contains areas in the brain that are most active when an individual's attention is not focused on any particular task. The activities of DMN are related to introspection, contextual memory, memory consolidation, integration of social and self-related cognition, cognition and emotion processes, and task independent free ideas.

The third network is a saliency network, also known as a cingulum island cap network (cingulo-opercular network). This network involves identifying significant stimuli and events, i.e., stimuli and events that other brain networks need to be concerned with. This network plays a central role in controlling mental processes and behaviors.

The fourth network is a backside attention network (DAN). DAN is related to a top-down, target-directed attention process.

The network does not operate independently. In fact, there are countless links between them. The cooperation between networks is critical to the functionality of a particular task.

Throughout the life cycle, the brain network undergoes functional reorganization with concurrent impact on cognition. Age-related changes are observed in higher order cognitive networks during healthy aging.

Patients suffering from cognitive dysfunction exhibit altered functional connections within and/or between resting state networks compared to age-matched healthy controls. Changes are observed within and/or between the default mode network, the executive network, the saliency network, and the back-side attention network.

In many cases, the resting state network involved in cognition is affected by mental or neurological disorders as discussed herein.

Resting state networks involving cognition are also affected by mental or neurological disorders that are the result of certain medical health disorders as well as unspecified neurocognitive disorders.

Furthermore, the resting state network involved in cognition may be affected by sleep disturbances (e.g., insomnia). In fact, cognitive dysfunction and sleep impairment are related.

Patients suffering from sleep disorders may have deteriorated cognitive function, and patients suffering from cognitive dysfunction often also suffer from impaired sleep.

Treatment of cognitive dysfunction

According to the present invention, cognitive dysfunction occurring in patients suffering from mental disorders or neurological disorders or medical health disorders resulting in related mental or neurological disorders can be treated. In addition, cognitive dysfunction that occurs in patients suffering from sleep disorders (e.g., insomnia) can be treated.

Cognitive dysfunction in unspecified neurocognitive disorders can also be treated.

In patients suffering from cognitive dysfunction associated with another disorder detailed above, treatment of cognitive dysfunction according to the present invention results in an improvement of the disorder associated with cognitive dysfunction.

The treatment according to the invention is by administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Administration of 5-MeO-DMT to a patient can disrupt established functional connection patterns within and/or between the resting state network. Such an interruption may result in a reset of ill-connected connections when the network is reconnected. A new, healthy functional connection is established and has a continuous impact.

Thus, according to the invention, affecting these networks by therapy as described herein will result in an improvement of cognitive dysfunction and, if the treated patient suffers from a mental or neurological disorder, will also result in an improvement of the relevant mental or neurological disorder if the treated patient suffers from a medical health disorder resulting in the relevant mental or neurological disorder, will also result in an improvement of sleep disorders (e.g. insomnia) if the treated patient suffers from sleep disorders (e.g. insomnia), and will also result in an improvement of one or more other symptoms of the disorder if the patient suffers from an unspecified neurological cognitive disorder.

To further support the clinical use of 5-MeO-DMT in patients suffering from cognitive dysfunction, the inventors evaluated clinical data related to the use of 5-MeO-DMT in patients receiving treatment for mental disorders and noted a particular improvement in cognitive dysfunction, which is often observed in patients suffering from other disorders as well.

The data were derived from a recently completed clinical trial using 5-MeO-DMT therapy to diagnose patients with treatment-resistant depression (TRD; see also the examples section below). While TRD is a particular disorder, as discussed in detail below, the inventors determined that certain clinical observations made in the trial were relevant to designing treatments for other disorders associated with cognitive dysfunction.

In clinical trials, 5-MeO-DMT was administered via inhalation (described in more detail in the examples section below). Patients are assigned to different groups. In the context of the present invention, it is of interest to have a group receiving a single 12 mg dose, and a group receiving an intra-day personalized dosing regimen (IDR) that allows for multiple increases in doses (6 mg, 12 mg and 18 mg) within a day, depending on the intensity of the patient's reported fantasy experience.

The data collected included an assessment of the treated patients for several scales including the montgomery-arabic depression rating scale (MADRS) and the Brief Psychosis Rating Scale (BPRS). While the focus of the trial is to demonstrate treatment efficacy through an increase in overall MADRS score, the inventors focused on the items that make up the various rating scales, and noted that specific sub-score items (e.g., items related to cognitive dysfunction) are related to other disorders in which cognitive dysfunction is based on similarly altered functional connections within and/or between default mode networks, executive control networks, saliency networks, and back attention networks.

The results demonstrated that the inventors' findings, 5-MeO-DMT, are a suitable compound for treating patients presenting with these symptoms.

More specifically, one aspect that can be treated by administration of 5-MeO-DMT is cognitive dysfunction, particularly where attention is hard to concentrate. The 5-MeO-DMT may be administered to a patient to reduce or eliminate cognitive dysfunction in the patient, particularly with difficulty in concentrating.

The MADRS project that is particularly relevant to concentrating and memory impairment is "hard to concentrate". This item represents the idea that it is difficult to collect individuals, resulting in a failure to concentrate on, with a score ranging from 0 to 6. If the patient has no difficulty concentrating, the score is 0. If it is occasionally difficult to collect personal ideas, the score is 2. If it is difficult to concentrate on and maintain thought difficulties, resulting in reduced reading or dialogue ability, the score is 4. If the patient is unable to read or talk easily, the score is 6.

In the study group receiving the personalized dosing regimen, the total score for the MADRS project "hard to focus" for all 8 patients was 30 at baseline.

After 2 hours, the score decreased to 11, which corresponds to a 19 point or 63% improvement. On day 1 after treatment, the score decreased to 1, which corresponds to 29 points or 97% improvement. On day 7 post-treatment, the score dropped to 9, which corresponds to a 21 point or 70% improvement.

In the 12 mg group, the total score for the MADRS project "hard to focus" for all 4 patients was 16 at baseline.

After 2 hours, the score decreased to 7, which corresponds to a 9 point or 56% improvement. On day 1 after treatment, the score dropped to 2, which corresponds to a 14 point or 88% improvement. On day 7 post-treatment, the score decreased to 3, which corresponds to a 13 point or 81% improvement.

Thus, according to the present invention, treating a patient suffering from cognitive dysfunction with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates cognitive dysfunction.

More specifically, according to the present invention, treating a patient with 5-MeO-DMT or a pharmaceutically acceptable salt thereof, wherein the patient is suffering from cognitive dysfunction, which is a deficit or impairment in one or more cognitive areas selected from complex attention, executive function, learning and memory, language, perceived motor function, and social cognition, reduces or eliminates cognitive dysfunction. For example, cognitive dysfunction is reduced or eliminated if cognitive dysfunction affects cognitive domain complex attention, such as one or more sub-domains of cognitive domain complex attention (selected from continuous attention, distraction, selective attention, and processing speed), particularly continuous attention.

In patients suffering from cognitive dysfunction associated with mental or neurological disorders, the treatment of cognitive dysfunction according to the present invention results in an improvement of the disorder associated with cognitive dysfunction.

While cognitive dysfunction may be considered a condition that should be treated, irrespective of any other condition, disorder or symptom an individual may suffer from, several mental disorders and neurological disorders are associated with cognitive dysfunction. Notably, the relationship between cognitive dysfunction and mental disorder is generally bi-directional. Mental disorders not only negatively affect cognitive function, but cognitive dysfunction may also be a predisposition to the onset, progression and prognosis of mental or neurological disorders.

In many cases, resting state networks involving cognitive dysfunction are also involved in the above mentioned disorders.

The 5-MeO-DMT can interrupt an established functional connection mode of the rest state network. When the network is reconnected, this disruption can lead to a reset of the ill-connected brain connection. A new, healthy functional connection is established and has a continuous impact.

Anxiety of people

Anxiety is sometimes defined as "a physical symptom expected of future risk or unfortunate anxiety, accompanied by a feeling of dysphoria or tension".

Anxiety is characterized by strong, excessive and persistent anxiety and fear for what is only thought to be a threat in principle, and is often accompanied by muscle tension, anxiety, fatigue, dyspnea, abdominal tightness, nausea and inattention.

In anxiety disorders or other mental or neurological disorders associated with anxiety, anxiety is difficult to control and interferes with daily activities.

Anxiety is a central feature of anxiety disorders, including separation anxiety disorder, specific phobia, social anxiety disorder (social phobia), panic disorder, generalized Anxiety Disorder (GAD), agoraphobia, and substance/drug induced anxiety disorder.

In addition, anxiety is associated with several other mental and neurological disorders. Anxiety is also associated with sleep disorders.

Measuring anxiety

Several scales for assessing anxiety are known in the art, and anxiety symptoms are also assessed as part of various scales for assessing mental and neurological disorders.

Hamiltonanxietyratingscale(HAM-a)wasdesignedtoevaluateanxietysymptoms. The scale is administered by a clinician. The scale has 14 items, which can be divided into groups of mental items (items 1-6 and 14) that specifically measure mental agitation and psychological distress, and groups of physical items (items 7-13) that specifically measure physical discomfort associated with anxiety.

TheHAM-Aitemisshowninthetablebelow.

Interviewees rated each item on a scale of 0 to 4 with 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe.

The total score is obtained by adding 14 items. The total score ranges from 0 to 56. The higher the score, the more severe the anxiety.

Score ∈7 was considered to represent no anxiety or very low anxiety, scores 8-14 for mild anxiety, scores 15-23 for moderate anxiety, and score ∈24 for severe anxiety.

The beck anxiety scale (BAI) is a 21-item self-reporting questionnaire developed to evaluate anxiety, focusing on somatic symptoms. The project was rated using the quartered Liket scale (LIKERT SCALE), ranging from zero (no at all) to three (severe: I'm is almost intolerable). The total score ranges from 0 to 63.

Theterm"subthresholdanxiety"asusedhereinparticularlymeansthatthepatienthasahamiltoniananxietyratingscale(HAM-a)scoreofatleast9butlessthan18and/orabeckeranxietyscale(bai)scoreofatleast11butlessthan16.

Potential mechanism of anxiety

Brain processes can be studied by functional magnetic resonance imaging (fMRI). Brain activity is related to blood flow and the time dependence of spontaneous Blood Oxygen Level Dependent (BOLD) signal fluctuations between different brain regions can be measured.

Functional images of the brain are obtained in a few minutes. A low frequency BOLD signal oscillation mode is observed throughout the brain. The decomposition of the spontaneous signal reveals a distribution region with correlated fluctuations and negatively correlated fluctuations.

In this way, resting state fMRI can be used to characterize a large scale functional network, the so-called Resting State Network (RSN), which is a set of spatially diverse brain regions that exhibit coordinated activity in the absence of any explicit cognitive tasks (i.e., at rest). The observed pattern characterizes a brain area network with a coherent pattern of signal changes, which is called a Resting State Network (RSN).

Different resting state networks have been identified and named based primarily on the spatial similarity between the resting state network and the activation pattern observed in the task fMRI experiments.

Thus, resting state fMRI can be used to assess the intrinsic functional tissue of the brain. The resting state network is characterized by aspects of attention, memory, cognitive control, default mode, motor and sensory systems.

RSN has proven to be responsible for various aspects of complex brain functions, and these connected networks have been found to be compromised in various disease states. Such disease states (including some forms of anxiety) are associated with changes in functional connectivity within a particular resting state network and/or between one or more regions in one or more additional resting state networks.

According to such studies, multiple brain regions are associated with anxiety and anxiety disorders. Thus, the pathophysiology of anxiety and anxiety disorders involves abnormal connections between the amygdala-frontal lobe region and frontal lobe-striatal region. Anxiety and anxiety disorders are associated with specific changes in the resting state network.

Anxiety and anxiety disorders exhibit abnormalities within and/or between the default pattern network, the saliency network, and the sensorimotor network. In different anxiety disorders, the resting state balance within and/or between each of these networks is different.

Treatment of anxiety

According to the present invention, anxiety that occurs in patients suffering from anxiety disorders or other mental or neurological disorders associated with anxiety may be treated. In addition, anxiety that arises in patients suffering from sleep disorders (e.g., insomnia) can be treated.

In patients suffering from anxiety associated with another mental or neurological disorder or sleep disorder (e.g. insomnia), the anxiety treatment according to the invention results in an improvement of anxiety-related disorders.

The treatment according to the invention is by administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Administration of 5-MeO-DMT to a patient can disrupt established functional connection patterns within and/or between the resting state network. Such an interruption may result in a reset of ill-connected connections when the network is reconnected. A new, healthy functional connection is established and has a continuous impact.

Thus, according to the invention, affecting these networks by therapy as described herein will result in an improvement of anxiety, and if the treated patient suffers from another anxiety-related disorder or a neurological disorder, the disorder will also be improved, and if the treated patient suffers from a sleep disorder, such as insomnia, the sleep disorder (e.g., insomnia) will also be improved.

To further support the clinical use of 5-MeO-DMT in patients suffering from anxiety, the inventors evaluated clinical data related to the use of 5-MeO-DMT in patients receiving treatment due to mental disorders and noted a particular improvement in anxiety, which is often observed in patients suffering from other disorders as well.

This data was derived from a recently completed clinical trial using 5-MeO-DMT therapy to treat patients diagnosed with drug resistant depression (TRD; see also the examples section below). While TRD is a particular disorder, as discussed in detail below, the inventors determined that certain clinical observations made in the trial were relevant to the treatment of design anxiety disorders and other anxiety-related disorders.

In clinical trials, 5-MeO-DMT was administered via inhalation (described in more detail in the examples section below). Patients are assigned to different groups. In the context of the present invention, it is of interest to have a group receiving a single 12 mg dose, and a group receiving an intra-day personalized dosing regimen (IDR) that allows for multiple increases in doses (6 mg, 12 mg and 18 mg) within a day, depending on the intensity of the patient's reported fantasy experience.

The data collected included an assessment of the treated patients for several scales including the montgomery-arabic depression rating scale (MADRS) and the Brief Psychosis Rating Scale (BPRS). While the focus of the trial was to demonstrate therapeutic efficacy through an increase in overall MADRS score, the inventors focused on the items that make up the various rating scales and noted that specific sub-score items (e.g., items related to anxiety) were related to other disorders in which anxiety was based on similarly altered functional links within and/or between resting state networks.

The results demonstrated that the inventors' findings, 5-MeO-DMT, are a suitable compound for treating patients presenting with these symptoms.

More specifically, one aspect that can be treated by administration of 5-MeO-DMT is anxiety. The 5-MeO-DMT may be administered to a patient to reduce or eliminate anxiety in the patient.

A BPRS item of particular relevance in this context is "anxiety". The item is associated with a reported anxiety, stress, fear, panic, or concern. Possible scores are:

1-anxiety free

2-Very mild. Some discomfort is reported due to concerns or infrequent concerns that occur more frequently than in most normal individuals.

3-Mild. There is frequent concern but the attention can be easily diverted to other things.

4-Moderate. Most of the time, the anxiety state is worried about, and the attention cannot be easily transferred to other things without impaired function, or anxiety occasionally occurs with autonomic symptoms without impaired function.

5-Moderate to severe. Anxiety frequently (but not daily) occurs with autonomic symptoms or some areas of function are disturbed by anxiety or anxiety.

6-Severe. Anxiety is accompanied by autonomic symptoms every day, but does not last for a whole day, or many functional areas are disturbed by anxiety or persistent anxiety.

7-Very severe. Anxiety is accompanied by autonomic symptoms that last for a whole day, or most areas of function are disturbed by anxiety or persistent anxiety.

In the study group receiving the personalized dosing regimen, the total score for BPRS project "anxiety" for all 8 patients was 37 at baseline.

After 3 hours, the score decreased to 19, which corresponds to an improvement of 18 points or 49%. On day 1 after treatment, the score was reduced to 16, which corresponds to 21 points or 57% improvement. On day 7 post-treatment, the score was reduced to 17, which corresponds to a 20 score or 54% improvement.

In the 12 mg group, the total score for the BPRS project "anxiety" for all 4 patients was 25 at baseline.

After 3 hours, the score decreased to 11, which corresponds to a 14 point or 56% improvement. On day 1 after treatment, the score decreased to 6, which corresponds to a 19 point or 76% improvement. On day 7 post-treatment, the score decreased to 6, which corresponds to a 19 point or 76% improvement.

The inventors concluded that 5-MeO-DMT can be used to treat anxiety in patients, such as patients suffering from anxiety disorders and patients suffering from mental or neurological disorders and related anxiety.

Thus, according to the present invention, treating a patient suffering from anxiety with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates anxiety.

The MADRS project "mental stress" represents an ambiguous feeling of discomfort, agitation, confusion, and exacerbation of mental stress as panic, fear, or pain. It is rated according to intensity, frequency, duration and degree of assurance required.

If the patient calms and has only a short internal stress, the score is 0. If occasional dysphoria and ambiguous discomfort were experienced, the score was 2. If there is a persistent internal stress or intermittent panic that the patient has difficulty controlling, the score is 4. If there is constant fear or pain and overwhelming panic, the score is 6.

In the above trial involving TRD patients, the total score of the MADRS project "internal stress" for all 8 patients in the study group receiving the personalized dosing regimen was 26 at baseline. After 2 hours, the score decreased to 11, which corresponds to a 15 point or 58% improvement. On day 1 after treatment, the score decreased to 6, which corresponds to a20 point or 77% improvement. On day 7 post-treatment, the score dropped to 12, which corresponds to a 14 point or 54% improvement.

In the 12 mg group, the total score for the MADRS project "mental stress" for all 4 patients was 13 at baseline. After 2 hours, the score decreased to 2, which corresponds to an improvement of 11 points or 85%. On day 1 after treatment, the score decreased to 3, which corresponds to a 10 point or 77% improvement. On day 7 post-treatment, the score decreased to 5, which corresponds to an 8 point or 62% improvement.

These results further support the inventors' conclusion that treatment according to the present invention reduces or eliminates symptoms of anxiety.

Treatmentaccordingtotheinventionresultsinaclinicalresponseinpatientssufferingfromanxietysymptoms,whichisreflectedinadecreaseofatleast50%inHAM-ascorecomparedtothecorrespondingscorebeforetreatment,about2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.about24hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday7,atday14,and/oratday28.

Theclinicalresponseofpatientssufferingfromanxietysymptoms(reflectedinatleasta50%decreaseinHAM-ascorecomparedtothecorrespondingscorepriortotreatment)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. theclinicalresponseofapatientsufferingfromanxietysymptoms,reflectedasadecreaseinHAM-ascoreofatleast50%,preferablypersistsuntilatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,inparticularuntilatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyuntilatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

ReliefofanxietysymptomsinpatientssufferingfromanxietysymptomsisreflectedinaHAM-ascoreof7orlessatabout2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,about24hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday7,atday14,and/oratday28.

Reliefofanxietysymptoms(reflectedinHAM-ascoresof7orless)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereofinpatientssufferingfromanxietysymptoms. thereliefofanxietysymptoms(reflectedinaHAM-ascoreof7orless)inapatientsufferingfromanxietysymptomspreferablylastsatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,inparticularatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

Thus, according to the present invention, treating a patient suffering from anxiety with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates anxiety.

Mental retardation

The key aspects observed in patients suffering from mental retardation are reduced energy and activity and reduced power.

Mental retardation involves a slowing of an individual's thinking and a reduction in physical movement. Psychomotor impairment can lead to a significant slowing of the physical and emotional response.

Mental retardation may be associated with mental disorders or neurological disorders or some other medical condition.

Mental or neurological disorders resulting in or associated with bradykinesia include disorders characterized by depressive episodes, such as Major Depressive Disorder (MDD), bipolar Disorder (BD), such as bipolar disorder type I and bipolar disorder type II, post Partum Depression (PPD), seasonal affective disorder and persistent depressive disorder, mental and behavioral disorders due to the use of psychoactive substances, such as Substance Use Disorder (SUD), psychotic disorders, such as schizophrenia, dementia, such as Alzheimer's Dementia (AD), dementia with Lewy bodies (DLB), vascular dementia and Parkinson's disease, chronic fatigue syndrome.

Mental retardation may also occur in patients suffering from sleep disorders (e.g., insomnia).

Measuring mental retardation

Mental retardation can be assessed by measuring various aspects. These may include, for example, various types of drawing tasks and tests, such as wire test (TMT), digital symbol replacement test (DSST), or Gibson spiral maze test (GSM), among other tests known in the art.

For example, in a wired test (TMT), subjects must connect 25 circles containing numbers (TMT a) or a combination of numbers and letters (TMT B) in ascending order. The task requirements of TMT-B are similar except that the subject must alternate between numbers and letters (1, a, 2, B, 3, C, etc.). Thus, the test evaluates processing speed (TMT a) or cognitive flexibility (TMT B). The score for each portion represents the amount of time required to complete the task.

Another test involving writing exercise ability is the Gibson Spiral Maze (GSM), which evaluates only psychomotor speed, not affected by cognitive ability. A subject who completes GSM must correctly track the spiral maze from the start point to the end point without touching the boundary line.

Digital Symbol Substitution Test (DSST) also measures psychomotor speed and consists of digital symbol pairs and a digital list. At each number, the subject should write the corresponding symbol as soon as possible. The score is determined by the number of correctly reported symbols in 90 s. Another example of a motion test is a finger tap test.

Thus, some tests combine measurements of motor and cognitive aspects of mental retardation, while other tests evaluate only motor aspects.

Speech analysis may serve as a further indicator of mental retardation.

Major scales that can be used for evaluation and measurement include the severity of mental retardation, the Salp E tri re retardation rating scale (SRRS) and the agonism and retardation scale (MARS).

Widl Salp E tri re retardation rating scale (SRRS) developed by cher evaluates cognitive and motor aspects through fifteen projects. The first three measures the quality of the movement, in particular the stride, and the slowness of movement of the limbs, trunk, head and neck. The next three projects focus on speech, including speech fluency, intonation, and answer length. Two items of visitor, observation and cognition functions are designed. These questions are based on interview conversations and measure the ability of a patient to approach and expand topics. Further items were subjective and assessed for craving, fatigue, level of interest, time perception, memory and attention. The last term of the scale is related to the overall assessment of mental retardation in the patient. The project scores ranged from 0 (asymptomatic) to 4 (severe), with a total score ranging from 0 to 60, based on the severity of the symptoms presented.

The Motor Agitation and Retardation Scale (MARS) only evaluates motor aspects. It is intended to evaluate mental movement disorders in depressive disorders. Mental disorders are divided into five body categories of eyes, face, voice, limbs and trunk, with 19 items on the scale. The eye category items include gaze direction, number of blinks, gaze and eye movement. Items related to facial categories include facial expressions and facial expressions. Sound categories are items including volume, ambiguity, pitch, and start time. Items under the limb category include hand, foot and leg movements, stride, slow motion and hand tension. Torso category items include posture, immobility, and axial movement. Each item has a severity of from 1 to 4, with 4 being the heaviest. Of these 19 items, 9 were associated with motor activation and 10 were assessed for bradykinesia. The retardation items include abnormal gait, physical/proximal limb inactivity, physical exertion, slow movement (i.e., limb and trunk categories), lack of facial expression, eye drop (i.e., eye and face categories), and reduced sound, slurred speech, delayed speech, and monotonous speech (i.e., sound categories). MARS scale allows rapid clinical assessment of motor signs.

Resting state network and mental retardation

Brain processes can be studied by functional magnetic resonance imaging (fMRI). Brain activity is related to blood flow and the time dependence of spontaneous Blood Oxygen Level Dependent (BOLD) signal fluctuations between different brain regions can be measured.

Functional images of the brain are obtained in a few minutes. A low frequency BOLD signal oscillation mode is observed throughout the brain. The decomposition of the spontaneous signal reveals a distribution region with correlated fluctuations and negatively correlated fluctuations.

In this way, resting state fMRI can be used to characterize a large scale functional network, the so-called Resting State Network (RSN), which is a set of spatially diverse brain regions that exhibit coordinated activity in the absence of any explicit cognitive tasks (i.e., at rest). The observed pattern characterizes a brain area network with a coherent pattern of signal changes, which is called a Resting State Network (RSN).

Different resting state networks have been identified and named based primarily on the spatial similarity between the resting state network and the activation pattern observed in the task fMRI experiments.

Thus, resting state fMRI can be used to assess the intrinsic functional tissue of the brain. The resting state network is characterized by aspects of attention, memory, cognitive control, default mode, motor and sensory systems.

RSN has proven to be responsible for various aspects of complex brain functions, and these connected networks have been found to be compromised in various disease states. Such disease states (including some forms of mental retardation) are associated with altered functional connections within a particular resting state network and/or between one or more areas in one or more additional resting state networks.

For example, dysfunctional connections from somatosensory-motor network (SMN) to Vision (VN), dorsal Awareness (DAN) and default mode networks are reported to be abnormal, which is associated with mental retardation and agitation in depressive disorders.

In many cases, the resting state network involved in mental retardation is affected by mental disorders or neurological disorders characterized by depressive episodes, such as Major Depressive Disorder (MDD), bipolar Disorder (BD), such as bipolar I and II, post Partum Depression (PPD), seasonal and persistent depressive disorders, mental and behavioral disorders due to the use of psychoactive substances, such as Substance Use Disorder (SUD), psychotic disorders, such as schizophrenia, dementia, such as Alzheimer's Dementia (AD), lewy body Dementia (DLB), vascular dementia and Parkinson's disease, chronic fatigue syndrome.

Resting state networks involving mental retardation may also be affected by sleep disturbances (e.g. insomnia). Indeed, mental retardation is associated with sleep impairment.

Treatment of mental retardation and mental or neurological disorders

According to the present invention, mental retardation in patients suffering from mental disorders or neurological disorders can be treated. In addition, mental retardation occurring in patients suffering from sleep disorders (e.g., insomnia) can be treated.

In patients suffering from bradykinesia associated with another disorder detailed above, the treatment of bradykinesia according to the invention results in an improvement of the disorder associated with bradykinesia.

The treatment according to the invention is by administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Administration of 5-MeO-DMT to a patient can disrupt established functional connection patterns within and/or between the resting state network. Such an interruption may result in a reset of ill-connected connections when the network is reconnected. A new, healthy functional connection is established and has a continuous impact.

Thus, according to the invention, affecting these resting state networks by therapy as described herein will result in an improvement of mental retardation, and if the treated patient suffers from a mental or neurological disorder, the disorder will also be improved, and if the treated patient suffers from a sleep disorder (e.g. insomnia), the sleep disorder (e.g. insomnia) will also be improved.

To further support the clinical use of 5-MeO-DMT in patients suffering from mental retardation, the inventors evaluated clinical data related to the use of 5-MeO-DMT in patients receiving treatment for mental diseases, and noted a particular improvement in mental retardation, which is often observed in patients suffering from other disorders as well.

This data was derived from a recently completed clinical trial using 5-MeO-DMT therapy to treat patients diagnosed with drug resistant depression (TRD; see also the examples section below). While TRD is a particular disorder, as discussed in detail below, the inventors determined that certain clinical observations made in the trial were relevant to designing treatments for other disorders associated with mental retardation.

In clinical trials, 5-MeO-DMT was administered via inhalation (described in more detail in the examples section below). Patients are assigned to different groups. In the context of the present invention, it is of interest to have a group receiving a single 12 mg dose, and a group receiving an intra-day personalized dosing regimen (IDR) that allows for multiple increases in doses (6 mg, 12 mg and 18 mg) within a day, depending on the intensity of the patient's reported fantasy experience.

The data collected includes an assessment of the patient treated against several scales including the montgomery-asberg depression rating scale (MADRS). While the focus of the trial was to demonstrate treatment efficacy by an increase in overall MADRS score, the inventors focused on the items that make up the various rating scales, and noted that specific sub-scored items (e.g., items related to mental retardation) were associated with other disorders in which mental retardation was based on similarly altered functional connections within and/or between the somatomotor/sensorimotor network, the visual network, the dorsal attention network and the default mode network.

The results demonstrated that the inventors' findings, 5-MeO-DMT, are a suitable compound for treating patients presenting with these symptoms.

More specifically, one aspect of treatment that may be performed by administration of 5-MeO-DMT is mental retardation. The 5-MeO-DMT may be administered to a patient to reduce or eliminate mental retardation in the patient.

An item of the MADRS scale that is particularly relevant to mental retardation is "lazy," which represents a slow rate of difficulty in starting or starting and performing daily activities.

A score of 0 means that there is little difficulty in starting and no feeling of retardation. If the patient encounters difficulty in initiating activity, the score is 2. Score 4 means that it is difficult to begin a simple daily activity that requires effort to accomplish. If the patient is completely lazy and cannot do anything without assistance, the score is 6.

In the study group receiving the personalized dosing regimen, the total score for the MADRS project "lazy" for all 8 patients was 27 at baseline.

After 2 hours, the score decreased to 10, which corresponds to a 17 score or 63% improvement. On day 1 after treatment, the score decreased to 5, which corresponds to a 22 point or 81% improvement. On day 7 post-treatment, the score decreased to 3, which corresponds to 24 points or 89% improvement.

In the 12 mg group, the total score for the MADRS project "lazy" for all 4 patients was 16 at baseline. After 2 hours, the score decreased to 10, which corresponds to a 6 point or 38% improvement. On day 1 after treatment, the score dropped to 0, which corresponds to a 16 point or 100% improvement. On day 7 post-treatment, the score decreased to 3, which corresponds to a 13 point or 81% improvement.

Thus, the scoring of the scale item "lazy" which is particularly relevant to mental retardation is significantly improved. The inventors concluded that 5-MeO-DMT can be used to treat mental retardation in patients, in particular patients also suffering from mental or neurological disorders or sleep disorders (e.g. insomnia).

Thus, according to the invention, treating a patient suffering from mental retardation with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates mental retardation.

Social/emotional withdrawal or distraction

Symptoms such as loss of pleasure, emotional withdrawal, and frigidity are categorized herein as social/emotional withdrawal or distraction. Social engagement reduction is another aspect related to social/emotional withdrawal or distraction.

A lack of pleasure refers to an inability to experience pleasure. If the ability to subjectively experience a hedonic effect is not reduced during daily activities, the patient will not suffer from a lack of hedonic effect. The lack of pleasure is mild if the pleasure obtained from the normally pleasant activities is slightly reduced, moderate if the pleasure obtained from the normally pleasant activities is significantly reduced or some of the pleasure obtained from the isolated activities is preserved, or severe if the pleasure cannot be experienced at all.

The absence of hedonia includes both consumer (or like) and prospective (or wanted) ingredients. Consumer hedonia refers to the "current" hedonia experienced by a subject when directly engaged in a pleasant activity, while predictive hedonia refers to a hedonic experience associated with future activities.

Frigidity characterizes the subjective perception of a reduction in the intensity or range of sensation or emotion. If no reduction in the intensity or range of sensation or emotion is perceived, the subject does not exhibit frigidity. The emotion frigidity is mild if the emotion scope is slightly reduced, or the sensory scope or intensity is temporarily reduced, moderate if the sensory scope or intensity is significantly reduced but some emotion is preserved, e.g., crying is not possible, and severe if the emotion scope is significantly and generally reduced, or normal emotion is not experienced.

Emotional withdrawal or distraction refers to the inability or unwilling to establish contact with others at the emotional level. For example, BPRS contains items related to emotional withdrawal, which is characterized by a defect in the ability of a subject to express emotion during an interview. According to this BPRS project description, there is no emotional withdrawal if there is no comment lacking emotional engagement, appearing to occasionally fail to respond, occasionally appear to be absent or stiff in smile, but most of the time interact spontaneously with interviewees. If there is a lack of emotional input, a comment appears to be apparently failing to respond, appear to be absent, or lack of enthusiasm, but will respond when interviewees are approaching, there is a slight emotional withdrawal. Emotion is retracted to moderate if there is no emotional contact during most interviews because the subject does not respond in detail, does not have eye contact, does not seem to care whether the interviewer is listening or may be immersed in the psychotic material. In addition, emotion is recessing to moderate severity if there is no emotion contact during most interviews. A severe form exists if the subject actively avoids affective engagement, or the subject often does not respond or responds with a yes/no answer or responds with only minimal affective. Emotion is collapsed to a severe degree if the subject is always prevented from emotional engagement, does not respond, or responds with a yes/no answer, or may leave during the interview or does not respond at all.

Reduced social engagement characterizes subjective reporting of reduced social and interpersonal engagement or interaction. If there is no report of social and interpersonal engagement or reduced interaction, there is no reduction in social engagement. Social engagement is reduced to mild if social engagement is reduced slightly but social or interpersonal function is not impaired, moderate if social engagement is reduced significantly and with some functional sequelae, such as avoidance of some social engagement or conversation, and severe if social interaction reduces significantly or avoids almost all forms of social contact, such as refusal to make a call or see friends or family.

Social/emotional withdrawal or distraction may be associated with mental or neurological disorders or some other medical condition.

Mental or neurological disorders resulting in or associated with social/affective withdrawal or separation include disorders characterized by depressive episodes, such as Major Depressive Disorder (MDD), bipolar Disorder (BD), such as bipolar I and bipolar II, post Partum Depression (PPD), seasonal affective disorders and persistent depressive disorders, anxiety disorders, such as Generalized Anxiety Disorder (GAD) and Social Anxiety Disorder (SAD), obsessive-compulsive and related disorders, such as obsessive-compulsive disorder (OCD) and physically dyscrasia disorder (BDD), post Traumatic Stress Disorder (PTSD), pain disorders, such as chronic pain and fibromyalgia, mental and behavioral disorders, such as Substance Use Disorders (SUD), psychotic disorders, such as schizophrenia, dementia, such as Alzheimer's Dementia (AD), dementia with Legend (DLB), vascular dementia and frontotemporal dementia (PD), parkinson's disease (ASD), autism Spectrum Disorders (ASD), attention Deficit Hyperactivity Disorder (ADHD) and eating disorders, and Borderline Personality Disorder (BPD).

Social/emotional withdrawal or distraction may also occur in patients suffering from sleep disorders (e.g., insomnia).

Social/emotional withdrawal or distraction may also occur in patients suffering from medical health disorders, including Traumatic Brain Injury (TBI), that lead to related mental or neurological disorders.

Measuring social/emotional withdrawal or distraction

Social/emotional withdrawal or distraction (often referred to herein as social/emotional withdrawal) or individual aspects thereof, such as hedonic deficit, emotional withdrawal, and emotional frigidity, may be evaluated by different tools, such as questionnaires or scales.

The questionnaire evaluates the mental state of the patient based on observations of the patient himself, the caregiver, or the clinician filling the questionnaire. A questionnaire for assessing whether a patient suffers from a particular mental or neurological disorder may include items related to social/emotional withdrawal or distraction.

The sness-hamilton hedonic scale (SHAPS) is a scale of 14 items that measures lack of hedonic effect, i.e., inability to experience hedonic effect. Areas of coverage for such items include social interactions, foods and beverages, sensory experience and interests/recreation. Scores of 2 or less constitute "normal" scores, while scores of 3 or more are defined as "abnormal" scores. There are four possible responses for each item, very disagree, agreeable or very agreeable. Any "disagree" response was scored as a score, and any "agree" response was scored as a score of 0. Thus, the final scoring range is 0 to 14.SHAPS have sufficient structural efficiency and satisfactory retest reliability. A high degree of internal consistency is also reported. SHAPS have been used to measure the loss of pleasure in depression, but it is also often used to evaluate the loss of pleasure in other patient populations.

In principle SHAPS uses 14 hypothesized items to measure the hedonic note over the last few days. However, due to the hypothetical nature of the project, a suitably shorter recall period may also be applied to an earlier evaluation time point.

Alternatively or additionally, a dimensional loss of hedonia rating scale (DARS) may be used to assess loss of hedonia that measures interests, motivation, effort, and consumer hedonia in four areas (hobbies, food/beverage, social activity, and sensory experience). The scale includes 17 items that evaluate the current state for absence of hedonia. DARS is rated on the quintessence scale, from 0 (no at all) to 4 (very many), with higher values indicating less loss of hedonic perception. The total score for all items is between 0 and 68. For four hedonic domains, i.e. hobbies (four items, total score 0-16), food/beverage (four items, total score 0-16), social activities (four items, total score 0-16) and sensory experience (5 items, total score 0-20), participants are required to provide two or three of their own favorite examples.

The DSM-5 personality scale (PID-5) -adult is a self-rated personality trait evaluation scale for 220 items of adults 18 years old and older. It evaluates 25 personality trait aspects including loss of pleasure, anxiety, seeking attention, coolness, fraud, depression, distraction, bizarre, emotional instability, large, hostile, impulsive, avoidance of intimacy, irresponsibility, manipulability, sensory disturbance, solidity, emotional restriction, stiff perfection, adventure, separation of unsafe, compliance, doubtful, unusual beliefs and experiences, and withdrawal, each trait aspect consisting of 4 to 14 items.

The anorgasmia trait aspect contains items 1, 23, 26, 30R, 124, 155R, 157, 189 (the reverse scoring items are labeled with the letter "R"), the flinching trait aspect contains items 10, 20, 75, 82, 136, 146, 147, 161, 182, 186, and the intimacy avoidance trait aspect contains items 89, 97R, 108, 120, 145, 203. These three characteristic aspects may be combined to create a broader field of trait, designated as defibering.

The measurements are made by the individual prior to visiting the clinician. Each item requires the individual to assess the extent to which the item describes his or her totality.

Each item in the measurement was rated on a 4-point scale. The response categories of the item are 0=very or frequently wrong, 1=sometimes or somewhat wrong, 2=sometimes or somewhat correct, 3=very or frequently correct. For items 7, 30, 35, 58, 87, 90, 96, 97, 98, 131, 142, 155, 164, 177, 210 and 215, the items are reverse coded prior to entry into the scale score calculation.

The scores for the items within each trait aspect should be added and entered into the appropriate original aspect score box. In addition, the clinician is also required to calculate and use an average score for each aspect and domain. The average score reduces the total score as well as the score for each domain to a 4-score scale, which enables the clinician to think about the individual's personality disorder relative to the observed norm. The average aspect score is calculated by dividing the original aspect score by the number of items in the aspect (e.g., if all items within the "lack of pleasure" aspect are rated as "sometimes or somewhat correct", the average aspect score will be 16/8=2, indicating a moderate lack of pleasure). The average domain score is calculated by adding and then averaging the 3 aspect scores that contribute primarily to the particular domain. For example, if the average aspect scores for hedonic deficits, avoidance intimacy, and withdrawal (scale of primary index deficits) are all 2, then the sum of these scores will be 6, and the average domain score will be 6/3=2. The higher the average score, the more severe the dysfunction in a particular personality trait or domain.

A high score in terms of aspects or areas may indicate that the individual receiving care has a significant and problematic area that may require further evaluation, treatment, and follow-up.

Resting state network and social/emotional withdrawal or distraction

Brain processes can be studied by functional magnetic resonance imaging (fMRI). Brain activity is related to blood flow and the time dependence of spontaneous Blood Oxygen Level Dependent (BOLD) signal fluctuations between different brain regions can be measured.

Functional images of the brain are obtained in a few minutes. A low frequency BOLD signal oscillation mode is observed throughout the brain. The decomposition of the spontaneous signal reveals a distribution region with correlated fluctuations and negatively correlated fluctuations.

In this way, resting state fMRI can be used to characterize a large scale functional network, the so-called Resting State Network (RSN), which is a set of spatially diverse brain regions that exhibit coordinated activity in the absence of any explicit cognitive tasks (i.e., at rest). The observed pattern characterizes a brain area network with a coherent pattern of signal changes, which is called a Resting State Network (RSN).

Different resting state networks have been identified and named, based mainly on their spatial similarity to the activation patterns observed in task fMRI experiments.

Thus, resting state fMRI can be used to assess the intrinsic functional tissue of the brain. The resting state network is characterized by aspects of attention, memory, cognitive control, default mode, motor and sensory systems.

RSN has proven to be responsible for various aspects of complex brain functions, and these connected networks have been found to be compromised in various disease states. Such disease states (including some form of social/emotional withdrawal or distraction) are associated with changing functional connections within a particular resting state network and/or between one or more areas in one or more additional resting state networks.

Changes in RSN also involve a lack of pleasure, a key aspect of social/emotional withdrawal or distraction. More specifically, the lack of pleasure is related to visual network hyperlinks and extensions to visual networks, back attention networks (DANs), and Default Mode Networks (DMNs). The lack of pleasure also involves a decline in network connections between DMN, salience, DAN, body movement and visual networks.

In addition, emotional withdrawal from adult psychosis is associated with structural abnormalities of dorsal DMN. Since the dorsal DMN has psychosis-associated functions, it is of particular interest in the development of psychosis. In particular, dorsal DMN and its attached regions (medial prefrontal cortex and Posterior Cingulate Cortex (PCC)) support emotional, social and ethical treatments. In adult psychosis, microstructural abnormalities within the dorsal DMN are associated with affective and interpersonal differences defining the disorder.

Thus, patients suffering from social/emotional withdrawal or distraction exhibit altered functional connections within and/or between RSNs compared to age-matched healthy controls. Changes are observed within and/or between DMN, salience, DAN, body movement and vision networks.

In many cases, RSNs involved in social/affective withdrawal or distraction are affected by mental or neurological disorders such as disorders characterized by depressive episodes, e.g. Major Depressive Disorder (MDD), bipolar Disorder (BD), such as bipolar I and II disorder, post-partum depression (PPD), seasonal affective disorder and persistent depressive disorder, anxiety disorders, e.g. Generalized Anxiety Disorder (GAD) and Social Anxiety Disorder (SAD), obsessive-compulsive and related disorders, e.g. obsessive-compulsive disorder (OCD) and Body Deformity Disorder (BDD), post-traumatic stress disorder (PTSD), pain disorders, e.g. chronic pain and fibromyalgia, mental and behavioral disorders due to the use of psychoactive substances, e.g. Substance Use Disorder (SUD), psychotic disorders, e.g. schizophrenia, dementia, e.g. Alzheimer's Dementia (AD), lewy body Dementia (DLB), vascular dementia and frontotemporal dementia (FTD), parkinson's disease (ASD), autism disorder, attention deficit disorder (ASD), attention deficit disorder (ADHD) and attention deficit disorder (BPD), and eating disorder (BPD) of borderline people.

Resting state networks involving social/emotional withdrawal or distraction can also be affected by mental or neurological disorders that are the result of certain medical health disorders such as Traumatic Brain Injury (TBI).

Resting state networks involving social/emotional withdrawal or distraction can also be affected by sleep disturbances (e.g., insomnia). In fact, social/emotional withdrawal or distraction is associated with sleep impairment.

Treatment of social/emotional withdrawal or distraction and mental or neurological disorders

According to the present invention, social/emotional withdrawal or distraction occurring in patients suffering from mental disorders or neurological disorders can be treated. In addition, social/emotional withdrawal or distraction that occurs in patients suffering from sleep disorders (e.g., insomnia) can be treated.

In patients suffering from social/emotional withdrawal or distraction associated with another disorder detailed above, the treatment of social/emotional withdrawal or distraction according to the invention results in an improvement of the disorder associated with social/emotional withdrawal or distraction.

The treatment according to the invention is by administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Administration of 5-MeO-DMT to a patient can disrupt established functional connection patterns within and/or between the resting state network. Such an interruption may result in a reset of ill-connected connections when the network is reconnected. A new, healthy functional connection is established and has a continuous impact.

Thus, according to the invention, affecting these networks by therapy as described herein will result in an improvement of social/emotional withdrawal or distraction, and if the treated patient suffers from a mental or neurological disorder, the disorder will also be improved, and if the treated patient suffers from a sleep disorder (e.g., insomnia), the sleep disorder (e.g., insomnia) will also be improved.

To further support the clinical use of 5-MeO-DMT in patients suffering from social/emotional withdrawal or distraction, the inventors evaluated clinical data related to the use of 5-MeO-DMT in patients receiving treatment for mental disorders, and noted a particular improvement in social/emotional withdrawal or distraction, which is often observed in patients suffering from other disorders as well.

The data were derived from a recently completed clinical trial using 5-MeO-DMT therapy to diagnose patients with treatment-resistant depression (TRD; see also the examples section below). While TRD is a particular disorder, as discussed in detail below, the inventors determined that certain clinical observations made in the trial were relevant to designing treatments for other disorders associated with social/emotional withdrawal or distraction.

In clinical trials, 5-MeO-DMT was administered via inhalation (described in more detail in the examples section below). Patients are assigned to different groups. In the context of the present invention, it is of interest to have a group receiving a single 12 mg dose, and a group receiving an intra-day personalized dosing regimen (IDR) that allows for multiple increases in doses (6 mg, 12 mg and 18 mg) within a day, depending on the intensity of the patient's reported fantasy experience.

The data collected included an assessment of the treated patients for several scales including the montgomery-arabic depression rating scale (MADRS) and the Brief Psychosis Rating Scale (BPRS). While the focus of the trial is to demonstrate treatment efficacy through an increase in overall MADRS score, the inventors focused on the items that make up the various rating scales, and noted that specific sub-scoring items (e.g., items related to social/emotional withdrawal or distraction) are related to other disorders in which social/emotional withdrawal or distraction is based on similarly altered functional connections within and/or between default pattern networks, saliency networks, dorsal attention networks, somatic exercise networks, and vision networks.

The results demonstrated that the inventors' findings, 5-MeO-DMT, are a suitable compound for treating patients presenting with these symptoms.

More specifically, one aspect that can be treated by administration of 5-MeO-DMT is social/emotional withdrawal or distraction, particularly loss of pleasure, emotional withdrawal, and/or emotional frigidity. Another therapeutic aspect is reduced social engagement. The 5-MeO-DMT may be administered to a patient to reduce or eliminate social/emotional withdrawal or distraction, particularly loss of pleasure, emotional withdrawal, and/or emotional frigidity, of the patient. In addition, social engagement reduction is improved, i.e., reduced or eliminated.

The MADRS scale item "sensory deficit" that is particularly relevant to social/emotional withdrawal or distraction represents a subjective experience of reduced interest in surrounding environments or activities that would normally bring about a sense of pleasure. The ability to respond fully to the environment or person is reduced.

A score of 0 indicates normal interest in the surrounding environment and others, and a score of 2 indicates a reduced ability to enjoy daily interests. If interest in the surrounding environment is lost and feelings are lost for friends and acquaintances, the score is 4. A score of 6 reflects the experience of emotional paralysis, inability to feel anger, sadness or pleasure, and complete or even painful loss of emotion to relatives and friends.

In the study group receiving the personalized dosing regimen, the total score for the MADRS project "sensory deficit" for all 8 patients was 36 at baseline. After 2 hours, the score decreased to 12, which corresponds to 24 points or 67% improvement. On day 1 after treatment, the score decreased to 2, which corresponds to 34 points or 94% improvement. On day 7 post-treatment, the score decreased to 6, which corresponds to 30 points or 83% improvement.

In the 12 mg group, the total score for the MADRS project "sensory deficit" for all 4 patients was 16 at baseline. After 2 hours, the score decreased to 9, which corresponds to a 7 point or 44% improvement. On day 1 after treatment, the score decreased to 1, which corresponds to a 15 point or 94% improvement. On day 7 post-treatment, the score decreased to 1, which corresponds to a 15 point or 94% improvement.

The BPRS scale items that are particularly relevant to social/emotional withdrawal or distraction are "emotional withdrawal" and "emotional dullness".

The BPRS project "emotional withdrawal" is related to the inability of a patient to express emotion during an interview. Possible scores are:

1-anecdotal recoil.

2-Very mild. Lack of emotional engagement, manifested as occasional failure to respond, occasional disconcerting, or smiling unnaturally, but most of the time spontaneously talking to interviewees.

3-Mild. Lack of emotional input manifests as a significant failure to respond, a lack of mind, or lack of enthusiasm, but responds when interviewees are approaching.

4-Moderate. There is no emotional contact during most interviews because the subject does not respond in detail, does not have eye contact, does not seem to care whether the interviewer is listening or may be immersed in psychotic material.

5-Moderate to severe. As with "4", but there is no emotional contact during most interviews.

6-Severe. Actively avoiding emotion participation. Often without or with yes/no answers (not just due to a harmful delusions). Responding with only minimal emotion.

7-Very severe. And emotion participation is avoided all the time. No response or yes/no response (not just due to a harmful delusions). May leave or not respond at all during the interview.

The overall score for BPRS project "emotional withdrawal" is 13 at baseline. After 3 hours, the score decreased to 8, which corresponds to a 5 point or 38% improvement. On day 1 after treatment, the score decreased to 8, which corresponds to a 5 point or 38% improvement. On day 7 post-treatment, the score decreased to 8, which corresponds to a 5 point or 38% improvement.

In group 12 mg, the overall score for the BPRS item "emotional withdrawal" is 13 at baseline. After 3 hours, the score decreased to 11, which corresponds to a 2 score or 15% improvement. On day 1 after treatment, the score decreased to 8, which corresponds to a 5 point or 38% improvement. On day 7 post-treatment, the score decreased to 6, which corresponds to a 7 point or 54% improvement.

The BPRS item "bradycardia" relates to limited range of emotional expressions of face, sound and gestures, and manifests itself as a pronounced indifference or frigidity even when discussing a distressing topic. Possible scores are:

1-anepithymia.

2-Very mild. The emotion range is slightly depressed or preserved, but shows proper facial expression and speech intonation, within normal range.

3-Mild. Overall, there is a reduced, sunken or preserved emotion scope, without many spontaneous and appropriate emotional responses. The mood is slightly monotonous.

4-Moderate. The emotional scope is significantly diminished and, except in rare cases, the patient does not show emotion, smile, or respond to a distressing topic. The speech intonation is monotonous or the spontaneous motion is significantly reduced. Emotion or gesture performance usually follows in that emotion resumes frigidity.

5-Moderate to severe. The emotion range is very diminished and the patient does not show emotion, smile, or react to painful topics, with the exception of minimal, few gestures, facial expression not changing frequently. Most of the time, speech utterances are monotonous.

6-Severe. There is very little emotional scope or expression. Most of the time speech and gestures are mechanical. The facial expression is unchanged. Most of the time the speech intonation is monotonous.

7-Very severe. There is little emotional range or expressive power and stiffness in motion. At all times, the speech intonation is monotonous.

The overall score for BPRS item "emotional dullness" is 15 at baseline. After 3 hours, the score was reduced to 11, which corresponds to a 4 point or 27% improvement. On day 1 after treatment, the score decreased to 8, which corresponds to a 7 point or 47% improvement. On day 7 post-treatment, the score decreased to 8, which corresponds to a 7 point or 47% improvement.

In group 12 mg, the overall score for the BPRS item "emotional dullness" is 11 at baseline. After 3 hours, the score decreased to 8, which corresponds to a 3 point or 27% improvement. On day 1 after treatment, the score decreased to 6, which corresponds to a5 point or 45% improvement. On day 7 post-treatment, the score decreased to 5, which corresponds to a6 point or 55% improvement.

Thus, scale items that are particularly relevant to social/emotional withdrawal or distraction, namely "sensory deficit" (MADRS), "emotional withdrawal" (BPRS), and "emotional retardation" (BPRS) score, are significantly improved. The inventors concluded that 5-MeO-DMT can be used to treat social/emotional withdrawal or distraction in patients, especially patients also suffering from mental or neurological disorders or sleep disorders (e.g. insomnia).

Thus, according to the invention, treating a patient suffering from social/emotional withdrawal or distraction with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates social/emotional withdrawal or distraction.

Negative thinking

Symptoms such as pessimistic, worthless, helplessness and hopeless, and morbid, excessive or inappropriate guilt are categorized herein as negative thoughts.

The helplessness and unconsciousness (also simply referred to as helplessness and unconsciousness) characterize the subjective perception of pessimism or destination, inability to cope with or lose control of the future. If the patient does not have such a sensation, there is no helplessness or hopelessness. The helplessness and prestige are mild if there is occasional mild feeling that it is not as good as usual or pessimistic, moderate if there is frequent feeling that it is not good as usual or there is significant helplessness or prestige but sometimes it is lost, or severe if there is significant and persistent pessimistic, helpless or prestige.

The invalidity (also simply referred to as invalidity) characterizes the subjective perception or idea of a decrease in self-value or self-valuation (self-worth). If the patient does not have such a sensation, there is no value. The invaluable may be mild, i.e. slightly reduced in self-value, moderate, i.e. some thoughts of invaluable and reduced self-value, or severe, i.e. obvious, general or persistent, e.g. perceived by others that they would not be much better and would not appreciate the positive quality.

Guilt sensation (also simply called guilt) characterizes the subjective sensation of self-responsibility, failure, or remorse of past true or imagined errors. If the patient does not have such sensation, there is no guilt. Guilt is mild if self-esteem drops slightly or self-criticizing increases, moderate if there is significant thought of failure, self-criticizing, inability to cope with or relate to past failures and their impact on others, moderate if excessive can be recognized, moderate if there is significant, generalized or persistent guilt, e.g., should be punished, or severe if excessive cannot be clearly recognized.

Negative thoughts may be associated with mental or neurological disorders or some other medical condition.

Disorders that lead to or are associated with negative thoughts include disorders characterized by depressive episodes, such as Major Depressive Disorder (MDD), bipolar Disorder (BD), such as bipolar disorder type I and bipolar disorder type II, post Partum Depression (PPD), seasonal affective disorder and persistent depressive disorder, anxiety disorders, such as Generalized Anxiety Disorder (GAD) and Social Anxiety Disorder (SAD), obsessive-compulsive disorder and related disorders, such as obsessive-compulsive disorder (OCD) and physically dyscrasia disorder (BDD), post-traumatic stress disorder (PTSD), pain disorders, such as chronic pain, mental and behavioral disorders due to the use of psychoactive substances, such as Substance Use Disorder (SUD), psychotic disorders, such as schizophrenia, dementia, such as Alzheimer's Dementia (AD), eating disorders, attention Deficit Hyperactivity Disorder (ADHD), personality disorders, such as split personality disorder and Borderline Personality Disorder (BPD).

Negative thoughts may also occur in patients suffering from sleep disorders (e.g., insomnia).

Negative thoughts may also occur in patients suffering from medical health disorders, including Traumatic Brain Injury (TBI), that lead to related mental or neurological disorders.

Measuring negative thinking

Negative thoughts or individual aspects thereof, such as worthless, helplessness and hopeless and guilt, may be evaluated by different tools, such as questionnaires or scales.

The questionnaire evaluates the mental state of the patient based on observations of the patient himself, the caregiver, or the clinician filling the questionnaire. A questionnaire for assessing whether a patient suffers from a particular mental or neurological disorder may include items related to negative thoughts.

Tools for evaluating negative mental related aspects include, for example, the Status Shame and Guilt Scale (SSGS), the positive and negative emotion scale-expanded version (PANAS-X), or the Status Hope Scale (SHS).

Status Shame and Guilt Scales (SSGS) are self-rating scales of the current (status) shame and guilt experience. The device comprises two sub-scales, a shame sub-scale and a guilt sub-scale. The shame sub-scale includes items 1,3, 5, 7, 9. Guilt sub-table includes items 2, 4, 6, 8, 10. All items were scored in the forward direction and rated on a 5-point licker-in scale. The scale contains some statements that may or may not describe the current feel of the patient. The higher the score, the stronger the sense of shame or guilt.

The positive and negative emotion scale-expanded version (PANAS-X) is an expanded version of PANAS of 60 items. PANAS-X measures 11 specific emotions, fear, sadness, guilt, hostile, shy, fatigue, surprise, happiness, confidence, concentration and calm. Thus PANAS-X provides two different levels of mood measurements. The basic passive emotion scales are fear, hostile, guilt and sadness, while the guilt scales cover six items, guilt, shame, deserted, own gas, aversion to oneself, dissatisfaction to oneself. Each answer should be scored on the scale of 1=very slight or no at all, 2=little, 3=medium, 4=quite numerous, or 5=extremely. However, researchers facing stricter time constraints can only select and evaluate the scales most relevant to their study.

The stronger the guilt feeling, the higher the score reflected on the guilt scale.

PANAS-X is simple and easy to apply. Most subjects completed the entire 60-item scale in 10 minutes or less. This scale consists of a number of words and phrases that describe different sensations and emotions. While it should be shown that the patient had this degree of sensation over the last few weeks, it was found that the trait scores on the PANAS-X scale were stable over time, including "current", "today" and "days past", indicating that a suitably shorter recall period could be applied.

The State Hope Scale (SHS) has three institutional items and three pathway items, and the answering machine describes himself based on their "current" status. The institutional sub-scale scores are derived by summing items 2,4 and 6, which are related to perceptibility of using the personal pathway to achieve the intended goal, and the pathway sub-scale scores are derived by summing items 1, 3 and 5, which are related to thinking for determining possible methods to achieve the goal. The state hope table total score is obtained by adding three organization items and three way items. The score can range from a low score of 6 to a high score of 48, with higher scores on this scale reflecting a greater desire.

Negative thoughts or aspects thereof are also reflected in other scales, such as HAM-D, MADRS, BPRS or BDRS, where relevant items of the scales may be commonly used to evaluate negative thoughts or aspects thereof.

Resting state network and negative thinking

Brain processes can be studied by functional magnetic resonance imaging (fMRI). Brain activity is related to blood flow and the time dependence of spontaneous Blood Oxygen Level Dependent (BOLD) signal fluctuations between different brain regions can be measured.

Functional images of the brain are obtained in a few minutes. A low frequency BOLD signal oscillation mode is observed throughout the brain. The decomposition of the spontaneous signal reveals a distribution region with correlated fluctuations and negatively correlated fluctuations.

In this way, resting state fMRI can be used to characterize a large scale functional network, the so-called Resting State Network (RSN), which is a set of spatially diverse brain regions that exhibit coordinated activity in the absence of any explicit cognitive tasks (i.e., at rest). The observed pattern characterizes a brain area network with a coherent pattern of signal changes, which is called a Resting State Network (RSN).

Different resting state networks have been identified and named, based mainly on their spatial similarity to the activation patterns observed in task fMRI experiments.

Thus, resting state fMRI can be used to assess the intrinsic functional tissue of the brain. The resting state network is characterized by aspects of attention, memory, cognitive control, default mode, motor and sensory systems.

RSN has proven to be responsible for various aspects of complex brain functions, and these connected networks have been found to be compromised in various disease states. Such disease states (including some form of negative thinking) are associated with altered functional connections within a particular resting state network and/or between one or more areas in one or more additional resting state networks.

Major Depressive Disorder (MDD) is a disorder characterized primarily by a high level of negative emotions and a lower level of positive emotions. More specifically, a lower level of positive emotion (such as hope) means a higher level of forfeit and a higher level of negative emotion (such as guilt). MDD has been the focus of research in the rs-fMRI field, indicating that MDD is an obstacle characterized by extensive network dysfunction. This dysfunction occurs mainly in networks and areas associated with affective modulation. These networks and regions include Default Mode Networks (DMN), saliency networks, affective networks, and prefrontal cortex. Thus, different aspects of negative thinking may be related to an abnormal resting state network.

Functional connectivity impairment of the resting state network of Repeat Negative Thoughts (RNT) patients, including left-hand executive control network and altered connectivity of the anterior prominence network with the ventral default mode network, is reported.

Thus, patients suffering from negative thoughts exhibit altered functional connections within and/or between resting state networks compared to age-matched healthy controls. Changes are observed at least within and/or between the default mode network, the executive control network, the significance network, the affective network, and the prefrontal cortex.

In many cases, the effects of passive thinking are involved in RSN fertilization mental or neurological disorders such as disorders characterized by depressive episodes, e.g. Major Depressive Disorder (MDD), bipolar Disorder (BD), such as bipolar I and II, post Partum Depression (PPD), seasonal affective disorder and persistent depressive disorder, anxiety disorders, e.g. Generalized Anxiety Disorder (GAD) and Social Anxiety Disorder (SAD), obsessive-compulsive and related disorders, e.g. obsessive-compulsive disorder (OCD) and physical deformity disorder (BDD), post Traumatic Stress Disorder (PTSD), pain disorders, e.g. chronic pain, mental and behavioral disorders due to the use of psychoactive substances, e.g. Substance Use Disorder (SUD), psychotic disorders, e.g. schizophrenia, dementia, e.g. Alzheimer's Dementia (AD), eating disorders, attention Deficit Hyperactivity Disorder (ADHD), personality disorders, e.g. split personality disorder and Borderline Personality Disorder (BPD).

Resting state networks involving negative thinking are also affected by mental or neurological disorders that are the result of certain medical health disorders, such as Traumatic Brain Injury (TBI).

Resting state networks involving negative thoughts can also be affected by sleep disorders (e.g., insomnia). In fact, negative thinking is related to sleep impairment.

Treatment of negative mental and psychiatric or neurological disorders

According to the present invention, negative thoughts occurring in patients suffering from mental disorders or neurological disorders can be treated. In addition, negative thoughts that occur in patients suffering from sleep disorders (e.g., insomnia) can be treated.

In patients suffering from negative thoughts related to another disorder detailed above, the treatment of negative thoughts according to the invention results in an improvement of the disorder related to negative thoughts.

The treatment according to the invention is by administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Administration of 5-MeO-DMT to a patient can disrupt established functional connection patterns within and/or between the resting state network. Such an interruption may result in a reset of ill-connected connections when the network is reconnected. A new, healthy functional connection is established and has a continuous impact.

Thus, according to the present invention, affecting these networks by therapy as described herein will result in an improvement of negative thoughts, and if the treated patient suffers from a mental or neurological disorder, the disorder will also be improved, and if the treated patient suffers from a sleep disorder (e.g., insomnia), the sleep disorder (e.g., insomnia) will also be improved.

To further support the clinical use of 5-MeO-DMT in patients suffering from negative thoughts, the inventors evaluated clinical data related to the use of 5-MeO-DMT in patients receiving treatment for mental disorders, and noted a particular improvement in negative thoughts, which is often observed in patients suffering from other disorders as well.

This data was derived from a recently completed clinical trial using 5-MeO-DMT therapy to treat patients diagnosed with drug resistant depression (TRD; see also the examples section below). While TRD is a particular disorder, as discussed in detail below, the inventors determined that certain clinical observations made in the trial were relevant to designing treatments for other disorders associated with negative thinking.

In clinical trials, 5-MeO-DMT was administered via inhalation (described in more detail in the examples section below). Patients are assigned to different groups. In the context of the present invention, it is of interest to have a group receiving a single 12 mg dose, and a group receiving an intra-day personalized dosing regimen (IDR) that allows for multiple increases in doses (6 mg, 12 mg and 18 mg) within a day, depending on the intensity of the patient's reported fantasy experience.

The data collected included an assessment of the treated patients for several scales including the montgomery-arabic depression rating scale (MADRS) and the Brief Psychosis Rating Scale (BPRS). While the focus of the trial was to demonstrate treatment efficacy through an increase in overall MADRS score, the inventors focused on the items that make up the various rating scales, and noted that specific sub-score items (e.g., items related to negative thoughts) were related to other disorders in which negative thoughts were based on default mode networks, executive control networks, saliency networks, affective networks, and similarly altered functional connections within and/or between frontal cortex.

The results demonstrated that the inventors' findings, 5-MeO-DMT, are a suitable compound for treating patients presenting with these symptoms.

More specifically, one aspect that can be treated by the administration of 5-MeO-DMT is negative thoughts, particularly worthless, helplessness and hopeless, and/or guilt. The 5-MeO-DMT may be administered to a patient to reduce or eliminate negative thoughts, particularly worthless, helplessness and hopeless, and/or guilt feelings, of the patient.

The MADRS scale item that is particularly relevant to negative thoughts is "pessimistic ideas" representing thoughts of guilt, spelt, self-responsibility, criminal, remorse, and devastation.

If there is no pessimistic idea, the score is 0. If there is a failure, responsibility, or denigrate oneself fluctuating idea, the score is 2. Scoring means sustained self-responsibility, or clear but still reasonable guilt or criminal thoughts, and the patient is becoming more pessimistic to the future. If there is a disfiguring delusions, remorse or irrecoverable criminal and paradoxical and immovable self-responsibility, the score is 6.

In the study group receiving the personalized dosing regimen, the total score of the MADRS project "pessimistic ideas" for all 8 patients was 28 at baseline.

After 2 hours, the score decreased to 7, which corresponds to a 21 point or 75% improvement. On day 1 after treatment, the score decreased to 4, which corresponds to 24 points or 86% improvement. On day 7 post-treatment, the score decreased to 3, which corresponds to 25 points or 89% improvement.

In the 12 mg group, the total score for the MADRS project "pessimistic ideas" for all 4 patients was 16 at baseline. After 2 hours, the score decreased to 8, which corresponds to an 8 score or 50% improvement. On day 1 after treatment, the score dropped to 7, which corresponds to a9 point or 56% improvement.

On day 7 post-treatment, the score decreased to 8, which corresponds to an 8 score or 50% improvement.

The BPRS item that is particularly relevant to negative thinking is "guilt feel". This item is associated with excessive attention or remorse to past behavior. Possible scores are:

1-no guilt feeling.

2-Very mild. There is a fear of frustrating someone or a fear of failing something but not careless. The idea can be easily transferred to other things.

3-Mild. There is a fear that someone is disappointed or there is a fear that something fails and is careless. Tending to express guilt to others.

4-Moderate. Excessive immersion, miswork, injury to others due to doing or not doing something, but can easily divert attention to other things.

5-Moderate to severe. Immersion in guilt, frustrating or failing someone, may divert attention to other things, but with great effort. Not delusional.

6-Severe, delusional guilt or irrational self-responsibility which is very disproportionate to the environment. There is a moderate absence of attention.

7-Very severe. Delusional guilt or irrational self-responsibility that is highly disproportionate to the environment. The subject is very immersed in guilt and may be exposed to others or act on delusions.

In the study group receiving the personalized dosing regimen, the total score of BPRS project "guilt feel" for all 8 patients was 34 at baseline.

After 3 hours, the score dropped to 14, which corresponds to a 20 point or 59% improvement. On day 1 after treatment, the score dropped to 11, which corresponds to a 23 point or 68% improvement. On day 7 post-treatment, the score dropped to 10, which corresponds to 24 points or 71% improvement.

In group 12 mg, the total score of the BPRS project "guilt feel" for all 4 patients was 18 at baseline.

After 3 hours, the score decreased to 9, which corresponds to a 9 score or 50% improvement. On day 1 after treatment, the score decreased to 5, which corresponds to a 13 point or 72% improvement. On day 7 post-treatment, the score decreased to 5, which corresponds to a 13 point or 72% improvement.

Thus, the score of the MADRS scale item "pessimistic ideas" particularly related to negative thoughts is significantly improved, and the score of the BPRS item "guilt feel" is also significantly improved. The inventors concluded that 5-MeO-DMT can be used to treat negative thoughts in patients, especially patients who also suffer from mental or neurological disorders or sleep disorders (e.g., insomnia).

Thus, according to the present invention, treating a patient suffering from negative thoughts with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates negative thoughts.

Mother's function

In addition to the above, the inventors believe that a mental or neurological disorder as defined herein, in particular a disorder involving one or more symptoms selected from sleep disorders, cognitive dysfunction, anxiety, bradykinesia, social/emotional withdrawal and negative thinking, may impair maternal function. In fact, each of the symptoms listed is likely to impair maternal function (and thus should be treated independently).

Especially the first year after delivery, is a critical window period for both the mother and the child. In most cases, the mother is the primary care giver and is therefore responsible for most of the work associated with baby care tasks.

Maternal functions include aspects of maternal capabilities related to infant interaction and maternal self-care.

Maternal function, including emotional aspects of the mother, is also important to the development of the child. In fact, the quality of the mother-child interaction within one year after birth affects the development of the infant. High levels of maternal function may be associated with positive infant developmental outcomes. Also, impaired post-partum function may prevent optimal development in infants.

Barkin maternal function index (BIMF) was designed to measure function within one year after delivery. BIMF are self-reporting function measurements of 20 items. Each item was scored from 0 to 6 such that the highest total score was 120 points. The higher the score, the better the assessment of maternal function.

BIMF identify critical functional areas of the mother during the postpartum period as self-care, baby care, mother-child interaction, mental health of the mother, social support, management and regulation.

A score of BIMF of 95 or less is herein considered to represent a mild impairment of maternal function, a score of 80 or less is herein considered to represent an impairment of maternal function, and a score of 65 or less is herein considered to represent a severe impairment of maternal function. The invention allows in particular to improve the maternal function of patients with a pre-treatment score of 80 or less and of patients with a score of even 65 or less.

As described above, the present invention allows for the treatment of patients suffering from mental or neurological disorders. The treatment not only results in a reduction in the score that evaluates the severity of depression, but also improves maternal function, as discussed in detail below.

To further support the clinical use of 5-MeO-DMT in patients suffering from mental or neurological disorders, the inventors evaluated clinical data related to the use of 5-MeO-DMT in patients receiving treatment for mental diseases and noted particular improvements in disease, which are often observed in patients suffering from mental or neurological disorders as well. The inventors have noted, inter alia, improvements in various symptoms and combinations of symptoms, which the inventors have determined may be related to maternal function.

This data was derived from a recently completed clinical trial using 5-MeO-DMT therapy to treat patients diagnosed with drug resistant depression (TRD; see also the examples section below). The results are confirmed in a recent trial of patients suffering from post-partum depression (see examples section below).

In a TRD clinical trial, 5-MeO-DMT was administered via inhalation (described in more detail in the examples section below). Patients are assigned to different groups. In the context of the present invention, it is of interest to have a group receiving a single 12 mg dose, and a group receiving an intra-day personalized dosing regimen (IDR) that allows for multiple increases in doses (6 mg, 12 mg and 18 mg) within a day, depending on the intensity of the patient's reported fantasy experience.

The data collected included an assessment of the treated patients for several scales including the Montgomery Arabidopsis Depression Rating Scale (MADRS) and the Brief Psychosis Rating Scale (BPRS). While the focus of the trial was to demonstrate treatment efficacy by an increase in overall MADRS score, the inventors focused on the items that make up the various rating scales, and noted that several sub-scored items were particularly relevant to patients with mental or neurological disorders and related to maternal function.

The results of the significant improvement exhibited by multiple patients in the recruited cohort in one or more of these sub-scoring programs demonstrate that the inventors' findings, 5-MeO-DMT, is a compound suitable for treating patients with mental or neurological disorders and improving the maternal function of those patients.

Specific sub-scoring items in each scale are determined in more detail below. The inventors concluded that the efficacy of treatment of one or more of these symptoms would lead to a significant improvement in the overall outcome of patients with mental or neurological disorders treated with 5-MeO-DMT.

Thus, treatment according to the present invention reduces or eliminates (or improves or eliminates) one aspect of the disease.

If the aspect is evaluated according to the MADRS scale, at least a fraction of improvement (decrease) or complete remission (elimination) of the patient after treatment, i.e., the corresponding aspect scores 0.

If the aspect is evaluated according to the BPRS scale, at least a fraction of improvement (decrease) or complete remission (elimination) of the patient after treatment, i.e. the corresponding aspect scores 1.

Clinical response may also be reflected by a decrease in clinical global impression-severity (CGI-S) score. According to the present invention, a decrease in CGI-S score means a decrease in CGI-S of at least 1 point. Preferably, CGI-S is reduced by at least 2 points and/or to 0 points. Particularly preferably, the CGI-S is reduced by at least 3 minutes and/or to 0 minutes.

The inventors further believe that the improvements observed in certain MADRS projects translate into improvements in maternal function.

Particularly relevant MADRS items are discussed in more detail below.

The MADRS project "mental stress" represents an ambiguous feeling of discomfort, agitation, confusion, and exacerbation of mental stress as panic, fear, or pain. It is rated according to intensity, frequency, duration and degree of assurance required.

If the patient calms and has only a short internal stress, the score is 0. If occasional dysphoria and ambiguous discomfort were experienced, the score was 2. If there is a persistent internal stress or intermittent panic that the patient has difficulty controlling, the score is 4. If there is constant fear or pain and overwhelming panic, the score is 6.

The inventors have determined that an increase in the score of the MADRS project "internal stress" has a negative impact on both aspects of maternal function (maternal capacity related to infant interaction and maternal self-care). As assessed by BIMF, an increase in the score of the MADRS project "internal stress" can impair mother-child interaction and mental health of the mother.

In contrast, improvements in this MADRS project may lead to improved maternal function, particularly in terms of maternal-maternal interactions and/or maternal mental health in the BIMF functional area.

In the above trial involving TRD patients, the total score of the MADRS project "internal stress" for all 8 patients in the study group receiving the personalized dosing regimen was 26 at baseline. After 2 hours, the score decreased to 11, which corresponds to a 15 point or 58% improvement. On day 1 after treatment, the score decreased to 6, which corresponds to a20 point or 77% improvement. On day 7 post-treatment, the score dropped to 12, which corresponds to a 14 point or 54% improvement.

In the 12 mg group, the total score for the MADRS project "mental stress" for all 4 patients was 13 at baseline. After 2 hours, the score decreased to 2, which corresponds to an improvement of 11 points or 85%. On day 1 after treatment, the score decreased to 3, which corresponds to a 10 point or 77% improvement. On day 7 post-treatment, the score decreased to 5, which corresponds to an 8 point or 62% improvement.

The inventors concluded that 5-MeO-DMT can be used to treat patients with mental or neurological disorders to achieve a reduction or elimination of internal stress.

Improvement in internal stress is reflected at least in an improvement in the score of the internal stress of the MADRS program at about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28.

Improvement in internal stress, reflected in a decrease in clinical global impression-severity (CGI-S) score, occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Additionally or alternatively, a decrease in the clinical global impression-severity (CGI-S) score occurs at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in internal stress (at least reflected as a "greatly improved" score in the clinical global impression-improvement (CGI-I) score or patient global impression-improvement (PGI-I) score) preferably occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in internal stress (reflected as a decrease in CGI-S score or at least as a "greatly improved" score in CGI-I score or PGI-I score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The inventors have also concluded that the reduction or elimination of internal stress achieved by treating patients with mental or neurological disorders results not only in a reduction of the total score of MADRS, but also in an improvement of maternal function, which is reflected in an increase in the BIMF score. This improvement will be achieved rapidly, i.e. within about 2 hours, and an increase in BIMF score will also be observed at day 1, e.g. after about 24 hours, at day 7, at day 14, and/or at day 28, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Since internal stress can also affect other aspects of mental or neurological disorders, the inventors concluded that the observed improvement in the "internal stress" program in MADRS would additionally contribute to the overall improvement in maternal function.

The MADRS item "lazy" represents a slow rate of difficulty in starting or starting and executing daily activities.

A score of 0 means that there is little difficulty in starting and no feeling of retardation. If the patient encounters difficulty in initiating activity, the score is 2. Score 4 means that it is difficult to begin a simple daily activity that requires effort to accomplish. If the patient is completely lazy and cannot do anything without assistance, the score is 6.

The inventors have determined that an increase in the score of the MADRS project "lazy" has a negative impact on both aspects of maternal function (maternal capacity related to infant interaction and maternal self-care). An increase in the score of the MADRS project "lazy" can impair infant care, self-care, mental health, management and regulation.

In contrast, improvements relating to this MADRS program will lead to improved maternal function, particularly in terms of infant care, self-care, mental health, management and/or regulation in the BIMF functional area.

In the study group receiving the personalized dosing regimen, the total score for the MADRS project "lazy" for all 8 patients was 27 at baseline. After 2 hours, the score decreased to 10, which corresponds to a 17 score or 63% improvement. On day 1 after treatment, the score decreased to 5, which corresponds to a 22 point or 81% improvement. On day 7 post-treatment, the score decreased to 3, which corresponds to 24 points or 89% improvement.

In the 12 mg group, the total score for the MADRS project "lazy" for all 4 patients was 16 at baseline. After 2 hours, the score decreased to 10, which corresponds to a 6 point or 38% improvement. On day 1 after treatment, the score dropped to 0, which corresponds to a 16 point or 100% improvement. On day 7 post-treatment, the score decreased to 3, which corresponds to a 13 point or 81% improvement.

The inventors concluded that 5-MeO-DMT can be used to treat patients with mental or neurological disorders to achieve reduction or elimination of lazy.

Improvement in lazy is reflected at least by an improvement in the score of MADRS project lazy at about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28.

Improvement in lazy effort, reflected in a decrease in clinical global impression-severity (CGI-S) score, occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Additionally or alternatively, a decrease in the clinical global impression-severity (CGI-S) score occurs at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in lazy (at least reflected in a "greatly improved" score in the clinical global impression-improvement (CGI-I) score or patient global impression-improvement (PGI-I) score) preferably occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in lazy (reflected as a decrease in CGI-S score or at least as a "greatly improved" score in CGI-I score or PGI-I score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, in particular until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The inventors have also concluded that the reduction or elimination of lazy achieved by treating patients with mental or neurological disorders not only results in a reduction of the total score of MADRS, but also in an improvement of maternal function, which is reflected in an increase of BIMF score. This improvement will be achieved rapidly, i.e. within about 2 hours, and an increase in BIMF score will also be observed at day 1, e.g. after about 24 hours, at day 7, at day 14, and/or at day 28, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Since lazy may also affect other aspects of mental or neurological disorders, the inventors concluded that the observed improvement in the "lazy" item in MADRS would otherwise contribute to the overall improvement in maternal function.

The MADRS project "sensory deficit" represents a subjective experience of reduced interest in surrounding environments or activities that typically bring about a sense of pleasure. The ability to respond fully to the environment or person is reduced.

A score of 0 indicates normal interest in the surrounding environment and others, and a score of 2 indicates a reduced ability to enjoy daily interests. If interest in the surrounding environment is lost and feelings are lost for friends and acquaintances, the score is 4. A score of 6 reflects the experience of emotional paralysis, inability to feel anger, sadness or pleasure, and complete or even painful loss of emotion to relatives and friends.

The inventors have determined that an increase in the score of the MADRS project "sensory deficit" has a negative impact on both aspects of maternal function (maternal capacity related to infant interaction and maternal self-care). An increase in the score of the MADRS project "sensory deficit" can impair maternal-maternal interactions and mental health.

In contrast, improvements in this MADRS project may lead to improved maternal function, particularly in terms of maternal-maternal interaction and/or mental health in the BIMF functional area.

In the study group receiving the personalized dosing regimen, the total score for the MADRS project "sensory deficit" for all 8 patients was 36 at baseline. After 2 hours, the score decreased to 12, which corresponds to 24 points or 67% improvement. On day 1 after treatment, the score decreased to 2, which corresponds to 34 points or 94% improvement. On day 7 post-treatment, the score decreased to 6, which corresponds to 30 points or 83% improvement.

In the 12 mg group, the total score for the MADRS project "sensory deficit" for all 4 patients was 16 at baseline. After 2 hours, the score decreased to 9, which corresponds to a 7 point or 44% improvement. On day 1 after treatment, the score decreased to 1, which corresponds to a 15 point or 94% improvement. On day 7 post-treatment, the score decreased to 1, which corresponds to a 15 point or 94% improvement.

The inventors concluded that 5-MeO-DMT can be used to treat patients with mental or neurological disorders to achieve the reduction or elimination of sensory loss.

Improvement in sensory deficit is reflected at least in an improvement in the score of MADRS project sensory deficit about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28.

Improvement of sensory deficit, reflected in a decrease in clinical global impression-severity (CGI-S) score, occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Additionally or alternatively, a decrease in the clinical global impression-severity (CGI-S) score occurs at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in sensory deficit (at least reflected in a "greatly improved" score in the clinical global impression-improvement (CGI-I) score or patient global impression-improvement (PGI-I) score) preferably occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in sensory deficit (reflected as a decrease in CGI-S score or at least as a "greatly improved" score in CGI-I score or PGI-I score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The inventors have also concluded that the reduction or elimination of sensory deficit achieved by treating patients with mental or neurological disorders results not only in a reduction in the total score of MADRS, but also in an improvement in maternal function, which is reflected in an increase in BIMF score. This improvement will be achieved rapidly, i.e. within about 2 hours, and an increase in BIMF score will also be observed at day 7, day 14, and/or day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. 13 since sensory deficit can also affect other aspects of mental or neurological disorders, the inventors concluded that the observed improvement in the "sensory deficit" program in MADRS would additionally contribute to the overall improvement in maternal function.

The MADRS project "hard to concentrate" represents the idea of having difficulty collecting individuals, resulting in a failure to concentrate.

If the patient has no difficulty concentrating, the score is 0. If it is occasionally difficult to collect personal ideas, the score is 2. If it is difficult to concentrate on and maintain thought difficulties, resulting in reduced reading or dialogue ability, the score is 4. If the patient is unable to read or talk easily, the score is 6.

The inventors have determined that an increase in the score of the MADRS project "hard to concentrate on" has a negative impact on both aspects of maternal function (maternal capacity related to infant interaction and maternal self-care). An increase in the score of the MADRS project "hard to concentrate on" can impair infant care and management.

Conversely, improvements relating to this MADRS program will lead to improved maternal function, particularly in terms of infant care and/or management in the BIMF functional area.

In the study group receiving the personalized dosing regimen, the total score for the MADRS project "hard to focus" for all 8 patients was 30 at baseline. After 2 hours, the score decreased to 11, which corresponds to a 19 point or 63% improvement. On day 1 after treatment, the score decreased to 1, which corresponds to 29 points or 97% improvement. On day 7 post-treatment, the score dropped to 9, which corresponds to a 21 point or 70% improvement.

In the 12 mg group, the total score for the MADRS project "hard to focus" for all 4 patients was 16 at baseline. After 2 hours, the score decreased to 7, which corresponds to a 9 point or 56% improvement. On day 1 after treatment, the score dropped to 2, which corresponds to a 14 point or 88% improvement. On day 7 post-treatment, the score decreased to 3, which corresponds to a 13 point or 81% improvement.

The inventors concluded that 5-MeO-DMT can be used to treat patients with mental or neurological disorders to achieve a reduction or elimination of difficulty in focusing attention.

The improvement in difficulty in focusing on is reflected at least in an improvement in the score of difficulty in focusing on the MADRS project at about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28.

Improvements in difficulty in focusing attention, reflected in a decrease in clinical global impression-severity (CGI-S) score, occur no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Additionally or alternatively, a decrease in the clinical global impression-severity (CGI-S) score occurs at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvements that are difficult to focus on (at least reflected in a "greatly improved" score in the clinical global impression-improvement (CGI-I) score or the patient global impression-improvement (PGI-I) score) preferably occur no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in difficulty in focusing attention (reflected in a decrease in the CGI-S score or at least in a "greatly improved" score in the CGI-I score or PGI-I score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, in particular until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The inventors have also concluded that the reduction or elimination of inattention by treatment of patients with mental or neurological disorders not only results in a reduction in the total score of MADRS, but also in an improvement in maternal function, which is reflected in an increase in the BIMF score. This improvement will be achieved rapidly, i.e. within about 2 hours, and an increase in BIMF score will also be observed at day 7, day 14, and/or day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Since difficulty focusing on other aspects of mental or neurological disorders also affects, the inventors concluded that the observed improvement in the "difficulty focusing" item in MADRS would additionally contribute to the overall improvement in maternal function.

The MADRS project "pessimistic ideas" stands for the ideas of guilt, spelt, responsibilities, criminal, remorse, and devastating.

If there is no pessimistic idea, the score is 0. If there is a failure, responsibility, or denigrate oneself fluctuating idea, the score is 2. Scoring means sustained self-responsibility, or clear but still reasonable guilt or criminal thoughts, and the patient is becoming more pessimistic to the future. If there is a disfiguring delusions, remorse or irrecoverable criminal and paradoxical and immovable self-responsibility, the score is 6.

The inventors have determined that an increase in the score of the MADRS project "pessimistic thoughts" has a negative impact on both aspects of maternal function (maternal ability related to infant interaction and maternal self-care). An increase in the score of the MADRS project "pessimistic ideas" can impair mental health, social support and management.

In contrast, improvements in terms of this MADRS project would lead to improved maternal function, particularly in terms of mental health, social support and/or management in the BIMF functional area.

In the study group receiving the personalized dosing regimen, the total score of the MADRS project "pessimistic ideas" for all 8 patients was 28 at baseline. After 2 hours, the score decreased to 7, which corresponds to a 21 point or 75% improvement. On day 1 after treatment, the score decreased to 4, which corresponds to 24 points or 86% improvement. On day 7 post-treatment, the score decreased to 3, which corresponds to 25 points or 89% improvement.

In the 12 mg group, the total score for the MADRS project "pessimistic ideas" for all 4 patients was 16 at baseline. After 2 hours, the score decreased to 8, which corresponds to an 8 score or 50% improvement. On day 1 after treatment, the score dropped to 7, which corresponds to a 9 point or 56% improvement. On day 7 post-treatment, the score decreased to 8, which corresponds to an 8 score or 50% improvement.

The inventors concluded that 5-MeO-DMT can be used to treat patients with mental or neurological disorders to achieve a reduction or elimination of pessimistic ideas.

Improvements in pessimistic thoughts are reflected at least in improvements in the scores of the MADRS project pessimistic thoughts at about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28.

Improvement in pessimistic ideas, reflected in a decrease in clinical global impression-severity (CGI-S) score, occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Additionally or alternatively, a decrease in the clinical global impression-severity (CGI-S) score occurs at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in pessimistic ideas (at least reflected in the "greatly improved" score in the clinical global impression-improvement (CGI-I) score or the patient global impression-improvement (PGI-I) score) preferably occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in pessimistic thoughts (reflected as a decrease in CGI-S score or at least as a "greatly improved" score in CGI-I score or PGI-I score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The inventors have also concluded that the reduction or elimination of pessimistic ideas achieved by treating patients with mental or neurological disorders not only results in a reduction in the total score of MADRS, but also in an improvement in maternal function, which is reflected in an increase in BIMF score. This improvement will be achieved rapidly, i.e. within about 2 hours, and an increase in BIMF score will also be observed at day 1, e.g. after about 24 hours, at day 7, at day 14, and/or at day 28, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Since pessimistic ideas can also affect other aspects of mental or neurological disorders, the inventors concluded that the observed improvement in the "pessimistic ideas" project in MADRS would otherwise contribute to the overall improvement in maternal function.

The MADRS project "sleep reduction" represents the experience of reduced sleep duration or depth compared to the normal mode when the subject is healthy itself.

When the subject sleep normally, the score is 0. Score 2 reflects a slight difficulty in falling asleep, or a slight decrease, shallowness, or intermittent sleep time. Score 4 means sleep time is reduced or discontinued for at least two hours. A score of 6 means that the sleep time is less than two hours or three hours.

The inventors have determined that an increase in the score of the MADRS project "sleep reduction" has a negative impact on both aspects of maternal function (maternal capacity related to infant interaction and maternal self-care). An increase in the score of the MADRS project "sleep reduction" can impair self-care, mental health and management.

In contrast, improvements in terms of this MADRS project would lead to improved maternal function, particularly in terms of self-care, mental health and/or management in the BIMF functional area.

In the study group receiving the personalized dosing regimen, the total score for the MADRS project "sleep reduction" for all 8 patients was 25 at baseline. On day 1 post-treatment, the earliest time point at which the effect of treatment on sleep was assessed, the score was reduced to 12, which corresponds to a 13 point or 52% improvement. On day 7 post-treatment, the score dropped to 9, which corresponds to a 16 point or 64% improvement.

In the 12 mg group, the total score for the MADRS project "sleep reduction" for all 4 patients was 12 at baseline. On day 1 after treatment, the score decreased to 10, which corresponds to a2 score or 17% improvement. On day 7 post-treatment, the score decreased to 6, which corresponds to a 6 score or 50% improvement.

The inventors concluded that 5-MeO-DMT can be used to treat patients with mental or neurological disorders to achieve a reduction or elimination of sleep loss.

The reduction or elimination of sleep reduction is reflected at least in an improvement in the score of the MADRS program sleep reduction at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in sleep reduction, reflected as a decrease in clinical global impression-severity (CGI-S) score, occurs no later than about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in sleep reduction (at least reflected in the "greatly improved" score in the clinical global impression-improvement (CGI-I) score or patient global impression-improvement (PGI-I) score) preferably occurs no later than about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in sleep reduction (reflected as a decrease in CGI-S score or at least as a "greatly improved" score in CGI-I score or PGI-I score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The inventors have also concluded that the reduction or elimination of sleep reduction achieved by treating patients with mental or neurological disorders results not only in a reduction in the total score of MADRS, but also in an improvement in maternal function, which is reflected in an increase in the BIMF score. This improvement will be achieved rapidly, i.e. within about 24 hours, and an increase in BIMF score will also be observed at day 1, e.g. after about 24 hours, at day 7, at day 14, and/or at day 28, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Since sleep loss can also affect other aspects of mental or neurological disorders, the inventors concluded that the observed improvement in the "sleep loss" program in MADRS would additionally contribute to the overall improvement in maternal function.

Another aspect of mental or neurological disorders that may be treated by the administration of 5-MeO-DMT is suicidal ideation. 5-MeO-DMT may be administered to patients with mental or neurological disorders to reduce or eliminate the suicidal ideation of the patient.

In the clinical study described above involving the administration of 5-MeO-DMT, the MADRS project "suicide idea" was evaluated, among others.

"Suicide ideas" represent a sensation that life is not worth moving, natural death is welcome, suicide ideas are present, and/or preparation for suicide. Suicide attempts should not themselves affect the rating of this MADRS project.

A score of 0 means that the patient enjoys life. A score of 2 is given if the patient with mental or neurological disorder is tired of life and/or has only a short suicidal thoughts. Score 4 means that the patient feels that death would be better, suicide ideas are very common and suicide is considered a possible solution, but the patient has no specific plan or intent. If the patient has an explicit suicide plan and/or is actively preparing, the score is 6 points.

This MADRS scale item is particularly relevant to suicidal ideation.

The inventors have determined that an increase in the score of the MADRS project "suicidal ideation" has a negative impact on both aspects of maternal function (maternal ability related to infant interaction and maternal self-care). An increase in the score of the MADRS project "suicidal ideation" can impair self-care, mental health and management.

In contrast, improvements in terms of this MADRS project would lead to improved maternal function, particularly in terms of self-care, mental health and/or management in the BIMF functional area.

In the study group receiving the personalized dosing regimen, the total score for the MADRS project "suicide idea" for all 8 patients was 11 at baseline. After 2 hours, the score decreased to 3, which corresponds to an improvement of 8 points or 73%. On day 1 after treatment, the score decreased to 1, which corresponds to a 10 point or 91% improvement. On day 7 post-treatment, the score decreased to 3, which corresponds to an 8 point or 73% improvement.

In the 12 mg group, the total score for the MADRS project "suicidal ideation" for all 4 patients was 8 at baseline. After 2 hours, the score decreased to 3, which corresponds to a5 point or 63% improvement. On day 1 after treatment, the score decreased to 5, which corresponds to a3 point or 38% improvement. On day 7 post-treatment, the score dropped to 7, which corresponds to a 1 point or 13% improvement.

Thus, the scale item "suicidal ideation" associated with suicidal ideation is a significant improvement in scoring, at least in individual dosing regimen patients. The inventors concluded that 5-MeO-DMT can be used to treat suicidal ideation in patients with mental or neurological disorders.

Thus, according to the present invention, treatment of a patient suffering from a mental or neurological disorder with suicidal ideation may reduce or eliminate suicidal ideation.

The reduction or elimination of suicide ideas is reflected at least in an improvement in the score of the MADRS project suicide ideas at least about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28.

If the patient suffers from suicidal ideation, the improvement in suicidal ideation is reflected in a decrease in clinical overall impression-severity (CGI-S) score at about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28.

Improvement of suicidal ideation, reflected in a decrease in clinical global impression-severity (CGI-S) score, occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Or a decrease in clinical global impression-severity (CGI-S) score occurs at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in suicidal ideation (at least assessed as a "greatly improved" score in the clinical global impression-improvement (CGI-I) score or the patient global impression-improvement (PGI-I) score) preferably occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement of suicide (assessed as a decrease in CGI-S score or at least as a "greatly improved" score in CGI-I score or PGI-I score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The inventors have also concluded that the reduction or elimination of suicide ideas achieved by treating patients with mental or neurological disorders not only results in a reduction of the total score of MADRS, but also results in an improvement of maternal function, which is reflected in an increase in the BIMF score. This improvement will be achieved rapidly, i.e. within about 2 hours, and an increase in BIMF score will also be observed at day 1, e.g. after about 24 hours, at day 7, at day 14, and/or at day 28, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Since suicide ideas can also affect other aspects of mental or neurological disorders, the inventors concluded that the observed improvement in the "suicide ideas" project in MADRS would additionally contribute to the overall improvement in maternal function.

The BPRS project "emotional withdrawal" is related to the inability of a patient to express emotion during an interview. Possible scores are:

1-anecdotal recoil.

2-Very mild. Lack of emotional engagement, manifested as occasional failure to respond, occasional disconcerting, or smiling unnaturally, but most of the time spontaneously talking to interviewees.

3-Mild. Lack of emotional input manifests as a significant failure to respond, a lack of mind, or lack of enthusiasm, but responds when interviewees are approaching.

4-Moderate. There is no emotional contact during most interviews because the subject does not respond in detail, does not have eye contact, does not seem to care whether the interviewer is listening or may be immersed in psychotic material.

5-Moderate to severe. As with "4", but there is no emotional contact during most interviews.

6-Severe. Actively avoiding emotion participation. Often without or with yes/no answers (not just due to a harmful delusions). Responding with only minimal emotion.

7-Very severe. And emotion participation is avoided all the time. No response or yes/no response (not just due to a harmful delusions). May leave or not respond at all during the interview.

The inventors have determined that an increase in the score of the BPRS project "affective retraction" has a negative impact on both aspects of maternal function (maternal capacity related to infant interaction and maternal self-care). An increase in the score of the BPRS project "emotional withdrawal" can impair mental health, maternal-maternal interactions, and social support.

Conversely, improvements in this BPRS project may lead to improved maternal function, particularly in terms of mental health, maternal-maternal interactions, and/or social support in the BIMF functional area.

In the study group receiving the personalized dosing regimen, the overall score for the BPRS project "emotional withdrawal" was 13 at baseline. After 3 hours, the score decreased to 8, which corresponds to a5 point or 38% improvement. On day 1 after treatment, the score decreased to 8, which corresponds to a5 point or 38% improvement. On day 7 post-treatment, the score decreased to 8, which corresponds to a5 point or 38% improvement.

In group 12 mg, the overall score for the BPRS item "emotional withdrawal" is 13 at baseline. After 3 hours, the score decreased to 11, which corresponds to a 2 score or 15% improvement. On day 1 after treatment, the score decreased to 8, which corresponds to a 5 point or 38% improvement. On day 7 post-treatment, the score decreased to 6, which corresponds to a 7 point or 54% improvement.

The inventors concluded that 5-MeO-DMT can be used to treat patients with mental or neurological disorders to achieve reduction or elimination of emotional withdrawal.

The reduction or elimination of emotional withdrawal is reflected at least in an improvement in the score of the emotional withdrawal of the BPRS project at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, after about 2 hours from the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in emotional withdrawal, reflected in a decrease in clinical global impression-severity (CGI-S) score, occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Additionally or alternatively, a decrease in the clinical global impression-severity (CGI-S) score occurs at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in emotional withdrawal (at least reflected in the "greatly improved" score in the clinical global impression-improvement (CGI-I) score or the patient global impression-improvement (PGI-I) score) preferably occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in emotional withdrawal (reflected as a decrease in the CGI-S score or at least as a "greatly improved" score in the CGI-I score or PGI-I score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, in particular until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The inventors have also concluded that the reduction or elimination of emotional withdrawal achieved by treating patients with mental or neurological disorders results not only in a reduction in the overall score of BPRS, but also in an improvement in maternal function, which is reflected in an increase in BIMF score. This improvement will be achieved rapidly, i.e. within about 2 hours, and an increase in BIMF score will also be observed at day 1, e.g. after about 24 hours, at day 7, at day 14, and/or at day 28, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Since emotional withdrawal may also affect other aspects of mental or neurological disorders, the inventors concluded that the improvement in the "emotional withdrawal" program in BPRS observed would otherwise contribute to the overall improvement in maternal function.

The BPRS item "bradycardia" relates to limited range of emotional expressions of face, sound and gestures, and manifests itself as a pronounced indifference or frigidity even when discussing a distressing topic. Possible scores are:

1-anepithymia.

2-Very mild. The emotion range is slightly depressed or preserved, but shows proper facial expression and speech intonation, within normal range.

3-Mild. Overall, there is a reduced, sunken or preserved emotion scope, without many spontaneous and appropriate emotional responses. The mood is slightly monotonous.

4-Moderate. The emotional scope is significantly diminished and, except in rare cases, the patient does not show emotion, smile, or respond to a distressing topic. The speech intonation is monotonous or the spontaneous motion is significantly reduced. Emotion or gesture performance usually follows in that emotion resumes frigidity.

5-Moderate to severe. The emotion range is very diminished and the patient does not show emotion, smile, or react to painful topics, with the exception of minimal, few gestures, facial expression not changing frequently. Most of the time, speech utterances are monotonous.

6-Severe. There is very little emotional scope or expression. Most of the time speech and gestures are mechanical. The facial expression is unchanged. Most of the time the speech intonation is monotonous.

7-Very severe. There is little emotional range or expressive power and stiffness in motion. At all times, the speech intonation is monotonous.

The inventors have determined that an increase in the score of BPRS project "emotional dullness" has a negative impact on both aspects of maternal function (maternal capacity related to infant interaction and maternal self-care). An increase in the score of BPRS project "emotional dullness" may impair mental health and mother-child interaction.

Conversely, improvements relating to this BPRS project would lead to improved maternal function, particularly in terms of mental health and/or maternal-maternal interactions in the BIMF functional area.

The overall score for BPRS item "emotional dullness" is 15 at baseline. After 3 hours, the score was reduced to 11, which corresponds to a 4 point or 27% improvement. On day 1 after treatment, the score decreased to 8, which corresponds to a 7 point or 47% improvement. On day 7 post-treatment, the score decreased to 8, which corresponds to a 7 point or 47% improvement.

In group 12 mg, the overall score for the BPRS item "emotional dullness" is 11 at baseline. After 3 hours, the score decreased to 8, which corresponds to a 3 point or 27% improvement. On day 1 after treatment, the score decreased to 6, which corresponds to a5 point or 45% improvement. On day 7 post-treatment, the score decreased to 5, which corresponds to a6 point or 55% improvement.

The inventors concluded that 5-MeO-DMT can be used to treat patients with mental or neurological disorders to achieve a reduction or elimination of affective retardation.

The reduction or elimination of emotional dullness is reflected at least in an improvement in the score of BPRS project emotional dullness about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28.

Improvement in emotional retardation, reflected in a decrease in clinical global impression-severity (CGI-S) score, occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Additionally or alternatively, a decrease in the clinical global impression-severity (CGI-S) score occurs at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in emotional retardation, at least reflected in the "greatly improved" score in the clinical global impression-improvement (CGI-I) score or the patient global impression-improvement (PGI-I) score, preferably occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in emotional retardation (reflected as a decrease in the CGI-S score or at least as a "greatly improved" score in the CGI-I score or PGI-I score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, in particular until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The inventors have also concluded that the reduction or elimination of affective disorder achieved by treatment of patients with mental or neurological disorders results not only in a reduction of BPRS overall score, but also in an improvement of maternal function, which is reflected in an increase in BIMF score. This improvement will be achieved rapidly, i.e. within about 2 hours, and an increase in BIMF score will also be observed at day 1, e.g. after about 24 hours, at day 7, at day 14, and/or at day 28, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Since emotional retardation can also affect other aspects of mental or neurological disorders, the inventors concluded that the improvement in the "emotional retardation" term in BPRS observed would additionally contribute to the overall improvement in maternal function.

The BPRS item "guilt feel" is related to excessive attention or remorse to past behavior. Possible scores are:

1-no guilt feeling.

2-Very mild. There is a fear of frustrating someone or a fear of failing something but not careless. The idea can be easily transferred to other things.

3-Mild. There is a fear that someone is disappointed or there is a fear that something fails and is careless. Tending to express guilt to others.

4-Moderate. Excessive immersion, miswork, injury to others due to doing or not doing something, but can easily divert attention to other things.

5-Moderate to severe. Immersion in guilt, frustrating or failing someone, may divert attention to other things, but with great effort. Not delusional.

6-Severe. Delusional guilt or irrational self-responsibility that is very disproportionate to the environment. There is a moderate absence of attention.

7-Very severe. Delusional guilt or irrational self-responsibility that is highly disproportionate to the environment. The subject is very immersed in guilt and may be exposed to others or act on delusions.

The inventors have determined that an increase in the score of the BPRS project "guilt feel" has a negative impact on both aspects of maternal function (maternal ability related to infant interaction and maternal self-care). An increase in the score of the BPRS project "guilt feel" can impair self-care, mother-child interaction, mental health and management.

Conversely, improvements in this BPRS project would result in improved maternal function, particularly in terms of self-care, maternal-maternal interaction, mental health, and/or management in the BIMF functional area.

In the study group receiving the personalized dosing regimen, the total score of BPRS project "guilt feel" for all 8 patients was 34 at baseline. After 3 hours, the score dropped to 14, which corresponds to a 20 point or 59% improvement. On day 1 after treatment, the score dropped to 11, which corresponds to a 23 point or 68% improvement. On day 7 post-treatment, the score dropped to 10, which corresponds to 24 points or 71% improvement.

In group 12 mg, the total score of the BPRS project "guilt feel" for all 4 patients was 18 at baseline. After 3 hours, the score decreased to 9, which corresponds to a 9 score or 50% improvement. On day 1 after treatment, the score decreased to 5, which corresponds to a 13 point or 72% improvement. On day 7 post-treatment, the score decreased to 5, which corresponds to a 13 point or 72% improvement.

The inventors concluded that 5-MeO-DMT can be used to treat patients with mental or neurological disorders to achieve a reduction or elimination of guilt.

The reduction or elimination of guilt is reflected at least in an improvement in the score of the guilt sensation in the BPRS program at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, after about 2 hours from the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in guilt sensation, reflected in a decrease in clinical global impression-severity (CGI-S) score, occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Additionally or alternatively, a decrease in the clinical global impression-severity (CGI-S) score occurs at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in guilt sensation (at least reflected as a "greatly improved" score in the clinical global impression-improvement (CGI-I) score or patient global impression-improvement (PGI-I) score) preferably occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in guilt (reflected as a decrease in CGI-S score or at least as a "greatly improved" score in CGI-I score or PGI-I score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The inventors have also concluded that the reduction or elimination of guilt sensation achieved by treating patients with mental or neurological disorders not only results in a reduction in the overall score of BPRS, but also results in an improvement in maternal function, which is reflected in an increase in BIMF score. This improvement will be achieved rapidly, i.e. within about 2 hours, and an increase in BIMF score will also be observed at day 1, e.g. after about 24 hours, at day 7, at day 14, and/or at day 28, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Since guilt sensation can also affect other aspects of mental or neurological disorders, the inventors concluded that the observed improvement in the term "guilt sensation" in BPRS would otherwise contribute to the overall improvement in maternal function.

The BPRS project "anxiety" is related to reported anxiety, tension, fear, panic, or anxiety. Possible scores are:

1-anxiolytic.

2-Very mild. Some discomfort is reported due to concerns or infrequent concerns that occur more frequently than in most normal individuals.

3-Mild. There is frequent concern but the attention can be easily diverted to other things.

4-Moderate. Most of the time, the anxiety state is worried about, and the attention cannot be easily transferred to other things without impaired function, or anxiety occasionally occurs with autonomic symptoms without impaired function.

5-Moderate to severe. Anxiety frequently (but not daily) occurs with autonomic symptoms or some areas of function are disturbed by anxiety or anxiety.

6-Severe. Anxiety is accompanied by autonomic symptoms every day, but does not last for a whole day, or many functional areas are disturbed by anxiety or persistent anxiety.

7-Very severe. Anxiety is accompanied by autonomic symptoms that last for a whole day, or most areas of function are disturbed by anxiety or persistent anxiety.

The inventors have determined that an increase in the score of the BPRS project "anxiety" has a negative impact on both aspects of maternal function (maternal ability related to infant interaction and maternal self-care). An increase in the score of the BPRS project "anxiety" can impair mental health, social support and management.

Conversely, improvements in this BPRS project would lead to improved maternal function, particularly in terms of mental health, social support and/or management in the BIMF functional area.

In the study group receiving the personalized dosing regimen, the total score for BPRS project "anxiety" for all 8 patients was 37 at baseline. After 3 hours, the score decreased to 19, which corresponds to an improvement of 18 points or 49%. On day 1 after treatment, the score was reduced to 16, which corresponds to 21 points or 57% improvement. On day 7 post-treatment, the score was reduced to 17, which corresponds to a 20 score or 54% improvement.

In the 12mg group, the total score for the BPRS project "anxiety" for all 4 patients was 25 at baseline. After 3 hours, the score decreased to 11, which corresponds to a 14 point or 56% improvement. On day 1 after treatment, the score decreased to 6, which corresponds to a 19 point or 76% improvement. On day 7 post-treatment, the score decreased to 6, which corresponds to a 19 point or 76% improvement.

The inventors concluded that 5-MeO-DMT can be used to treat patients with mental or neurological disorders to achieve reduction or elimination of anxiety.

The reduction or elimination of anxiety is reflected at least in an improvement in the score of BPRS project anxiety about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28.

Improvement in anxiety, reflected as a decrease in clinical global impression-severity (CGI-S) score, occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Additionally or alternatively, a decrease in the clinical overall impression-severity (CGIS) score occurs on day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in anxiety (at least reflected in a "greatly improved" score in the clinical global impression-improvement (CGI-I) score or patient global impression-improvement (PGI-I) score) preferably occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in anxiety (reflected as a decrease in CGI-S score or at least as a "greatly improved" score in CGI-I score or PGI-I score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The inventors have also concluded that the reduction or elimination of anxiety achieved by treating patients with mental or neurological disorders not only results in a reduction of BPRS score overall, but also results in an improvement in maternal function, which is reflected in an increase in BIMF score. This improvement will be achieved rapidly, i.e. within about 2 hours, and an increase in BIMF score will also be observed at day 1, e.g. after about 24 hours, at day 7, at day 14, and/or at day 28, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Since anxiety may also affect other aspects of mental or neurological disorders, the inventors concluded that the observed improvement in the "anxiety" program in BPRS would otherwise contribute to the overall improvement in maternal function.

The BPRS project "stress" is related to stress, "stress (nervousness)" and the observed physical and motor manifestations of agitation. Possible scores are

1-No stress.

2-Very mild. More annoying than most people but in the normal range. Some transient stress signs, such as scratching nails, shaking feet, grabbing the scalp multiple times, or tapping the fingers.

3-Mild. As with "2", but the stress signs are more frequent or exaggerated.

4-Moderate. Many and frequent exercise stress signs, sometimes with simultaneous appearance of one or more signs, e.g., twisting the hands while shaking the feet. Sometimes there is no sign of stress.

5-Moderate to severe. Many and frequent motor stress signs, often with one or more signs. There are still very few signs of stress that are not present.

6-Severe. The same as "5" but the stress sign is sustained.

7-Very severe. Tension in various athletic performances persists, such as continuous pacing and twisting hands.

The inventors have determined that an increase in the score of the BPRS project "tension" has a negative impact on both aspects of maternal function (maternal capacity related to infant interaction and maternal self-care). An increase in the "tension" score of the BPRS project can impair mother-child interaction and mental health.

Conversely, improvements relating to this BPRS project may result in improved maternal function, particularly in terms of maternal-maternal interaction and/or mental health in the BIMF functional area.

In the study group receiving the personalized dosing regimen, the total score for BPRS project "stress" for all 8 patients was 16 at baseline. After 3 hours, the score decreased to 11, which corresponds to a 5 point or 31% improvement. On day 1 after treatment, the score dropped to 11, which corresponds to a 5 point or 31% improvement. On day 7 post-treatment, the score dropped to 10, which corresponds to a6 point or 38% improvement.

In the 12 mg group, the total score for BPRS project "stress" for all 4 patients was 14 at baseline. After 3 hours, the score decreased to 9, which corresponds to a 5 point or 36% improvement. On day 1 after treatment, the score decreased to 6, which corresponds to 8 points or 57% improvement. On day 7 post-treatment, the score decreased to 6, which corresponds to an 8 point or 57% improvement.

The inventors concluded that 5-MeO-DMT can be used to treat patients with mental or neurological disorders to achieve a reduction or elimination of stress.

The reduction or elimination of stress is reflected at least in an improvement in the score of BPRS project stress at about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28.

Improvement in stress, reflected in a decrease in clinical global impression-severity (CGI-S) score, occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Additionally or alternatively, a decrease in the clinical global impression-severity (CGI-S) score occurs at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in stress (at least reflected in a "greatly improved" score in the clinical global impression-improvement (CGI-I) score or the patient global impression-improvement (PGI-I) score) preferably occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in stress (reflected as a decrease in CGI-S score or at least as a "greatly improved" score in CGI-I score or PGI-I score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The inventors have also concluded that the reduction or elimination of stress achieved by treating patients with mental or neurological disorders not only results in a reduction in the overall score of BPRS, but also in an improvement in maternal function, which is reflected in an increase in the BIMF score. This improvement will be achieved rapidly, i.e. within about 2 hours, and an increase in BIMF score will also be observed at day 1, e.g. after about 24 hours, at day 7, at day 14, and/or at day 28, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Since stress can also affect other aspects of mental or neurological disorders, the inventors concluded that the observed improvement in the "stress" program in BPRS would additionally contribute to the overall improvement in maternal function.

Improvements in one or more aspects of mental or neurological disorders will also result in an overall improvement. Preferably, the treatment results in relief.

Relief from symptoms of depression may be reflected in a MADRS score of 10 or less and occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Further alternatively or additionally, relief of symptoms of depression may be reflected in a HAM-D score equal to or less than 7 and occurring no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

From the foregoing, it is clear that treatment of patients with mental or neurological disorders with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results not only in a decrease in MADRS score (including particularly the sub-scores detailed above), but also in an improvement in the BIMF scale field. As discussed in the examples section below, clinical data confirm a decrease in MADRS score and an improvement in maternal function.

Improvements in maternal function include improvements in the area of self-care function. For example, improvement in MADRS project lazy and/or sleep reduction may result in an increase in BIMF scale scores reflecting self-care. The improvement in cumulative score of BIMF scale items reflecting self-care is preferably at least 10%, more preferably at least 20%.

Improvements in maternal function include improvements in the area of baby care functions. For example, improvement in MADRS program lazy and/or inattention may result in an increase in BIMF scale scores reflecting baby care. The improvement in cumulative score of BIMF scale items reflecting self-care is preferably at least 15%, more preferably at least 25%.

Improvement of mother functions includes improvement of the field of mother-child interaction functions. For example, an improvement in MADRS project sensory deficit and internal stress would result in an increase in BIMF scale scores reflecting maternal-maternal interactions. The improvement in cumulative score of BIMF scale items reflecting parent-child interaction is preferably at least 5%, more preferably at least 15%.

Improvements in maternal function include improvements in the area of mental health functions. For example, improvement in MADRS project lazy, pessimistic ideas, sensory deficit, internal stress, and/or sleep reduction may result in an increase in BIMF scale scores reflecting mental health. The improvement in cumulative score of BIMF scale items reflecting mental health is preferably at least 25%, more preferably at least 35%.

Improvements in maternal function include improvements in the area of social support functions. For example, improvement of pessimistic ideas of MADRS project would result in an increase in BIMF scale scores reflecting social support. The improvement in cumulative score of BIMF scale items reflecting social support is preferably at least 10%, more preferably at least 20%.

Improvements in maternal function include improvements in the area of management functions. For example, improvement in MADRS project lazy, pessimistic ideas, and/or hard to focus on may result in an increase in BIMF scale scores reflecting management. The improvement in cumulative score reflecting managed BIMF scale items is preferably at least 20%, more preferably at least 30%.

Improvements in maternal function include improvements in the area of regulatory function. For example, improvement in MADRS project lazy results in an increase in BIMF scale scores reflecting adjustments. The improvement in cumulative score reflecting the adjusted BIMF-scale item is preferably at least 5%, more preferably at least 15%.

Improvement of maternal function involves one or more, in particular two or more, areas of function selected from self-care, baby care, maternal and maternal interactions, maternal mental health, social support, management and regulation according to Barkin maternal function index (BIMF).

BIMF total score is improved by 10% or more, preferably by 20% or more.

Breast feeding

The term breast feeding, as used herein, is the process of feeding a child with human breast milk. Breast feeding includes feeding breast milk directly from the breast, and feeding the child with milk that is expressed first and then fed to the baby bottle.

As mentioned above, for many medications, a breastfed patient may be faced with a situation where it is necessary to decide whether to stop breastfeeding or stop/forego treatment.

If it is decided to stop breast feeding for treatment, this decision will negatively affect the mother's function, especially in the area of functions that impair mother-child interaction and mental health.

The present invention also addresses the need to treat mental or neurological disorders in breast-feeding mothers without almost completely interrupting breast-feeding.

According to the invention, breast feeding can be resumed shortly after treatment.

The inventors studied the pharmacokinetic properties and metabolism of 5-MeO-DMT to determine from which point in time after administration of 5-MeO-DMT or a pharmaceutically acceptable salt breast feeding could be performed without any associated risk to breast fed infants.

In addition, breast milk was obtained from breast-fed patients receiving 5-MeO-DMT treatment PPD. As described in more detail in the examples section, breast-fed patients suffering from PPD received a dose of 6 mg of 5-MeO-DMT, and after 1 hour, a dose of 12 mg of 5-MeO-DMT.

At several time points after the last administration of 5-MeO-DMT, breast milk samples as well as serum and urine samples were analyzed to determine the presence of 5-MeO-DMT, bufogenin (the major metabolite of 5-MeO-DMT) and 5-MIAA (the final metabolite of 5-MeO-DMT).

Regarding the administered compound 5-MeO-DMT, which is itself rapidly absorbed and distributed, for example, upon administration by inhalation or injection, the maximum concentration and pharmacological effect can be observed during and immediately after administration.

The plasma protein binding rate was low (13-23%).

Pharmacokinetic analysis of 5-MeO-DMT after inhalation showed a very rapid decrease in plasma concentration. 10 minutes after administration, the concentration was reduced to 10% or less of Cmax, after 2 hours, the concentration was 1% or less of Cmax, and after 3 hours, 5-MeO-DMT was no longer detected in the plasma. This applies to the full dose range tested (6 mg, 12 mg, 18 mg). No accumulation was observed after repeated administration over a period ranging from 1 to 4 hours. Upregulation as disclosed herein does not lead to accumulation and therefore does not lead to higher 5-MeO-DMT plasma concentrations, e.g. 10 minutes, 2 hours or 3 hours after administration.

The rapid decrease in plasma concentration resulted in a short period of time for which 5-MeO-DMT was able to enter breast milk. Thus, 5-MeO-DMT is found only in breast milk for a short period of time.

The obtained patient data confirm that the concentration of 5-MeO-DMT in breast milk decreases rapidly (see example 12). No 5-MeO-DMT was detected by measurement after 24 hours.

In determining the effect that maternal drug administration may have on breast-fed infants, it is standard practice to calculate the Relative Infant Dose (RID) (Bennett, p.n. and L. J. Notarianni. "Risk from drugs in breast milk: an analysis by relative dose."Br J Clin Pharmacol 42.5 (1996): P673-4).RID are the doses to which the infant is exposed by ingestion of breast milk (in μg/kg/day), divided by the dose received by the mother (in μg/kg/day).

Based on the estimated daily intake of breast milk and the number of feeds and the measured concentration of breast milk, the exposure of the infant can be determined.

For example, the estimated value published for the daily intake of breast milk versus infant weight is 150 ml/kg/day. To simulate exposure, it is assumed that a 5 kg infant is fed three times within 24 hours, each time receiving 250 ml breast milk. For the first feeding, it was assumed that the 5-MeO-DMT concentration was 2167.0 pg/ml (value measured at 1 hour), the concentration for the second feeding was 560.6 pg/ml (value measured at 2.5 hours), and the concentration for the third feeding was 42.1 pg/ml (value measured at 8.5 hours). On this basis, the total exposure of the infants (daily infant dose, DID) was 692425 pg 5-MeO-DMT/day (0.000692425 mg/day), which corresponds to 0.000138485 mg/kg/day.

Regarding maternal 5-MeO-DMT exposure, the total dose was 18 mg (the first dose was 6 mg and the second dose was 12 mg depending on the up-titration protocol applied).

Since the dose actually delivered to the patient may be lower than the indicated dose, the RID will also be calculated assuming that the actual delivered amount is only 50% of the indicated dose, to avoid any potential underestimation of the infant exposure.

Assuming a maternal standard body weight of 60 kg, a RID of 0.092% (9 mg based on maternal exposure) to 0.046% (18 mg based on maternal exposure) can be obtained.

The accepted threshold for "low risk" RID is 10%. It is clear from the calculated values that the 5-MeO-DMT RID is significantly below this threshold.

Furthermore, it is noted that the range of 0.046% to 0.092% is a conservative estimate. It is assumed that the concentration of 5-MeO-DMT remains constant (although the actual concentration will drop rapidly) before the next feeding, and the fact that more than three feeds per day are possible is ignored, i.e. the volume of each feed is small and the concentration of 5-MeO-DMT to which the infant is exposed gradually decreases over time.

Further, at the time of evaluation, it is assumed that no breast milk is expressed and discarded.

Thus, the actual RID will be lower than the estimated value.

5-MeO-DMT metabolites that may occur in humans were identified to assess the potential relevance of such metabolites. In the in vitro metabolism identification study of human hepatocytes, 5-MeO-DMT free base was incubated at 10. Mu.M for up to 120 minutes. The compounds identified and their relative proportions are shown in table 1 below:

TABLE 1

Notably, subsequent assays failed to detect the presence of 5-methoxy tryptol multiple times, but could repeatedly indicate that 5-MIAA was present as the primary metabolite. 5-methoxy chromanol does not play any important role in vivo.

The metabolites listed in the above table are formed by three different pathways.

The two most important metabolites, 5-methoxyindole acetic acid and 5-methoxyindole-3-ethanol, are formed by oxidative deamination. This involves enzymatic removal of the N-methyl group and oxidation such that acetaldehyde is formed:

The reaction shown is catalyzed by monoamine oxidase A (MAO-A).

Secondary amines, primary amines and aldehydes were not identified, indicating that they were not present at any time in significant concentrations.

The aldehyde intermediate metabolite undergoes 2 independent biotransformations in human hepatocytes. The aldehyde intermediate metabolite is oxidized to 5-methoxyindole acetic acid (5-MIAA) or reduced to 5-methoxyindole-3-ethanol.

Both resulting metabolites are endogenous substances and are formed in humans, for example, during the synthesis and metabolism of melatonin and serotonin (see, e.g., chapter 3 Biochemistry of the pinal Arendt J (editions) Chapman & Hall, 1995; chapter 3 SYNTHESIS AND Metabolism of Melatonin IN THE SKIN AND RETINAL PIGMENT Epithium, watson RR (editions) CRC Press 2012 in Melatonin AND THE MAMMALIAN PINEAL Gland. Slominski R and Slominski AT. Melatonin in the Promotion of health).

Since the primary pathway of 5-MeO-DMT metabolism rapidly produces metabolites that are also part of the endogenous metabolic pathway, the inventors determined that oxidative deamination of 5-MeO-DMT does not involve metabolites that require restrictions on breast feeding.

Furthermore, as detailed in the examples section, incubation of 5-methoxy tryptol with human hepatocytes showed a high metabolic turnover rate, the compound disappeared completely within 24 h. The intrinsic clearance of 5-methoxy chromanol in vitro was 16.2. Mu.l/min/million cells (half-life 142 min) at the 1. Mu.M test concentration.

Thus, the plasma concentration of 5-methoxy tryptol (even if formed) will decrease rapidly and reach endogenous levels.

5-MIAA has been identified as the major human metabolite.

Incubation of 5-MIAA with human hepatocytes indicated a low turnover rate of metabolism, with a residual 5-MIAA concentration of 75-82% after 72 h. 5-MIAA is considered the final metabolite of 5-MeO-DMT.

5-MIAA showed a relatively low plasma binding rate (average unbound score (Fu); see example section) of about 50%. After renal clearance, 5-MIAA remains in circulation.

If the endogenous formation of 5-MIAA is disregarded, and if it is assumed that the compound is immediately converted to 5-MIAA after a single administration of a single dose of 5-MeO-DMT, 5-MIAA is cleared from the circulation and excreted from the body through urine in about 1-2 hours, as inferred from the standard glomerular filtration rate (90-120 ml/min).

For example, a 5-MIAA urine concentration measured after 2.5 hours at 12.980/501 pg/ml (about 12.98 mg/l) indicates that most of the 5-MIAA formed is rapidly excreted from the body.

Thus, the plasma concentration of 5-MIAA will decrease rapidly.

In order to more accurately estimate the development of plasma concentrations of 5-MIAA, a number of factors must be considered, including the size of the patient and the increase in blood volume during pregnancy. It is understood that there are individual differences in glomerular filtration rate and metabolic rate of 5-MeO-DMT.

Furthermore, although the formation of 5-MIAA is rapid, pharmacokinetic data in healthy volunteers as well as PPD patients indicate that small amounts of 5-MeO-DMT (corresponding to less than 10% of Cmax) may still be present after about 1 hour. Thus, after administration of 5-MeO-DMT, 5-MIAA is actually formed over a period of time.

Furthermore, in the case of administration of more than one dose of 5-MeO-DMT, accumulation of 5-MeO-DMT does not occur if the administration interval is at least about 1 hour, because there is still a measurable amount of 5-MIAA in the serum at 2.5 hours, and if the subject is administered 1 hour apart, there is some accumulation of this metabolite.

5-MIAA is a weak acid that will exist in plasma in ionized form, thereby reducing the likelihood of the compound entering breast milk.

Nevertheless, it is assumed that there will be some amount of 5-MIAA entering breast milk during the limited period of time when the 5-MIAA plasma concentration is relatively high.

For additional information on the concentration time curve, please see the measured concentration of 5-MIAA in breast milk described in example 12. Using these data, the infant exposure to 5-MIAA can be calculated.

For the first feeding of 250 ml, it was assumed that the 5-MIAA concentration was 13945.2 pg/ml (value measured at 1 hour), the concentration for the second feeding was 13240.9 pg/ml (value measured at 2.5 hours), and the concentration for the third feeding was 359.4 pg/ml (value measured at 8.5 hours). On this basis, the total exposure (DID) of the infant was 0.00688638 mg 5-MIAA/day, which corresponds to 0.00137728 mg/kg/day.

Notably, the concentration of 5-MIAA in breast milk was approximately 400 times lower at 24 hours than at one hour, so that after 1 day there would be no more relevant exposure.

The amount of parent exposure to 5-MIAA can be estimated based on the amount of 5-MeO-DMT administered and the ratio of conversion of 5-MeO-DMT to 5-MIAA.

In the above metabolic experiments, the mixture contained about 60% 5-MIAA after 2 hours. The actual ratio of conversion of 5-MeO-DMT to 5-MIAA will be higher due to incomplete metabolism. It can be assumed that more than 60% to nearly 100% of 5-MeO-DMT will be converted to the final metabolite 5-MIAA, which is subsequently excreted in vitro.

Considering the molecular weight (218.29 g/mol for 5-MeO-DMT and 205.21 g/mol for 5-MIAA), a total dose of 18 mg 5-MeO-DMT would yield 10.15 mg 5-MIAA (60% conversion) to 16.92 mg 5-MIAA (100% conversion). As described above, assuming that the delivery amount of 5-MeO-DMT is only 9 mg, 5.08 mg of 5-MIAA (60% conversion) to 8.46 mg of 5-MIAA (100% conversion) is formed.

Thus, maternal exposure will be between 0.085 mg/kg/day and 00.282 mg/kg/day. This results in an estimate of RID between 0.49% and 1.62%.

As mentioned, the acceptable threshold for "low risk" RID is 10% and it is apparent from the calculated values representing the conservative estimates that the 5-MIAA RID is significantly below this threshold.

Furthermore, the risk is low considering that the daily RID value of 5-MIAA does not reach the threshold and that the compound is an endogenous metabolite of certain naturally occurring tryptophan derivatives such as serotonin.

Finally, levels of bufotaline, the major metabolite of 5-MeO-DMT in urine, serum and breast milk, were evaluated as described in example 12. Notably, bufogenin was not detected in serum and breast milk at any time point, and was detected in urine only at the time point of 2.5 hours (32.3 pg/ml). This data further demonstrates that bufogenin does not increase the risk of 5-MeO-DMT.

The above calculation was based on an up-titration protocol involving 6 mg and 12 mg doses of 5-MeO-DMT. The conclusion was also applicable to single doses up to 12 mg, which resulted in reduced exposure to 5-MeO-DMT and its metabolites.

Assuming a linear relationship between dose increase and breast milk concentration increase (and hence infant exposure increase), it follows that higher doses would be inferred, the conclusion is that the RID of 5-MeO-DMT as well as 5-MIAA would still be significantly lower than 10% for breast fed mothers treated with higher doses (e.g. 18 mg or 25 mg, as single doses or as final doses of an up-titration regimen).

This is true even if the depot effect of 5-MIAA in breast milk is considered.

Based on the observed linear pharmacokinetic profile of 5-MeO-DMT, linear extrapolation is reasonable.

Finally, when considering risk to infants, one must consider the case of single day administration, as this eliminates the need to consider the cumulative exposure of infants over a longer period of time, which is required for chronic treatment regimens.

Another identified metabolite, bufotiamine, is the result of O-demethylation catalyzed by CYP2D 6. The resulting metabolite is then glucuronylated under UGT catalysis:

as part of the pharmacokinetic study, it was determined that barely bufogenin was detectable in human serum. In any case, bufogenin was not detected 15 minutes after 5-MeO-DMT administration. A small amount was detected in urine at 2.5 hours (example 12).

Bufogenin glucuronic acid cannot bind to the receptor and does not play any role. Furthermore, the concentration of bufomesalamine glucuronic acid is so low that it is not detected in the hepatocyte assay. Further conversion of bufomesalamine glucuronic acid to 5-hydroxyindoleacetic acid:

5-hydroxy indoleacetic acid is an endogenous substance, for example, it is present in the metabolism of melatonin and serotonin (see above).

Since the O-demethylation pathway of 5-MeO-DMT only plays a secondary role and produces the major metabolite bufotaline, which is rapidly cleared from plasma, and further metabolism produces compounds that are only present in very low concentrations and ultimately metabolites that are also part of the endogenous metabolic pathway, the inventors determined that O-demethylation of 5-MeO-DMT does not involve metabolites that require restrictions on breast feeding.

The third metabolic pathway involves N-oxidation:

In the computer simulation of the formed metabolites, 5-MeO-DMT-N-oxide was considered non-genotoxic, consistent with negative in vitro genotoxicity assessment of the parent molecule. As demonstrated by observations on rats, the compounds are soluble in water and rapidly excreted (Sitaram, B.R., Lockett, L., Blackman, G. L., McLeod, W. R., 1987. Urinary excretion of 5-methoxy-N,N-dimethyltryptamine, N,N-dimethyltryptamine and their N-oxides in the rat. Biochemical Pharmacology 36: 2235-2231). since the 5-MeO-DMT metabolic pathway involved in N-oxidation plays only a minor role and results in a low proportion of non-significantly toxic metabolites that would be rapidly excreted, so the inventors determined that N-oxidation of 5-MeO-DMT does not involve metabolites that require restrictions on breast feeding.

Based on the above, the inventors determined that breast feeding could be resumed shortly after treatment with 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

For breast-fed patients, it is safe to stop breast-feeding only temporarily. Breast feeding is often not possible during the actual treatment, i.e. during administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and during the subsequent fantasy experience. However, once the immediate effect of administration subsides, breast-fed patients can safely resume breast-feeding.

Has significant advantages for nursing patients, their mental health and the mental health of infants, and recovering breast feeding as early as possible.

It may be advisable for the mother receiving the treatment to temporarily stop breast feeding, for example, to pause for a certain period of time or until a certain event occurs.

Stopping breast feeding means that the infant is no longer fed directly through the breast, nor through breast milk that is expressed when breast feeding is not recommended. However, the breast milk prepared in advance may be fed with a milk bottle. The point in time at which breast milk is expressed (rather than the time at which the child is fed) is decisive.

Breast feeding may be resumed immediately after a specified period of time or event.

For example, it is recommended that the mother temporarily stop breast feeding only during the actual treatment, e.g., until a discharge ready Clinical Assessment (CADR) indicates that discharge is ready.

Discharge ready clinical evaluations (CADR) were performed to confirm that the patient was home without clinical impediments.

Determining discharge preparation from CADR requires confirmation that any adverse events have been resolved or not resolved but do not prevent discharge, that the patient has been fully awake, that the patient has no hallucination or perceived distortion, that the patient is alert (immediate response to a person speaking in normal tone; improved observer alertness/sedation assessment score of 5), that there is no clinically significant change in vital signs from baseline, and that the treating physician considers the patient as ready for discharge.

About 1 hour after the last dose is administered, CADR may be administered. Or the warranty professional may self-prepare the assessment for discharge based on relevant factors such as patient vital signs and/or alertness/sedation.

Breast feeding is not resumed, suggesting within 6 hours (based on later) after discharge and after the last dose, preferably within 3 hours (based on later) after discharge or after the last dose, more preferably within 2 hours (based on later) after discharge or after the last dose, especially within 1 hour (based on later) after discharge or after the last dose.

Breast feeding may also be resumed after a longer period of time, e.g., until the concentration of 5-MeO-DMT and/or its metabolites in the breast milk sample falls below a particular threshold.

For example, breast feeding may be temporarily stopped before the concentration of 5-MeO-DMT in the breast milk sample falls below 2000 pg/ml, 500 pg/ml, or 75 pg/ml, and/or the concentration of 5-MIAA in the breast milk falls below 14000 pg/ml, 2000 pg/ml, or 75 pg/ml.

Alternatively, breast milk may be expressed and discarded until the concentration of 5-MeO-DMT and/or 5-MIAA falls below a specified level.

Furthermore, based on clinical experience, breast feeding may be temporarily stopped for a period of time when the concentration of 5-MeO-DMT and/or its metabolites in breast milk reaches a certain level. In one example, the patient is advised to stop breast feeding until 48 hours after receiving the last dose of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. It is recommended that the patient preferably stop breastfeeding until 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably stop breastfeeding until 12 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Still more preferably, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, breast feeding must be discontinued for only 6 hours, even more preferably, for only 3 hours, especially for only 2 hours, and most preferably, for only 1 hour.

This brief interruption and the possibility of resumption of breast feeding shortly after treatment contributes to the success of the treatment and in particular to the maternal function and the health and development of the infant.

In order to avoid any associated risk to the unweaned child, it is desirable to reduce the concentration of 5-MeO-DMT and/or 5-MIAA in breast milk as much as possible. Any associated risk to non-weaned children can be avoided as long as any expressed breast milk is discarded when the concentration of 5-MeO-DMT and/or 5-MIAA in the breast milk exceeds a predetermined threshold, or breast feeding is resumed only when the concentration of 5-MeO-DMT and/or 5-MIAA in the breast milk is below a predetermined threshold. In a preferred embodiment, the threshold value for 5-MeO-DMT in breast milk should be as low as possible. In another preferred embodiment, the threshold value for 5-MIAA in breast milk should be as low as possible. In the most preferred embodiment, the threshold values for 5-MeO-DMT and 5-MIAA in breast milk should be as low as possible.

Different preferred thresholds for 5-MeO-DMT and/or 5-MIAA in expressed breast milk are provided below:

delivery of Infant Doses (DID) of 5-MeO-DMT and/or 5-MIAA

The Delivered Infant Dose (DID) of 5-MeO-DMT and/or 5-MIAA should be kept as low as possible. In a preferred embodiment, the DID of 5-MeO-DMT is kept as low as possible. In another preferred embodiment, the DID of the 5-MIAA is kept as low as possible. In the most preferred embodiment, the DID of 5-MeO-DMT and 5-MIAA are kept as low as possible.

The relevant DID of the 5-MeO-DMT and/or 5-MIAA of the present invention is as follows:

to achieve the above DID, breast feeding requires adjustment. This adjustment is selected from the selection of an appropriate point in time to resume breast feeding, feeding a suitable number of times within the first 24 hours after resumption of breast feeding, aspiration and discard of breast milk for a suitable period of time, or a combination of these measures.

Relative Infant Dose (RID) of 5-MeO-DMT and/or 5-MIAA

The Relative Infant Dose (RID) of 5-MeO-DMT and/or 5-MIAA should be as low as possible. In a preferred embodiment, the RID of 5-MeO-DMT is kept as low as possible. In another preferred embodiment, the RID of the 5-MIAA is kept as low as possible. In the most preferred embodiment, the RID of 5-MeO-DMT and 5-MIAA are kept as low as possible.

The relevant RID of the 5-MeO-DMT and/or 5-MIAA of the present invention is as follows:

To achieve the RID described above, breast feeding requires adjustment. This adjustment is selected from the selection of an appropriate point in time to resume breast feeding, feeding a suitable number of times within the first 24 hours after resumption of breast feeding, aspiration and discard of breast milk for a suitable period of time, or a combination of these measures.

Combination of a Delivered Infant Dose (DID) of 5-MeO-DMT and/or 5-MIAA and a Relative Infant Dose (RID)

It is described that DID and RID of 5-MeO-DMT and/or 5-MIAA are important aspects of the present invention. While each individual aspect is equally important, in a preferred embodiment of the invention, the two aspects of DID of 5-MeO-DMT and/or 5-MIAA and RID of 5-MeO-DMT and/or 5-MIAA are considered in combination. The present invention provides combinable correlated DID and correlated RID.

In one embodiment, the DID of 5-MeO-DMT and the RID of 5-MeO-DMT are combined. In a preferred embodiment, the DID and RID of 5-MeO-DMT are kept as low as possible. The present invention provides combinable correlated DID and correlated RID.

In another embodiment, the DID of 5-MIAA and the RID of 5-MIAA are combined. In a preferred embodiment, the DID and RID of the 5-MIAA are kept as low as possible. The present invention provides combinable correlated DID and correlated RID.

In another embodiment, the DID of 5-MeO-DMT and the RID of 5-MIAA are combined. In a preferred embodiment, the DID of 5-MeO-DMT and the RID of 5-MIAA are kept as low as possible. The present invention provides combinable correlated DID and correlated RID.

In another embodiment, the RID of 5-MeO-DMT and the DID of 5-MIAA are combined. In a preferred embodiment, the RID of 5-MeO-DMT and the DID of 5-MIAA are kept as low as possible. The present invention provides combinable correlated DID and correlated RID.

In a more preferred embodiment, the DID of 5-MeO-DMT and 5-MIAA and the RID of 5-MeO-DMT and 5-MIAA are combined. In a preferred embodiment, the DID of 5-MeO-DMT and 5-MIAA and the RID of 5-MeO-DMT and 5-MIAA are kept as low as possible. The present invention provides combinable correlated DID and correlated RID.

Treatment of mental or neurological disorders

Disorders characterized by depressive episodes

There are several disorders characterized by depressive episodes.

A depressive episode is a period of depressed mood and/or loss of interest in most activities.

For example, according to DSM-V, major depressive episodes are characterized by five or more symptoms that occur within the same 2 weeks and that represent a change from a previous function, at least one of which is (1) depressed mood or (2) lost interest or pleasure.

Patients suffering from a disorder characterized by depressive episodes may suffer from a therapeutically resistant form of the disorder.

Disorders characterized by depressive episodes involve one or more of sleep disorders, cognitive dysfunction, anxiety, bradykinesia, social/emotional withdrawal, and negative thoughts.

For example, severity and treatment success may be assessed by Montgomery-Arabidopsis depression rating scale (MADRS) or Hamiltonian depression rating scale (HAM-D).

In patients suffering from disorders characterized by depressive episodes, altered functional connections are observed inside and/or between several brain regions involved in processing, regulation, emotional memory, cognitive processes related to jeopardy, impaired concentration and physiological arousal.

Treatment of a patient suffering from a disorder characterized by a depressive episode (including a therapeutically resistant form of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement of the disorder characterized by a depressive episode.

Improvement of the disorder characterized by depressive episodes (reflected as a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement of the disorder characterized by depressive episodes in the patient (reflected in a decrease in CGI-S score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement of the disorder characterized by depressive episodes (reflected in a decrease in CGI-S score) preferably lasts until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, in particular until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement of the disorder characterized by depressive episodes (reflected as a decrease in MADRS score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28 following the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement of the disorder characterized by depressive episodes (reflected in a decrease in MADRS score) in the patient occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement of the disorder characterized by depressive episodes (reflected in a decrease in MADRS score) preferably lasts until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, in particular until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement of the disorder characterized by depressive episodes (reflected as a decrease in HAM-D score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28 following the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement of the disorder characterized by depressive episodes (reflected in a decrease in HAM-D score) in the patient occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement of the disorder characterized by depressive episodes (reflected in a decrease in HAM-D score) preferably lasts until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, in particular until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from disorders characterized by depressive episodes is reflected at least by an improvement in total score at day 7, day 14, and/or day BIMF following the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from disorders characterized by depressive episodes occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Major Depressive Disorder (MDD) is a mood disorder that causes a sustained sadness and loss of interest. Major depressive disorder affects a person's feel, thinking and behavior and can lead to a variety of affective and physical problems.

The patient may be suffering from moderate or severe MDD, expressed as a montgomery-asberg depression rating scale (MADRS) score of 20 or more, or a hamilton depression rating scale (HAM-D) score of 17 or more. It is further contemplated that the patient may be suffering from major depressive disorder, expressed as montgomery-asberg depression rating scale (MADRS) score of 35 or higher, or hamilton depression rating scale (HAM-D) score of 25 or higher.

Patients suffering from MDD may suffer from a Therapeutically Resistant (TRD) form of the disorder.

MDD involves one or more of sleep disorders, cognitive dysfunction, anxiety, bradykinesia, social/emotional withdrawal, and negative thinking.

For example, severity and treatment success may be assessed by Montgomery-Arabidopsis depression rating scale (MADRS) or Hamiltonian depression rating scale (HAM-D).

In patients suffering from MDD, dysfunctional connections and regulation are observed inside and/or between multiple resting state networks (including DMN, saliency network, executive control network, and edge network). Functional linkage is significantly different from that observed in healthy controls.

Treatment of a patient suffering from MDD (including a therapeutically resistant form of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement in MDD.

Improvement in MDD (reflected in a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in MDD in the patient (reflected in a decrease in CGI-S score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in MDD (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in MDD (reflected in a decrease in MADRS score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in MDD in the patient (reflected in a decrease in MADRS score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in MDD (reflected in a decrease in MADRS score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in MDD (reflected in a decrease in HAM-D score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in MDD in the patient (reflected in a decrease in HAM-D score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in MDD (reflected in a decrease in HAM-D score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from MDD is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from MDD occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Persistent depressive disorder

Persistent depressive disorder, also known as dysthymia, is a chronic form of depression. Persistent depressive disorder is diagnosed if depression is present for a majority of the day for a period of at least two years. Any asymptomatic phase is less than 2 months.

In depression, two or more of 1. Desperate, 2. Insufficient energy or fatigue, 3. Self-esteem, 4. Reduced sleep (insomnia) or increased sleep (hypersomnia) 5. Loss of appetite or binge eating, 6. Difficulty in making decisions or inattention must be present.

Patients suffering from persistent depressive disorders may suffer from a therapeutically resistant form of the disorder.

Persistent depressive disorders involve one or more of sleep disorders, cognitive dysfunction, anxiety, bradykinesia, social/emotional withdrawal, and negative thinking.

For example, severity and treatment success may be assessed by Montgomery-Arabidopsis depression rating scale (MADRS) or Hamiltonian depression rating scale (HAM-D).

In patients suffering from persistent depressive disorders, altered functional connections are observed within and/or between several brain regions associated with processing, regulation, emotional memory, cognitive processes associated with jeopardy, impaired concentration and physiological arousal. Functional connectivity impairments are observed inside and/or between DMN, saliency network, executive control network and edge network. Functional linkage is significantly different from that observed in healthy controls.

Treatment of a patient suffering from a persistent depressive disorder (including therapeutically resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement in the persistent depressive disorder.

Improvement in persistent depressive disorder (reflected in a decrease in CGI-S score) is observed at about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28.

Improvement of persistent depressive disorder in patients (reflected in a decrease in CGI-S score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in persistent depressive disorder (reflected in a decrease in CGI-S score) preferably lasts until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, in particular until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in persistent depressive disorder (reflected in a decrease in MADRS score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28 following the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in persistent depressive disorder (reflected in a decrease in MADRS score) in the patient occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in persistent depressive disorder (reflected in a decrease in MADRS score) preferably lasts until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, in particular until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in persistent depressive disorder (reflected in a decrease in HAM-D score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28 following the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in persistent depressive disorder (reflected in a decrease in HAM-D score) in the patient occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in persistent depressive disorder (reflected in a decrease in HAM-D score) preferably lasts until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, in particular until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from persistent depressive disorder is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from persistent depressive disorder occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Seasonal affective disorder

Seasonal affective disorder is one with a seasonal pattern, the symptoms usually starting in autumn and alleviating in spring. Many people experience sadness, frustration, loss of interest in activities, tiredness, and social withdrawal.

Patients suffering from seasonal affective disorders may suffer from a therapeutically resistant form of the disorder.

Seasonal affective disorders involve one or more of sleep disorders, cognitive dysfunction, anxiety, bradykinesia, social/emotional withdrawal and negative thinking.

For example, severity and treatment success may be assessed by Montgomery-Arabidopsis depression rating scale (MADRS) or Hamiltonian depression rating scale (HAM-D).

In patients suffering from seasonal affective disorders, altered functional connections are observed within and/or between several brain regions associated with processing, regulation, emotional memory, cognitive processes associated with jeopardy, impaired concentration and physiological arousal. Functional connectivity impairments are observed inside and/or between DMN, saliency network, executive control network and edge network. Functional linkage is significantly different from that observed in healthy controls.

Treatment of a patient suffering from seasonal affective disorder (including a therapeutically resistant form of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement of the seasonal affective disorder.

Improvement in seasonal affective disorder (reflected in a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement of seasonal affective disorder (reflected in a decrease in CGI-S score) in the patient occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement of seasonal affective disorder (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, in particular until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in seasonal affective disorder (reflected in a decrease in MADRS score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28 following the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in seasonal affective disorder (reflected in a decrease in MADRS score) in the patient occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement of seasonal affective disorder (reflected in a decrease in MADRS score) preferably lasts at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, in particular at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in seasonal affective disorder (reflected in a decrease in HAM-D score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28 following the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in seasonal affective disorder (reflected in a decrease in HAM-D score) in the patient occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement of seasonal affective disorder (reflected in a decrease in HAM-D score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, in particular until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from seasonal affective disorder is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from seasonal affective disorder occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Bipolar disorder

Bipolar Disorder (BD) is a mental health disorder characterized by severe mood swings, including depressed mood (major depressive episode) and elevated mood (manic or hypomanic episodes). BD is a recurrent chronic disorder affecting more than 1% of the population worldwide, regardless of its ethnic origin or socioeconomic status.

Patients suffering from BD may suffer from a therapeutically resistant form of the disorder.

BD is classified as bipolar disorder type I if at least one manic episode (whether accompanied by a depressive episode or not) occurs. BD is classified as bipolar disorder type II if at least one hypomanic episode (but not a complete manic episode) and one major depressive episode occurs. If these symptoms are caused by a drug or medical problem, the symptoms are not diagnosed as bipolar disorder.

Patients suffering from BD, whether diagnosed as bipolar II or I, in particular will suffer from current major depressive episodes.

The montgomery-asberg depression rating scale (MADRS) may be used to assess the severity of the current major depressive episode. The patient may have a total score equal to or greater than 19, such as greater than or equal to 24, particularly greater than or equal to 37.

Alternatively or additionally, the patient may have a total score of 19 on the Bipolar Depression Rating Scale (BDRS), such as greater than or equal to 24, specifically greater than or equal to 37.

BD relates to one or more of sleep disorders, cognitive dysfunction, anxiety, bradykinesia, social/emotional withdrawal and negative thinking.

For example, severity and treatment success may be assessed by the Montgomery-Arabidopsis depression rating scale (MADRS), the Hamiltonian depression rating scale (HAM-D), or the Bipolar Depression Rating Scale (BDRS).

BDRS is designed to measure the severity of depressive symptoms in bipolar depression. BDRS have been validated by trained raters and are available for clinical use. The BDRS item assesses the severity of depression and/or mixed symptoms present in patients and exhibited over the past several days according to a clinical interview. If the current symptoms are inconsistent with symptoms over the past few days, the assessment should reflect the current symptoms. The scale contains 20 questions and the highest score possible is 60. The higher the score, the higher the severity.

The problems are depression, sleep disturbance, appetite disturbance, social engagement decrease, energy and activity decrease, power decrease, attention and memory impairment, anxiety, pleasure loss, frigidity, worthless sensation, helplessness and unconsciousness, suicidal ideation, guilt sensation, psychotic symptoms, irritability, instability, increased motor drive, increased speech, agitation.

Each of these aspects was evaluated and scored as 0,1, 2 or 3.

Patients suffering from BD exhibit an intrinsic organization of characteristic abnormalities and interconnectivity of the resting state network. The resting state functional magnetic resonance imaging study demonstrated a change in functional connectivity of specific areas within and/or between the default mode network, the saliency network, and the central executive network as compared to the healthy controls. Functional connection changes within the default mode network are also observed, particularly in patients suffering from sleep disorders.

Treatment of patients suffering from BD (including therapeutically resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement in BD.

Improvement in BD (reflected in a decrease in CGI-S score) was observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in BD of the patient (reflected in a decrease in CGI-S score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in BD (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in BD (reflected in a decrease in MADRS score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in BD (reflected in a decrease in MADRS score) in patients occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in BD (reflected in a decrease in MADRS score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in BD (reflected in a decrease in HAM-D score) was observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in BD (reflected in a decrease in HAM-D score) in the patient occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in BD (reflected in a decrease in HAM-D score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in BD (reflected in a decrease in BDRS score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28 following the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in BD of the patient (reflected in a decrease in BDRS score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in BD (reflected in a decrease in BDRS score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from BD is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from BD occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Anxiety disorders

Anxiety disorder is a mental health condition. Symptoms include tension, panic and fear, sweating and acceleration of heart beat. Anxiety involves complex cognitive, affective, physiological and behavioral response systems that are related to the preparation of an expected event or situation that is considered a threat.

Anxiety disorders also involve one or more of sleep disorders, cognitive dysfunction, social/emotional withdrawal, and negative thinking.

Patients suffering from anxiety disorders may suffer from a therapeutically resistant form of the disorder.

The beck anxiety scale (BAI) may be used to assess the severity of anxiety disorders. theseveritymayalsobeassessedbyusingtheHamiltoniananxietyratingscale(HAM-A),thementalanxietysub-scaleofHAM-A(sumofitems1-6anditem14),theanxietymooditemofHAM-A(item1),thebriefmentaldisorderratingscale(BPRS)item"anxiety".

Furthermore, anxiety disorders are associated with suicidal ideation.

The suicidal ideation can be evaluated using the Columbia suicide severity rating scale (C-SSRS).

Anxiety disorders were studied by functional magnetic resonance imaging. Generally, all anxiety disorders exhibit abnormalities in the Default Mode Network (DMN). Other networks affected by these obstacles are the Saliency Network (SN) and the sensorimotor network (SMN). The resting state balance within and/or between each of these networks (e.g., SMN and SN) may be abnormal in different anxiety disorders relative to DMN.

Treatment of patients suffering from anxiety disorders (including therapeutically resistant forms of the disorders) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates anxiety.

A reduction or elimination of anxiety in a patient suffering from anxiety disorder is observed about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 1 day, e.g., about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 7 days, 14 days, and/or 28 days.

The reduction or elimination of anxiety in a patient suffering from anxiety disorder occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of anxiety preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Theclinicalresponseofapatientsufferingfromanxietydisorder(includingatherapeuticallyresistantformofthedisorder)isreflectedinadecreaseinHAM-ascoreofatleast50%comparedtothecorrespondingscorepriortotreatmentatabout2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,about24hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday7,atday14,and/oratday28.

Theclinicalresponseofpatientssufferingfromanxietydisorders(includingtreatment-resistantformsofthedisorders),reflectedinadecreaseinHAM-ascoreofatleast50%comparedtothecorrespondingscorepriortotreatment,occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. theclinicalresponse(reflectedinadecreaseinHAM-ascoreofatleast50%)inpatientssufferingfromanxietydisorders(includingtherapeuticallyresistantformsofthedisorders)preferablylastsatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,inparticularatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

Thereliefofanxietyinpatientssufferingfromsuchanxietydisorders,includingtherapeuticallyresistantformsofthedisorders,isreflectedinaHAM-ascoreof7orlessatabout2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,about24hours,afterday7,atday14,and/oratday28,afterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof.

Reliefofanxiety(reflectedinaHAM-ascoreof7orless)inpatientssufferingfromsuchanxietydisorders(includingtherapeuticallyresistantformsofthedisorders)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thealleviationofanxiety(reflectedinaHAM-ascoreof7orless)inapatientsufferingfromsuchanxietydisorders(includingtherapeuticallyresistantformsofthedisorder)preferablylastsatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,inparticularatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,afterabout24hours,atday7,atday14,and/oratday28,areductionoreliminationofanxiety(reflectedasadecreaseinscoresofthementalanxietysub-scaleofHAM-A(sumofitems1-6and14))isobservedinpatientssufferingfromanxietydisorders(includingtreatment-resistantformsofthedisorder).

Thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreofthementalanxietysub-scaleofHAM-a(sumofitems1-6and14))inpatientssufferingfromanxietydisorders(includingtherapeuticallyresistantformsofthedisorders)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietysub-scaleofHAM-a(sumofitems1-6and14))preferablycontinuesuntilatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,particularlyuntilatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,andmorepreferablyuntilatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,afterabout24hours,atday7,atday14,and/oratday28,areductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietymoodprogram(project1)ofHAM-a)isobservedinpatientssufferingfromanxietydisorders,includingtreatment-resistantformsofthedisorder.

Thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietymoodprogramofHAM-a(item1))inapatientsufferingfromanxietydisorders,includingtherapeuticallyresistantformsofthedisorders,occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thereductionoreliminationofanxiety,reflectedasadecreaseinthescoreoftheanxietymoodprogramofHAM-a(item1),preferablycontinuesuntilatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,particularlyuntilatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyuntilatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, a reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS project "anxiety") in patients suffering from anxiety disorders (including treatment-resistant forms of the disorder) is observed.

The reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS project "anxiety") in patients suffering from anxiety disorders (including therapeutically resistant forms of the disorders) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS project "anxiety") preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Treatment of patients suffering from anxiety disorders (including therapeutically resistant forms of the disorders) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates suicidal ideation.

The suicidal ideation is reduced or eliminated in patients suffering from anxiety disorders (including treatment resistant forms of the disorder) is observed about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 1 day, e.g., about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 7 days, 14 days, and/or 28 days.

The reduction or elimination of suicide ideas in patients suffering from anxiety disorders (including therapeutically resistant forms of the disorders) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of suicide preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The foregoing generally applies to anxiety disorders, including the specific disorders discussed in detail below, as well as anxiety disorders caused by medical disorders, which occur when a medical disorder causes extreme fear, anxiety, or panic, other specific anxiety disorders that may be diagnosed if the patient meets most, but not all, criteria for an anxiety disorder, and unspecified anxiety disorders that may be typically diagnosed if the patient experiences anxiety or panic, but lacks information to fully diagnose another anxiety disorder.

Improvement in maternal function in patients suffering from anxiety disorders is reflected at least in an improvement in the total score of BIMF at day 7, day 14, and/or day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from anxiety disorders occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Separation anxiety disorders are characterized by patients experiencing excessive anxiety from individuals who leave home and/or are strongly loved from the patient.

The separated condition can cause significant confusion for the patient, and they can be difficult to learn or work with due to separation. Patients suffering from separation anxiety disorders may also experience excessive anxiety in the event of undesirable events occurring to life-important people, such as family members.

Separation anxiety disorders also involve one or more of sleep disorders, cognitive dysfunction, social/emotional withdrawal, and negative thinking.

Patients suffering from separation anxiety disorders may suffer from a therapeutically resistant form of the disorder.

The beck anxiety scale (BAI) may be used to assess the severity of separation anxiety disorders. theseveritymayalsobeassessedbyusingtheHamiltoniananxietyratingscale(HAM-A),thementalanxietysub-scaleofHAM-A(sumofitems1-6anditem14),theanxietymooditemofHAM-A(item1),thebriefmentaldisorderratingscale(BPRS)item"anxiety".

Furthermore, separation anxiety disorders are associated with suicidal ideation.

The suicidal ideation can be evaluated using the Columbia suicide severity rating scale (C-SSRS).

Separation anxiety disorders were studied by functional magnetic resonance imaging. Generally, all anxiety disorders exhibit abnormalities in the Default Mode Network (DMN). Other networks affected by these obstacles are the Saliency Network (SN) and the sensorimotor network (SMN). The resting state balance within and/or between each of these networks (e.g., SMN and SN) may be abnormal in different anxiety disorders relative to DMN.

Treatment of patients suffering from separation anxiety disorders (including therapeutically resistant forms of the disorders) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates anxiety.

A reduction or elimination of anxiety in a patient suffering from separation anxiety disorder is observed about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 1 day, e.g., about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 7 days, 14 days, and/or 28 days.

The reduction or elimination of anxiety in a patient suffering from separation anxiety disorder occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of anxiety preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Theclinicalresponseofapatientsufferingfromseparationanxietydisorder,includingatherapeuticallyresistantformofthedisorder,isreflectedinadecreaseinHAM-ascoreofatleast50%comparedtothecorrespondingscorepriortotreatmentatabout2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,about24hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday7,atday14,and/oratday28.

Theclinicalresponseofpatientssufferingfromseparationanxietydisorders(includingtherapeuticallyresistantformsofthedisorders),reflectedinatleasta50%decreaseinHAM-ascorecomparedtothecorrespondingscorepriortotreatment,occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. theclinicalresponse(reflectedinadecreaseinHAM-ascoreofatleast50%)inpatientssufferingfromseparationanxietydisorders(includingtherapeuticallyresistantformsofthedisorders)preferablylastsatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,inparticularatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

Thereliefofanxietyinpatientssufferingfromsuchseparationanxietydisorders,includingtherapeuticallyresistantformsofthedisorders,isreflectedinaHAM-ascoreof7orlessatabout2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,about24hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday7,atday14,and/oratday28.

Reliefofanxiety(reflectedinaHAM-ascoreof7orless)inpatientssufferingfromsuchseparationanxietydisorders(includingtherapeuticallyresistantformsofthedisorders)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thealleviationofanxiety(reflectedinaHAM-ascoreof7orless)inapatientsufferingfromsuchseparationanxietydisorders(includingtherapeuticallyresistantformsofthedisorders)preferablylastsatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,inparticularatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,afterabout24hours,atday7,atday14,and/oratday28,areductionoreliminationofanxiety(reflectedasadecreaseinthescoreofthementalanxietysub-scaleofHAM-A(sumofitems1-6and14))isobservedinpatientssufferingfromseparationanxietydisorders,includingtreatment-resistantformsofthedisorder.

Thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreofthementalanxietysub-scaleofHAM-a(sumofitems1-6and14))inpatientssufferingfromseparationanxietydisorders,includingtherapeuticallyresistantformsofthedisorders,occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietysub-scaleofHAM-a(sumofitems1-6and14))preferablycontinuesuntilatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,particularlyuntilatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,andmorepreferablyuntilatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,afterabout24hours,atday7,atday14,and/oratday28,areductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietymoodprogramofHAM-a(item1))isobservedinpatientssufferingfromseparationanxietydisorders,includingtreatmentresistantformsofthedisorder.

Thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietymoodprojectofHAM-a(item1))inapatientsufferingfromanisolatedanxietydisorder,includingatherapeuticallyresistantformofthedisorder,occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thereductionoreliminationofanxiety,reflectedasadecreaseinthescoreoftheanxietymoodprogramofHAM-a(item1),preferablycontinuesuntilatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,particularlyuntilatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyuntilatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, a reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS project "anxiety") in patients suffering from separation anxiety disorders (including treatment resistant forms of the disorder) is observed at day 1, e.g., about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 7, at day 14, and/or at day 28.

The reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS project "anxiety") in patients suffering from separation anxiety disorders (including therapeutically resistant forms of the disorders) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS project "anxiety") preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Treatment of patients suffering from separation anxiety disorders (including therapeutically resistant forms of the disorders) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates suicidal ideation.

The reduction or elimination of suicidal ideation in patients suffering from separation anxiety disorder (including treatment resistant forms of the disorder) is observed about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 1 day, e.g., about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 7 days, 14 days, and/or 28 days.

The reduction or elimination of suicide ideas in patients suffering from separation anxiety disorders, including therapeutically resistant forms of the disorders, occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of suicide preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from dysregulation is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from dyskinesia occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Agoraphobia is a fear of a situation or place that may cause a sense of panic, trapped, unassisted or embarrassed.

Patients suffering from agoraphobia may have difficulty leaving home. The idea of leaving home may cause considerable anxiety and even escape. Fear of people, travel, elevators, movie theatres, malls etc. can pose significant challenges.

Panic attacks may also occur repeatedly in agoraphobia patients.

Agoraphobia also involves one or more of sleep disorders, cognitive dysfunction, social/emotional withdrawal, and negative thinking.

Patients suffering from agoraphobia may suffer from a therapeutically resistant form of the disorder.

The Becky anxiety scale (BAI) may be used to assess the severity of agoraphobia. theseveritymayalsobeassessedbyusingtheHamiltoniananxietyratingscale(HAM-A),thementalanxietysub-scaleofHAM-A(sumofitems1-6anditem14),theanxietymooditemofHAM-A(item1),thebriefmentaldisorderratingscale(BPRS)item"anxiety".

In addition, agoraphobia is associated with suicidal ideation.

The suicidal ideation can be evaluated using the Columbia suicide severity rating scale (C-SSRS).

Functional magnetic resonance imaging of individuals suffering from agoraphobia reveals changes in functional connections within and/or between resting state networks involved in anxiety.

Treatment of patients suffering from agoraphobia (including therapeutically resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates anxiety.

A reduction or elimination of anxiety in patients suffering from agoraphobia is observed about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 1 day, e.g. about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 7 days, 14 days, and/or 28 days.

The reduction or elimination of anxiety in patients suffering from agoraphobia occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of anxiety preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Theclinicalresponseofapatientsufferingfromagoraphobia(includingatreatment-resistantformofthedisorder)isreflectedinadecreaseofatleast50%inHAM-ascorecomparedtothecorrespondingscorebeforetreatment,about2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.about24hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday7,atday14,and/oratday28.

Theclinicalresponseofpatientssufferingfromagoraphobia(includingthetreatment-resistantformofthedisorder),reflectedinadecreaseinHAM-ascoreofatleast50%comparedtothecorrespondingscorepriortotreatment,occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. theclinicalresponse(reflectedinadecreaseinHAM-ascoreofatleast50%)inpatientssufferingfromagoraphobia(includingatherapeuticallyresistantformofthedisorder)preferablylastsatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,inparticularatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

Thereliefofanxietyinpatientssufferingfromsuchagoraphobia(includingtherapeuticresistantformsofthedisorder)isreflectedinabout2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,about24hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday7,atday14,and/oratday28,theHAM-ascoreis7orless.

Reliefofanxiety(reflectedinaHAM-ascoreof7orless)inpatientssufferingfromsuchagoraphobia(includingtherapeuticresistantformsofthedisorder)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thereliefofanxiety(reflectedinaHAM-ascoreof7orless)inpatientssufferingfromsuchagoraphobia(includingtreatment-resistantformsofthedisorder)preferablylastsatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,inparticularatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

Adecreaseinthescoreofanxiety(reflectedinthementalanxietysub-scaleofHAM-a(sumofitems1-6and14))isobservedinpatientssufferingfromagoraphobia(includingtreatment-resistantformsofthedisorder)about2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,about24hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday7,atday14,and/oratday28.

Thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreofthementalanxietysub-scaleofHAM-a(sumofitems1-6and14))inpatientssufferingfromagoraphobia(includingthetherapeuticallyresistantformofthedisorder)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietysub-scaleofHAM-a(sumofitems1-6and14))preferablycontinuesuntilatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,particularlyuntilatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,andmorepreferablyuntilatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,adecreaseinanxietyorelimination(reflectedasadecreaseinscoreofanxietymoodprogram(item1)ofHAM-a)wasobservedinpatientssufferingfromagoraphobia(includingtreatmentresistantformsofthedisorder)atday1,e.g.,afterabout24hours,atday7,atday14,and/oratday28,afterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof.

Thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietymoodprojectofHAM-a(item1))inpatientssufferingfromagoraphobia,includingthetherapeuticallyresistantformofthedisorder,occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thereductionoreliminationofanxiety,reflectedasadecreaseinthescoreoftheanxietymoodprogramofHAM-a(item1),preferablycontinuesuntilatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,particularlyuntilatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyuntilatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

A reduction or elimination of anxiety (reflected as a decrease in the score of BPRS project "anxiety") in patients suffering from agoraphobia (including a treatment resistant form of the disorder) is observed about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 1 day, e.g., about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 7 days, 14 days, and/or 28 days.

The reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS project "anxiety") in patients suffering from agoraphobia (including the therapeutically resistant form of the disorder) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS project "anxiety") preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Treatment of patients suffering from agoraphobia (including therapeutic resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates suicidal ideation.

The reduction or elimination of suicide ideas in patients suffering from agoraphobia (including the treatment-resistant forms of the disorder) is observed about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 1 day, e.g., about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 7 days, 14 days, and/or 28 days.

The reduction or elimination of suicide ideas in patients suffering from agoraphobia (including therapeutic resistant forms of the disorder) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The reduction or elimination of suicide preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from agoraphobia is reflected at least by an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from agoraphobia occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Generalized Anxiety Disorder (GAD) is characterized by persistent and excessive, uncontrollable concerns over a wide variety of conditions and problems. Patients suffering from GAD may anticipate disasters and may be overly concerned about monetary, health, home, work, or other issues.

An individual is diagnosed as GAD when the individual feels a persistent concern about daily challenges and the concern is not proportional to the threat considered. GAD patients often experience excessive fear lasting from months to years.

GADs can interfere with social, professional, or other important functional areas.

GAD also relates to one or more of sleep disorders, cognitive dysfunction, social/emotional withdrawal, and negative thoughts.

Patients suffering from GAD may suffer from a therapeutically resistant form of the disorder.

The becker anxiety scale (BAI) may be used to assess the severity of GAD. theseveritymayalsobeassessedbyusingtheHamiltoniananxietyratingscale(HAM-A),thementalanxietysub-scaleofHAM-A(sumofitems1-6anditem14),theanxietymooditemofHAM-A(item1),thebriefmentaldisorderratingscale(BPRS)item"anxiety".

In addition, GAD is associated with suicidal ideation.

The suicidal ideation may be evaluated using the Columbia suicide severity rating scale (CSSR-S).

The GAD patient also exhibits changed functional connections, especially within the default mode network.

Treatment of patients suffering from GAD (including therapeutically resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates anxiety.

A reduction or elimination of anxiety in a patient suffering from GAD is observed about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 1 day, e.g., about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 7 days, 14 days, and/or 28 days.

The reduction or elimination of anxiety in a patient suffering from GAD occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of anxiety preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

TheclinicalresponseofapatientsufferingfromGAD(includingatreatment-resistantformofthedisorder)isreflectedinadecreaseinHAM-ascoreofatleast50%comparedtothecorrespondingscorepriortotreatmentatabout2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,about24hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday7,atday14,and/oratday28.

TheclinicalresponseofpatientssufferingfromGAD(includingtreatment-resistantformsofthedisorder),reflectedinadecreaseinHAM-ascoreofatleast50%comparedtothecorrespondingscorepriortotreatment,occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. theclinicalresponse(reflectedinadecreaseinHAM-ascoreofatleast50%)inpatientssufferingfromGAD(includingtreatment-resistantformsofthedisorder)preferablylastsatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,inparticularatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

ThereliefofanxietyinpatientssufferingfromsuchGAD(includingtreatment-resistantformsofthedisorder)isreflectedinaHAM-ascoreof7orlessatabout2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,about24hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday7,atday14,and/oratday28.

Reliefofanxiety(reflectedinHAM-ascoresof7orless)inpatientssufferingfromsuchGAD(includingtreatment-resistantformsofthedisorder)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thealleviationofanxiety(reflectedinaHAM-ascoreof7orless)inapatientsufferingfromsuchGAD(includingatherapeuticallyresistantformofthedisorder)preferablylastsatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,inparticularatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,afterabout24hours,atday7,atday14,and/oratday28,areductionoreliminationofanxiety(reflectedasadecreaseinscoresofthementalanxietysub-scaleofHAM-A(sumofitems1-6and14))wasobservedinpatientssufferingfromGAD(includingtreatmentresistantformsofthedisorder).

Thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreofthementalanxietysub-scaleofHAM-a(sumofitems1-6and14))inpatientssufferingfromGAD(includingtreatment-resistantformsofthedisorder)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietysub-scaleofHAM-a(sumofitems1-6and14))preferablycontinuesuntilatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,particularlyuntilatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,andmorepreferablyuntilatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,afterabout24hours,atday7,atday14,and/oratday28,areductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietymoodprogram(project1)ofHAM-a)inpatientssufferingfromGAD(includingtreatmentresistantformsofthedisorder)isobserved.

Thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietymoodprogramofHAM-a(item1))inpatientssufferingfromGAD(includingtreatmentresistantformsofthedisorder)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thereductionoreliminationofanxiety,reflectedasadecreaseinthescoreoftheanxietymoodprogramofHAM-a(item1),preferablycontinuesuntilatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,particularlyuntilatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyuntilatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, a reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS program "anxiety") in patients suffering from GAD (including treatment resistant forms of the disorder) is observed.

The reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS program "anxiety") in patients suffering from GAD (including treatment resistant forms of the disorder) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS project "anxiety") preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Treatment of patients suffering from GAD (including therapeutically resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates suicidal ideation.

The suicidal ideation is reduced or eliminated in patients suffering from GAD (including treatment-resistant forms of the disorder) at about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of suicide concept in patients suffering from GAD (including therapeutic resistant forms of the disorder) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The reduction or elimination of suicide preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from GAD is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from GAD occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Social Anxiety Disorder (SAD), also known as social phobia, is one of the most common types of anxiety.

SAD is characterized by intense anxiety or fear of being judged, negatively rated, or rejected in social or performance situations. This typically results in evasion from the social setting and may cause impairment of learning, work or personal relationships.

SAD also relates to one or more of sleep disorders, cognitive dysfunction, social/emotional withdrawal, and negative thoughts.

Patients suffering from SAD may suffer from a therapeutically resistant form of the disorder.

The Becky anxiety scale (BAI) may be used to evaluate the severity of SADs. theseveritymayalsobeassessedbyusingtheHamiltoniananxietyratingscale(HAM-A),thementalanxietysub-scaleofHAM-A(sumofitems1-6anditem14),theanxietymooditemofHAM-A(item1),thebriefmentaldisorderratingscale(BPRS)item"anxiety".

In addition, SAD is related to suicidal ideation.

The suicidal ideation may be evaluated using the Columbia suicide severity rating scale (CSSR-S).

In SAD patients, changes in functional connections within and/or between resting state networks (such as default mode networks and saliency networks) are observed.

Treatment of patients suffering from SAD (including therapeutically resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates anxiety.

Reduction or elimination of anxiety in patients suffering from SAD is observed at about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The reduction or elimination of anxiety in a patient suffering from SAD occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of anxiety preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

TheclinicalresponseofapatientsufferingfromSAD(includingatreatment-resistantformofthedisorder)isreflectedinadecreaseofatleast50%inHAM-ascorecomparedtothecorrespondingscorebeforetreatmentatabout2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,at1day,e.g.about24hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,at7days,at14days,and/orat28days.

Clinicalresponse(reflectedasatleasta50%decreaseinHAM-ascorecomparedtothecorrespondingscorepriortotreatment)inpatientssufferingfromSAD(includingtreatment-resistantformsofthedisorder)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. theclinicalresponse(reflectedinadecreaseinHAM-ascoreofatleast50%)inpatientssufferingfromSAD(includingtreatmentresistantformsofthedisorder)preferablylastsatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,inparticularatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

ThereliefofanxietyinpatientssufferingfromsuchSAD(includingtreatment-resistantformsofthedisorder)isreflectedinabout2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.about24hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday7,atday14,and/oratday28,theHAM-ascoreis7orless.

Reliefofanxiety(reflectedinHAM-ascoresof7orless)inpatientssufferingfromsuchSAD(includingtreatmentresistantformsofthedisorder)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thealleviationofanxiety(reflectedinaHAM-ascoreof7orless)inapatientsufferingfromsuchSAD(includingatherapeuticallyresistantformofthedisorder)preferablylastsatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,inparticularatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,afterabout24hours,atday7,atday14,and/oratday28,areductionoreliminationofanxiety(reflectedasadecreaseinscoresoftheanxietysub-scaleofHAM-A(sumofitems1-6and14))isobservedinpatientssufferingfromSAD(includingtreatment-resistantformsofthedisorder).

Thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreofthementalanxietysub-scaleofHAM-a(sumofitems1-6and14))inpatientssufferingfromSAD(includingtreatmentresistantformsofthedisorder)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietysub-scaleofHAM-a(sumofitems1-6and14))preferablycontinuesuntilatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,particularlyuntilatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,andmorepreferablyuntilatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,afterabout24hours,atday7,atday14,and/oratday28,areductionoreliminationofanxiety(reflectedinadecreaseinscoreofanxietymooditems(item1)ofHAM-a)inpatientssufferingfromSAD(includingtreatmentresistantformsofthedisorder)isobserved.

Thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietymoodprogramofHAM-a(item1))inpatientssufferingfromSAD(includingtherapeuticresistantformsofthedisorder)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thereductionoreliminationofanxiety,reflectedasadecreaseinthescoreoftheanxietymoodprogramofHAM-a(item1),preferablycontinuesuntilatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,particularlyuntilatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyuntilatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, a reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS program "anxiety") in patients suffering from SAD (including treatment resistant forms of the disorder) is observed.

The reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS project "anxiety") in patients suffering from SAD (including treatment resistant forms of the disorder) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS project "anxiety") preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Treatment of patients suffering from SAD (including therapeutic resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates suicidal ideation.

The suicidal ideation is reduced or eliminated in patients suffering from SAD (including treatment resistant forms of the disorder) at about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The reduction or elimination of suicide ideas in patients suffering from SAD (including therapeutic resistant forms of the disorder) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of suicide preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from SAD is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from SAD occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Anxiety is a central feature of panic disorder. Patients suffering from panic disorder experience spontaneous panic attacks and a sudden strong fear or discomfort that peaks in a few minutes.

Panic attacks are characterized by the appearance of a variety of somatic symptoms of anxiety, including sweating, tremors, headache, palpitations, shortness of breath, chest pain, abdominal pain, and nausea.

Furthermore, the disorder may often be characterized by anxiety about future panic attacks. The patient may be very concerned about worrying about the disease again.

Panic disorder also involves one or more of sleep disorders, cognitive dysfunction, social/emotional withdrawal, and negative thinking.

Patients suffering from panic disorder may suffer from a therapeutically resistant form of the disorder.

The beck anxiety scale (BAI) may be used to assess the severity of substance/drug induced panic disorder. theseveritymayalsobeassessedbyusingtheHamiltoniananxietyratingscale(HAM-A),thementalanxietysub-scaleofHAM-A(sumofitems1-6anditem14),theanxietymooditemofHAM-A(item1),thebriefmentaldisorderratingscale(BPRS)item"anxiety".

Furthermore, panic disorder is associated with suicidal ideation.

The suicidal ideation may be evaluated using the Columbia suicide severity rating scale (CSSR-S).

Patients with panic disorder exhibit a change in the functional connections within and/or between the default mode network and the sensorimotor network.

Treatment of patients suffering from panic disorder (including therapeutically resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates anxiety.

A reduction or elimination of anxiety in a patient suffering from panic disorder is observed about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 1 day, e.g., about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 7 days, 14 days, and/or 28 days.

The reduction or elimination of anxiety in a patient suffering from panic disorder occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of anxiety preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Theclinicalresponseofapatientsufferingfrompanicdisorder(includingatherapeuticallyresistantformofthedisorder)isreflectedinadecreaseinHAM-ascoreofatleast50%comparedtothecorrespondingscorepriortotreatmentatabout2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.about24hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday7,atday14,and/oratday28.

Theclinicalresponseofpatientssufferingfrompanicdisorder(includingtreatment-resistantformsofthedisorder),reflectedinatleasta50%decreaseinHAM-ascorecomparedtothecorrespondingscorepriortotreatment,occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. The clinical response of a patient suffering from panic disorder (including a therapeutically resistant form of the disorder), reflected in a decrease in HAMA score of at least 50% compared to the corresponding score before treatment, preferably lasts at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, in particular at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Thereliefofanxietyinpatientssufferingfromsuchpanicdisorder(includingtherapeuticallyresistantformsofthedisorder)isreflectedinaHAM-ascoreof7orlessabout2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,1day,e.g.,about24hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,7days,14days,and/or28days.

Reliefofanxiety(reflectedinaHAM-ascoreof7orless)inpatientssufferingfromsuchpanicdisorder(includingtherapeuticallyresistantformsofthedisorder)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thealleviationofanxiety(reflectedinaHAM-ascoreof7orless)inpatientssufferingfromsuchpanicdisorder(includingtherapeuticallyresistantformsofthedisorder)preferablylastsforatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,inparticularforatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyforatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,afterabout24hours,atday7,atday14,and/oratday28,areductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietysub-scaleofHAM-A(sumofitems1-6and14))isobservedinpatientssufferingfrompanicdisorder,includingatreatmentresistantformofthedisorder.

Thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreofthementalanxietysub-scaleofHAM-a(sumofitems1-6and14))inpatientssufferingfrompanicdisorder(includingtherapeuticallyresistantformsofthedisorder)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietysub-scaleofHAM-a(sumofitems1-6and14))preferablycontinuesuntilatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,particularlyuntilatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,andmorepreferablyuntilatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,afterabout24hours,atday7,atday14,and/oratday28,areductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietymoodprogramofHAM-a(item1))isobservedinpatientssufferingfrompanicdisorder,includingatreatmentresistantformofthedisorder.

Thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietymoodprogramofHAM-a(item1))inpatientssufferingfrompanicdisorder,includingtherapeuticallyresistantformsofthedisorder,occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thereductionoreliminationofanxiety,reflectedasadecreaseinthescoreoftheanxietymoodprogramofHAM-a(item1),preferablycontinuesuntilatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,particularlyuntilatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyuntilatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

A reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS project "anxiety") in patients suffering from panic disorder (including a treatment resistant form of the disorder) is observed at about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS program "anxiety") in patients suffering from panic disorder (including therapeutically resistant forms of the disorder) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS project "anxiety") preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Treatment of patients suffering from panic disorder (including therapeutically resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates suicidal ideation.

The reduction or elimination of suicidal ideation in patients suffering from panic disorder (including treatment resistant forms of the disorder) is observed about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 1 day, e.g., about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 7 days, 14 days, and/or 28 days.

The reduction or elimination of suicide ideas in patients suffering from panic disorder (including therapeutically resistant forms of the disorder) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The reduction or elimination of suicide preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from panic disorder is reflected at least by an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from panic disorder occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Phobia is an anxiety disorder defined as a sustained excessive fear of an object or condition. Patients suffering from phobia experience anxiety when expected to be exposed to or to a stimulus that makes them frightened. There are animal (spider, snake, dog) phobia, natural environment (tornado, high, water, fire) phobia, blood injection (needle, medical procedure) phobia, situational (airplane, enclosure) phobia and other types of phobia (phobia not belonging to the aforementioned classes).

Phobia generally results in a rapid onset of fear and is usually present for more than six months. The patient may try to avoid the fear of irritation. Fear and avoidance can cause serious confusion and/or impairment of professional, academic or social functions.

Phobia also involves one or more of sleep disorders, cognitive dysfunction, social/emotional withdrawal, and negative thinking.

Patients suffering from phobia may suffer from a therapeutically resistant form of the disorder.

The Becky anxiety scale (BAI) may be used to assess the severity of phobia. theseveritymayalsobeassessedbyusingtheHamiltoniananxietyratingscale(HAM-A),thementalanxietysub-scaleofHAM-A(sumofitems1-6anditem14),theanxietymooditemofHAM-A(item1),thebriefmentaldisorderratingscale(BPRS)item"anxiety".

Furthermore, phobia is associated with suicidal ideation.

The suicidal ideation can be evaluated using the Columbia suicide severity rating scale (C-SSRS).

In individuals with specific phobia, amygdala, anterior Cingulate Cortex (ACC) and islet cortex all appear to exhibit an excessive response to phobia-related stimuli. For example, functional neuroimaging studies have found that the dorsal portion of the anterior cingulate cortex (dACC), which is part of the significance network, exhibits an excessive response to phobia-related stimuli or to the expectation of such stimuli.

Treatment of patients suffering from phobia (including therapeutically resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates anxiety.

A reduction or elimination of anxiety in a patient suffering from phobia is observed about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 7, at day 14, and/or at day 28.

The reduction or elimination of anxiety in a patient suffering from phobia occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of anxiety preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Theclinicalresponseofapatientsufferingfromphobia(includingatherapeuticallyresistantformofthedisorder)isreflectedinadecreaseinHAM-ascoreofatleast50%comparedtothecorrespondingscorepriortotreatmentatabout2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.about24hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday7,atday14,and/oratday28.

Theclinicalresponseofpatientssufferingfromphobia(includingtreatment-resistantformsofthedisorder),reflectedinatleasta50%decreaseinHAM-ascorecomparedtothecorrespondingscorepriortotreatment,occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. theclinicalresponse(reflectedinadecreaseinHAM-ascoreofatleast50%)inpatientssufferingfromphobia(includingtreatmentresistantformsofthedisorder)preferablylastsatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,inparticularatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

Thereliefofanxietyinpatientssufferingfromsuchphobia(includingtreatment-resistantformsofthedisorder)isreflectedinabout2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,about24hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday7,atday14,and/oratday28,theHAM-ascoreis7orless.

Reliefofanxiety(reflectedinaHAM-ascoreof7orless)inpatientssufferingfromsuchphobia(includingtreatmentresistantformsofthedisorder)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thereliefofanxiety(reflectedinaHAM-ascoreof7orless)inpatientssufferingfromsuchphobia(includingtreatmentresistantformsofthedisorder)preferablylastsatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,inparticularatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,adecreaseinthescoreoftheanxietysub-scale(reflectedasthesumofitems1-6and14)ofHAM-Awasobservedatday1,e.g.,afterabout24hours,atday7,atday14,and/oratday28inpatientssufferingfromphobia(includingtreatmentresistantformsofthedisorder).

Thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreofthementalanxietysub-scaleofHAM-a(sumofitems1-6and14))inpatientssufferingfromphobia(includingtreatmentresistantformsofthedisorder)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietysub-scaleofHAM-a(sumofitems1-6and14))preferablycontinuesuntilatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,particularlyuntilatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,andmorepreferablyuntilatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,afterabout24hours,atday7,atday14,and/oratday28,areductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietymoodprogramofHAM-A(project1))isobservedinpatientssufferingfromphobia,includingatreatmentresistantformofthedisorder.

Thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietymoodprogramofHAM-a(item1))inpatientssufferingfromphobia,includingthetherapeuticallyresistantformofthedisorder,occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thereductionoreliminationofanxiety,reflectedasadecreaseinthescoreoftheanxietymoodprogramofHAM-a(item1),preferablycontinuesuntilatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,particularlyuntilatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyuntilatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

Reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS project "anxiety") in patients suffering from phobia (including treatment resistant forms of the disorder) is observed at about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS program "anxiety") in patients suffering from phobia (including treatment resistant forms of the disorder) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS project "anxiety") preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Treatment of patients suffering from phobia (including therapeutically resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates suicidal ideation.

The reduction or elimination of suicidal ideation in patients suffering from phobia (including treatment resistant forms of the disorder) is observed about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 1 day, e.g., about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 7 days, 14 days, and/or 28 days.

The reduction or elimination of suicide ideas in patients suffering from phobia (including therapeutic resistant forms of the disorder) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of suicide preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from phobia is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from phobia occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Substance/drug induced anxiety disorder is an anxiety disorder that is anxiety or panic after the use of alcohol, abuse of drugs, or the use of drugs or after exposure to toxins. Substance/drug induced anxiety disorders can lead to overt panic or anxiety symptoms and can occur during periods of intoxication or withdrawal with substances or drugs.

The disorder may cause serious confusion and/or impairment in social, professional, or other important areas of function.

Individuals suffering from substance/drug-induced anxiety disorders may feel stress and anxiety, experience negative mental symptoms, may have difficulty concentrating on or remembering things, may fear of losing control or being confused or dying, may lose weight due to gastrointestinal problems, may develop cold, hot flushes, sweating, tremors, numbness or acceleration of the heartbeat, dyspnea, dysphagia, or chest pain, and the like, at the time of or shortly after administration of the substance or drug.

Substance/drug induced anxiety disorders also involve one or more of sleep disorders, cognitive dysfunction, social/emotional withdrawal, and negative thoughts.

The beck anxiety scale (BAI) may be used to assess the severity of substance/drug induced anxiety disorders. theseveritymayalsobeassessedbyusingtheHamiltoniananxietyratingscale(HAM-A),thementalanxietysub-scaleofHAM-A(sumofitems1-6anditem14),theanxietymooditemofHAM-A(item1),thebriefmentaldisorderratingscale(BPRS)item"anxiety".

Furthermore, substance/drug induced anxiety disorders are associated with suicidal ideation.

The suicidal ideation may be evaluated using the Columbia suicide severity rating scale (CSSR-S).

Functional magnetic resonance imaging of individuals suffering from substance/drug induced anxiety disorders reveals alterations in functional connections within and/or between resting state networks involved in anxiety.

Treatment of patients suffering from substance/drug induced anxiety disorders (including therapeutically resistant forms of the disorders) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates anxiety.

A reduction or elimination of anxiety in a patient suffering from substance/drug induced anxiety disorder is observed about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 7, at day 14, and/or at day 28.

The reduction or elimination of anxiety in a patient suffering from a substance/drug induced anxiety disorder occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of anxiety preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Theclinicalresponseofapatientsufferingfromsubstance/druginducedanxietydisorder(includingatherapeuticallyresistantformofthedisorder)isreflectedinadecreaseofatleast50%inHAM-ascorecomparedtothecorrespondingscorepriortotreatmentatabout2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.about24hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday7,atday14,and/oratday28.

Theclinicalresponseofapatientsufferingfromsubstance/druginducedanxietydisorder(includingatherapeuticallyresistantformofthedisorder),reflectedinadecreaseinHAM-ascoreofatleast50%comparedtothecorrespondingscorepriortotreatment,occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. theclinicalresponse(reflectedinadecreaseinHAM-ascoreofatleast50%)inpatientssufferingfromsubstance/druginducedanxietydisorder(includingtherapeuticallyresistantformsofthedisorder)preferablylastsatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,inparticularatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

Reliefofanxietyinpatientssufferingfromsuchsubstance/drug-inducedanxietydisorders(includingtherapeuticallyresistantformsofthedisorders)isreflectedinabout2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday1,e.g.,about24hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,atday7,atday14,and/oratday28,theHAM-ascoreis7orless.

Reliefofanxiety(reflectedinaHAM-ascoreof7orless)inpatientssufferingfromsuchsubstance/druginducedanxietydisorders(includingtherapeuticallyresistantformsofthedisorders)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thealleviationofanxiety(reflectedinaHAM-ascoreof7orless)inapatientsufferingfromsuchsubstance/druginducedanxietydisorder(includingatherapeuticallyresistantformofthedisorder)preferablylastsforatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,inparticularforatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyforatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,adecreaseinscoresofthementalanxietysub-scale(sumofitems1-6and14)reflectedinHAM-Awasobservedatday1,e.g.,afterabout24hours,atday7,atday14,and/oratday28,inpatientssufferingfromsubstance/drug-inducedanxietydisorders(includingtreatment-resistantformsofthedisorder).

Thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreofthementalanxietysub-scaleofHAM-a(sumofitems1-6and14))inpatientssufferingfromsubstance/druginducedanxietydisorder(includingtherapeuticallyresistantformsofthedisorder)occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietysub-scaleofHAM-a(sumofitems1-6and14))preferablycontinuesuntilatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,particularlyuntilatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,andmorepreferablyuntilatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,adecreaseoreliminationofanxiety(reflectedasadecreaseinscoreofanxietyitems(item1)ofHAM-a)wasobservedinpatientssufferingfromsubstance/drug-inducedanxietydisorders(includingtreatmentresistantformsofthedisorders),atday1,e.g.,afterabout24hours,atday7,atday14,and/oratday28,afterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof.

Thereductionoreliminationofanxiety(reflectedasadecreaseinthescoreoftheanxietymoodprojectofHAM-a(item1))inapatientsufferingfromasubstance/drug-inducedanxietydisorder,includingatherapeuticallyresistantformofthedisorder,occursnolaterthanabout2hoursafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof. thereductionoreliminationofanxiety,reflectedasadecreaseinthescoreoftheanxietymoodprogramofHAM-a(item1),preferablycontinuesuntilatleast6daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,particularlyuntilatleast14daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof,morepreferablyuntilatleast28daysafterthelastadministrationof5-meo-dmtorapharmaceuticallyacceptablesaltthereof.

About 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, a reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS project "anxiety") in patients suffering from substance/drug induced anxiety disorders (including treatment resistant forms of the disorder) is observed at day 1, e.g., about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 7, at day 14, and/or at day 28.

The reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS project "anxiety") in patients suffering from substance/drug-induced anxiety disorders (including therapeutically resistant forms of the disorders) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of anxiety (reflected as a decrease in the score of the BPRS project "anxiety") preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Treatment of patients suffering from substance/drug induced anxiety disorders (including therapeutically resistant forms of the disorders) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates suicidal ideation.

A reduction or elimination of suicide ideas in patients suffering from substance/drug induced anxiety disorders, including treatment resistant forms of the disorder, is observed about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 1 day, e.g., about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, 7 days, 14 days, and/or 28 days.

The reduction or elimination of suicide ideas in patients suffering from substance/drug induced anxiety disorders (including therapeutically resistant forms of the disorders) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of suicide preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from substance/drug induced anxiety disorders is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from substance/drug induced anxiety disorders occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Physical symptom disorder

Somatic symptom disorder is a mental disorder that is diagnosed when a person is excessively concerned about physical symptoms such as pain, weakness, or shortness of breath, so as to cause serious trouble and/or functional problems and/or cause the daily life to be disturbed. The sensations and behaviors associated with the disease are excessive or disproportionate.

The quality of life associated with health is often compromised, both physically and mentally. In severe somatic symptom disorders, lesions are evident and when lesions persist, the disorder may lead to disability.

Somatic symptom disorders involve one or more of sleep disorders, cognitive dysfunction, and anxiety.

Analysis of brain functional connections revealed changes in and/or between resting state networks in somatically impaired patients compared to healthy controls. Changes are found inside and/or between the Default Mode Network (DMN), the saliency network, the back attention network (DAN), and the sensorimotor network. Somatic symptom disorders may be associated with changes in the sensory recognition process of somatic symptoms that are affected by emotional processes.

Treatment of a patient suffering from a somatic symptom disorder (including a therapeutically resistant form of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement in the somatic symptom disorder.

Improvement in somatic symptom disorders (reflected in a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement of the physical symptom disorder in the patient (reflected in a decrease in CGI-S score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement of somatic symptom disorder (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from somatic symptom disorders is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from somatic symptom disorders occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Obsessive compulsive disorder and related disorders

Obsessive Compulsive Disorder (OCD) is a mental disorder that causes repeated unwanted ideas or sensations (obsessive compulsive ideas) or impulses to do something one time after the other (compulsive behavior). The patient may suffer from both obsessive-compulsive concept and obsessive-compulsive behavior.

Patients suffering from OCD may suffer from a therapeutically resistant form of the disorder.

OCD relates to one or more of sleep disorders, cognitive dysfunction, anxiety, social/emotional withdrawal, and negative thinking.

Neuroimaging studies using functional magnetic resonance imaging on patients suffering from OCD show functional connection changes inside and/or between frontal top network, saliency network and default mode network. Altered functional connections of affected networks, particularly default mode networks, are also associated with sleep disturbances.

Treatment of a patient suffering from OCD (including a therapeutically resistant form of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement in OCD.

Improvement in OCD (reflected as a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in the patient' S OCD (reflected in a decrease in CGI-S score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in OCD (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from OCD is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from OCD occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Patients suffering from a Body Deformity Disorder (BDD) erroneously perceive defects in their appearance, thereby disrupting their ability to live daily with discomfortable thinking, ceremonies and emotional distress.

Patients suffering from BDD may suffer from a therapeutically resistant form of the disorder.

BDD involves one or more of sleep disorders, cognitive dysfunction, anxiety, social/emotional withdrawal, and negative thinking.

Functional magnetic resonance imaging of patients suffering from BDD reveals changes within and/or between certain brain regions located within the default mode network, the dorsal awareness network, and the saliency network. Altered functional connections of affected networks, particularly default mode networks, are also associated with sleep disturbances.

Treatment of patients suffering from BDD (including therapeutically resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement in BDD.

Improvement in BDD (reflected in a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in BDD in the patient (reflected in a decrease in CGI-S score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in BDD (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from BDD is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from BDD occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Post-traumatic stress disorder (PTSD)

Post-traumatic stress disorder (PTSD) is a mental health condition that may develop based on a terrible event that a patient experiences or witnessed in person. Symptoms may include flashback, nightmare, and severe anxiety, and an idea of uncontrollable events.

Patients suffering from PTSD may suffer from a therapeutically resistant form of the disorder.

PTSD involves one or more of sleep disorders, cognitive dysfunction, anxiety, social/emotional withdrawal, and negative thinking.

Resting state functional magnetic resonance imaging analysis of a patient suffering from PTSD reveals changes within and/or between regions within the default mode network and the saliency network.

Treatment of patients suffering from PTSD (including therapeutically resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement in PTSD.

Improvement in PTSD (reflected in a decrease in CGI-S score) is observed at about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28.

Improvement in patient PTSD (reflected in a decrease in CGI-S score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in PTSD (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from PTSD is reflected at least in improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from PTSD occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Pain disorders

Sleep disorders occur in patients suffering from pain and are associated with chronic pain.

Chronic pain, also known as persistent pain, is long-term pain that persists beyond the normal recovery period (e.g., after injury or surgery) despite receiving medication or treatment. Patients may also suffer from chronic pain without any obvious cause (such as injury or surgical history).

Chronic pain involves one or more of sleep disorders, cognitive dysfunction, anxiety, social/emotional withdrawal, and negative thinking.

Chronic pain patients exhibit brain changes in terms of brain function and structure. These changes are associated with the duration of pain, which is long after the initial nociceptive input has disappeared. Resting state functional magnetic resonance imaging reveals changes in different regions within and/or between default mode networks, somatomotor/sensorimotor networks, and saliency networks.

Treatment of a patient suffering from chronic pain (including a therapeutically resistant form of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement in chronic pain.

Improvement in chronic pain (reflected in a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in chronic pain in the patient (reflected in a decrease in CGI-S score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in chronic pain (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from chronic pain is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from chronic pain occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Fibromyalgia is a chronic disorder characterized by generalized musculoskeletal pain in the whole body or in multiple locations, and is accompanied by fatigue, sleep disorders, memory and mood problems. Patients may also experience stiffness in muscles and joints, tenderness, numbness or tingling in the arms and legs, difficulty in concentrating, unclear thinking and impaired memory (sometimes referred to as "fiber mist"), increased sensitivity to light, noise, smell and temperature, or digestive problems such as abdominal distension or constipation.

Studies have shown that fibromyalgia patients are highly sensitive to pain and therefore feel pain when others do not feel pain.

Fibromyalgia relates to one or more of sleep disorders, cognitive dysfunction, anxiety, social/emotional withdrawal, and negative thinking.

Brain imaging studies and other studies have found evidence of altered signaling in the neural pathways that transmit and receive pain in fibromyalgia patients. These changes may also lead to fatigue, sleep disorders and cognitive problems in many people suffering from the disorder.

Resting state functional magnetic resonance imaging of fibromyalgia patients shows a change in the functional connection between the DMN and the executive attention network and between the DMN and the cortex of the islanding (the area of the brain known to be pain-inducing by treatment).

Treatment of a patient suffering from fibromyalgia (including treatment-resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement in fibromyalgia.

Improvement in fibromyalgia (reflected in a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in fibromyalgia (reflected in a decrease in CGI-S score) in the patient occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement of fibromyalgia (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from fibromyalgia is reflected at least by an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from fibromyalgia occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Migraine is a headache that can cause severe pulsatile pain or a feeling of pulsation, usually occurring on one side of the head. Migraine is often accompanied by nausea, vomiting, and extreme sensitivity to light and sound. Migraine attacks can last from hours to days, and pain can be so severe as to interfere with daily activities.

In some patients, a symptom called aura may occur before or concurrent with the headache. This symptom may include visual disturbances such as glints or blind spots, or other disturbances such as facial side or arm or leg stings and difficulty speaking.

Migraine is related to one or more of sleep disorders, cognitive dysfunction, anxiety, social/emotional withdrawal, and negative thinking.

Headache disorders are associated with atypical functional connections within and/or between multiple core rest state networks (including significance and default mode networks) in pain management related areas.

In patients suffering from migraine, resting state network analysis showed differences from healthy controls. Studies during migraine attacks revealed significant abnormalities in the relevant networks of cognitive, attention, somatosensory and affective components that mediate pain.

Treatment of patients suffering from migraine (including treatment-resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement in migraine.

Improvement in migraine (reflected in a decrease in CGI-S score) was observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in migraine pain (reflected in a decrease in CGI-S score) in patients occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in migraine pain (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from migraine is reflected at least in an improvement in the total score of BIMF at day 7, day 14, and/or day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from migraine occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Mental and behavioral disorders resulting from the use of psychoactive substances

Sleep disorders occur in patients suffering from certain mental and behavioral disorders resulting from the use of psychoactive substances.

Substance Use Disorder (SUD) is a mental disorder that affects a person's behavior, resulting in a person having no control over his use of a substance, such as a legal or illegal drug, alcohol, or medication. Symptoms can range from moderate to severe, and addiction is the most severe form of SUD.

Substance use disorders involve one or more of sleep disorders, cognitive dysfunction, anxiety, social/emotional withdrawal, negative thinking and mental retardation.

It was found that resting state functional connections (rsFC) were altered not only in sleep disordered patients, but also in substance use impaired patients. Specifically, cognitive control deficiencies are associated with connections that change inside and/or between rest state networks (such as default mode networks, saliency networks, central execution networks, edge networks, and rewards networks).

Treatment of a patient suffering from a substance use disorder (including a therapeutically resistant form of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement in the substance use disorder.

Improvement in substance use disorder (reflected in a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in substance use disorder (reflected in a decrease in CGI-S score) in patients occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in substance use disorder (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from substance use disorders is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from substance use disorders occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Psychotic disorder

Psychotic disorders are severe mental disorders that cause abnormal thinking and perception. Psychotic disorders are characterized by significant impairment of the ability to test for reality and altered behavior, manifested as positive symptoms such as sustained delusions, sustained hallucinations, confusion of thinking (often manifested as speech confusion), severe confusion of behavior, and a passive and controlled experience, negative symptoms such as emotional dullness or dullness, loss of mind, and psychomotor disturbances.

Patients suffering from psychotic disorders may suffer from a therapeutically resistant form of the disorder.

Psychotic disorders involve one or more of sleep disorders, cognitive dysfunction, anxiety, social/emotional withdrawal, negative thinking and mental retardation.

Imaging the brain of a patient suffering from psychotic disorders by functional magnetic resonance imaging of the brain resting state network reveals significant changes in different areas within and/or between the central executive network, default mode network, and significance network. Even in a patient population at risk of psychosis, changes in resting state networks can be identified.

Treatment of a patient suffering from a psychotic disorder (including a therapeutically resistant form of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement in the psychotic disorder.

Improvement in psychotic disorder (reflected in a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in the patient' S psychotic disorder (reflected in a decrease in CGI-S score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement of psychotic disorder (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, in particular until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from psychotic disorders is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from psychotic disorders occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Schizophrenia (schizophrenia)

Schizophrenia is a severe mental health disorder characterized by a disturbance of a variety of mental patterns, including thinking, perception, self-experience, cognition, volition, emotion and behavior. Mental disorders, including stress, may occur.

Patients suffering from schizophrenia may suffer from a therapeutically resistant form of the disorder.

Schizophrenia involves one or more of sleep disorders, cognitive dysfunction, anxiety, social/emotional withdrawal, negative thinking, and mental retardation.

Abnormal resting state functional connections are reported in individuals with schizophrenia, particularly within and/or between default mode networks, frontal and prominent networks. Several studies have found a correlation between sleep disturbance and symptom severity in high risk groups of psychosis and those diagnosed with schizophrenia.

Treatment of patients suffering from schizophrenia (including therapeutically resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement in schizophrenia.

Improvement in schizophrenia (reflected in a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in schizophrenia (reflected in a decrease in CGI-S score) in the patient occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement of schizophrenia (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, in particular until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from schizophrenia is reflected at least in an improvement in the total score of BIMF at day 7, day 14, and/or day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from schizophrenia occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Eating disorders

Eating disorders are mental disorders characterized by abnormal eating behaviors that negatively affect a person's physical or mental well-being.

Patients suffering from a eating disorder may suffer from a therapeutically resistant form of the disorder.

Eating disorders involve one or more of sleep disorders, cognitive dysfunction, anxiety, social/emotional withdrawal, and negative thinking.

For patients suffering from eating disorders, the results of functional network connection studies indicate that resting state connections within and/or between the executive network, default mode network, and significance network are broken.

Treatment of a patient suffering from a eating disorder (including a therapeutically resistant form of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement in the eating disorder.

Improvement in eating disorders (reflected in a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in the patient' S eating disorder (reflected in a decrease in CGI-S score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in eating disorders (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from eating disorders is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from eating disorders occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Attention Deficit Hyperactivity Disorder (ADHD)

Attention Deficit Hyperactivity Disorder (ADHD) is a disorder that affects the behavior of patients. Patients suffering from ADHD may look restless, may be difficult to concentrate on, and may be impulsive.

ADHD involves one or more of sleep disorders, cognitive dysfunction, anxiety, social/emotional withdrawal, and negative thinking.

Analysis of resting state networks in patients suffering from ADHD revealed dysfunctional connections between multiple brain resting state networks, particularly within and/or between different areas of default mode networks, dorsal awareness networks, and prominent networks.

Treatment of patients suffering from ADHD (including therapeutically resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement in ADHD.

Improvement in ADHD (reflected in a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in ADHD in the patient (reflected in a decrease in CGI-S score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in ADHD (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from ADHD is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from ADHD occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Personality disorder

Split personality disorder is a mental health condition characterized by persistent discomfort to personal relationships and social interactions. Patients suffering from split personality disorders have abnormal ideas, speech and behavior, which hinders their ability to form and maintain relationships.

Patients suffering from split personality disorders may suffer from a therapeutically resistant form of the disorder.

Split personality disorders involve one or more of sleep disorders, cognitive dysfunction, anxiety, social/emotional withdrawal, and negative thinking.

In schizophrenic patients, the DMN functional link (in particular, the functional link involved in cognitive or affective regulation) is altered. Neural image analysis of fMRI further reveals changes within and/or between frontal and dorsal attention networks.

Treatment of a patient suffering from a split personality disorder (including a therapeutically resistant form of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement in the split personality disorder.

Improvement in split personality disorder (reflected in a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement of the patient' S split personality disorder (reflected in a decrease in CGI-S score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement of split personality disorder (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from split personality disorder is reflected at least in improvement in the total score of BIMF at day 7, day 14, and/or day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from split personality disorder occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Sustained mood swings, impulses, acceptance disorders, and interpersonal dysfunction are features of Borderline Personality Disorder (BPD).

Patients suffering from BPD may suffer from a therapeutically resistant form of the disorder.

BPD involves one or more of sleep disorders, cognitive dysfunction, anxiety, social/emotional withdrawal, and negative thinking.

Borderline personality disorder patients exhibit abnormal patterns of connectivity of the resting state network. Analysis of functional connections of brain resting state networks using functional magnetic resonance imaging reveals changes within and/or between various networks such as, for example, default mode networks and significance networks.

Treatment of patients suffering from BPD (including therapeutically resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement in BPD.

Improvement in BPD (reflected in a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in BPD in the patient (reflected in a decrease in CGI-S score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in BPD (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from BPD is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from BPD occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Autism Spectrum Disorder (ASD)

Patients suffering from Autism Spectrum Disorder (ASD), including autism, asperger's syndrome, and atypical autism, have sustained deficiencies in the ability to initiate and maintain mutual social interactions and social communications. In addition, the disorder has a series of restricted, repetitive and stiff patterns of behavior, interest or activity that are obviously atypical or excessive for the age and socio-cultural background of the individual.

The disorder is developed during the developmental stage, but symptoms may not be fully manifested until later. The defect is severe enough to affect the patient's ability to function in personal, home, social, educational, professional, or other areas.

ASD involves one or more of sleep disorders, cognitive dysfunction, anxiety and social/emotional withdrawal.

ASD is a disorder of brain network connectivity. Neuroimaging studies have shown that ASD is associated with abnormal responses in certain brain regions, significant changes in brain networks, including changes in functional connections within and/or between Default Mode Networks (DMNs) and sensory processing networks, and dyssynchrony between brain regions.

Treatment of patients suffering from ASD (including therapeutically resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement in ASD.

Improvement in ASD (reflected in a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in ASD (reflected in a decrease in CGI-S score) in patients occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in ASD (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from ASD is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from ASD occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Chronic fatigue syndrome

Fatigue describes a feeling of exhaustion, lack of fine effort and decline in energy. Fatigue refers to the weakness or exhaustion of a person's physical or mental resources. Although it is considered normal that fatigue occurs after a period of mental or physical exertion, it is still possible that fatigue is a symptom of a healthy condition in the absence of such exertion.

Furthermore, chronic fatigue with increased activity is a major symptom of chronic fatigue syndrome. In this disorder, severe fatigue is accompanied by neurocognitive symptoms, autonomic symptoms and immune symptoms.

There have been reported a number of abnormalities in the normal sleep pattern of patients with chronic fatigue syndrome that can act as maintenance factors.

Patients with chronic fatigue syndrome often complain of excessive sleep in the early stages of the disease. Once the disease enters a more chronic stage, it often results in a general decline in sleep efficiency. Even if the patient sleeps for a long time, they will not feel refreshing when they wake up.

Compensation for non-restorative night sleep may result in a change in circadian rhythms. In addition, the occurrence of vivid dreams, periodic limb movements during sleep and restless leg syndrome are often reported.

Chronic fatigue syndrome involves one or more of sleep disorders, cognitive dysfunction, and anxiety.

Patients suffering from chronic fatigue syndrome exhibit abnormal resting state functional connections, which are significantly related to the severity of their chronic fatigue. The network involved also relates to sleep regulation.

Treatment of a patient suffering from chronic fatigue syndrome (including a therapeutically resistant form of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement of chronic fatigue syndrome.

Improvement in chronic fatigue syndrome (reflected in a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in chronic fatigue syndrome (reflected in a decrease in CGI-S score) in patients occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement of chronic fatigue syndrome (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, in particular until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from chronic fatigue syndrome is reflected at least by an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from chronic fatigue syndrome occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Medical health conditions leading to related mental or neurological conditions

Traumatic brain injury patient

Traumatic Brain Injury (TBI) is a brain injury caused by external forces.

Traumatic brain injury is classified as either primary or secondary. Primary brain injury refers to structural damage that occurs upon contact, acceleration-deceleration, and/or impact of rotational forces. Secondary brain injury refers to injury caused by cellular processes following primary injury (i.e., hypoxia and/or elevated intracranial pressure).

TBI causes one or more of sleep disorders, cognitive dysfunction, anxiety, social/emotional withdrawal, and negative thinking.

The resting state functional connection analysis reveals changes in overall functional connections within and/or between resting state networks (such as DMN, frontal top network, executive network, and sensorimotor network). For example, highly connected regions found within DMN's are particularly susceptible to changes in functional connectivity following traumatic brain injury.

Treatment of patients suffering from TBI (including therapeutically resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement of TBI.

Improvement in TBI (reflected in a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in the patient' S TBI (reflected in a decrease in CGI-S score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in TBI (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from TBI is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from TBI occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

HIV-infected patient

HIV disease is caused by infection with human immunodeficiency virus type 1 (HIV-1). Despite the use of combination antiretroviral therapy, patients infected with HIV still develop symptoms of neurological disorders.

HIV causes one or more of sleep disorders, cognitive dysfunction, anxiety, social/emotional withdrawal, and negative thoughts.

Resting state functional connection analysis of patients suffering from neurocognitive impairment due to HIV infection shows impaired functional connection within and/or between default mode networks, saliency networks, and certain areas of the executive network.

Treatment of patients suffering from HIV (including therapeutically resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in improvement of HIV.

Improvement in HIV (reflected in a decrease in CGI-S score) is observed at about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28.

Improvement in patient HIV (reflected in a decrease in CGI-S score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement of HIV (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from HIV is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from HIV occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

COVID sequelae patients

2019 Coronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

COVID sequelae (sometimes referred to as "long term COVID") is a multi-system disorder that typically involves severe symptoms following SARS-CoV-2 infection. This is a disease that is often debilitating and occurs in at least 10% of infections.

The World Health Organization (WHO) defines this disorder as a syndrome that occurs within 3 months after infection, persists for at least 2 months, may fluctuate, and cannot be explained by other diagnostics.

COVID sequelae can include a variety of persistent health problems, which can last weeks, months, or years, and sometimes also lead to disability.

The most commonly reported typical symptoms such as fatigue, shortness of breath, and cognitive disorders in individuals suffering from COVID sequelae, such as, for example, difficulty in thinking or concentrating attention (sometimes referred to as "brain mist"). But patients may also experience respiratory and cardiac symptoms, neurological symptoms such as sleep problems (e.g., insomnia) and digestive system symptoms.

Even after survival from mild disease, COVID sequelae patients often experience symptoms that are persistent, such as anxiety. Anxiety in COVID sequelae may be a direct consequence of SARS-CoV-2 infection, and may also be caused by hospitalization associated with acute SARS-CoV-2 infection, particularly in intensive care units.

Individuals suffering from COVID sequelae-induced anxiety often have a bearing on health and rehabilitation problems, fear of lost business and financial conditions being affected, and fear of family and friends also becoming ill. Furthermore, COVID sequelae-induced anxiety can also lead to sleep difficulties, inattention, memory loss, mood changes, flashback, respiratory dysfunction, chest pain, and mood disorders.

COVID sequelae relate to one or more of sleep disorders, cognitive dysfunction and anxiety.

Functional magnetic resonance imaging of patients suffering from COVID sequelae reveals changes within and/or between resting state networks. Most often, the default mode network is affected.

Treatment of a patient suffering from COVID sequelae (including treatment resistant forms of the disorder) with 5-MeO-DMT or a pharmaceutically acceptable salt thereof results in an improvement of COVID sequelae.

Improvement in COVID sequelae (reflected in a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement of the patient' S COVID sequelae (reflected in a decrease in CGI-S score) occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The improvement in COVID sequelae (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function in patients suffering from COVID sequelae is reflected at least in an improvement in the total score of BIMF at day 7, day 14, and/or day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as improvement in BIMF overall score) in patients suffering from COVID sequelae occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Idiopathic sleep disorders

Treatment of a patient suffering from an idiopathic sleep disorder with 5-MeO-DMT or a pharmaceutically acceptable salt thereof reduces or eliminates the idiopathic sleep disorder.

The reduction or elimination of idiopathic sleep disorders is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The reduction or elimination of idiopathic sleep disorders preferably occurs no later than about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. The reduction or elimination of idiopathic sleep disorders preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

In embodiments, the reduction or elimination of idiopathic sleep disorders is observed at day 7 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and preferably continues for up to at least 14 days, more preferably up to at least 28 days.

In the case of idiopathic sleep disorders, clinical response may be reflected by a decrease in clinical global impression-severity (CGI-S) score. According to the present invention, a decrease in CGI-S score means a decrease in CGI-S of at least 1 point. Preferably, CGI-S is reduced by at least 2 points and/or to 0 points. Particularly preferably, the CGI-S is reduced by at least 3 minutes and/or to 0 minutes.

Improvement in idiopathic sleep disorders (reflected in a decrease in CGI-S score) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28 following the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement of idiopathic sleep disorders (reflected in a decrease in CGI-S score) occurs no later than about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement of idiopathic sleep disorders (reflected in a decrease in CGI-S score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

In embodiments, improvement in idiopathic sleep disorders (reflected in a decrease in CGI-S score) is observed at day 7 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, and preferably continues for up to at least 14 days, more preferably up to at least 28 days.

In the case of idiopathic sleep disorders, improvement in sleep disorders (at least reflected as a "substantial improvement" in clinical global impression-improvement (CGI-I) scores or patient global impression-improvement (PGI-I) scores) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28, following the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement of idiopathic sleep disorders (at least reflected as a "greatly improved" score in CGI-I score or PGI-I score) preferably occurs no later than about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

The improvement in sleep disturbance (at least reflected in a "greatly improved" score in the CGI-I score or PGI-I score) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, in particular until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

In embodiments, improvement in idiopathic sleep disorders (at least reflected as a "greatly improved" score in CGI-I score or PGI-I score) is observed at day 7 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof), and preferably continues for up to at least 14 days, more preferably up to at least 28 days.

Improvement of idiopathic sleep disorders can also be assessed by any other scale as described above that reflects changes in sleep quality or quantity, such as the Pittsburgh Sleep Quality Index (PSQI).

If PSQI is used to evaluate the outcome of the treatment, treatment success is expressed as a drop in (i) total score, preferably (ii) total score of 5 or less. The recall period applied does not begin earlier than the point in time at which the acute fantasy experience subsides after the last administration.

Improvement of idiopathic sleep disorders (reflected by a drop in PSQI-S score, particularly to 5 or less) preferably occurs no later than about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

This improvement in idiopathic sleep disorders (reflected as a drop in PSQI-S score, particularly to 5 or less) preferably continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, particularly until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement of idiopathic sleep disorders (reflected as a reduction in PSQI-S score, particularly to 5 or less) is observed at day 1, e.g., after about 24 hours, at day 7, at day 14, and/or at day 28 following the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

In embodiments, an improvement in idiopathic sleep disorders (reflected as a decrease in PSQI total score, particularly to 5 or less) is observed at day 7, and preferably continues until day 14, more preferably until day 28.

Improvement in maternal function in patients suffering from sleep disorders is reflected at least in an improvement in total score at day 7, day 14, and/or day BIMF after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Improvement in maternal function (reflected as an improvement in BIMF total score) in patients suffering from sleep disorders occurs no later than about 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Improvement in maternal function (reflected as an improvement in BIMF total score) preferably continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Further therapeutic aspects

Specific aspects of the treatment of major depressive disorder are summarized below.

A 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use in the treatment of a patient diagnosed by a medical professional as major depressive disorder according to accepted medical practice, wherein the 5-MeO-DMT is administered via intravenous, intramuscular or subcutaneous route, and wherein the patient is breast-feeding mother who is advised to stop breast-feeding until 48 hours, such as 24 hours, preferably 6 hours, more preferably 3 hours, most preferably 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

2. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to aspect 1, wherein the disorder is diagnosed according to the manual for diagnosis and statistics of mental disorders, fifth edition (DSM-5), issued by the american society of psychiatry.

3. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to aspect 1 or 2, wherein the patient suffers from a moderate or severe major depressive disorder, said disorder being represented by a montgomery-asberg depression rating scale (MADRS) score of 20 or more, or a 17-item hamilton depression rating scale (HAM-D) score of 17 or more.

4. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 3, wherein the patient suffers from major depressive disorder, expressed as a MADRS score of 35 or higher, or a HAM-D score of 25 or higher.

5. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to aspects 1 to 4, wherein the patient is diagnosed with a therapeutically resistant form of major depressive disorder.

6. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to aspects 1 to 5, wherein the patient also suffers from suicidal ideation.

7. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 6, wherein the patient suffers from suicidal ideation and is intended to take action.

8. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to aspects 1 to 7, wherein the patient is at risk of impending suicide.

9. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1 to 8, wherein the 5-MeO-DMT or salt thereof is administered at a dose or dose regimen that causes the patient to experience a peak fantasy experience.

10. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 9, wherein a dose of about 1 mg to about 10mg of 5-MeO-DMT is administered, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered instead of 5-MeO-DMT.

11. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 9, wherein a dose of about 2 mg, or about 5mg, or about 8 mg is administered, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered instead of 5-MeO-DMT.

12. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 10, wherein the 5-MeO-DMT or salt thereof is administered in a first dose at the time of a first administration and the 5-MeO-DMT or salt thereof is administered in zero to six subsequent administrations, wherein each subsequent administration uses a higher dose than the previous administration unless the patient experiences a peak fantasy experience.

13. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-10 or 12, wherein the 5-MeO-DMT is administered at a dose of about 0.5 mg to about 1.5 mg when administered for the first time, then increased to a dose of about 1.5 mg to about 2.5 mg when administered for the second time unless the patient has experienced a peak vagal experience, then increased to a dose of about 2.5 mg to about 3.5 mg when administered for the third time unless the patient has experienced a peak vagal experience, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.

14. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 13, wherein the first dose of 5-MeO-DMT is about 1mg, the second dose of 5-MeO-DMT is about 2 mg, and the third dose of 5-MeO-DMT is about 3 mg, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.

15. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to aspects 12 to 14, wherein the interval between two administrations is not less than 1 hour and not more than 24 hours, such as about 2 to 4 hours.

16. The 5-MeO-DMT for use as in aspects 9-15, or a pharmaceutically acceptable salt thereof, wherein the occurrence of the peak fantasy experience is identified by reaching at least 60% of the highest possible score in each of four sub-scales (mystery, active emotion, overrun time and space, and self-evident) of a revised mystery experience questionnaire (MEQ 30) of 30 items, or by reaching at least 60% of the highest possible score of the marine-like no-margin (OBN) dimension in a state of consciousness change (ASC) questionnaire, or by reaching a peak fantasy experience questionnaire (PPEQ) total score of at least 75.

17. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 16, wherein the occurrence of a peak fantasy experience is identified by reaching a peak fantasy experience questionnaire (PPEQ) total score of at least 75.

18. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of any one of the preceding aspects, wherein the 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, is administered via intravenous injection.

19. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 18, wherein a clinical response reflected as a decrease in clinical overall impression-severity (CGI-S) score occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

20. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-19, wherein the clinical response is continued until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, said clinical response being reflected in a decrease in the clinical overall impression-severity (CGI-S) score.

21. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 20, wherein the clinical response is continued until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, said clinical response being reflected in a decrease in the clinical global impression-severity (CGI-S) score.

22. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 21, wherein the clinical response is continued until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, said clinical response being reflected in a decrease in the clinical global impression-severity (CGI-S) score.

23. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-22, wherein a clinical response occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the clinical response assessed as an improvement in MADRS or HAM-D score of at least 50% compared to the corresponding score prior to treatment.

24. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-23, wherein alleviation of symptoms of depression, assessed as a MADRS score of 10 or less or a HAM-D score of 7 or less, occurs no later than about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

25. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-24, wherein the clinical response is continued until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which clinical response is assessed as an improvement in MADRS or HAM-D score of at least 50% compared to the corresponding score prior to treatment.

26. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-25, wherein a clinical response is present at day 7 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which clinical response is assessed as an improvement in MADRS or HAM-D score of at least 75% compared to the corresponding score prior to treatment.

27. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-26, wherein the patient is in a state of remission of depressive symptoms at day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, the remission of depressive symptoms being assessed as a MADRS score of equal to or less than 10 or a HAM-D score of equal to or less than 7.

28. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-27, wherein the clinical response continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the clinical response being assessed as an improvement in MADRS or HAM-D score of at least 50% compared to the corresponding score prior to treatment.

29. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-28, wherein a clinical response is present at day 14 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which clinical response is assessed as an improvement in MADRS or HAM-D score of at least 75% compared to the corresponding score prior to treatment.

30. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-29, wherein the patient is in a state of remission of depressive symptoms at day 14 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, the remission of depressive symptoms being assessed as a MADRS score of equal to or less than 10 or a HAM-D score of equal to or less than 7.

31. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-30, wherein the clinical response is continued until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which clinical response is assessed as an improvement in MADRS or HAM-D score of at least 50% compared to the corresponding score prior to treatment.

32. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-31, wherein a clinical response is present at day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which clinical response is assessed as an improvement in MADRS or HAM-D score of at least 75% compared to the corresponding score prior to treatment.

33. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-32, wherein the patient is in remission of depressive symptoms at day 28 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, the remission of depressive symptoms being assessed as a MADRS score of equal to or less than 10 or a HAM-D score of equal to or less than 7.

34. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-33, wherein the patient is a lactating woman who is advised to stop breast feeding until 48 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

35. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-33, wherein the patient is a lactating woman who is advised to stop breast feeding until 24 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

36. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-33, wherein the patient is a lactating woman who is advised to stop breast feeding until 6 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

37. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of any one of claims 1 to 33, wherein the patient is a lactating woman who is advised to stop breast feeding until 3 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

38. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-33, wherein the patient is a lactating woman who is advised to stop breast feeding until 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

39. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to aspects 1 to 38, wherein the treatment improves maternal function.

40. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 39, wherein the improvement relates to one or more, in particular two or more, functional areas selected from self-care, baby care, mother-child interaction, mental health of the mother, social support, management and regulation according to Barkin mother's functional index (BIMF).

41. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspect 39 or 40, wherein BIMF score is improved by 10% or more, preferably 20% or more.

Specific aspects of bipolar disorder treatment are listed below.

A 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use in the treatment of a patient diagnosed with bipolar disorder, wherein the 5-MeO-DMT is administered via an intravenous, intramuscular or subcutaneous route, and wherein the patient is a breast feeding mother who is advised to stop breast feeding until 48 hours, such as 24 hours, preferably 6 hours, more preferably 3 hours, most preferably 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

2. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to aspect 1, wherein the patient is diagnosed with bipolar disorder type II.

3. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to aspect 1, wherein the patient is diagnosed with bipolar disorder type I.

4. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to aspects 1 to 3, wherein the patient suffers from a current major depressive episode.

5. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspect 4, wherein the patient has a montgomery-asberg depression rating scale (MADRS) total score equal to or greater than 19, such as equal to or greater than 24, in particular equal to or greater than 37.

6. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to aspect 4 or aspect 5, wherein the patient's Bipolar Depression Rating Scale (BDRS) has a total score equal to or greater than 19, such as equal to or greater than 24, in particular equal to or greater than 37.

7. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to aspects 1 to 6, wherein the patient is not substantially improved after at least two substantial courses of treatment.

8. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-6, wherein the patient is not substantially improved after at least two substantial courses of treatment, wherein at least one of the two courses of treatment is a drug therapy.

9. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to aspects 1 to 6, wherein the patient is not substantially improved after at least two substantial drug courses.

10. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to aspects 1 to 9, wherein the patient has a total score of less than or equal to 8 on the Yankee Mania Rating Scale (YMRS).

11. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1 to 10, wherein the 5-MeO-DMT or salt thereof is administered at a dose or dose regimen that causes the patient to experience a peak fantasy experience.

12. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use as described in aspects 1 to 11, wherein a dose of about 1 mg to about 10 mg of 5-MeO-DMT is administered, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.

13. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 11, wherein a dose of about 2 mg, or about 5 mg, or about 8mg is administered, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered instead of 5-MeO-DMT.

14. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 11, wherein a dose of about 1mg, or about 2 mg, or about 3mg is administered, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered instead of 5-MeO-DMT.

15. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 12, wherein the 5-MeO-DMT or salt thereof is administered in a first dose at a first administration and the 5-MeO-DMT or salt thereof is administered in zero to six subsequent administrations, wherein each subsequent administration uses a higher dose than the previous administration unless the patient experiences a peak fantasy experience.

16. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-12 or 15, wherein the 5-MeO-DMT is administered at a dose of about 1 mg to about 3 mg when administered for the first time, then increased to a dose of about 4 mg to about 6 mg when administered for the second time unless the patient has experienced a peak vagal experience, then increased to a dose of about 7 mg to about 9 mg when administered for the third time unless the patient has experienced a peak vagal experience, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.

17. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 16, wherein the first dose of 5-MeO-DMT is about 2 mg, the second dose of 5-MeO-DMT is about 5 mg, and the third dose of 5-MeO-DMT is about 8mg, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.

18. The 5-MeO-DMT for use of aspects 1-12 or 15, or a pharmaceutically acceptable salt thereof, wherein the 5-MeO-DMT is administered at a dose of about 0.5 mg to about 1.5 mg when administered for the first time, then increases to a dose of about 1.5 mg to about 2.5 mg when administered for the second time unless the patient has experienced a peak vagal experience, then increases to a dose of about 2.5 mg to about 3.5 mg when administered for the third time unless the patient has experienced a peak vagal experience, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.

19. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 18, wherein the first dose of 5-MeO-DMT is about 1mg, the second dose of 5-MeO-DMT is about 2 mg, and the third dose of 5-MeO-DMT is about 3 mg, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.

20. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to aspects 15 to 19, wherein the interval between two administrations is not less than 1 hour and not more than 24 hours, such as about 1 to 4 hours, preferably 1 to 2 hours.

21. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use as in aspects 11-20, wherein the occurrence of peak fantasy experience is identified by reaching at least 60% of the highest possible score in each of the four sub-scales (mystery, active emotion, override time and space, and self-evident) of the 30 project revised mystery experience questionnaire (MEQ 30), or by reaching at least 60% of the highest possible score of the marine-like borderless (OBN) dimension in the state of consciousness change (ASC) questionnaire, or by reaching at least 75 Peak Experience Scale (PES) total score.

22. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 21, wherein the occurrence of peak illusion experience is identified by reaching a Peak Experience Scale (PES) score of at least 75.

23. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of any one of the preceding aspects, wherein the 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, is administered via intravenous injection.

24. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 23, wherein a clinical response reflected as a decrease in clinical overall impression-severity (CGI-S) score occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

25. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 24, wherein a clinical response is observed at day 1, e.g. about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, said clinical response being reflected in a decrease in the clinical overall impression-severity (CGI-S) score.

26. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspect 1 or 25, wherein the clinical response is continued until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, said clinical response being reflected in a decrease in the clinical global impression-severity (CGI-S) score.

27. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 26, wherein the clinical response is continued until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, said clinical response being reflected in a decrease in the clinical global impression-severity (CGI-S) score.

28. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-27, wherein the clinical response is continued until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the clinical response being reflected in a decrease in the clinical overall impression-severity (CGI-S) score.

29. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-28, wherein a clinical response occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, said clinical response being reflected in an improvement in MADRS or HAM-D score of at least 50% compared to the corresponding score prior to treatment.

30. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-29, wherein the alleviation of symptoms of depression, reflected in BDRS scores equal to or less than 10, madrs scores equal to or less than 10, or HAM-D scores equal to or less than 7, occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

31. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 30, wherein a clinical response is observed on day 1, e.g. about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, said clinical response being reflected in an improvement of at least 50% in MADRS or HAM-D score compared to the corresponding score before treatment.

32. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 31, wherein on day 1 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, a relief of depressive symptoms is observed, for example about 24 hours, reflected in a BDRS score equal to or less than 10, a madrs score equal to or less than 10, or a HAM-D score equal to or less than 7.

33. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-32, wherein the clinical response is continued until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, said clinical response being reflected in an improvement of at least 50% in MADRS or HAM-D scores compared to the corresponding scores before treatment.

34. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-33, wherein a clinical response is present at day 7 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, said clinical response being reflected in an improvement of at least 75% in MADRS or HAM-D scores compared to the corresponding scores prior to treatment.

35. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-34, wherein the patient is in a state of remission of depressive symptoms at day 7 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the remission of depressive symptoms being reflected in BDRS scores equal to or less than 10, madrs scores equal to or less than 10, or HAM-D scores equal to or less than 7.

36. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-35, wherein the clinical response is continued until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, said clinical response being reflected in an improvement of at least 50% in MADRS or HAM-D scores compared to the corresponding scores before treatment.

37. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-36, wherein a clinical response is present at day 14 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, said clinical response being reflected in an improvement of at least 75% in MADRS or HAM-D scores compared to the corresponding scores prior to treatment.

38. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-37, wherein the patient is in a state of remission of depressive symptoms at day 14 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, the remission of depressive symptoms being reflected in BDRS scores equal to or less than 10, madrs scores equal to or less than 10, or HAM-D scores equal to or less than 7.

39. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 38, wherein the clinical response is continued until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, said clinical response being reflected in an improvement of at least 50% in MADRS or HAM-D scores compared to the corresponding scores before treatment.

40. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-39, wherein a clinical response is present at day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, said clinical response being reflected in a BDRS; MADRS or HAM-D score improvement of at least 75% compared to the corresponding score prior to treatment.

41. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-40, wherein the patient is in a state of remission of depressive symptoms at day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the remission of depressive symptoms being reflected in BDRS scores equal to or less than 10, madrs scores equal to or less than 10, or HAM-D scores equal to or less than 7.

42. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to aspects 1 to 41, wherein the patient does not experience mania or hypomania caused by treatment.

43. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 42, wherein the patient has a total score of less than or equal to 15, preferably less than or equal to 12, on the Yankee Mania Rating Scale (YMRS) at about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

44. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 43, wherein the patient has a total score of less than or equal to 15, preferably less than or equal to 12 on the Young Mania Rating Scale (YMRS) at day 1, e.g. at about 24 hours, of evaluation after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

45. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 44, wherein the patient has a total score of less than or equal to 15, preferably less than or equal to 12, on the Yankee Mania Rating Scale (YMRS) at the time of evaluation on day 7 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

46. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 45, wherein the patient has a total score of less than or equal to 15, preferably less than or equal to 12, on the Yankee Mania Rating Scale (YMRS) at the 14 th day after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

47. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to aspects 1 to 46, wherein the patient has a total score of less than or equal to 15, preferably less than or equal to 12, on the Yankee Mania Rating Scale (YMRS) at the time of evaluation on day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

48. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-47, wherein the treatment results in an improvement in at least one of sleep disorders, bradykinesia, negative thinking, anxiety, cognitive dysfunction, and social/emotional withdrawal or deficits.

49. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-48, wherein the patient suffers from a sleep disorder and the treatment reduces or eliminates the sleep disorder.

50. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 49, wherein the patient suffers from insomnia and the treatment reduces or eliminates insomnia.

51. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 49, wherein the patient suffers from excessive sleep and the treatment reduces or eliminates excessive sleep.

52. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 49-51, wherein the reduction or elimination of sleep disturbance is reflected at least in an improvement in the score of sleep disturbance as item BDRS at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

53. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 49-52, wherein the reduction or elimination of sleep disturbance is reflected at least in an improvement in the score of item BDRS of sleep disturbance at day 7 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

54. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 49-53, wherein the reduction or elimination of sleep disturbance is reflected at least in an improvement in the score of item BDRS of sleep disturbance at day 14 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

55. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 49-54, wherein the reduction or elimination of sleep disturbance is reflected at least in an improvement in the score of item BDRS of sleep disturbance at day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

56. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 49, wherein the reduction or elimination of sleep disturbance occurs no later than about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score of the sleep disturbance of item BDRS.

57. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 56, wherein the reduction or elimination of sleep disorder persists until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score for sleep disorder under item BDRS.

58. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 56, wherein the reduction or elimination of sleep disorder persists until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score for sleep disorder under item BDRS.

59. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 56, wherein the reduction or elimination of sleep disorder persists until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score for sleep disorder under item BDRS.

60. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 49, wherein the sleep disorder is reduced sleep and the reduction or elimination of sleep disorder is reflected at least in an improvement in the score of reduced sleep for the MADRS project at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

61. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 49 or 60, wherein the sleep disorder is reduced sleep and the reduction or elimination of sleep disorder is reflected at least in an improvement in the score of the reduced sleep of the MADRS project at day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

62. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 49, 60, or 61, wherein the sleep disorder is reduced sleep and the reduction or elimination of sleep disorder is reflected at least in an improvement in the score of the reduction in MADRS project sleep at day 14 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

63. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 49 or 60-62, wherein the sleep disorder is reduced sleep and the reduction or elimination of sleep disorder is reflected at least in an improvement in the score of the reduction in MADRS project sleep at day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

64. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 49, wherein the sleep disorder is reduced sleep and the reduction or elimination of sleep disorder occurs no later than about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the reduction or elimination reflecting an improvement in the score for reduced sleep for the MADRS program.

65. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 64, wherein the sleep disorder is reduced sleep and the reduction or elimination of sleep disorder continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination reflects an improvement in the score for reduced sleep for the MADRS project.

66. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 64, wherein the sleep disorder is reduced sleep and the reduction or elimination of sleep disorder continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination reflects an improvement in the score for reduced sleep for the MADRS project.

67. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 64, wherein the sleep disorder is reduced sleep and the reduction or elimination of sleep disorder continues until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination reflects an improvement in the score for reduced sleep for the MADRS project.

68. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 49, wherein the patient suffers from a sleep disorder and the improvement in sleep disorder is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

69. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 49 or 68, wherein the patient suffers from a sleep disorder and the improvement in sleep disorder is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 7 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

70. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 49, 68, or 69, wherein the patient suffers from a sleep disorder and improvement in sleep disorder is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 14 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

71. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 49 or 68-70, wherein the patient suffers from a sleep disorder and the improvement in sleep disorder is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

72. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-48, wherein the patient suffers from a sleep disorder and improvement in the sleep disorder occurs no later than about 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical overall impression-severity (CGI-S) score.

73. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 72, wherein the improvement in sleep disorder persists until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical global impression-severity (CGI-S) score.

74. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 72, wherein the improvement in sleep disorder persists until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical global impression-severity (CGI-S) score.

75. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 72, wherein the improvement in sleep disorder persists until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical global impression-severity (CGI-S) score.

76. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-48, wherein the patient suffers from a sleep disorder and the reduction or elimination of a sleep disorder is reflected in an improvement in the overall score of the Pittsburgh Sleep Quality Index (PSQI) at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, wherein the recall period is from the point in time when the acute illusive experience subsides after the last administration to the point in time of evaluation.

77. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-48 or 76, wherein the patient suffers from a sleep disorder and the reduction or elimination of a sleep disorder is reflected in an improvement in the overall score of the Pittsburgh Sleep Quality Index (PSQI) on day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, wherein the recall period is from the point in time when the acute illusive experience subsides after the last administration to the point in time of evaluation.

78. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-48, 76, or 77, wherein the patient suffers from a sleep disorder and the reduction or elimination of a sleep disorder is reflected in an improvement in the total score of the Pittsburgh Sleep Quality Index (PSQI) on day 14 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, wherein the recall period is from the point in time when the acute illusive experience subsides after the last administration to the point in time of evaluation.

79. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-48 or 76-78, wherein the patient suffers from a sleep disorder and the reduction or elimination of a sleep disorder is reflected in an improvement in the total score of the Pittsburgh Sleep Quality Index (PSQI) at day 28 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, wherein the recall period is from the point in time when the acute illusive experience subsides after the last administration to the point in time of evaluation.

80. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 49, wherein the patient suffers from a sleep disorder and the reduction or elimination of the sleep disorder occurs no later than about 24 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, the reduction or elimination being reflected as an improvement in the overall score of the Pittsburgh Sleep Quality Index (PSQI), wherein the recall period is from the point in time when the acute illusive experience subsides after the last administration to the point in time of evaluation.

81. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect or 80, wherein the patient suffers from a sleep disorder and the reduction or elimination of sleep disorder continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the reduction or elimination being reflected as an improvement in the overall score of the Pittsburgh Sleep Quality Index (PSQI), wherein the recall period is from the point in time when the acute illusive experience subsides after the last administration to the point in time of evaluation.

82. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect or 80, wherein the patient suffers from a sleep disorder and the reduction or elimination of sleep disorder continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the reduction or elimination being reflected as an improvement in the overall score of the Pittsburgh Sleep Quality Index (PSQI), wherein the recall period is from the point in time when the acute illusive experience subsides after the last administration to the point in time of evaluation.

83. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect or 80, wherein the patient suffers from a sleep disorder and the reduction or elimination of sleep disorder continues until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the reduction or elimination being reflected as an improvement in the overall score of the Pittsburgh Sleep Quality Index (PSQI), wherein the recall period is from the point in time when the acute illusive experience subsides after the last administration to the point in time of evaluation.

84. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-83, wherein the patient suffers from mental retardation and the treatment reduces or eliminates the mental retardation.

85. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 84, wherein the treatment improves or eliminates reduced energy and activity and/or reduced power.

86. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 84 or 85, wherein the reduction or elimination of mental retardation is reflected at least in an improvement in the score of the reduced energy and activity and/or reduced power of item BDRS hours following the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

87. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 84-86, wherein the reduction or elimination of mental retardation is reflected at least in an improvement in the score of reduced energy and activity and/or reduced power, e.g., item BDRS, at day 1 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

88. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 84-87, wherein the reduction or elimination of mental retardation is reflected at least in an improvement in the score of the BDRS items of reduced energy and activity and/or reduced power at day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

89. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 84-88, wherein the reduction or elimination of mental retardation is reflected at least in an improvement in the score of the BDRS items of reduced energy and activity and/or reduced power at day 14 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

90. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 84-89, wherein the reduction or elimination of mental retardation is reflected at least in an improvement in the score of the BDRS items of reduced energy and activity and/or reduced power at day 28 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

91. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 84 or 85, wherein the reduction or elimination of mental retardation occurs no later than about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score of the project BDRS for reduced energy and activity and/or reduced power.

92. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 91, wherein the reduction or elimination of mental retardation continues until at least 6 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score of the project BDRS for reduced energy and activity and/or reduced power.

93. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 91, wherein the reduction or elimination of mental retardation continues until at least 14 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score of the project BDRS for reduced energy and activity and/or reduced power.

94. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 91, wherein the reduction or elimination of mental retardation continues until at least 28 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score of the project BDRS for reduced energy and activity and/or reduced power.

95. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 84, wherein the reduction or elimination of mental retardation is reflected at least in an improvement in the score of MADRS project lazy about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

96. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 84 or 95, wherein said reduction or elimination of mental retardation is reflected at least in an improvement in the score of MADRS project lazy at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

97. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 84, 95, or 96, wherein the reduction or elimination of mental retardation is reflected at least in an improvement in the score of MADRS project lazy at day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

98. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 84 or 95-97, wherein the reduction or elimination of mental retardation is reflected at least in an improvement in the score of MADRS project lazy at day 14 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

99. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 84 or 95-98, wherein the reduction or elimination of mental retardation is reflected at least in an improvement in the score of MADRS project lazy at day 28 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

100. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 84, wherein the reduction or elimination of mental retardation occurs no later than about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination reflects an improvement in the score of MADRS project lazy.

101. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 100, wherein the reduction or elimination of mental retardation continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score of MADRS project lazy.

102. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 100, wherein the reduction or elimination of mental retardation continues until at least 14 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score of MADRS project lazy.

103. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 100, wherein the reduction or elimination of mental retardation continues until at least 28 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score of MADRS project lazy.

104. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 84, wherein the patient suffers from bradykinesia and improvement in bradykinesia is reflected in a decrease in clinical overall impression-severity (CGI-S) score about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

105. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 84 or 104, wherein the patient suffers from bradykinesia and improvement in bradykinesia is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

106. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 84, 104, or 105, wherein the patient suffers from bradykinesia and improvement in bradykinesia is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 7 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

107. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 84 or 104-106, wherein the patient suffers from bradykinesia and improvement in bradykinesia is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 14 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

108. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 84 or 104-107, wherein the patient suffers from bradykinesia and improvement in bradykinesia is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

109. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-83, wherein the patient suffers from bradykinesia and improvement in bradykinesia occurs no later than about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, said improvement being reflected in a decrease in clinical global impression-severity (CGI-S) score.

110. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 109, wherein the improvement in mental retardation continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical global impression-severity (CGI-S) score.

111. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 109, wherein the improvement in mental retardation continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical global impression-severity (CGI-S) score.

112. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 109, wherein the improvement in mental retardation continues until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which improvement is reflected in a decrease in clinical global impression-severity (CGI-S) score.

113. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-112, wherein the patient suffers from negative thoughts and the treatment reduces or eliminates the negative thoughts.

114. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 113, wherein the treatment reduces or eliminates a feeling of invalidity, a feeling of helplessness and helplessness, and/or a feeling of guilt.

115. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to aspects 113 or 114, wherein said reduction or elimination of negative thinking is reflected at least in the invaluable, helplessness and prestige, and/or improvement in the score of guilt about 2 hours BDRS project after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

116. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to aspects 113-115, wherein said reduction or elimination of negative thoughts is reflected at least in the invaluable, helplessness and hopeless, and/or improvement in the score of guilt on day 1 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, e.g., item BDRS.

117. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of any one of aspects 113-116, wherein said reduction or elimination of negative thinking is reflected at least in the invaluable, helplessness and prestige items BDRS on day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, and/or improvement in the score of guilt.

118. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of any one of aspects 113-117, wherein said reduction or elimination of negative thinking is reflected at least in the invaluable, helplessness and prestige items BDRS on day 14 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, and/or improvement in the score of guilt.

119. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of any one of aspects 113-118, wherein said reduction or elimination of negative thinking is reflected at least in the invaluable, helplessness and prestige, and/or improvement in the score of guilt at 28 days BDRS after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

120. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 113 or 114, wherein the reduction or elimination of negative thoughts occurs no later than about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in the invaluable, helplessness and prestige items BDRS, and/or improvement in the score of guilt.

121. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 120, wherein the reduction or elimination of negative thoughts continues until at least 6 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in the non-value of item BDRS, the helplessness and the hopelessness, and/or the improvement in the score of guilt.

122. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 120, wherein the reduction or elimination of negative thoughts continues until at least 14 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in the non-value of item BDRS, the helplessness and the hopelessness, and/or the improvement in the score of guilt.

123. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 120, wherein the reduction or elimination of negative thoughts continues until at least 28 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in the non-value of item BDRS, the helplessness and the hopelessness, and/or the improvement in the score of guilt.

124. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 113 or 114, wherein the reduction or elimination of negative thinking is reflected at least in an improvement in the score of the pessimistic ideas of the MADRS project about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

125. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 113, 114, or 124, wherein the reduction or elimination of negative thoughts is reflected at least in an improvement in the score of pessimistic ideas of the MADRS project, e.g., about 24 hours, at day 1 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

126. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 113, 114, 124, or 125, wherein the reduction or elimination of negative thoughts is reflected at least in an improvement in the score of the pessimistic ideas of the MADRS project at day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

127. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 113, 114, or 124-126, wherein the reduction or elimination of negative thoughts is reflected at least in an improvement in the score of the pessimistic ideas of the MADRS project at day 14 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

128. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 113, 114, or 124-127, wherein the reduction or elimination of negative thoughts is reflected at least in an improvement in the score of the pessimistic ideas of the MADRS project at day 28 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

129. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 113 or 114, wherein the reduction or elimination of negative thoughts occurs no later than about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination reflects an improvement in the score of pessimistic thoughts for the MADRS project.

130. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 129, wherein the reduction or elimination of negative thinking continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof reflects an improvement in the score of pessimistic ideas for the MADRS project.

131. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 129, wherein the reduction or elimination of negative thinking continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination reflects an improvement in the score of pessimistic ideas for the MADRS project.

132. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 129, wherein the reduction or elimination of negative thinking continues until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination reflects an improvement in the score of pessimistic ideas for the MADRS project.

133. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of claim 113 or 114, wherein said reduction or elimination of negative thinking is reflected at least in an improvement in the score of the guilt sensation in the BPRS project about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

134. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 113, 114, or 133, wherein said reduction or elimination of negative cravings is reflected at least in an improvement in the score of, e.g., about 24 hours BPRS project guilt feel at day 1 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

135. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 113, 114, 133, or 134, wherein said reduction or elimination of negative craving is reflected at least in an improvement in the score of the guilt sensation of the BPRS project at day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

136. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 113, 114, or 133-135, wherein said reduction or elimination of negative craving is reflected at least in an improvement in the score of the guilt sensation of the BPRS project at day 14 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

137. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 113, 114, or 133-136, wherein said reduction or elimination of negative craving is reflected at least in an improvement in the score of the guilt sensation of the BPRS project at day 28 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

138. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 113 or 114, wherein said reduction or elimination of negative thoughts occurs no later than about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, said reduction or elimination reflecting an improvement in the score of guilt sensation in the BPRS project.

139. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 138, wherein said reduction or elimination of negative thinking continues until at least 6 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, said reduction or elimination reflecting an improvement in the score of guilt sensation in the BPRS project.

140. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 138, wherein said reduction or elimination of negative thinking continues until at least 14 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, said reduction or elimination reflecting an improvement in the score of guilt feel in the BPRS project.

141. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 138, wherein said reduction or elimination of negative thinking continues until at least 28 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, said reduction or elimination reflecting an improvement in the score of guilt sensation in the BPRS project.

142. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 113 or 114, wherein the patient suffers from negative thoughts and improvement in negative thoughts is reflected in a decrease in clinical overall impression-severity (CGI-S) score about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

143. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 113, 114 or 142, wherein the patient suffers from negative thoughts and improvement in negative thoughts is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

144. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 113, 114, 142, or 143, wherein the patient suffers from negative thinking and improvement in negative thinking is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

145. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 113, 114, or 142-144, wherein the patient suffers from negative thinking and improvement in negative thinking is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 14 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

146. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 113, 114, or 142-145, wherein the patient suffers from negative thinking and improvement in negative thinking is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

147. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-112, wherein the patient suffers from negative thoughts and improvement in negative thoughts occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical overall impression-severity (CGI-S) score.

148. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 147, wherein the improvement in negative thinking continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical overall impression-severity (CGI-S) score.

149. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 147, wherein the improvement in negative thinking continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical overall impression-severity (CGI-S) score.

150. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 147, wherein the improvement in negative thinking continues until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical overall impression-severity (CGI-S) score.

151. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1 to 150, wherein the patient suffers from anxiety and the treatment reduces or eliminates the anxiety.

152. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of claim 151, wherein the reduction or elimination of anxiety is reflected at least in an improvement in the score of item BDRS of anxiety 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

153. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 151 or 152, wherein the reduction or elimination of anxiety is reflected at least in an improvement in the score of anxiety as set forth in item BDRS at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

154. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 151-153, wherein the reduction or elimination of anxiety is reflected at least in an improvement in the score of item BDRS at day 7 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

155. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 151-154, wherein the reduction or elimination of anxiety is reflected at least in an improvement in the score of item BDRS at day 14 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

156. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 151-155, wherein the reduction or elimination of anxiety is reflected at least in an improvement in the score of item BDRS at day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

157. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 151, wherein the reduction or elimination of anxiety occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score of item BDRS anxiety.

158. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 157, wherein the reduction or elimination of anxiety persists until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score of item BDRS anxiety.

159. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 157, wherein the reduction or elimination of anxiety persists until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score of item BDRS anxiety.

160. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 157, wherein the reduction or elimination of anxiety persists until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination reflects an improvement in the score of item BDRS anxiety.

161. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 151, wherein the reduction or elimination of anxiety is reflected at least in an improvement in the score of BPRS project anxiety about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

162. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 151 or 161, wherein the reduction or elimination of anxiety is reflected at least in an improvement in the score of BPRS project anxiety at day 1 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

163. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 151, 161, or 162, wherein the reduction or elimination of anxiety is reflected at least in an improvement in the score of the BPRS project anxiety at day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

164. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 151 or 161-163, wherein the reduction or elimination of anxiety is reflected at least in an improvement in the score of BPRS project anxiety at day 14 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

165. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 151 or 161-164, wherein the reduction or elimination of anxiety is reflected at least in an improvement in the score of BPRS project anxiety at day 28 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

166. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 151, wherein the reduction or elimination of anxiety occurs no later than about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score of anxiety for the BPRS project.

167. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 166, wherein the reduction or elimination of anxiety persists until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination reflects an improvement in the score of anxiety for the BPRS project.

168. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 166, wherein the reduction or elimination of anxiety persists until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination reflects an improvement in the score of anxiety for the BPRS project.

169. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 166, wherein the reduction or elimination of anxiety persists until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination reflects an improvement in the score of anxiety for the BPRS project.

170. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 151, wherein the patient suffers from anxiety and the improvement in anxiety is reflected in a decrease in clinical overall impression-severity (CGI-S) score about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

171. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 151 or 170, wherein the patient suffers from anxiety and the improvement in anxiety is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

172. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 151, 170, or 171, wherein the patient suffers from anxiety and the improvement in anxiety is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

173. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 151 or 170-172, wherein the patient suffers from anxiety and the improvement in anxiety is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 14 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

174. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 151 or 170-173, wherein the patient suffers from anxiety and the improvement in anxiety is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 28 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

175. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-150, wherein the patient suffers from anxiety and improvement in anxiety occurs no later than about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical overall impression-severity (CGI-S) score.

176. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 175, wherein the improvement in anxiety persists until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical overall impression-severity (CGI-S) score.

177. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 175, wherein the improvement in anxiety persists until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical overall impression-severity (CGI-S) score.

178. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 175, wherein the improvement in anxiety persists until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical overall impression-severity (CGI-S) score.

179. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-178, wherein the patient suffers from cognitive dysfunction and the treatment reduces or eliminates the cognitive dysfunction.

180. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 179, wherein the reduction or elimination of cognitive dysfunction is reflected at least in an improvement in the score of the concentration and memory impairment of item BDRS about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

181. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 179 or 180, wherein the reduction or elimination of cognitive dysfunction is reflected at least in an improvement in the score of impaired concentration and memory for items BDRS, e.g., about 24 hours, at day 1 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

182. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 179 to 181, wherein the reduction or elimination of cognitive dysfunction is reflected at least in an improvement in the score of BDRS items concentration and memory impairment at day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

183. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 179-182, wherein the reduction or elimination of cognitive dysfunction is reflected at least in an improvement in the score of BDRS items concentration and memory impairment at day 14 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

184. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 179-183, wherein the reduction or elimination of cognitive dysfunction is reflected at least in an improvement in the score of BDRS items concentration and memory impairment at day 28 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

185. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 179, wherein the reduction or elimination of cognitive dysfunction occurs no later than about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score for the BDRS project concentration and memory impairment.

186. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 185, wherein the reduction or elimination of cognitive dysfunction continues until at least 6 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score of the BDRS project concentration and memory impairment.

187. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 185, wherein the reduction or elimination of cognitive dysfunction continues until at least 14 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score of the BDRS project concentration and memory impairment.

188. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 185, wherein the reduction or elimination of cognitive dysfunction continues until at least 28 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score of the BDRS project concentration and memory impairment.

189. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of claim 179, wherein the reduction or elimination of cognitive dysfunction is reflected at least in an improvement in scores that are hard to focus on by the MADRS program about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

190. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 179 or 189, wherein the reduction or elimination of cognitive dysfunction is reflected at least in an improvement in the score that is hard to concentrate on day 1 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, e.g., for about 24 hours, the MADRS program.

191. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of claim 179, 189 or 190, wherein the reduction or elimination of cognitive dysfunction is reflected at least in an improvement in the score that MADRS project is refractory to attention at day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

192. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of any one of aspects 179 or 189-191, wherein the reduction or elimination of cognitive dysfunction is reflected at least in an improvement in the score that the MADRS project is refractory to on day 14 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

193. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of any one of aspects 179 or 189-192, wherein the reduction or elimination of cognitive dysfunction is reflected at least in an improvement in the score that MADRS project is refractory to attention at day 28 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

194. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 179, wherein the reduction or elimination of cognitive dysfunction occurs no later than about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination reflects an improvement in scores that are refractory to MADRS programs.

195. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 194, wherein the reduction or elimination of cognitive dysfunction continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination reflects an improvement in the score that is refractory to the MADRS program.

196. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 194, wherein the reduction or elimination of cognitive dysfunction continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination reflects an improvement in the score that is refractory to the MADRS program.

197. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 194, wherein the reduction or elimination of cognitive dysfunction continues until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination reflects an improvement in the score that is refractory to the MADRS program.

198. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 179, wherein the patient suffers from cognitive dysfunction and improvement in cognitive dysfunction is reflected in a decrease in clinical overall impression-severity (CGI-S) score about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

199. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 179 or 198, wherein the patient suffers from cognitive dysfunction and improvement in cognitive dysfunction is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

200. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 179, 198, or 199, wherein the patient suffers from cognitive dysfunction and improvement in cognitive dysfunction is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 7 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

201. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 179 or 198-200, wherein the patient suffers from cognitive dysfunction and improvement in cognitive dysfunction is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 14 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

202. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 179 or 198-201, wherein the patient suffers from cognitive dysfunction and improvement in cognitive dysfunction is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 28 following the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

203. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-178, wherein the patient suffers from cognitive dysfunction and improvement in cognitive dysfunction occurs no later than about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical overall impression-severity (CGI-S) score.

204. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 203, wherein the improvement in cognitive dysfunction persists until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical global impression-severity (CGI-S) score.

205. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 203, wherein the improvement in cognitive dysfunction persists until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical global impression-severity (CGI-S) score.

206. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 203, wherein the improvement in cognitive dysfunction persists until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which improvement is reflected in a decrease in clinical global impression-severity (CGI-S) score.

207. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-206, wherein the patient suffers from social/emotional withdrawal or distraction, and the treatment reduces or eliminates the social/emotional withdrawal or distraction.

208. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of claim 207, wherein the treatment reduces or eliminates at least one of a loss of hedonia, emotional withdrawal, and emotional frigidity.

209. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207 or 208, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of BDRS items of hedonia, emotional withdrawal, and/or emotional frigidity about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

210. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207-209, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of e.g., about 24 hours BDRS of lack of hedonia, emotional withdrawal, and/or emotional frigidity at day 1 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

211. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207-210, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of the BDRS items hedonia, emotional withdrawal, and/or emotional frigidity at day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

212. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207-211, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of the BDRS items hedonia, emotional withdrawal, and/or emotional frigidity at day 14 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

213. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207-212, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of the BDRS items hedonia, emotional withdrawal, and/or emotional frigidity at day 28 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

214. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207 or 208, wherein said reduction or elimination of social/emotional withdrawal or distraction occurs no later than about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, said reduction or elimination reflecting an improvement in the score of the BDRS items hedonia, emotional withdrawal, and/or emotional frigidity.

215. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 214, wherein the reduction or elimination of social/emotional withdrawal or distraction continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the reduction or elimination reflecting an improvement in the score of the BDRS items hedonia, emotional withdrawal, and/or emotional frigidity.

216. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 214, wherein the reduction or elimination of social/emotional withdrawal or distraction continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the reduction or elimination reflecting an improvement in the score of the BDRS items for hedonia, emotional withdrawal, and/or emotional frigidity.

217. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 214, wherein the reduction or elimination of social/emotional withdrawal or distraction continues until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the reduction or elimination reflecting an improvement in the score of the BDRS items hedonia, emotional withdrawal, and/or emotional frigidity.

218. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 207 or 208, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of MADRS project sensory deficit about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

219. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 207, 208, or 218, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of MADRS project sensory deficit at day 1 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, e.g., about 24 hours.

220. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207, 208, 218, or 219, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of MADRS project sensory deficit at day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

221. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207, 208, or 218 to 220, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of MADRS project sensory deficit at day 14 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

222. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207, 208, or 218 to 221, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of MADRS project sensory deficit at day 28 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

223. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 207 or 208, wherein said reduction or elimination of social/emotional withdrawal or distraction occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, said reduction or elimination reflecting an improvement in the score for MADRS project sensory deficit.

224. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 223, wherein the reduction or elimination of social/emotional withdrawal or distraction continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the reduction or elimination reflecting an improvement in the score for MADRS project sensory deficit.

225. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 223, wherein the reduction or elimination of social/emotional withdrawal or distraction continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the reduction or elimination reflecting an improvement in the score for MADRS project sensory deficit.

226. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 223, wherein the reduction or elimination of social/emotional withdrawal or distraction continues until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the reduction or elimination reflecting an improvement in the score for MADRS project sensory deficit.

227. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207 or 208, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of the emotional withdrawal of the BPRS project about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

228. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 207, 208, or 227, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of the emotional withdrawal of the BPRS project at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

229. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207, 208, 227, or 228, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of the emotional withdrawal of the BPRS project at day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

230. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207, 208, or 227-229, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of the emotional withdrawal of the BPRS project at day 14 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

231. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207, 208, or 227-230, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of the emotional withdrawal of the BPRS project at day 28 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

232. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207 or 208, wherein said reduction or elimination of social/emotional withdrawal or distraction occurs no later than about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, said reduction or elimination reflecting an improvement in the score of emotional withdrawal for the BPRS project.

233. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 232, wherein the reduction or elimination of social/emotional withdrawal or distraction continues until at least 6 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, the reduction or elimination reflecting an improvement in the score of emotional withdrawal for the BPRS project.

234. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 232, wherein the reduction or elimination of social/emotional withdrawal or distraction continues until at least 14 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, the reduction or elimination reflecting an improvement in the score of emotional withdrawal for the BPRS project.

235. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 232, wherein the reduction or elimination of social/emotional withdrawal or distraction continues until at least 28 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, the reduction or elimination reflecting an improvement in the score of emotional withdrawal for the BPRS project.

236. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207 or 208, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of BPRS project emotional dullness about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

237. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 207, 208, or 236, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of emotional retardation of the BPRS project at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

238. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207, 208, 236, or 237, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of BPRS project emotional dullness at day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

239. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207, 208, or 236-238, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of BPRS project emotional dullness at day 14 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

240. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207, 208, or 236-239, wherein said reduction or elimination of social/emotional withdrawal or distraction is reflected at least in an improvement in the score of BPRS project emotional dullness at day 28 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

241. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207 or 208, wherein said reduction or elimination of social/emotional withdrawal or distraction occurs no later than about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, said reduction or elimination reflecting an improvement in the score of the emotional dullness of the BPRS program.

242. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 241, wherein the reduction or elimination of social/emotional withdrawal or distraction continues until at least 6 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, the reduction or elimination reflecting an improvement in the score of the emotional retardation of the BPRS project.

243. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 241, wherein the reduction or elimination of social/emotional withdrawal or distraction continues until at least 14 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, the reduction or elimination reflecting an improvement in the score of the emotional retardation of the BPRS project.

244. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 241, wherein the reduction or elimination of social/emotional withdrawal or distraction continues until at least 28 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, the reduction or elimination reflecting an improvement in the score of the emotional retardation of the BPRS project.

245. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 207 or 208, wherein the patient suffers from social/emotional withdrawal or distraction and improvement in social/emotional withdrawal or distraction is reflected in a decrease in clinical overall impression-severity (CGI-S) score about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

246. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 207, 208 or 245, wherein the patient suffers from social/emotional withdrawal or distraction and an improvement in social/emotional withdrawal or distraction is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

247. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207, 208, 245, or 246, wherein the patient suffers from social/emotional withdrawal or distraction and improvement in social/emotional withdrawal or distraction is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

248. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207, 208, or 245-247, wherein the patient suffers from social/emotional withdrawal or distraction and improvement in social/emotional withdrawal or distraction is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 14 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

249. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 207, 208, or 245 to 248, wherein the patient suffers from social/emotional withdrawal or distraction and improvement in social/emotional withdrawal or distraction is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 28 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

250. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-206, wherein the patient suffers from social/emotional withdrawal or distraction and improvement in social/emotional withdrawal or distraction occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected at least in a decrease in clinical overall impression-severity (CGI-S) score.

251. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 250, wherein the improvement in social/emotional withdrawal or distraction continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected at least in a decrease in clinical global impression-severity (CGI-S) score.

252. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 251, wherein the improvement in social/emotional withdrawal or distraction continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected at least in a decrease in clinical global impression-severity (CGI-S) score.

253. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 251, wherein the improvement in social/emotional withdrawal or distraction continues until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected at least in a decrease in clinical global impression-severity (CGI-S) score.

254. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-253, wherein the treatment reduces or eliminates suicidal ideation.

255. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of claim 254, wherein the reduction or elimination of suicidal ideation is reflected at least in an improvement in the score of item BDRS of suicidal ideation about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

256. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 254 or 255, wherein said reduction or elimination of suicide concept is reflected at least in an improvement in the score of item BDRS suicide concept on day 1 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for example about 24 hours.

257. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 254-256, wherein the reduction or elimination of suicidal ideation is reflected at least in an improvement in the score of item BDRS of suicidal ideation at day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

258. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 254-257, wherein the reduction or elimination of suicidal ideation is reflected at least in an improvement in the score of item BDRS of suicidal ideation at day 14 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

259. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 254-258, wherein the reduction or elimination of suicidal ideation is reflected at least in an improvement in the score of item BDRS of suicidal ideation at day 28 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

260. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 254, wherein the reduction or elimination of suicidal ideation occurs no later than about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination reflects an improvement in the score of the suicide concept of item BDRS.

261. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 260, wherein the reduction or elimination of suicidal ideation continues until at least 6 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score of the suicide of item BDRS.

262. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 260, wherein the reduction or elimination of suicidal ideation continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the reduction or elimination reflecting an improvement in the score of the suicide of item BDRS.

263. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 260, wherein the reduction or elimination of suicidal ideation continues until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the reduction or elimination reflecting an improvement in the score of the suicide of item BDRS.

264. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of claim 254, wherein the reduction or elimination of suicide concept is reflected at least in an improvement in the score of MADRS project suicide concept about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

265. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of claim 254 or 264, wherein the reduction or elimination of suicide concept is reflected at least in an improvement in the score of the MADRS project suicide idea on day 1 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for example, 24 hours.

266. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 254, 264, or 265, wherein the reduction or elimination of suicide ideas is reflected at least in an improvement in the score of the MADRS project suicide ideas at day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

267. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of any one of aspects 254 or 264-266, wherein the reduction or elimination of suicide ideas is reflected at least in an improvement in the score of MADRS project suicide ideas at day 14 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

268. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of any one of aspects 254 or 264-267, wherein the reduction or elimination of suicide ideas is reflected at least in an improvement in the score of MADRS project suicide ideas at day 28 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

269. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 254, wherein the reduction or elimination of suicide concept occurs no later than about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination reflects an improvement in the score of the suicide idea for the MADRS project.

270. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 269, wherein the reduction or elimination of suicidal ideation continues until at least 6 days after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score of the MADRS project suicidal ideation.

271. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 269, wherein the reduction or elimination of suicidal ideation continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination is reflected in an improvement in the score of the MADRS project suicidal ideation.

272. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 269, wherein the reduction or elimination of suicidal ideation continues until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, which reduction or elimination reflects an improvement in the score of the MADRS project suicidal ideation.

273. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspect 254, wherein the patient suffers from suicidal ideation and improvement in suicidal ideation is reflected in a decrease in clinical overall impression-severity (CGI-S) score of about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

274. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 254 or 273, wherein the patient suffers from suicidal ideation and improvement in suicidal ideation is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

275. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 254, 273 or 274, wherein the patient suffers from suicidal ideation and improvement in suicidal ideation is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 7 after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

276. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 254 or 273-275, wherein the patient suffers from suicidal ideation and improvement in suicidal ideation is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 14 after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

277. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 254 or 273-276, wherein the patient suffers from suicidal ideation and improvement in suicidal ideation is reflected in a decrease in clinical overall impression-severity (CGI-S) score at day 28 following the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

278. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-253, wherein the patient suffers from suicidal ideation and improvement in suicidal ideation occurs no later than about 2 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, the improvement being reflected in a reduction in clinical overall impression-severity (CGI-S) score.

279. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 278, wherein the improvement in suicidal ideation continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical overall impression-severity (CGI-S) score.

280. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 278, wherein the improvement in suicidal ideation continues until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical overall impression-severity (CGI-S) score.

281. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 278, wherein the improvement in suicidal ideation continues until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in clinical overall impression-severity (CGI-S) score.

282. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspects 1-281, wherein the treatment reduces or eliminates at least one of psychotic symptoms, irritability, instability, increased motor drive, increased speech, agitation.

283. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-282, wherein the patient is a lactating woman who is advised to stop breast feeding until 48 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

284. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-282, wherein the patient is a lactating woman who is advised to stop breast feeding until 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

285. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-282, wherein the patient is a lactating woman who is advised to stop breast feeding until 6 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

286. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of any one of aspects 1-282, wherein the patient is a lactating woman who is advised to stop breast feeding until 3 hours after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof.

287. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of aspects 1-282, wherein the patient is a lactating woman who is advised to stop breast feeding until 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

288. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of any one of aspects 1-287, wherein the treatment improves maternal function.

289. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of aspect 288, wherein the improvement relates to one or more, particularly two or more, functional areas selected from self care, baby care, maternal-maternal interaction, mental health, social support, management and regulation of the mother according to Barkin maternal function index (BIMF).

290. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 288 or 289, wherein BIMF score is improved by 10% or more, preferably 20% or more.

Other specific points

A 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT), or a pharmaceutically acceptable salt thereof, for use in the treatment of a mental or neurological disorder in a mother who has a child of 18 months or less of age, wherein the 5-MeO-DMT is administered via an intravenous, intramuscular or subcutaneous route.

2. The 5-MeO-DMT for use of point 1, or a pharmaceutically acceptable salt thereof, wherein the mental or neurological disorder involves one or more symptoms selected from sleep disorders, cognitive dysfunction, anxiety, bradykinesia, social/emotional withdrawal, and negative thinking.

3. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of point 1 or 2, wherein the patient is suffering from a therapeutically resistant form of the disorder.

4. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use as claimed in point 3, wherein an improvement in the disorder is observed at day 1, e.g. after about 24 hours, at day 7, at day 14, and/or at day 28, after about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, said improvement being reflected in a decrease in CGI-S score.

5. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use as recited in point 3, wherein the improvement in the disorder occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, the improvement being reflected in a decrease in CGI-S score.

6. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use as in point 3 or 5, wherein the improvement of the disorder continues until at least 6 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, in particular until at least 14 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, more preferably until at least 28 days after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, said improvement being reflected in a decrease in CGI-S score.

7. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of points 1-6, wherein the patient also suffers from mildly impaired, impaired or severely impaired maternal function.

8. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of point 7, wherein the patient has a Barkin maternal function index (BIMF) score of 95 or less, such as 80 or less, particularly 65 or less.

9. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use as described in points 1 to 8, wherein the treatment improves maternal function.

10. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of points 1 to 9, wherein the improvement relates to one or more, in particular two or more, functional areas selected from self care, baby care, maternal and maternal interactions, mental health, social support, management and regulation according to Barkin maternal function index (BIMF).

11. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use as described in points 8 to 10, wherein the BIMF score is improved by 10% or more, preferably 20% or more.

12. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of points 1-11, wherein the 5-MeO-DMT or salt thereof is administered at a dose or dose regimen that causes the patient to experience a peak fantasy experience.

13. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use as described in points 1 to 12, wherein a dose of about 1mg to about 10 mg of 5-MeO-DMT is administered, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.

14. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use as described in points 1 to 12, wherein a dose of about 2 mg, or about 5mg, or about 8 mg is administered, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered instead of 5-MeO-DMT.

15. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use as described in points 1 to 12, wherein a dose of about 1 mg, or about 2 mg, or about 3mg is administered, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered instead of 5-MeO-DMT.

16. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of points 1-13, wherein the 5-MeO-DMT or salt thereof is administered in a first dose at a first administration and the 5-MeO-DMT or salt thereof is administered in zero to six subsequent administrations, wherein each subsequent administration uses a higher dose than the previous administration unless the patient experiences a peak fantasy experience.

17. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use as recited in points 1-13 or 16, wherein the 5-MeO-DMT is administered at a dose of about 1 mg to about 3 mg when administered for the first time, then increases to a dose of about 4 mg to about 6 mg when administered for the second time unless the patient has experienced a peak magic experience, then increases to a dose of about 7 mg to about 9 mg when administered for the third time unless the patient has experienced a peak magic experience, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.

18. The 5-MeO-DMT for use of point 17, or a pharmaceutically acceptable salt thereof, wherein the first dose of 5-MeO-DMT is about 2 mg, the second dose of 5-MeO-DMT is about 5 mg, and the third dose of 5-MeO-DMT is about 8 mg, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.

19. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use as recited in points 1-13 or 16, wherein the 5-MeO-DMT is administered at a dose of about 0.5 mg to about 1.5 mg when administered for the first time, then increases to a dose of about 1.5 mg to about 2.5 mg when administered for the second time unless the patient has experienced a peak vagal experience, then increases to a dose of about 2.5 mg to about 3.5 mg when administered for the third time unless the patient has experienced a peak vagal experience, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.

20. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of point 19, wherein the first dose of 5-MeO-DMT is about 1 mg, the second dose of 5-MeO-DMT is about 2 mg, and the third dose of 5-MeO-DMT is about 3 mg, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.

21. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use as claimed in points 16 to 20, wherein the interval between two administrations is not less than 1 hour and not more than 24 hours, such as about 1 to 4 hours, preferably about 1 to 2 hours.

22. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use as claimed in points 12 to 21, wherein the occurrence of the peak fantasy experience is identified by reaching at least 60% of the highest possible score in each of the four sub-scales (mystery, active emotion, overrun time and space and self evident) of the 30 project revised mystery experience questionnaire (MEQ 30), or by reaching at least 60% of the highest possible score of the marine-like borderless (OBN) dimension in the state of consciousness change (ASC) questionnaire, or by reaching at least 75 Peak Experience Scale (PES) total score.

23. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use as in point 22, wherein the occurrence of peak illusion experience is identified by reaching a Peak Experience Scale (PES) score of at least 75.

24. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of points 1-23, wherein the 5-MeO-DMT or a pharmaceutically acceptable salt thereof is administered via intravenous injection.

25. The 5-MeO-DMT for use according to points 1 to 24, wherein the disorder is a disorder characterized by depressive episodes, such as Major Depressive Disorder (MDD), persistent depressive disorder, seasonal affective disorder and bipolar affective disorder (BD), such as bipolar affective disorder type I and bipolar affective disorder type II, anxiety disorders, such as separation anxiety disorder, agoraphobia, generalized Anxiety Disorder (GAD), social Anxiety Disorder (SAD), panic disorder, phobia and substance/drug induced anxiety disorder, somatic symptom disorder, obsessive compulsive disorder and related disorders, such as Obsessive Compulsive Disorder (OCD) and physical deformity disorder (BDD), post Traumatic Stress Disorder (PTSD), pain disorders, such as chronic pain, fibromyalgia and migraine, psychotic and behavioral disorders due to the use of a psychoactive substance, such as Substance Use Disorder (SUD), psychotic disorders, such as schizophrenia, eating disorders, attention deficit hyperactivity disorder (d), adhgrid disorders, such as split-phase disorder and borderline disorder, auto-and autism, chronic personality disorder, chronic or post-traumatic injury to the human system, or to the human brain system.

26. The 5-MeO-DMT for use of points 1 to 25, wherein the patient suffers from sleep disorder.

27. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use of any one of points 1 to 26, wherein the patient is breast-fed mother who is advised to stop breast-feeding until 48 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

28. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use of any one of points 1 to 26, wherein the patient is breast-fed mother who is advised to stop breast-feeding until 24 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

29. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use of any one of points 1 to 26, wherein the patient is breast-fed mother who is advised to stop breast-feeding until 6 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

30. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use of any one of points 1 to 26, wherein the patient is breast-fed mother who is advised to stop breast-feeding until 3 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

31. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use of any one of points 1 to 26, wherein the patient is breast-fed mother who is advised to stop breast-feeding until 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

Other specific items

5-Methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use in the treatment of a disorder of the mental or nervous system of a breast-feeding mother,

Wherein about 1 mg to about 10 mg doses of 5-MeO-DMT or equimolar amounts of the pharmaceutically acceptable salt are administered in a single dose or in the highest dose in an up-titration regimen involving an administration interval of at least about 1 hour,

Wherein said 5-MeO-DMT or said pharmaceutically acceptable salt thereof is administered via intravenous, intramuscular, or subcutaneous routes,

Wherein the patient is advised to temporarily stop breast feeding.

2. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to item 1, wherein the patient is advised to temporarily stop breast feeding 1 hour or more before receiving the first dose and not to resume breast feeding for at least 24 hours after the last dose.

3. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to item 1, wherein the patient is advised to temporarily stop breast feeding 1 hour or more before receiving the first dose and not to resume breast feeding for at least 12 hours after the last dose.

4. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to item 1, wherein the patient is advised to temporarily stop breast feeding 1 hour or more before receiving the first dose and not to resume breast feeding for at least 6 hours after the last dose.

5. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to item 1, wherein the patient is advised to temporarily stop breast feeding 1 hour or more before receiving the first dose and not to resume breast feeding for at least 2 hours after the last dose.

6. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to item 1, wherein the patient is advised to temporarily stop breast feeding 1 hour or more before receiving the first dose and not to resume breast feeding for at least 1 hour after the last dose.

7. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to item 1, wherein the patient is recommended to start temporarily stopping breast feeding before receiving the first dose and not to resume breast feeding for at least 24 hours after the last dose.

8. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to item 1, wherein the patient is recommended to start temporarily stopping breast feeding before receiving the first dose and not to resume breast feeding for at least 12 hours after the last dose.

9. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to item 1, wherein the patient is recommended to start temporarily stopping breast feeding before receiving the first dose and not to resume breast feeding for at least 6 hours after the last dose.

10. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to item 1, wherein the patient is recommended to start temporarily stopping breast feeding before receiving the first dose and not to resume breast feeding for at least 2 hours after the last dose.

11. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to item 1, wherein the patient is recommended to start temporarily stopping breast feeding before receiving the first dose and not to resume breast feeding for at least 1 hour after the last dose.

12. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to item 1, wherein it is recommended that the patient temporarily stops breast feeding only during the actual treatment.

13. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to items 1 to 12, wherein the patient is advised to start temporarily stopping breast feeding until ready for discharge before receiving the first dose.

14. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to item 13, wherein the determination of the discharge preparation is performed about 1 hour after the last dose.

15. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to item 13 or 14, wherein the patient is advised not to restart breast feeding within 6 hours before discharge and after the last dose, whichever is later.

16. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to items 1 to 15, wherein it is recommended that the patient does not restart breast feeding within 3 hours before discharge and after the last dose, whichever is later.

17. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to items 1 to 15, wherein it is recommended that the patient does not restart breast feeding within 2 hours before discharge and after the last dose, whichever is later.

18. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to items 1 to 15, wherein it is recommended that the patient does not restart breast feeding within 1 hour before discharge and after the last dose, whichever is later.

19. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to items 1 to 18, wherein the patient is advised to start temporarily stopping breast feeding before receiving the first dose until at least 24 hours after the last dose and to discard all expressed breast milk within a 24 hour period.

20. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to items 1 to 18, wherein the patient is advised to start temporarily stopping breast feeding before receiving the first dose until at least 2.5 hours after the last dose and to aspirate and discard breast milk 2.5 hours after the last dose.

21. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to items 1 to 20, wherein the patient is advised to aspirate and discard breast milk 24 hours after the last dose before restarting breast feeding.

22. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to items 1 to 21, wherein the patient is recommended to breast-feed the child no more than 2 times within the first 12 hours after the last dose.

23. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use as described in items 1 to 22, wherein any expressed breast milk is discarded as long as the concentration of 5-MeO-DMT and/or 5-MIAA in the breast milk exceeds a predetermined threshold.

24. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to item 23, wherein the threshold value of 5-MeO-DMT is 2000 pg.

25. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to item 23, wherein the threshold value of 5-MeO-DMT is 500 pg.

26. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to item 23, wherein the threshold value of 5-MeO-DMT is 75 pg.

27. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to clauses 23-26, wherein the threshold value of 5-MIAA is 14000 pg.

28. The 5-methoxy-N, N-dimethylprimary amine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to clauses 23 to 26, wherein the threshold value of 5-MIAA is 2000 pg.

29. The 5-methoxy-N, N-dimethylprimary amine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to clauses 23 to 26, wherein the threshold value of 5-MIAA is 75 pg.

30. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to items 1 to 22, which resumes breast feeding when the 5-MeO-DMT concentration and/or the 5-MIAA concentration in breast milk is below a predetermined threshold.

31. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to item 30, wherein the threshold value of 5-MeO-DMT is 2000 pg.

32. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to item 30, wherein the threshold value of 5-MeO-DMT is 500 pg.

33. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to item 30, wherein the threshold value of 5-MeO-DMT is 75 pg.

34. The 5-methoxy-N, N-dimethylprimary amine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use of any one of clauses 30-33, wherein the threshold value of 5-MIAA is 14000 pg.

35. The 5-methoxy-N, N-dimethylprimary amine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use of any one of clauses 30-33, wherein the threshold value of 5-MIAA is 2000 pg.

36. The 5-methoxy-N, N-dimethylprimary amine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use of any one of clauses 30-33, wherein the threshold value of 5-MIAA is 75 pg.

37. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use as described in items 1 to 36, wherein breast feeding is adjusted such that the DID of 5-MeO-DMT per kg of infant body weight is 1 μg/kg/day or less during the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting the appropriate point in time to resume breast feeding, the appropriate number of feeds during the first 24 hours after resumption of breast feeding, sucking and discarding breast milk during the appropriate period, or a combination of these measures.

38. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use as described in items 1 to 36, wherein breast feeding is adjusted such that the DID of 5-MeO-DMT per kg of infant body weight is 0.4 μg/kg/day or less during the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting the appropriate point in time to resumption of breast feeding, the appropriate number of feeds during the first 24 hours after resumption of breast feeding, aspiration and discard of breast milk during the appropriate period, or a combination of these measures.

39. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use as described in items 1 to 36, wherein breast feeding is adjusted such that the DID of 5-MeO-DMT per kg of infant body weight is 0.2 μg/kg/day or less during the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting the appropriate point in time for resumption of breast feeding, the appropriate number of feeds during the first 24 hours after resumption of breast feeding, aspiration and discard of breast milk during the appropriate period, or a combination of these measures.

40. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to items 1 to 39, wherein breast feeding is adjusted such that the RID of 5-MeO-DMT is 10% or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting the appropriate point in time to resumption of breast feeding, the appropriate number of feeds within the first 24 hours of resumption of breast feeding, sucking and discarding breast milk during the appropriate period of time, or a combination of these measures.

41. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to items 1 to 39, wherein breast feeding is adjusted such that the RID of 5-MeO-DMT is 5% or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting the appropriate point in time to resumption of breast feeding, the appropriate number of feeds within the first 24 hours of resumption of breast feeding, sucking and discarding breast milk during the appropriate period of time, or a combination of these measures.

42. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to items 1 to 39, wherein breast feeding is adjusted such that the RID of 5-MeO-DMT is 1% or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting the appropriate point in time to resumption of breast feeding, the appropriate number of feeds within the first 24 hours of resumption of breast feeding, sucking and discarding breast milk during the appropriate period of time, or a combination of these measures.

43. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to items 1 to 42, wherein breast feeding is adjusted such that the DID of the final metabolite 5-MIAA per kg of infant body weight is 4 μg/kg/day or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting the appropriate point in time for resumption of breast feeding, the appropriate number of feeds within the first 24 hours of resumption of breast feeding, aspiration and discard of breast milk during the appropriate period of time, or a combination of these measures.

44. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to items 1 to 42, wherein breast feeding is adjusted such that the DID of the final metabolite 5-MIAA per kg of infant body weight is 2 μg/kg/day or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting the appropriate point in time for resumption of breast feeding, the appropriate number of feeds within the first 24 hours of resumption of breast feeding, aspiration and discard of breast milk during the appropriate period of time, or a combination of these measures.

45. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to items 1 to 42, wherein breast feeding is adjusted such that the DID of the final metabolite 5-MIAA per kg of infant body weight is 1 μg/kg/day or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting the appropriate point in time for resumption of breast feeding, the appropriate number of feeds within the first 24 hours of resumption of breast feeding, aspiration and discard of breast milk during the appropriate period of time, or a combination of these measures.

46. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to items 1 to 45, wherein breast feeding is adjusted such that the RID of the terminal metabolite 5-MIAA is 4% or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting an appropriate point in time for resumption of breast feeding, an appropriate number of feeds within the first 24 hours of resumption of breast feeding, aspiration and discard of breast milk during an appropriate period of time, or a combination of these measures.

47. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to items 1 to 45, wherein breast feeding is adjusted such that the RID of the terminal metabolite 5-MIAA is 2% or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting the appropriate point in time for resumption of breast feeding, the appropriate number of feeds within the first 24 hours of resumption of breast feeding, aspiration and discard of breast milk during the appropriate period of time, or a combination of these measures.

48. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to items 1 to 45, wherein breast feeding is adjusted such that the RID of the terminal metabolite 5-MIAA is 1% or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting an appropriate point in time for resumption of breast feeding, an appropriate number of feeds within the first 24 hours of resumption of breast feeding, aspiration and discard of breast milk during an appropriate period of time, or a combination of these measures.

49. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of clauses 1-48, wherein the patient is suffering from PPD.

50. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of clause 49, wherein the alleviation of symptoms of depression, assessed as a MADRS score of equal to or less than 10, occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

51. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of clause 50, wherein the alleviation of symptoms of depression, assessed as having a HAM-D score of 7 or less, occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.

52. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of clauses 1-51, wherein maternal function is improved according to the Barkin maternal function index (BIMF) of maternal-maternal interactions and mental health, which is reflected in improvements in the area of function.

53. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of item 52, wherein the improvement in cumulative score for a BIMF-scale item reflecting mental health is at least 25% and the improvement in cumulative score for a BIMF-scale item reflecting maternal-maternal interaction is at least 5%.

54. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of item 52 or 53, wherein an improvement in the MADRS item of lazy, pessimistic ideas, sensory deficit, internal stress, and/or sleep reduction results in an increase in the BIMF scale score reflecting mental health, and an improvement in the MADRS item sensory deficit and internal stress results in an increase in the BIMF scale score reflecting maternal-to-maternal interaction.

55. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of any one of clauses 1-54, wherein the patient suffers from a mental or neurological disorder involving one or more symptoms selected from sleep disorders and anxiety, wherein each of these symptoms impairs maternal function.

56. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of clause 55, wherein the patient suffers from a mental or neurological disorder in which anxiety symptoms are involved, and wherein the treatment reduces or eliminates the symptoms of anxiety, particularly mental stress.

57. The5-MeO-DMTorapharmaceuticallyacceptablesaltthereofforuseofclause56,whereinabout2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,theclinicalresponseresultingfromtreatmentisreflectedinadecreaseintheHAM-ascoreofatleast50%comparedtothecorrespondingscorepriortotreatment.

58. The5-MeO-DMTorapharmaceuticallyacceptablesaltthereofforuseofclause56or57,whereinatday1afterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,e.g.,afterabout24hours,theclinicalresponseresultingfromthetreatmentisreflectedinadecreaseintheHAM-ascoreofatleast50%comparedtothecorrespondingscorepriortothetreatment.

59. The5-MeO-DMTorapharmaceuticallyacceptablesaltthereofforuseofclauses56-58,whereintheclinicalresponseresultingfromthetreatmentatday7afterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereofisreflectedinadecreaseintheHAM-ascoreofatleast50%comparedtothecorrespondingscorepriortothetreatment.

60. The5-MeO-DMTorapharmaceuticallyacceptablesaltthereofforuseofclauses56-59,whereintheclinicalresponseresultingfromthetreatmentatday14afterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereofisreflectedinadecreaseintheHAM-ascoreofatleast50%comparedtothecorrespondingscorepriortothetreatment.

61. The5-MeO-DMTorapharmaceuticallyacceptablesaltthereofforuseofclauses56-60,whereintheclinicalresponseresultingfromthetreatmentatday28afterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereofisreflectedinadecreaseintheHAM-ascoreofatleast50%comparedtothecorrespondingscorepriortothetreatment.

62. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of clauses 55 to 61, wherein the patient suffers from a mental or neurological disorder that involves symptoms of a sleep disorder, and wherein the treatment reduces or eliminates the symptoms of a sleep disorder.

63. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of clause 62, wherein the patient suffers from a sleep disorder reflected as a Pittsburgh Sleep Quality Index (PSQI) overall score of >5.

64. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of clause 62 or 63, wherein the treatment reduces or eliminates sleep disorders and the reduction or elimination of sleep disorders is reflected in an improvement in the total score of the Pittsburgh Sleep Quality Index (PSQI) at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, wherein the recall period is from the point in time when the acute illusive experience subsides after the last administration to the point in time of evaluation.

65. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of clauses 62 to 64, wherein the treatment success is represented by a decrease in the PSQI total points.

66. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of clauses 62-65, wherein the treatment success is represented by a decrease in at least four of the seven component scores of PSQI.

67. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of clauses 62-66, wherein the success of the treatment is indicated by a total decrease of said PSQI to 5 or less.

68. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of clauses 62-67, wherein the sleep disorder is insomnia.

69. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of any one of clauses 1-68, wherein the 5-MeO-DMT or salt thereof is administered at a dose or dose regimen that causes the patient to experience a peak fantasy experience.

70. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of clauses 1-69, wherein a dose of about 2 mg, or about 5 mg, or about 8 mg is administered, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of the 5-MeO-DMT.

71. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of clauses 1-69, wherein a dose of about 1mg, or about 2 mg, or about 3 mg is administered, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of the 5-MeO-DMT.

72. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of clauses 1-69, wherein a dose of about 2 mg, or about 4 mg, or about 6 mg is administered, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of the 5-MeO-DMT.

73. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of clauses 1-69, wherein the 5-MeO-DMT or salt thereof is administered in a first dose at the time of first administration and the 5-MeO-DMT or salt thereof is administered in zero to six subsequent administrations, wherein each subsequent administration uses a higher dose than the previous administration unless the patient experiences a peak fantasy experience.

74. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of clauses 1-69 or 73, wherein the 5-MeO-DMT is administered at a dose of about 1mg to about 3 mg when administered for the first time, then is increased to a dose of about 4mg to about 6 mg when administered for the second time unless the patient has experienced a peak magic experience, then is increased to a dose of about 7 mg to about 9 mg when administered for the third time unless the patient has experienced a peak magic experience, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.

75. The 5-MeO-DMT for use of clause 74, or a pharmaceutically acceptable salt thereof, wherein the first dose of 5-MeO-DMT is about 2 mg, the second dose of 5-MeO-DMT is about 5 mg, and the third dose of 5-MeO-DMT is about 8 mg, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered instead of 5-MeO-DMT.

76. The 5-MeO-DMT for use of clauses 1-69 or 73, or a pharmaceutically acceptable salt thereof, wherein the 5-MeO-DMT is administered at a dose of about 0.5 mg to about 1.5 mg when administered for the first time, then is increased to a dose of about 1.5 mg to about 2.5 mg when administered for the second time unless the patient has experienced a peak vagal experience, then is increased to a dose of about 2.5 mg to about 3.5 mg when administered for the third time unless the patient has experienced a peak vagal experience, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.

77. The 5-MeO-DMT for use of clause 76, or a pharmaceutically acceptable salt thereof, wherein the first dose of 5-MeO-DMT is about 1mg, the second dose of 5-MeO-DMT is about 2 mg, and the third dose of 5-MeO-DMT is about 3 mg, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.

78. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of clauses 1-69 or 73, wherein the 5-MeO-DMT is administered at a dose of about 2mg to about 3 mg when administered for the first time, then is increased to a dose of about 4mg to about 5mg when administered for the second time unless the patient has experienced a peak magic experience, then is increased to a dose of about 6mg to about 7.5 mg when administered for the third time unless the patient has experienced a peak magic experience, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.

79. The 5-MeO-DMT for use of clause 78, wherein the first dose of 5-MeO-DMT is about 2 mg, the second dose of 5-MeO-DMT is about 4 mg, and the third dose of 5-MeO-DMT is about 6 mg, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.

80. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of clauses 73 to 79, wherein the interval between two administrations is not less than 1 hour and not more than 24 hours, such as about 1 to 4 hours, preferably 1 to 2 hours.

81. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use as described in items 1 to 69,

Wherein about 1 mg to about 5 mg doses of 5-MeO-DMT or equimolar amounts of the pharmaceutically acceptable salt are administered in a single dose or in the highest dose in an up-titration regimen involving an administration interval of at least about 1 hour,

Wherein said 5-MeO-DMT or said pharmaceutically acceptable salt thereof is administered via intravenous, intramuscular, or subcutaneous routes,

Wherein the patient is advised to temporarily stop breast feeding.

82. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of clause 81, wherein a dose of about 1 mg, or about 5mg, is administered, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.

83. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of clause 82, wherein the 5-MeO-DMT or salt thereof is administered at a first dose when administered for the first time and the 5-MeO-DMT or salt thereof is administered in zero to six subsequent administrations, wherein each subsequent administration uses a higher dose than the previous administration unless the patient experiences a peak illusive experience.

84. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of clause 83, wherein the interval between two administrations is not less than 1 hour and not more than 24 hours, such as about 1 to 4 hours, preferably 1 to 2 hours.

85. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use as claimed in items 69 to 84, wherein the occurrence of peak fantasy experience is identified by reaching at least 60% of the highest possible score in each of the four sub-scales (mystery, active emotion, overrun time and space and self-evident) of the 30 items revised mystery experience questionnaire (MEQ 30), or by reaching at least 60% of the highest possible score of the marine-like borderless (OBN) dimension in the state of consciousness change (ASC) questionnaire, or by reaching at least 75 Peak Experience Scale (PES) total score.

86. The 5-MeO-DMT for use of item 85, or a pharmaceutically acceptable salt thereof, wherein the occurrence of peak illusion experience is identified by reaching a Peak Experience Scale (PES) score of at least 75.

87. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of clauses 1-86, wherein the 5-MeO-DMT or a pharmaceutically acceptable salt thereof is administered via intravenous injection.

Examples

The following examples are set forth to aid in the understanding of the invention and are not intended to, and should not be construed to, limit in any way the invention as set forth in the claims that follow.

Examples 1-5-MeO-DMT aerosol generation and administration

Step 1A stock solution of 5-MeO-DMT free base in 100% ethanol was prepared in a volumetric flask such that 200. Mu.l of the solution volume contained the target dose of 5-MeO-DMT free base to be administered to volunteers or patients via inhalation. Typical target doses are 1 mg to 25 mg of 5-MeO-DMT. For example, for a target dose of 18 mg 5-MeO-DMT, 90 mg of 5-MeO-DMT was dissolved in 100% ethanol and the final solution volume was 1 ml. An aliquot of the stock solution can then be stored in a vial until further use.

Step 2. Mu.l of the solution was transferred to a dosing capsule (Storz & Bickel, germany) containing a drip pad, and then the dosing capsule was capped.

Step 3 the dosing capsule containing 5-MeO-DMT ethanol solution was transferred to the filling chamber of the first Volcano Medic vaporizer, which was preheated and set to a temperature of 55 ℃. The gasifier gas flow was then turned on for 60 seconds at a preset rate of about 12 l/min. Heated air will flow through the dosing capsule allowing the ethanol to evaporate while the target dose of 5-MeO-DMT remains in the capsule as a thin layer covering the stainless steel mesh. By demonstrating that the final weight gain of the capsule compared to the empty capsule weight is approximately equal to the target dose of 5-MeO-DMT, accurate manufacture of the administered capsule can be confirmed.

And 4, taking the prepared administration capsule out of the filling chamber. It is then transferred to the filling chamber of a second Volcano Medic vaporizer, which has been preheated, set to a temperature of 210 ℃, and the gas flow is turned on for at least 5 minutes, and then turned off immediately before transfer. A valved inhalation balloon (Storz & Bickel, germany) was mounted on the socket of the filling chamber, the filling chamber was tightly closed, then immediately the air flow was turned on at a preset flow rate of about 12 a 1/min for 15 seconds, then closed. This will allow the full dose of 5-MeO-DMT to be aerosolized and distributed in approximately 3 liters of air in the inhalation balloon. By proving that the capsule weight had recovered to about its original weight, accurate aerosolization of 5-MeO-DMT could be confirmed.

And 5, disconnecting the balloon from the filling chamber, and automatically closing the valve by the filling chamber. After attaching the mouthpiece to the balloon, the aerosol is ready for immediate administration to the volunteer or patient.

Step 6, in order to prepare for administration, the patient is required to perform deep inhalation 1-2 times first, to exhale completely, and finally to end the process with deep exhalation. The mouthpiece is then held firmly against the lips, the entire volume of the inhalation balloon is inhaled in one inhalation, breath hold for 10 (±2.5) seconds, and then normal exhalation. After completion of the inhalation procedure, the patient is instructed to lie down.

Further details regarding the administration of 5-MeO-DMT by inhalation are disclosed in example 1 of WO 2020/169850 A1, the contents of which are incorporated herein by reference.

EXAMPLE 2 preparation of high purity 5-MeO-DMT

5-MeO-DMT (2.0 g) was dissolved in MTBE (4 mL,2.0 volumes) at 35 to 40℃and then cooled to room temperature over 30 minutes. After 50 minutes of stirring at room temperature, no crystallization was observed, and therefore the batch temperature was reduced to 7 to 12 ℃ in 30 minutes. Crystallization occurs after stirring for 10 minutes at 7 to 12 ℃. Then stirred at 7 to 12 ℃ for 1 hour, followed by filtration of the batch. After washing with MTBE (1 ml,0.5 vol) at 7 to 12 ℃, the batch was dried under vacuum for 3.5 hours to give 1.02 g g of pale orange solid (50% recovery). The purity of the isolated solid was analyzed by HPLC as described in WO 2020/169850 A1. The purity was 99.74% area.

The analysis results further showed that the level of individual impurities was below 0.10% area. Solvent analysis of the sample indicated an MTBE level of 17 ppm.

Example 3-5 preparation of MeO-DMT hydrobromide

5-MeO-DMT HBr was prepared on a 100mg scale.

The 5-MeO-DMT free base was combined with isopropyl acetate (10 volumes) and the resulting 5-MeO-DMT solution was heated to 50 ℃. HBr (1 m in ethanol, 1 eq) was loaded as a single aliquot. The mixture was kept at this temperature and equilibrated for 3 hours.

After 1 hour, a suspension was formed. Finally the suspension was cooled to room temperature and equilibrated for 18 hours. The solid was isolated by filtration and dried under vacuum at 40 ℃ for 18 hours.

An off-white crystalline material was obtained.

The salt has a melting point of 174 ℃ and is characterized by an X-ray diffraction pattern comprising a peak at 14.5°2θ±0.2°2θ;16.7°2θ±0.2°2θ;17.0°2θ±0.2°2θ;20.6°2θ±0.2°2θ;20.7°2θ±0.2°2θ;21.4°2θ±0.2°2θ;24.2°2θ±0.2°2θ;24.8°2θ±0.2°2θ;25.3°2θ±0.2°2θ;27.4°2θ±0.2°2θ, measured using Cu ka radiation.

Example 4-determination of the inhibition constants of Central 5-HT1A and 5-HT2A receptors in post-mortem human brain membrane preparations

In this study, the affinities of three fantasy test compounds (dephosphorylated nupharin, DMT and 5-MeO-DMT) for 5-HT1A and 5-HT2A receptors in post-mortem human brain tissue (from hippocampus and frontal cortex, respectively) were determined using radioligand binding techniques.

Human brain samples were obtained from Edinburgh sudden death think tank. All donors were sudden death with no history of coma, mental or neurological disease, age below 65 years, and post-mortem intervals of less than or equal to 72 hours.

Binding to 5-HT1A receptors in post-mortem human hippocampus

The hippocampus was homogenized in ice-cold 0.25M sucrose (1:30 weight/volume) using an electric teflon pestle (12 grinds at 120 rpm). Myelin and cell debris were removed by centrifugation at 1,000g for 10 min. The supernatant was stored on ice and the pellet was re-homogenized in 0.25M sucrose (1:15 weight/volume) and centrifuged at 750g for 10 minutes. The supernatants were combined and diluted with ice-cold membrane preparation buffer (1:100 weight/volume), using a tightly fitted glass/teflon homogenizer (12 times, 800 rpm), and centrifuged at 20,500 g for 10 minutes. The pellet was resuspended in ice-cold membrane preparation buffer and incubated at 37 ℃ for 10 minutes, then centrifuged at 20,500 g for 10 minutes. The pellet was resuspended and centrifuged a final time to wash the tissue (20,500 Xg,10 min). The resulting pellet was then resuspended in ice-cold assay buffer at a tissue concentration equal to 3.125 mg wet tissue weight/ml. All centrifuges were performed at 4 ℃. The membrane preparation buffer consisted of 50 mM Tris-HCl, pH 7.7, 4. 4mM CaCl ₂ and 0.1% ascorbic acid. The assay buffer consisted of 50 mM Tris, pH 7.7, 4mM CaCl ₂, 0.1% ascorbic acid and 10 μm Pargyline (PARGYLINE).

For saturation binding assays, hippocampal membranes (400. Mu.l; equivalent to 1.25 mg wet weight tissue/tube) were incubated with 50. Mu.l 0.075-9.6 nM [ ³ H ]8-OH-DPAT and 50. Mu.l assay buffer (total) or 50. Mu.l 1. Mu.M WAY 100635 (non-specific binding) for 30 min at 25 ℃. The wash buffer consisted of 50 mM Tris, pH 7.7.

In the displacement assay, hippocampal membranes (400. Mu.l; equivalent to 1.25 mg wet weight tissue/tube) were incubated with 50. Mu.l of 0.6 nM [ ³ H ]8-OH-DPAT and 50. Mu.l of assay buffer (total) or 50. Mu.l of one of the ten concentrations of test compound between 1 and 10000 nM or 50. Mu.l of 1. Mu.M WAY 100635 (non-specific binding) at 25℃for 30min.

The membrane bound radioactivity was recovered by vacuum filtration through a Skatron 11731 filter pre-soaked in 0.5% Polyethylenimine (PEI) using a Skatron cell harvester. Filters were washed rapidly with ice-cold wash buffer (wash setup 0,9,9) and radioactivity was determined by liquid scintillation counting (1 ml Packard MV Gold scintillation counter).

Nonlinear regression was used to calculate the concentration of compound (IC ₅₀) required to inhibit 50% of specific binding and the hill slope. K _i was calculated using a single site binding model that allowed for ligand depletion.

Binding to 5-HT2A receptors in the cortex of the frontal lobe of post-mortem humans

Frontal cortex was homogenized in ice cold 0.25: 0.25M sucrose (1:30 weight/volume) using an electric teflon pestle (12 grinds at 120 rpm). Myelin and cell debris were removed by centrifugation at 1,000g for 10 min. The supernatant was stored on ice and the pellet was re-homogenized in 0.25M sucrose (1:15 weight/volume) and centrifuged at 750g for 10 minutes. The supernatants were combined and diluted with ice-cold 50 mM Tris-HCl assay buffer, pH 7.4 (1:100 weight/volume), homogenized using a tightly fitted glass/teflon homogenizer (12 times, 800 rpm), and centrifuged at 20,500 g for 10 minutes. The pellet was further centrifuged twice to wash the tissue (20,500×g,10 min). The resulting pellet was then resuspended in ice-cold 50 mM Tris-HCl assay buffer, pH 7.4, at a tissue concentration equal to 10 mg wet tissue/ml. All centrifuges were performed at 4 ℃.

For saturation binding assays, frontal cortex membranes (400. Mu.l; equivalent to 4 mg wet tissue weight/tube) were incubated with 50. Mu.l 0.00625-0.8 nM [ ³ H ] MDL-100,907 or 50. Mu.l assay buffer or 50. Mu.l 10. Mu.M ketanserin (ketanserin) (non-specific binding) for 60 min at 25 ℃. The assay and wash buffer consisted of 50mM Tris-HCl buffer pH 7.4.

In the displacement assay, frontal cortex membranes (400. Mu.l; equivalent to 4 mg wet weight tissue/tube) were incubated with 50. Mu.l of 0.1 nM [3H ] MDL-100,907 and 50. Mu.l of assay buffer (total) or 50. Mu.l of one of the ten concentrations of test compounds between 1 and 10000 nM, either 10. Mu.M ketanserin (non-specific binding) or 50. Mu.l, for 60 minutes at 25 ℃.

Membrane-bound radioactivity was recovered and determined as described above. Data analysis was also performed as described above.

Results

Dissociation constants (K _d values) for the 5-HT1A receptor in hippocampal membranes of postmortem human brain tissue of [ ³ H ]8-OH-DPAT and each of the three donors were determined. The dissociation constants (K _d values) obtained were 0.51, 0.28 and 0.52 nM, respectively.

The average inhibition constants (K _i values) for nupharin dephosphorylation, DMT and 5-MeO-DMT were 48, 38 and 1.80 nM (average n=3), respectively. The hill slope of all compounds was nearly uniform, indicating the existence of a single-site binding model.

Dissociation constants (K _d values) for the 5-HT2A receptor in the frontal cortex membranes of postmortem human brain tissue of [ ³ H ] MDL-100,907 and each of the three donors were determined. The dissociation constants (K _d values) obtained were 0.11, 0.08 and 0.08 nM, respectively.

The average inhibition constants (K _i values) for nupharin dephosphorylation, DMT and 5-MeO-DMT were 37, 117 and 122 nM (average n=3), respectively. The hill slope of all compounds was nearly uniform, indicating the existence of a single-site binding model.

The selectivity ratio of des-phosphate, DMT and 5-MeO-DMT for 5-HT2A receptor over 5-HT1A receptor was 0.78, 3.1 and 68, respectively.

EXAMPLE 5 clinical trial of patients suffering from TRD

Phase 1/2 clinical trials of 5-MeO-DMT administered via inhalation as described herein have been completed in the treatment of drug resistant major depressive disorder (TRD) patients. The test is designed in two parts. Part a is an open label, single arm, single dose phase 1 trial with two dose levels (12 mg (n=4) and 18 mg (n=4)). Part B is an open label, single arm phase 2 trial, employing a personalized dosing regimen, and increasing the 5-MeO-DMT dose step-wise in the patient. Patients (n=8) received at least one dose, up to three doses of 5-MeO-DMT (6 mg, 12 mg, and 18 mg) per day, with higher doses administered only if the previously administered dose did not achieve the peak experience. The primary endpoint of part a was to assess the safety and tolerability of single administration of 5-MeO-DMT in TRD patients. The primary endpoint of part B was to evaluate the effect on the severity of depression as assessed by the proportion of patients who were relieved on the seventh day after dosing, defined as a total MADRS score of less than or equal to 10.

In part a, 3 of the 4 patients in the two groups (12 mg and 18 mg) experienced at least one ADR, all of which were mild and self-relieving. No SAE are reported.

12 Two of the four patients in the mg group (50%) and one of the four patients in the 18 mg group (25%) had MADRS remission at the seventh day post-dose, and the other patient in the 18 mg group (25%) had MADRS clinical response at the seventh day post-dose. 12 The average MADRS change from baseline on day seven was-21.0 (-65%) for the mg group, while the 18 mg group was-12.8 (-41%).

In part B, 7 out of 8 patients (87.5%) experienced at least one ADR. All ADRs were self-alleviating. No SAE are reported.

On day seven, seven of the eight patients (87.5%) achieved MADRS remission, achieving the primary endpoint (p < 0.0001). The average MADRS change from baseline on day seven was 24.4 (76%).

No clinically significant changes were observed in any of the safety laboratory analyses, vital signs, mental safety assessments or cognitive function measurements of either part a or part B.

The results are summarized in the following table.

Table 2-a scores recorded for relevant MADRS and BPRS projects assigned to patients on an intra-day personalized dosing regimen (IDR). The project score represents the sum of the individual patient scores of all patients in the IDR group (n=8). Evaluation 2 hours (MADRS) or 3 hours (BPRS) after administration of the last dose.

Table 2-B scores recorded for relevant MADRS and BPRS projects assigned to patients on an intra-day personalized dosing regimen (IDR). The project score represents the sum of the individual patient scores of all patients in the IDR group (n=8). Evaluation on day 1.

Table 2-c. scores recorded for relevant MADRS and BPRS projects assigned to patients on an intra-day personalized dosing regimen (IDR). The project score represents the sum of the individual patient scores of all patients in the IDR group (n=8). Evaluation at day 7.

Table 3-a scores recorded for relevant MADRS and BPRS projects for patients assigned to the 12mg dosing regimen. The project score represents the sum of individual patient scores for all patients in the 12mg group (n=4). Evaluation of 2 hours (MADRS) or 3 hours (BPRS) after dosing.

Table 3-B scores recorded for relevant MADRS and BPRS projects for patients assigned to the 12mg dosing regimen. The project score represents the sum of individual patient scores for all patients in the 12mg group (n=4). Evaluation on day 1.

Table 3-c. Scores recorded for relevant MADRS and BPRS projects for patients assigned to the 12mg dosing regimen. The project score represents the sum of individual patient scores for all patients in the 12mg group (n=4). Evaluation at day 7.

Example 6-5-MeO-DMT and bufogenin pharmacokinetic assessment

To study the pharmacokinetic properties of 5-MeO-DMT, the subjects were divided into three groups of 8 subjects each. A single dose of 6 mg, 12 mg or 18 mg of 5-MeO-DMT is administered to the subject via inhalation. 1, 2, 4, 7, 10, 15, 20, 30, 45 minutes after administration, respectively; and 1;1.5;2;3;4 hours.

The 5-MeO-DMT concentration was determined using LC-MS/MS. PK parameters were generated by algebraic analysis of the concentration versus time profile for each individual. Analysis was performed using software Phoenix WinNonlin 6.3.3.

The median Cmax values obtained for the three groups were 11.85 ng/ml (6 mg group), 22.90 ng/ml (12 mg group) and 38.45 ng/ml (18 mg group), respectively.

Table 4 below shows the median percentages of plasma concentrations relative to Cmax determined at the indicated time points.

Pharmacokinetic measurements were also performed on dosing regimens that rely on up-titration. Substantially similar results were obtained.

The blood concentration of the 5-MeO-DMT metabolite bufogliptin was also determined. In only a few samples, the concentration was above the lower limit of quantification (LLOQ) (25 pg/ml). From 15 minutes, bufogenin concentration was consistently lower than LLOQ.

Substantially similar observations were also obtained when subjects receiving the up-titration regimen were included.

Example 7-5-MeO-DMT toxicology test

5-MeO-DMT did not induce mutations in four histidine-requiring strains of Salmonella typhimurium (Salmonella typhimurium) (TA 98, TA100, TA1535 and TA 1537) and one tryptophan-requiring strain of E.coli (ESCHERICHIA COLI) (WP 2 uvrA pKM 101). These conditions included treatment at concentrations up to 5000 μg/plate (maximum concentration recommended according to current regulatory guidelines), in the absence and presence of the rat liver metabolic activation system (S-9).

Example 8-5-MeO-DMT binding to human plasma proteins

In vitro binding of 5-MeO-DMT to plasma proteins was determined using high throughput dialysis. Human plasma was used to determine equilibration time and non-specific binding at a nominal 5-MeO-DMT concentration of 1. Mu.M. After evaluating the equilibration data, plasma protein binding was studied at nominal concentrations of 0.1, 1 and 10 μm using a 4 hour dialysis time. The concentration of 5-MeO-DMT in the samples from the plasma and buffer compartments was determined by LC-MS/MS. The protein binding results are shown below:

TABLE 5 percentage of 5-MeO-DMT free fraction in human plasma

Example 9-5 human metabolism of MeO-DMT

5-MeO-DMT at nominal concentrations of 1. Mu.M and 10. Mu.M was incubated with human hepatocytes (1X 106 cells/mL) suspended in Leibovitz L-15 medium.

A standard stock solution of 20 mM-MeO-DMT was prepared in ethanol and further diluted to a concentration of 2mM with Leibovitz L-15 medium. For incubation with cryopreserved hepatocytes, the 2mM stock solution was diluted to a concentration of 20. Mu.M or 2. Mu.M with Leibovitz L-15 medium. Aliquots (250. Mu.L) of the 20. Mu.M and 2. Mu.M test substance preparation were added to each hepatocyte incubation sample (250. Mu.L) as appropriate, such that the final test substance concentration in the incubation liquid was 10. Mu.M or 1. Mu.M, respectively, and the incubation liquid contained less than 1% (volume/volume) solvent.

Incubation was performed in a shaking water bath at about 37 ℃ (total incubation volume 0.5 mL). For 1 μm, incubation was terminated after 0,5, 10, 20, 30, 60 and 120 minutes by addition of ice-cold acetonitrile (0.5 mL). For 10. Mu.M, incubation was terminated after 0, 10, 30, 60 and 120 minutes by adding ice-cold acetonitrile containing an internal standard (1. Mu.g/mL dephosphorylated galectin-d 10).

The samples were vortexed and centrifuged at about 13,000 rpm for 10 minutes at room temperature. After centrifugation, the protein-free supernatant was removed for analysis.

A blank incubation was performed using Leibovitz L-15 medium instead of the test substance. For cell-free control samples, leibovitz L-15 medium was used instead of hepatocytes. An aliquot of the blank control sample was taken at 120 minutes, whereas for 1 μm incubation, cell-free control samples were taken at 0, 30 and 120 minutes, and for 10 μm incubation, cell-free control samples were taken at 0 and 120 minutes.

All 1. Mu.M incubations were repeated, while all 10. Mu.M incubations were performed in a single pass. All samples were stored at-80 ℃ prior to analysis (nominal).

Suitable chromatographic conditions were developed to retain the parent compound and give a suitable chromatographic response. The 0, 30 and 120 minute incubation samples generated after 10 μm 5-MeO-DMT incubation were analyzed using reverse phase LC-MS analysis to generate high and low energy Mass Spectra (MSE). Prior to sample analysis, 100 μl aliquots of each sample were evaporated to near dryness at room temperature under a steady stream of nitrogen, then reconstituted in 50 μl mobile phase a (0.1% formic acid in water). Each sample (0, 30 and 120 minutes, 10 μm) was analyzed using accurate mass LC-MS to determine the relative levels of parent compound at each time point and to determine the profile of metabolites formed. Appropriate blank and control samples were also analyzed. 10. Mu.M incubation samples for 10 min and 60 min were not analyzed and stored at-80 ℃.

Screening software (UNIFI version 1.9.4) and user-defined search parameters are used to query the data for the presence of metabolites by comparing retention times to test substance reference standards and based on the exact quality of potential metabolites. To confirm suspected metabolites, the measured exact mass of the detected peaks in the sample for structural analysis must be within 5 ppm of theoretical mass to confirm molecular formula.

Table 1 above summarizes the results obtained.

EXAMPLE 10 Metabolic stability of 5-methoxyindole-3-acetic acid (5-MIAA) and 5-methoxy-tryptol in human hepatocyte Co-culture model

The metabolic stability of 5-MIAA and 5-methoxy chromanol was studied in a hμrel co-culture assay with human hepatocytes (hμ rel HumanPool ^TM, primary liver co-culture model from Visikol inc.).

Incubation was performed using initial concentrations of 1 and 10 μm and samples were taken at time points of 0, 1,2, 4, 8, 24, 48 and 72 hours (h). Samples were analyzed using UPLC/QE-orbitrap-MS.

The following table shows the remaining LC/MS peak areas of the test compounds detected using the hμrel co-culture assay after each incubation time point relative to the corresponding 0min incubated samples. The results (disappearance half-life) of the control diazepam (diazepam) were determined to indicate that the enzyme activity was within normal levels.

Tables 6-0-72 h relative LC/MS peak area of 5-MIAA after incubation. Initial substrate concentrations were 1 and 10 μm (n=2 at 1 μm, n=1 at 10 μm).

Tables 7-0-72 h relative LC/MS peak area of 5-methoxy chromanol after incubation. Initial substrate concentrations were 1 and 10 μm (n=2 at 1 μm, n=1 at 10 μm).

The metabolic turnover rate of 5-MIAA was observed to be low, with residual abundance after 72h being 75-82% in the presence of hepatocytes, whereas no disappearance was observed in the stromal cell control.

For 5-methoxy tryptol, a high metabolic turnover rate was observed, which completely disappeared within 24h in the presence of hepatocytes, but not in the stromal cell control.

Using human hepatocytes and a 1. Mu.M test concentration, the intrinsic clearance of 5-MIAA in vitro was 0.15. Mu.l/min/million cells (half-life 15.400 min), while the corresponding value for 5-methoxy tryptol was 16.2. Mu.l/min/million cells (half-life 142 min).

The predicted liver extraction rate of 5-MIAA was 2%, and the predicted liver extraction rate of 5-methoxy tryptol was 67%.

Example 11-5-MIAA plasma binding

Binding to human plasma proteins was determined. Unbound scores (fu) and average unbound scores, standard deviation, and average recovery for three replicates are reported (table 8).

Example 12 clinical trial of administration of 5-MeO-DMT to post-partum depressed patients via inhalation

The single arm open label clinical trial will involve 15 adult female patients clinically diagnosed with Post Partum Depression (PPD).

Patients received a single day personalized 5-MeO-DMT dosing regimen via post-gasification inhalation.

More specifically, the patient will receive up to three doses of 5-MeO-DMT at day 0, 6 mg, 12 mg, and 18 mg.

1. All patients will receive an initial dose of 6 mg 5-MeO-DMT.

2. The second dose (12 mg) will be applied only if:

a. Peak experience (total score > 75) was not achieved after 6 mg doses, and

B. According to the researchers, the 6 mg dose was safe, well tolerated,

C. any psychoactive effects (PsE) of the previous dose have been resolved, and

D. The pre-dosing vital signs and force effort per second (FEV 1) were within normal range or if outside of normal range, according to the investigator, clinically insignificant.

3. Likewise, the third dose (18 mg) would be administered only if:

a. 12 Peak experience was not achieved after mg dose (total score > 75), and

B. According to the researchers, the 12 mg dose was safe and well tolerated, and

C. any PsE of the previous dose had resolved, and

D. The pre-dosing vital signs and force effort per second (FEV 1) were within normal range or if outside of normal range, according to the investigator, clinically insignificant.

The patient will receive an assessment of peak illusion experience (visual analog scale based on patient score, i.e., PE scale), sedation and other endpoints after administration. Follow-up on days 1 and 7 after dosing was planned.

All patients considered to participate in the clinical trial must meet the following criteria:

1. is female and is between 18 and 45 years of age (inclusive) at the time of screening.

2. Body Mass Index (BMI) at screening was in the range of 18.5 to 35 kg/m ² (inclusive).

3. Meets the test criteria for PPD evaluated by the test psychiatrist or the registered psychologist:

a. major depressive disorder diagnosed as not accompanied by psychotic features was confirmed by simple international neuropsychiatric interviews (MINI), and perinatal period onset time was no earlier than gestation and no later than 4 weeks before post partum.

B. the Montgomery-Arabidopsis depression rating scale (MADRS) total score at screening and prior to administration on day 0 is equal to or greater than 28.

6. It is necessary to stop breast feeding at screening, or if breast feeding is still being fed or active at screening, it is necessary to agree to stop breast feeding temporarily for 24 hours from the time of day 0 before receiving study medication to the time of the last dose, and aspirate and discard all breast milk as needed within these 24 hours, but it is necessary to aspirate/discard breast milk 2.5 hours after the last dose and 24 hours after the last dose before restarting breast feeding.

4. It must be agreed to either completely abstinence (complete avoidance of sexuality) or use a highly effective (failure rate < 1%) and medically approved contraceptive method within 30 days prior to administration and 90 days after administration of 5-MeO-DMT. The pregnancy test results for the patients at the time of screening and the day prior to the test (day-1) must be negative.

5. It is desirable to delay the initial use of other antidepressants or anxiolytics until after the end of the trial on day 7 and agree to keep any psychotherapy unchanged during the trial.

Potential patients meeting any of the following critical exclusion criteria will be excluded from the trial:

1. Based on the medical history, psychiatric assessment and MINI assessment, it is currently or previously diagnosed with bipolar disorder, manic or hypomanic episodes, psychotic disorder, major Depressive Disorder (MDD) or other mood disorders characterized by psychosis, obsessive compulsive disorder, post Traumatic Stress Disorder (PTSD), autism spectrum disorder, borderline personality disorder, schizophrenia, delusional disorder, paranoid personality disorder, schizoaffective disorder, clinically significant intellectual impairment, or at the discretion of the researcher, resulting in a patient unsuitable for participation in any other psychotic co-disorder tested.

2. One or more primary or secondary relatives are currently or previously diagnosed with bipolar disorder, psychotic disorder, or other mood disorder characterized by psychosis (including MDD).

3. The test psychiatrist or registered psychiatrist judged that there was a significant risk of suicidal activity based on medical history, psychiatrist assessment and the assessment of suicidal ideation and behavior based on the Columbia suicide severity rating scale (C-SSRS).

4. Antidepressants are administered orally 14 days or 5 half-lives (longer, as in the case of fluoxetine, for the past 5 weeks).

5. Any other drug having monoamine oxidase inhibitor (MAOI) activity was administered orally 14 days or 5 half-lives (longer).

6. At the discretion of the investigator, serious adverse reactions have previously occurred to magic or hallucinogens (e.g., nupharin, nupharia species (Psilocybe spp.) mushrooms, 5-MeO-DMT, dead rattan water, LSD, and mescaline).

7. Allergy or hypersensitivity to 5-MeO-DMT or any other contraindications are known.

8. At the discretion of the investigator, suffering from any current or past clinically significant condition that would render the patient unsuitable for participation in the trial (e.g., severe infection, pulmonary disease, uncontrolled hypertension, gestational hypertension disorder during pregnancy or after-delivery new episodes (e.g., gestational hypertension, preeclampsia, eclampsia), uncontrolled diabetes, severe cardiovascular disease, severe liver or kidney failure, severe brain disorder (including epilepsy, stroke, dementia, degenerative neurological disorders, meningitis, encephalitis, and head injury with loss of consciousness).

9. At the discretion of the investigator, any medications or other substances that render the patient unsuitable for participation in the trial are administered.

10. At the discretion of the investigator, there are clinically significant abnormalities in physical examination, vital signs, ECG, or clinical laboratory parameters that render the patient unsuitable for participation in the trial.

11. Patients were positive for pregnancy tests at screening or the day prior to testing (day-1), had been pregnant, or were scheduled to become pregnant during the course of the test and up to 90 days after administration of 5-MeO-DMT.

12. Patients had DSM-5 drug or alcohol usage disorders within 6 months prior to screening.

The main objective of the trial was to determine the onset time and 7-day duration of antidepressant effect using a single day personalized regimen (6 mg, 12 mg and 18 mg 5-MeO-DMT) for adult female PPD patients.

The secondary objective was to determine the antidepressant effect, anxiolytic effect, effect on maternal behaviour, safety and tolerability, intensity and duration of psychoactive effect (PsE) on adult female PPD patients, influence on cognitive outcome, of a single day personalized dosing regimen (6 mg, 12mg and 18 mg 5-MeO-DMT).

Exploratory purposes were to determine the amounts of 5-MeO-DMT and metabolites, bufogenin and 5-methoxyindole-3-acetic acid (5-MIAA) in breast milk, blood and urine (metabolite identification screening can be performed as needed) after single daily administration of single day personalized IDR (6 mg, 12 mg and 18 mg 5-MeO-DMT) to adult female PPD patients, as measured by LC/MS.

The primary endpoint of this study was to assess the antidepressant effect of 5-MeO-DMT by the change in MADRS from baseline assessed on day 7.

Secondary endpoints included evaluation of the antidepressant effect of 5-MeO-DMT by:

the antidepressant effect of 5-MeO-DMT was evaluated by:

the proportion of patients who were relieved (MADRS. Ltoreq.10) on day 02, day 1 and day 7 after the final study drug administration;

Changes from baseline in MADRS assessed 2 hours and day 1 post-drug administration at day 0 final study;

2 hours, 1 day and 7 days after the final study drug administration at day 0, the proportion of responders (total MADRS decrease by > 50% from baseline);

Changes in clinical global impression-severity (CGI-S) from baseline at day 0 at 2 hours, day 1 and day 7 post-drug administration of the final study;

the effect on maternal behavior as assessed by the change in the total and sub-scale scores of Barkin maternal function index (BIMF) from baseline to day 7;

Exposure of 5-MeO-DMT and bufotiamine in breast milk obtained on the day before testing (day-1), 1 hour after the last administration of study drug, at discharge, at night on day 0, and on days 1 and 7;

exposure of 5-MeO-DMT and bufotaline in blood obtained on the day before testing (day-1), 1 hour after the last administration of study drug, at discharge, and on day 1 and day 7;

Safety and tolerability of 5-MeO-DMT was evaluated by:

reporting adverse events (TEAE) occurring in the treatment;

clinically significant changes from baseline in ECG, vital signs, safety laboratory assessment, peak flow respirometry;

sedation assessment (modified observer alertness and sedation assessment scale [ MOAA/S ]) was performed after each dose (when pses resolved and 60 minutes after each study medication administration) and as part of discharge assessment on day 0;

variation of the clinical administration split status scale (CADSS) from baseline assessed as part of discharge evaluations on day 0, day 1 and day 7;

Changes from baseline on the Brief Psychosis Rating Scale (BPRS) assessed as part of discharge evaluations on day 0, day 1 and day 7;

Changes from baseline in C-SSRS assessed as part of discharge evaluations on day 0, day 1 and day 7;

Change from baseline of YMRS assessed as part of discharge evaluations on day 0, day 1, and day 7;

the patient experience of pses reported 30 to 60 minutes after each dose, at which time the pses have resolved:

A PsE evaluation of evaluating the implementation of PE using a Peak Experience (PE) scale (PE scale total score. Gtoreq.75);

challenge Experience Questionnaire (CEQ);

Mystery experience questionnaire (MEQ-30);

The PsE duration is defined as the time from study drug administration to the time the PsE has resolved (study score and patient score), completed 30 to 60 minutes after each administration;

Currently, a patient diagnosed with post-partum depression by a psychiatrist has been enrolled in clinical trials. Major depressive disorder diagnosed as not accompanied by psychotic features was confirmed by simple international neuropsychiatric interviews (MINI) (v7.0.2), and perinatal morbidity time was no earlier than gestation and no later than 4 weeks before parturition. The patient was diagnosed with post partum depression after birth with third birth. The patient completed all planned visit days. The inhalation procedure is performed adequately by the patient and is well tolerated without adverse events associated with inhalation.

Results

Apart from the temporary, clinically irrelevant increases in heart rate and blood pressure shortly after administration of 5-MeO-DMT, no other noticeable changes in vital parameters occurred. Assessment of ECG (3 hours post administration) and safety laboratory analysis (7 days), CADSS (3 hours, 1 day, and 7 days) was not abnormal. The few adverse events reported (left abdominal cramping pain and headache, both occurring on day 0) were mild in symptoms, short in duration, and self-alleviating at the end of the study.

Regarding the intensity of the fantasy experience, the PES score recorded achieved upon exposure to the 6mg nominal dose was 17.3. This score indicates that following higher doses of 12mg need to be continued as designed for the personalized dosing regimen. The PES score achieved at this dose was 85.7 and ≡ 75, indicating that this patient had a peak vague experience and completed IDR.

Importantly, patients reported significant improvement in their depressive symptoms as assessed by MADRS at the earliest assessment time point (2 hours) after drug administration, and the effect was maintained over time (table 9). The patient also met criteria for MADRS response (improvement of at least 50% over baseline) and MADRS remission (MADRS score equal to or less than 10).

TABLE 9 MADRS/BPRS score Table

Significant improvements in several MADRS projects are particularly noted. The individual items are summarized in table 9. The baseline scores of some of the patient's projects reflect the absence of symptoms (decreased appetite, difficulty concentrating, suicidal ideation) while the project scores reflect significant improvement in severe symptoms (e.g., reduced sleep, mental stress).

Also, several BPRS projects have improved, including physical problems, anxiety, emotional withdrawal, guilt, and tension.

In addition, as summarized in table 10, an increase in BIMF score recorded on day 7 demonstrated an improvement in maternal function, with a total score increase of 92 to 105, and a 14% increase (total score up to 120).

Several functional areas of maternal function as defined by Barkin et al were also evaluated. Table 11 outlines the improvements for each functional area in more detail.

Here, significant improvements in self-care, mental health, and management were achieved, with% improvement ranging from 18% (management) to (44%) (self-care). These improvements strengthen the relationship between improvements in depression programs as assessed by improvements in MADRS and maternal function.

Notably, the patient score is relatively high already prior to treatment. In some functional areas, the score is at or near a maximum (see table 11), making the range of improvement by therapy limited.

Tables 10-BIMF score table

Table 11-BIMF functional Domain scoring Table

Summary and conclusions

A. A personalized dosing regimen, i.e. administration of 6mg 5-MeO-DMT via inhalation followed by administration of 12 mg 5-MeO-DMT, was adopted which was well tolerated and induced a surprising and very significant clinical response in patients formally diagnosed with post-partum depression.

B. clinical response occurred rapidly within 2 hours after 5-MeO-DMT administration. This rapid onset of action is not common and has not been seen in the traditional antidepressant classes including tricyclic antidepressants, monoamine oxidase inhibitors, selective Serotonin Reuptake Inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and the like, which typically take 4 to 6 weeks to exhibit an effect.

C. according to IDR, patients developed clinical remission within 2 hours after administration of 5-MeO-DMT. This is superior to any approved post-partum depression therapy and all previously tested hallucinogens.

D. Although 5-MeO-DMT was given only once and was no longer effectively present in vivo during this time frame (see pharmacokinetic data in example 6 above), significant clinical response persisted for a7 day follow-up period. This observation supports the superior clinical properties of 5-MeO-DMT and allows for convenient dosing intervals.

E. in addition to antidepressant effects, the assessment of endpoints of other symptoms such as somatic problems, emotional withdrawal, anxiety, guilt and tension is positively affected, which supports the use of 5-MeO-DMT in other psychotic patients.

F. in addition to antidepressant effects, the end points of the assessed maternal functions (such as self-care, mental health and management) assessed using BIMF are also positively affected. This supports the additional benefit of 5-MeO-DMT in addition to improving the symptoms of core depression in patients suffering from PPD.

The prominent aspect shows that 5-MeO-DMT has significantly improved efficacy when used according to the invention compared to approved post-partum depression medications and all previously tested hallucinogens.

In combination with the short duration of the acute illusive effect and good safety, these data demonstrate that the present invention solves the technical problem of providing improved psychoactive therapy for post-partum depressed patients.

A second patient diagnosed with post-partum depression by a psychiatrist has been enrolled in a clinical trial. Major depressive disorder diagnosed as not accompanied by psychotic features was confirmed by simple international neuropsychiatric interviews (MINI) (v7.0.2), and perinatal morbidity time was no earlier than gestation and no later than 4 weeks before parturition. The patient completed all planned visit days (here day 5, but not day 7). The inhalation procedure is performed adequately by the patient and is well tolerated without adverse events associated with inhalation.

Apart from the temporary, clinically irrelevant increase in heart rate shortly after administration of 5-MeO-DMT, no other noticeable change in vital parameters occurred. Assessment of ECG (3 hours post administration) and safety laboratory analysis (3 hours and 7 days), CADSS (3 hours, 1 day and 7 days) were not abnormal. The few adverse events reported (emesis on day 0, headache on day 5) were mild in symptoms, short in duration, and self-relieving at the end of the study.

Regarding the intensity of the fantasy experience, the PES score recorded as achieved upon exposure to 6 mg nominal doses was 1. This score indicates that one hour after the first administration, a subsequent higher dose of 12mg needs to be continued, as designed for the personalized dosing regimen. The PES score achieved at this dose was 94.7 and ≡ 75, indicating that this patient had a peak vague experience and completed IDR.

Importantly, patients reported significant improvement in their depressive symptoms as assessed by MADRS at the earliest assessment time point (2 hours) after drug administration, and the effect was maintained over time. The patient also met criteria for MADRS response (improvement of at least 50% over baseline) and MADRS remission (MADRS score equal to or less than 10).

The second patient was in lactation and breast milk samples were collected at various time points prior to dosing and after the last dose was administered according to the clinical trial protocol. These samples were then analyzed by LC-MS/MS assay to detect 5-MeO-DMT, bufogenin (the major metabolite of 5-MeO-DMT) and 5-MIAA (the final metabolite of 5-MeO-DMT). Similar analyses were performed on patient serum and urine samples. The data are summarized in the following table.

ND, undetermined.

BLQ below the limit of quantitation. The lower limit of the quantitation of 5-MeO-DMT and 5-MIAA in serum and breast milk was 25pg/ml, the lower limit of the quantitation of 5-MeO-DMT in urine was 25pg/ml, and the lower limit of the quantitation of 5-MIAA in urine was 250 pg/ml.

The data show that 5-MeO-DMT has been rapidly cleared from serum at the first measurement time point 1 hour after the last dose, at which point the concentration detected was 132.9 pg/ml, and subsequently the concentrations at all time points were below the lower limit of quantification for the assay. In addition, endogenous levels of 5-MIAA were confirmed in serum prior to dosing, the highest concentration was detected at the first measurement time point (1 hour after dosing), and returned to baseline levels within 1 day. Urine measurement data showed that the concentration of 5-MeO-DMT was about four times the concentration detected in serum at 1 hour (indicating that there was a significant excretion at this time), and rapidly dropped to undetectable levels after this time point, whereas the concentration of 5-MIAA peaked at 2.5 hours, about 127 times the concentration detected in serum, and rapidly dropped to endogenous levels within 7 days. Bufogenin was not detected in urine at any time point except urine at 2.5 hours post-dose. Taken together, these data demonstrate rapid metabolism and clearance of 5-MeO-DMT in vivo.

Breast milk sample analysis showed the absence of bufogenin and the concentration of 5-MeO-DMT was 2167 pg/ml one hour after administration, rapidly decreasing to a level similar to the endogenous level of serum prior to administration 8.5 hours after administration. A similar trend was observed for 5-MIAA.

Example 13-clinical trial of administration of 5-MeO-DMT to bipolar disorder type II patients via intravenous injection-prophetic example

This clinical trial will involve adult patients with bipolar disorder type II and current major depressive episodes.

Patients currently taking antidepressants need to either stop taking the medication or gradually decrease the medication over time.

Patients received a single day personalized 5-MeO-DMT dosing regimen by intravenous injection. The 5-MeO-DMT will be provided in the form of its hydrobromide salt and intravenous injection formulations. It should be understood that the dosages of 5-MeO-DMT referred to below are related to the weight of the free base, while the dosages of 5-MeO-DMT hydrobromide can be calculated assuming equimolar amounts.

More specifically, patients will receive up to three doses of 5-MeO-DMT 2 mg, 5 mg, and 8 mg on the day of administration (day 0).

1. All patients will receive an initial dose of 2 mg of 5-MeO-DMT.

2. The second dose (5 mg) was only applied if:

a. peak experience (PES score ≡ 75) was not achieved after 2 mg doses, and

B. The 2 mg dose was safe and well tolerated.

3. Likewise, the third dose (8 mg) would be administered only if:

a. peak experience (PES score ≡ 75) was not achieved after 5 mg doses, and

B. the 5 mg dose was safe and well tolerated.

The peak illusive experience of the patient will be assessed based on the PES scored by the patient, sedation after administration, and other endpoints described above. Follow-up on days 1 and 7 after dosing was planned.

Patient selection is based on the following key inclusion criteria:

1. the nature of the clinical trial is understood and written informed consent is provided for signing and dating in accordance with local regulations prior to any trial-related procedures.

2. Is male or female and is selected between 18 and 64 years of age (inclusive).

3. Meets the test criteria for bipolar disorder type II and is experiencing major depressive episode as assessed by a test psychiatrist or registered clinical psychologist:

a. Meets the diagnostic criteria for bipolar disorder type II of the manual for diagnosis and statistics of mental disorders fifth edition (DSM-5) and confirms the current onset of major depressive disorder via simple international neuropsychiatric interview (MINI);

b. the Montgomery-Abbe depression rating scale (MADRS) total score of 24 or greater before the first administration at screening and day 0;

4. The total score of the Young Mania Rating Scale (YMRS) at screening and prior to the first administration on day 0 is less than or equal to 8;

5. the consent was to keep any psychotherapy unchanged and no new psychoactive drugs were started during the trial.

6. Female patients must be treated by surgical sterilization (hysterectomy, tubal ligation or bilateral ovariectomy (6 months prior to screening)), either postmenopausal and amenorrhea or complete abstinence (complete avoidance of anisotropic intercourse) over the last 2 years, or by using medically approved high-efficiency (failure rate < 1%) contraceptive methods including, but not limited to, bilateral tubal ligation/occlusion, hormonal contraceptives to inhibit ovulation, intrauterine devices (including hormone-releasing intrauterine devices/systems), and serum pregnancy tests must be negative at screening and urine pregnancy tests negative the day prior to testing (day-1).

7. Male patients must use prophylactic contraceptives (i.e., use of spermicidal condoms or abstinence) and must not donate sperm within 30 days after 5-MeO-DMT administration.

Potential patients meeting any of the following critical exclusion criteria will be excluded from the trial:

1. Based on the medical history, psychiatric and MINI assessments, it is currently or previously diagnosed with bipolar I disorder, manic episodes, psychotic disorders, major Depressive Disorder (MDD) or other mood disorders characterized by psychosis, obsessive compulsive disorder, post Traumatic Stress Disorder (PTSD), autism spectrum disorders, borderline personality disorder, schizophrenia, delusional disorder, paranoid personality disorder, schizoaffective disorder, clinically significant intellectual disorders, or any other psychotic co-disorder at the discretion of the researcher that results in a patient unsuitable for participation in the trial.

2. One or more primary or secondary relatives are currently or previously diagnosed with psychotic disorder, bipolar disorder type I or MDD with psychotic features.

3. There is a significant risk of suicide defined as (a) the occurrence of the suicidal ideation as set forth in C-SSRS clause 4 or 5 over the past year, during screening, or at baseline, or (b) the occurrence of suicidal behavior over the past year, or (C) a clinical assessment of significant suicide risk during a clinical interview, or (d) the occurrence of non-suicidal sui-C-ic behavior over the past year.

4. Antidepressants are administered orally 7 days or 5 half-lives (longer, as in the case of fluoxetine, for the past 5 weeks).

5. Drugs with monoamine oxidase inhibitor (MAOI) activity were administered orally 14 days or 5 half-lives (whichever is longer) prior to administration.

6. Mood stabilizer therapy (e.g., lamotrigine (lamotrigine), valproic acid (valproate), atypical antipsychotics) was received 14 days (28 days lithium) or 5 half-lives (whichever is longer) prior to dosing, or mood stabilizer therapy was received at screening, or mood stabilizer therapy was expected to be needed during the study (at the discretion of the investigator).

7. At the discretion of the investigator, serious adverse reactions have previously occurred to hallucinogens or hallucinogens.

8. Allergy or hypersensitivity to 5-MeO-DMT or any other contraindications are known.

9. Suffering from any current or past clinically significant condition (e.g., severe infection, severe pulmonary disease, uncontrolled hypertension, uncontrolled diabetes, severe cardiovascular disease, severe liver or kidney failure, severe brain disorders (including epilepsy, stroke, dementia, degenerative neurological disorders, meningitis, encephalitis, and head injury with loss of consciousness), which may interfere with interpretation of test results, constitute a risk to the health of the patient, or render the patient unsuitable for participation in the test at the discretion of the researcher.

10. At the discretion of the investigator, any medications or other substances that render the patient unsuitable for participation in the trial are administered.

11. At the discretion of the researcher, there are clinically significant abnormalities in physical examination, vital signs, electrocardiogram (ECG), or clinical laboratory parameters that render the patient unsuitable for participation in the trial.

12. Female patients were positive for pregnancy tests at screening or the day prior to testing (day-1), had been pregnant or lactating, or were scheduled to become pregnant during the course of the test and up to 30 days after administration of 5-MeO-DMT.

13. Patients with DSM-5, alcohol or substance use disorders (excluding tobacco or caffeine use disorders) within 6 months prior to screening.

The main objective of the trial was to determine the onset time and persistence of antidepressant effect using a single day personalized regimen (2 mg, 5mg and 8mg 5-MeO-DMT) for patients with bipolar II disorder and current major depressive episode. The secondary objective was to determine the effect of a single day personalized dosing regimen (2 mg, 5mg and 8mg 5-MeO-DMT) on depressive symptoms and overall clinical status of patients with bipolar II disorder and current major depressive episodes, safety and tolerability, intensity and duration of psychoactive effects (pses), effect on sleep quality, effect on cognitive outcome.

The primary endpoint of this study was to assess the antidepressant effect of 5-MeO-DMT by the change in MADRS from baseline assessed on day 7.

Secondary endpoints include:

The antidepressant effect of 5-MeO-DMT via intravenous injection was evaluated by:

the proportion of patients who were relieved (MADRS. Ltoreq.10) on day 02, day 1 and day 7 after the final study drug administration;

Changes from baseline in MADRS assessed 2 hours and day 1 post-drug administration at day 0 final study;

2 hours, 1 day and 7 days after the final study drug administration at day 0, the proportion of responders (total MADRS decrease by > 50% from baseline);

Changes from baseline in CGI-S assessed at day 0, 2 hours and day 1 and day 7 post-drug dosing of the final study.

Change from baseline of BDRS on day 1 and day 7

Safety and tolerability of 5-MeO-DMT via intravenous injection was evaluated by:

reporting adverse events (TEAE) occurring in the treatment;

Clinically significant changes from baseline for ECG, vital signs, safety laboratory assessment, and spirometry assessment;

sedation assessment (modified observer alertness and sedation assessment scale [ MOAA/S ]) was performed after each dose (when pses resolved and 60 minutes after each study medication administration) and as part of discharge assessment on day 0;

incidence of Adverse Events (AE) of mania or hypomania (assessed using the mania/hypomania DSM-5 standard);

Change from baseline of YMRS assessed as part of discharge evaluations on day 0, day 1, and day 7;

variation of the clinical administration split status scale (CADSS) from baseline assessed as part of discharge evaluations on day 0, day 1 and day 7;

assessing patient discharge readiness at day 0 of discharge using discharge readiness Clinical Assessment (CADR);

Changes from baseline on the Brief Psychosis Rating Scale (BPRS) assessed as part of discharge evaluations on day 0, day 1 and day 7;

C-SSRS classification based on Columbia suicide evaluation classification algorithm (C-CASA).

The patient experience of pses reported 30 to 60 minutes after each dose, at which time the pses have resolved:

A PsE evaluation using a Peak Experience (PE) scale (PES) to evaluate the implementation of PE (PES total score. Gtoreq.75);

challenge Experience Questionnaire (CEQ);

mystery experience questionnaire (MEQ-30).

The PsE duration is defined as the time from the administration of the study drug to the time the PsE has resolved, completed 30 to 60 minutes after each administration.

The effect on sleep quality, as assessed by changes in the Pittsburgh Sleep Quality Index (PSQI) from the day before the test (day-1) to day 1 and to day 7.

The effect on cognitive outcome, as assessed from day before test (day-1) to day 0 discharge, to day 1 and to day 7:

a rapid visual information processing (RVP) test;

a speech recognition memory (VRM) test;

a Space Working Memory (SWM) test;

The Digital Symbol Substitution Test (DSST).

Example 14-clinical trial of administration of 5-MeO-DMT to bipolar disorder type II patients via intravenous injection-prophetic example

This clinical trial will involve adult patients with bipolar disorder type II and current major depressive episodes.

Patients currently taking antidepressants need to either stop taking the medication or gradually decrease the medication over time.

Patients received a single day personalized 5-MeO-DMT dosing regimen by intravenous injection. The 5-MeO-DMT will be provided in the form of its hydrobromide salt and intravenous injection formulations. It should be understood that the dosages of 5-MeO-DMT referred to below are related to the weight of the free base, while the dosages of 5-MeO-DMT hydrobromide can be calculated assuming equimolar amounts.

More specifically, patients will receive up to three doses of 5-MeO-DMT 1 mg, 2 mg, and 3 mg on the day of administration (day 0).

1. All patients will receive an initial dose of 1 mg 5-MeO-DMT.

2. The second dose (2 mg) was only applied if:

a. Peak experience (PES score ≡ 75) was not achieved after 1 mg doses, and

B. The 1 mg dose was safe and well tolerated.

3. Likewise, the third dose (3 mg) would be administered only if:

a. peak experience (PES score ≡ 75) was not achieved after 2 mg doses, and

B. The 2 mg dose was safe and well tolerated.

The peak illusive experience of the patient will be assessed based on the PES scored by the patient, sedation after administration, and other endpoints described above. Follow-up on days 1 and 7 after dosing was planned.

Patient selection is based on the following key inclusion criteria:

1. the nature of the clinical trial is understood and written informed consent is provided for signing and dating in accordance with local regulations prior to any trial-related procedures.

2. Is male or female and is selected between 18 and 64 years of age (inclusive).

3. Meets the test criteria for bipolar disorder type II and is experiencing major depressive episode as assessed by a test psychiatrist or registered clinical psychologist:

a. Meets the diagnostic criteria for bipolar disorder type II of the manual for diagnosis and statistics of mental disorders fifth edition (DSM-5) and confirms the current onset of major depressive disorder via simple international neuropsychiatric interview (MINI);

b. the Montgomery-Abbe depression rating scale (MADRS) total score of 24 or greater before the first administration at screening and day 0;

4. The total score of the Young Mania Rating Scale (YMRS) at screening and prior to the first administration on day 0 is less than or equal to 8;

5. the consent was to keep any psychotherapy unchanged and no new psychoactive drugs were started during the trial.

6. Female patients must be treated by surgical sterilization (hysterectomy, tubal ligation or bilateral ovariectomy (6 months prior to screening)), either postmenopausal and amenorrhea or complete abstinence (complete avoidance of anisotropic intercourse) over the last 2 years, or by using medically approved high-efficiency (failure rate < 1%) contraceptive methods including, but not limited to, bilateral tubal ligation/occlusion, hormonal contraceptives to inhibit ovulation, intrauterine devices (including hormone-releasing intrauterine devices/systems), and serum pregnancy tests must be negative at screening and urine pregnancy tests negative the day prior to testing (day-1).

7. Male patients must use prophylactic contraceptives (i.e., use of spermicidal condoms or abstinence) and must not donate sperm within 30 days after 5-MeO-DMT administration.

Potential patients meeting any of the following critical exclusion criteria will be excluded from the trial:

1. Based on the medical history, psychiatric and MINI assessments, it is currently or previously diagnosed with bipolar I disorder, manic episodes, psychotic disorders, major Depressive Disorder (MDD) or other mood disorders characterized by psychosis, obsessive compulsive disorder, post Traumatic Stress Disorder (PTSD), autism spectrum disorders, borderline personality disorder, schizophrenia, delusional disorder, paranoid personality disorder, schizoaffective disorder, clinically significant intellectual disorders, or any other psychotic co-disorder at the discretion of the researcher that results in a patient unsuitable for participation in the trial.

2. One or more primary or secondary relatives are currently or previously diagnosed with psychotic disorder, bipolar disorder type I or MDD with psychotic features.

3. There is a significant risk of suicide defined as (a) the occurrence of the suicidal ideation as set forth in C-SSRS clause 4 or 5 over the past year, during screening, or at baseline, or (b) the occurrence of suicidal behavior over the past year, or (C) a clinical assessment of significant suicide risk during a clinical interview, or (d) the occurrence of non-suicidal sui-C-ic behavior over the past year.

4. Antidepressants are administered orally 7 days or 5 half-lives (longer, as in the case of fluoxetine, for the past 5 weeks).

5. Drugs with monoamine oxidase inhibitor (MAOI) activity were administered orally 14 days or 5 half-lives (whichever is longer) prior to administration.

6. Mood stabilizer therapy (e.g., lamotrigine, valproic acid, atypical antipsychotics) was received 14 days (28 days for lithium) or 5 half-lives (whichever is longer) prior to dosing, or at the time of screening, or was expected to be needed during the study (at the discretion of the investigator).

7. At the discretion of the investigator, serious adverse reactions have previously occurred to hallucinogens or hallucinogens.

8. Allergy or hypersensitivity to 5-MeO-DMT or any other contraindications are known.

9. Suffering from any current or past clinically significant condition (e.g., severe infection, severe pulmonary disease, uncontrolled hypertension, uncontrolled diabetes, severe cardiovascular disease, severe liver or kidney failure, severe brain disorders (including epilepsy, stroke, dementia, degenerative neurological disorders, meningitis, encephalitis, and head injury with loss of consciousness), which may interfere with interpretation of test results, constitute a risk to the health of the patient, or render the patient unsuitable for participation in the test at the discretion of the researcher.

10. At the discretion of the investigator, any medications or other substances that render the patient unsuitable for participation in the trial are administered.

11. At the discretion of the researcher, there are clinically significant abnormalities in physical examination, vital signs, electrocardiogram (ECG), or clinical laboratory parameters that render the patient unsuitable for participation in the trial.

12. Female patients were positive for pregnancy tests at screening or the day prior to testing (day-1), had been pregnant or lactating, or were scheduled to become pregnant during the course of the test and up to 30 days after administration of 5-MeO-DMT.

13. Patients with DSM-5, alcohol or substance use disorders (excluding tobacco or caffeine use disorders) within 6 months prior to screening.

The main objective of the trial was to determine the onset time and duration of antidepressant effect using a single day personalized regimen (1 mg, 2mg and 3mg 5-MeO-DMT) for patients with bipolar II disorder and current major depressive episode. The secondary objective was to determine the effect of a single day personalized dosing regimen (1 mg, 2mg and 3mg 5-MeO-DMT) on depressive symptoms and overall clinical status of patients with bipolar II disorder and current major depressive episodes, safety and tolerability, intensity and duration of psychoactive effects (pses), effect on sleep quality, effect on cognitive outcome.

The primary endpoint of this study was to assess the antidepressant effect of 5-MeO-DMT by the change in MADRS from baseline assessed on day 7.

Secondary endpoints include:

The antidepressant effect of 5-MeO-DMT via intravenous injection was evaluated by:

the proportion of patients who were relieved (MADRS. Ltoreq.10) on day 02, day 1 and day 7 after the final study drug administration;

Changes from baseline in MADRS assessed 2 hours and day 1 post-drug administration at day 0 final study;

2 hours, 1 day and 7 days after the final study drug administration at day 0, the proportion of responders (total MADRS decrease by > 50% from baseline);

Changes from baseline in CGI-S assessed at day 0, 2 hours and day 1 and day 7 post-drug dosing of the final study.

Change from baseline of BDRS on day 1 and day 7

Safety and tolerability of 5-MeO-DMT via intravenous injection was evaluated by:

reporting adverse events (TEAE) occurring in the treatment;

Clinically significant changes from baseline for ECG, vital signs, safety laboratory assessment, and spirometry assessment;

sedation assessment (modified observer alertness and sedation assessment scale [ MOAA/S ]) was performed after each dose (when pses resolved and 60 minutes after each study medication administration) and as part of discharge assessment on day 0;

incidence of Adverse Events (AE) of mania or hypomania (assessed using the mania/hypomania DSM-5 standard);

Change from baseline of YMRS assessed as part of discharge evaluations on day 0, day 1, and day 7;

variation of the clinical administration split status scale (CADSS) from baseline assessed as part of discharge evaluations on day 0, day 1 and day 7;

assessing patient discharge readiness at day 0 of discharge using discharge readiness Clinical Assessment (CADR);

Changes from baseline on the Brief Psychosis Rating Scale (BPRS) assessed as part of discharge evaluations on day 0, day 1 and day 7;

C-SSRS classification based on Columbia suicide evaluation classification algorithm (C-CASA).

The patient experience of pses reported 30 to 60 minutes after each dose, at which time the pses have resolved:

A PsE evaluation using a Peak Experience (PE) scale (PES) to evaluate the implementation of PE (PES total score. Gtoreq.75);

challenge Experience Questionnaire (CEQ);

mystery experience questionnaire (MEQ-30).

The PsE duration is defined as the time from the administration of the study drug to the time the PsE has resolved, completed 30 to 60 minutes after each administration.

The effect on sleep quality, as assessed by changes in the Pittsburgh Sleep Quality Index (PSQI) from the day before the test (day-1) to day 1 and to day 7.

The effect on cognitive outcome, as assessed from day before test (day-1) to day 0 discharge, to day 1 and to day 7:

a rapid visual information processing (RVP) test;

a speech recognition memory (VRM) test;

a Space Working Memory (SWM) test;

The Digital Symbol Substitution Test (DSST).

Example 15-clinical trial of administration of 5-MeO-DMT to post-partum depressed patients via intravenous injection-prophetic example

The present clinical trial will involve adult female patients clinically diagnosed with post-partum depression (PPD).

Patients received a single day personalized 5-MeO-DMT dosing regimen by intravenous injection. The 5-MeO-DMT will be provided in the form of its hydrobromide salt and intravenous injection formulations. It should be understood that the dosages of 5-MeO-DMT referred to below are related to the weight of the free base, while the dosages of 5-MeO-DMT hydrobromide can be calculated assuming equimolar amounts.

More specifically, patients will receive up to three doses of 5-MeO-DMT at day 0, 2 mg, 5 mg, and 8 mg.

1. All patients will receive an initial dose of 2 mg of 5-MeO-DMT.

2. The second dose (5 mg) was only applied if:

a. peak experience (total score > 75) was not achieved after 2 mg doses, and

B. according to the researchers, the 2 mg dose was safe, well tolerated,

C. any psychoactive effects (PsE) of the previous dose have been resolved, and

D. The pre-dosing vital signs and force effort per second (FEV 1) were within normal range or if outside of normal range, according to the investigator, clinically insignificant.

3. Likewise, the third dose (8 mg) would be administered only if:

a. Peak experience (total score > 75) was not achieved after 5mg doses, and

B. According to the researchers, the 5 mg dose was safe, well tolerated,

C. any PsE of the previous dose had resolved, and

D. The pre-dosing vital signs and force effort per second (FEV 1) were within normal range or if outside of normal range, according to the investigator, clinically insignificant.

The patient will receive an assessment of peak illusion experience (visual analog scale based on patient score, i.e., PE scale), sedation and other endpoints after administration. Follow-up on days 1 and 7 after dosing was planned.

All patients considered to participate in the clinical trial must meet the following criteria:

1. is female and is between 18 and 45 years of age (inclusive) at the time of screening.

2. Body Mass Index (BMI) at screening was in the range of 18.5 to 35 kg/m ² (inclusive).

3. Meets the test criteria for PPD evaluated by the test psychiatrist or the registered psychologist:

a. major depressive disorder diagnosed as not accompanied by psychotic features was confirmed by simple international neuropsychiatric interviews (MINI), and perinatal period onset time was no earlier than gestation and no later than 4 weeks before post partum.

B. the Montgomery-Arabidopsis depression rating scale (MADRS) total score at screening and prior to administration on day 0 is equal to or greater than 28.

6. It is necessary to stop breast feeding at screening, or if breast feeding is still being fed or active at screening, it is necessary to agree to stop breast feeding temporarily for 24 hours from the time of day 0 before receiving study medication to the time of the last dose, and aspirate and discard all breast milk as needed within these 24 hours, but it is necessary to aspirate/discard breast milk 2.5 hours after the last dose and 24 hours after the last dose before restarting breast feeding.

4. It must be agreed to either completely abstinence (complete avoidance of sexuality) or use a highly effective (failure rate < 1%) and medically approved contraceptive method within 30 days prior to administration and 90 days after administration of 5-MeO-DMT. The pregnancy test results for the patients at the time of screening and the day prior to the test (day-1) must be negative.

5. It is desirable to delay the initial use of other antidepressants or anxiolytics until after the end of the trial on day 7 and agree to keep any psychotherapy unchanged during the trial.

Potential patients meeting any of the following critical exclusion criteria will be excluded from the trial:

1. Based on the medical history, psychiatric assessment and MINI assessment, it is currently or previously diagnosed with bipolar disorder, manic or hypomanic episodes, psychotic disorder, major Depressive Disorder (MDD) or other mood disorders characterized by psychosis, obsessive compulsive disorder, post Traumatic Stress Disorder (PTSD), autism spectrum disorder, borderline personality disorder, schizophrenia, delusional disorder, paranoid personality disorder, schizoaffective disorder, clinically significant intellectual impairment, or at the discretion of the researcher, resulting in a patient unsuitable for participation in any other psychotic co-disorder tested.

2. One or more primary or secondary relatives are currently or previously diagnosed with bipolar disorder, psychotic disorder, or other mood disorder characterized by psychosis (including MDD).

3. The test psychiatrist or registered psychiatrist judged that there was a significant risk of suicidal activity based on medical history, psychiatrist assessment and the assessment of suicidal ideation and behavior based on the Columbia suicide severity rating scale (C-SSRS).

4. Antidepressants are administered orally 14 days or 5 half-lives (longer, as in the case of fluoxetine, for the past 5 weeks).

5. Any other drug having monoamine oxidase inhibitor (MAOI) activity was administered orally 14 days or 5 half-lives (longer).

6. At the discretion of the investigator, serious adverse reactions have previously occurred to phantom or hallucinogens (e.g., nupharin, nupharia species mushrooms, 5-MeO-DMT, dead rattan water, LSD, michelin).

7. Allergy or hypersensitivity to 5-MeO-DMT or any other contraindications are known.

8. At the discretion of the investigator, suffering from any current or past clinically significant condition that would render the patient unsuitable for participation in the trial (e.g., severe infection, pulmonary disease, uncontrolled hypertension, gestational hypertension disorder during pregnancy or after-delivery new episodes (e.g., gestational hypertension, preeclampsia, eclampsia), uncontrolled diabetes, severe cardiovascular disease, severe liver or kidney failure, severe brain disorder (including epilepsy, stroke, dementia, degenerative neurological disorders, meningitis, encephalitis, and head injury with loss of consciousness).

9. At the discretion of the investigator, any medications or other substances that render the patient unsuitable for participation in the trial are administered.

10. At the discretion of the investigator, there are clinically significant abnormalities in physical examination, vital signs, ECG, or clinical laboratory parameters that render the patient unsuitable for participation in the trial.

11. Patients were positive for pregnancy tests at screening or the day prior to testing (day-1), had been pregnant, or were scheduled to become pregnant during the course of the test and up to 90 days after administration of 5-MeO-DMT.

12. Patients had DSM-5 drug or alcohol usage disorders within 6 months prior to screening.

The main objective of the trial was to determine the onset time and 7-day duration of antidepressant effect using a single day personalized regimen (2 mg, 5 mg and 8 mg 5-MeO-DMT) for adult female PPD patients.

The secondary objective was to determine the antidepressant effect, anxiolytic effect, effect on maternal behaviour, safety and tolerability, intensity and duration of psychoactive effect (PsE) on adult female PPD patients, influence on cognitive outcome, of a single day personalized dosing regimen (2 mg, 5mg and 8 mg 5-MeO-DMT).

Exploratory purposes were to determine the amounts of 5-MeO-DMT and metabolites, bufogenin and 5-methoxyindole-3-acetic acid (5-MIAA) in breast milk, blood and urine (metabolite identification screening can be performed as needed) after single daily administration of single day personalized IDR (2 mg, 5 mg and 8 mg 5-MeO-DMT) to adult female PPD patients, as measured by LC/MS.

The primary endpoint of this study was to assess the antidepressant effect of 5-MeO-DMT by the change in MADRS from baseline assessed on day 7.

Secondary endpoints included evaluation of the antidepressant effect of 5-MeO-DMT by:

the antidepressant effect of 5-MeO-DMT was evaluated by:

the proportion of patients who were relieved (MADRS. Ltoreq.10) on day 02, day 1 and day 7 after the final study drug administration;

Changes from baseline in MADRS assessed 2 hours and day 1 post-drug administration at day 0 final study;

2 hours, 1 day and 7 days after the final study drug administration at day 0, the proportion of responders (total MADRS decrease by > 50% from baseline);

Changes in clinical global impression-severity (CGI-S) from baseline at day 0 at 2 hours, day 1 and day 7 post-drug administration of the final study;

the effect on maternal behavior as assessed by the change in the total and sub-scale scores of Barkin maternal function index (BIMF) from baseline to day 7;

Exposure of 5-MeO-DMT and bufotiamine in breast milk obtained on the day before testing (day-1), 1 hour after the last administration of study drug, at discharge, at night on day 0, and on days 1 and 7;

exposure of 5-MeO-DMT and bufotaline in blood obtained on the day before testing (day-1), 1 hour after the last administration of study drug, at discharge, and on day 1 and day 7;

Safety and tolerability of 5-MeO-DMT was evaluated by:

reporting adverse events (TEAE) occurring in the treatment;

clinically significant changes from baseline in ECG, vital signs, safety laboratory assessment, peak flow respirometry;

sedation assessment (modified observer alertness and sedation assessment scale [ MOAA/S ]) was performed after each dose (when pses resolved and 60 minutes after each study medication administration) and as part of discharge assessment on day 0;

variation of the clinical administration split status scale (CADSS) from baseline assessed as part of discharge evaluations on day 0, day 1 and day 7;

Changes from baseline on the Brief Psychosis Rating Scale (BPRS) assessed as part of discharge evaluations on day 0, day 1 and day 7;

changes from baseline in C-SSRS assessed as part of discharge evaluations on day 0, day 1 and day 7;

Change from baseline of YMRS assessed as part of discharge evaluations on day 0, day 1, and day 7;

the patient experience of pses reported 30 to 60 minutes after each dose, at which time the pses have resolved:

A PsE evaluation of evaluating the implementation of PE using a Peak Experience (PE) scale (PE scale total score. Gtoreq.75);

challenge Experience Questionnaire (CEQ);

Mystery experience questionnaire (MEQ-30);

The PsE duration is defined as the time from study drug administration to the time the PsE has resolved (study score and patient score), completed 30 to 60 minutes after each administration;

example 16-clinical trial of administration of 5-MeO-DMT to post-partum depressed patients via intravenous injection-prophetic example

The present clinical trial will involve adult female patients clinically diagnosed with post-partum depression (PPD).

Patients received a single day personalized 5-MeO-DMT dosing regimen by intravenous injection. The 5-MeO-DMT will be provided in the form of its hydrobromide salt and intravenous injection formulations. It should be understood that the dosages of 5-MeO-DMT referred to below are related to the weight of the free base, while the dosages of 5-MeO-DMT hydrobromide can be calculated assuming equimolar amounts.

More specifically, patients will receive up to three doses of 5-MeO-DMT 1 mg, 2 mg, and 3 mg on day 0.

1. All patients will receive an initial dose of 1 mg 5-MeO-DMT.

2. The second dose (2 mg) was only applied if:

a. Peak experience (total score > 75) was not achieved after 1 mg doses, and

B. according to the researchers, the 1 mg dose was safe, well tolerated,

C. any psychoactive effects (PsE) of the previous dose have been resolved, and

D. The pre-dosing vital signs and force effort per second (FEV 1) were within normal range or if outside of normal range, according to the investigator, clinically insignificant.

3. Likewise, the third dose (3 mg) would be administered only if:

a. peak experience (total score > 75) was not achieved after 2 mg doses, and

B. according to the researchers, the 2 mg dose was safe, well tolerated,

C. any PsE of the previous dose had resolved, and

D. The pre-dosing vital signs and force effort per second (FEV 1) were within normal range or if outside of normal range, according to the investigator, clinically insignificant.

The patient will receive an assessment of peak illusion experience (visual analog scale based on patient score, i.e., PE scale), sedation and other endpoints after administration. Follow-up on days 1 and 7 after dosing was planned.

All patients considered to participate in the clinical trial must meet the following criteria:

1. is female and is between 18 and 45 years of age (inclusive) at the time of screening.

2. Body Mass Index (BMI) at screening was in the range of 18.5 to 35 kg/m ² (inclusive).

3. Meets the test criteria for PPD evaluated by the test psychiatrist or the registered psychologist:

a. major depressive disorder diagnosed as not accompanied by psychotic features was confirmed by simple international neuropsychiatric interviews (MINI), and perinatal period onset time was no earlier than gestation and no later than 4 weeks before post partum.

B. the Montgomery-Arabidopsis depression rating scale (MADRS) total score at screening and prior to administration on day 0 is equal to or greater than 28.

6. It is necessary to stop breast feeding at screening, or if breast feeding is still being fed or active at screening, it is necessary to agree to stop breast feeding temporarily for 24 hours from the time of day 0 before receiving study medication to the time of the last dose, and aspirate and discard all breast milk as needed within these 24 hours, but it is necessary to aspirate/discard breast milk 2.5 hours after the last dose and 24 hours after the last dose before restarting breast feeding.

4. It must be agreed to either completely abstinence (complete avoidance of sexuality) or use a highly effective (failure rate < 1%) and medically approved contraceptive method within 30 days prior to administration and 90 days after administration of 5-MeO-DMT. The pregnancy test results for the patients at the time of screening and the day prior to the test (day-1) must be negative.

5. It is desirable to delay the initial use of other antidepressants or anxiolytics until after the end of the trial on day 7 and agree to keep any psychotherapy unchanged during the trial.

Potential patients meeting any of the following critical exclusion criteria will be excluded from the trial:

1. Based on the medical history, psychiatric assessment and MINI assessment, it is currently or previously diagnosed with bipolar disorder, manic or hypomanic episodes, psychotic disorder, major Depressive Disorder (MDD) or other mood disorders characterized by psychosis, obsessive compulsive disorder, post Traumatic Stress Disorder (PTSD), autism spectrum disorder, borderline personality disorder, schizophrenia, delusional disorder, paranoid personality disorder, schizoaffective disorder, clinically significant intellectual impairment, or at the discretion of the researcher, resulting in a patient unsuitable for participation in any other psychotic co-disorder tested.

2. One or more primary or secondary relatives are currently or previously diagnosed with bipolar disorder, psychotic disorder, or other mood disorder characterized by psychosis (including MDD).

3. The test psychiatrist or registered psychiatrist judged that there was a significant risk of suicidal activity based on medical history, psychiatrist assessment and the assessment of suicidal ideation and behavior based on the Columbia suicide severity rating scale (C-SSRS).

4. Antidepressants are administered orally 14 days or 5 half-lives (longer, as in the case of fluoxetine, for the past 5 weeks).

5. Any other drug having monoamine oxidase inhibitor (MAOI) activity was administered orally 14 days or 5 half-lives (longer).

6. At the discretion of the investigator, serious adverse reactions have previously occurred to phantom or hallucinogens (e.g., nupharin, nupharia species mushrooms, 5-MeO-DMT, dead rattan water, LSD, michelin).

7. Allergy or hypersensitivity to 5-MeO-DMT or any other contraindications are known.

8. At the discretion of the investigator, suffering from any current or past clinically significant condition that would render the patient unsuitable for participation in the trial (e.g., severe infection, pulmonary disease, uncontrolled hypertension, gestational hypertension disorder during pregnancy or after-delivery new episodes (e.g., gestational hypertension, preeclampsia, eclampsia), uncontrolled diabetes, severe cardiovascular disease, severe liver or kidney failure, severe brain disorder (including epilepsy, stroke, dementia, degenerative neurological disorders, meningitis, encephalitis, and head injury with loss of consciousness).

9. At the discretion of the investigator, any medications or other substances that render the patient unsuitable for participation in the trial are administered.

10. At the discretion of the investigator, there are clinically significant abnormalities in physical examination, vital signs, ECG, or clinical laboratory parameters that render the patient unsuitable for participation in the trial.

11. Patients were positive for pregnancy tests at screening or the day prior to testing (day-1), had been pregnant, or were scheduled to become pregnant during the course of the test and up to 90 days after administration of 5-MeO-DMT.

12. Patients had DSM-5 drug or alcohol usage disorders within 6 months prior to screening.

The main objective of the trial was to determine the onset time and 7-day duration of antidepressant effect using a single day personalized regimen (1 mg, 2 mg and 3 mg 5-MeO-DMT) for adult female PPD patients.

The secondary objective was to determine the antidepressant effect, anxiolytic effect, effect on maternal behaviour, safety and tolerability, intensity and duration of psychoactive effect (PsE) on adult female PPD patients, influence on cognitive outcome, of a single day personalized dosing regimen (1 mg, 2 mg and 3 mg 5-MeO-DMT).

Exploratory purposes were to determine the amounts of 5-MeO-DMT and metabolites, bufogenin and 5-methoxyindole-3-acetic acid (5-MIAA) in breast milk, blood and urine (metabolite identification screening can be performed as needed) after single daily administration of single day personalized IDR (1 mg, 2 mg and 3 mg 5-MeO-DMT) to adult female PPD patients, as measured by LC/MS.

The primary endpoint of this study was to assess the antidepressant effect of 5-MeO-DMT by the change in MADRS from baseline assessed on day 7.

Secondary endpoints included evaluation of the antidepressant effect of 5-MeO-DMT by:

the antidepressant effect of 5-MeO-DMT was evaluated by:

the proportion of patients who were relieved (MADRS. Ltoreq.10) on day 02, day 1 and day 7 after the final study drug administration;

Changes from baseline in MADRS assessed 2 hours and day 1 post-drug administration at day 0 final study;

2 hours, 1 day and 7 days after the final study drug administration at day 0, the proportion of responders (total MADRS decrease by > 50% from baseline);

Changes in clinical global impression-severity (CGI-S) from baseline at day 0 at 2 hours, day 1 and day 7 post-drug administration of the final study;

the effect on maternal behavior as assessed by the change in the total and sub-scale scores of Barkin maternal function index (BIMF) from baseline to day 7;

Exposure of 5-MeO-DMT and bufotiamine in breast milk obtained on the day before testing (day-1), 1 hour after the last administration of study drug, at discharge, at night on day 0, and on days 1 and 7;

exposure of 5-MeO-DMT and bufotaline in blood obtained on the day before testing (day-1), 1 hour after the last administration of study drug, at discharge, and on day 1 and day 7;

Safety and tolerability of 5-MeO-DMT was evaluated by:

reporting adverse events (TEAE) occurring in the treatment;

clinically significant changes from baseline in ECG, vital signs, safety laboratory assessment, peak flow respirometry;

sedation assessment (modified observer alertness and sedation assessment scale [ MOAA/S ]) was performed after each dose (when pses resolved and 60 minutes after each study medication administration) and as part of discharge assessment on day 0;

variation of the clinical administration split status scale (CADSS) from baseline assessed as part of discharge evaluations on day 0, day 1 and day 7;

Changes from baseline on the Brief Psychosis Rating Scale (BPRS) assessed as part of discharge evaluations on day 0, day 1 and day 7;

Changes from baseline in C-SSRS assessed as part of discharge evaluations on day 0, day 1 and day 7;

Change from baseline of YMRS assessed as part of discharge evaluations on day 0, day 1, and day 7;

the patient experience of pses reported 30 to 60 minutes after each dose, at which time the pses have resolved:

A PsE evaluation of evaluating the implementation of PE using a Peak Experience (PE) scale (PE scale total score. Gtoreq.75);

challenge Experience Questionnaire (CEQ);

Mystery experience questionnaire (MEQ-30);

The PsE duration is defined as the time from study drug administration to the time the PsE has resolved (study score and patient score), and is completed 30 to 60 minutes after each administration.

Claims (87)

1. 5-Methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use in the treatment of a disorder of the mental or nervous system of a breast-feeding mother,

   Wherein about 1 mg to about 10 mg doses of 5-MeO-DMT or equimolar amounts of the pharmaceutically acceptable salt are administered in a single dose or in the highest dose in an up-titration regimen involving an administration interval of at least about 1 hour,

   Wherein said 5-MeO-DMT or said pharmaceutically acceptable salt thereof is administered via intravenous, intramuscular, or subcutaneous routes,

   Wherein the patient is advised to temporarily stop breast feeding.
2. 2. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claim 1, wherein the patient is advised to temporarily stop breast feeding 1 hour or more before receiving the first dose and not to resume breast feeding for at least 24 hours after the last dose.
3. 3. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claim 1, wherein the patient is advised to temporarily stop breast feeding 1 hour or more before receiving the first dose and not to resume breast feeding for at least 12 hours after the last dose.
4. 4. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claim 1, wherein the patient is advised to temporarily stop breast feeding 1 hour or more before receiving the first dose and not to resume breast feeding for at least 6 hours after the last dose.
5. 5. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claim 1, wherein the patient is advised to temporarily stop breast feeding 1 hour or more before receiving the first dose and not to resume breast feeding for at least 2 hours after the last dose.
6. 6. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claim 1, wherein the patient is advised to temporarily stop breast feeding 1 hour or more before receiving the first dose and not to resume breast feeding for at least 1 hour after the last dose.
7. 7. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claim 1, wherein the patient is advised to start temporarily stopping breast feeding before receiving the first dose and not to resume breast feeding for at least 24 hours after the last dose.
8. 8. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claim 1, wherein the patient is advised to start temporarily stopping breast feeding before receiving the first dose and not to resume breast feeding for at least 12 hours after the last dose.
9. 9. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claim 1, wherein the patient is advised to start temporarily stopping breast feeding before receiving the first dose and not to resume breast feeding for at least 6 hours after the last dose.
10. 10. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claim 1, wherein the patient is advised to start temporarily stopping breast feeding before receiving the first dose and not to resume breast feeding for at least 2 hours after the last dose.
11. 11. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claim 1, wherein the patient is advised to start temporarily stopping breast feeding before receiving the first dose and not to resume breast feeding for at least 1 hour after the last dose.
12. 12. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claim 1, wherein the patient is advised to temporarily stop breast feeding only during the actual treatment.
13. 13. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 1 to 12, wherein the patient is advised to start temporarily stopping breast feeding until ready for discharge before receiving the first dose.
14. 14. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claim 13, wherein the determination of the discharge preparation is performed about 1 hour after the last dose.
15. 15. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claim 13 or 14, wherein the patient is advised not to restart breast feeding within 6 hours before discharge and after the last dose, whichever is later.
16. 16. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 1 to 15, wherein it is recommended that the patient does not restart breast feeding within 3 hours before discharge and after the last dose, whichever is later.
17. 17. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 1 to 15, wherein it is recommended that the patient does not restart breast feeding within 2 hours before discharge and after the last dose, whichever is later.
18. 18. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 1 to 15, wherein it is recommended that the patient does not restart breast feeding within 1 hour before discharge and after the last dose, whichever is later.
19. 19. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 1 to 18, wherein the patient is advised to start temporarily stopping breast feeding before receiving the first dose until at least 24 hours after the last dose and to discard all expressed breast milk within a 24 hour period.
20. 20. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 1 to 18, wherein the patient is advised to start temporarily stopping breast feeding before receiving the first dose until at least 2.5 hours after the last dose and to aspirate and discard breast milk 2.5 hours after the last dose.
21. 21. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 1 to 20, wherein the patient is advised to aspirate and discard breast milk 24 hours after the last dose before restarting breast feeding.
22. 22. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 1 to 21, wherein the patient is recommended to breast-feed the child no more than 2 times within the first 12 hours after the last dose.
23. 23. 5-Methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 1 to 22, wherein any expressed breast milk is discarded as long as the concentration of 5-MeO-DMT and/or 5-MIAA in the breast milk exceeds a predetermined threshold.
24. 24. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claim 23, wherein the threshold value of 5-MeO-DMT is 2000 pg.
25. 25. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claim 23, wherein the threshold value of 5-MeO-DMT is 500 pg.
26. 26. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claim 23, wherein the threshold value of 5-MeO-DMT is 75 pg.
27. 27. 5-Methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 23 to 26, wherein the threshold value of 5-MIAA is 14000 pg.
28. 28. 5-Methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 23 to 26, wherein the threshold value of 5-MIAA is 2000 pg.
29. 29. 5-Methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 23 to 26, wherein the threshold value of 5-MIAA is 75 pg.
30. 30. A 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 1 to 22, which resumes breast feeding when the 5-MeO-DMT concentration and/or the 5-MIAA concentration in breast milk is below a predetermined threshold.
31. 31. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claim 30, wherein the threshold value of 5-MeO-DMT is 2000 pg.
32. 32. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claim 30, wherein the threshold value of 5-MeO-DMT is 500 pg.
33. 33. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claim 30, wherein the threshold value of 5-MeO-DMT is 75 pg.
34. 34. A 5-methoxy-N, N-dimethylprimary amine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to any one of claims 30 to 33 wherein the threshold value for 5-MIAA is 14000 pg.
35. 35. A 5-methoxy-N, N-dimethylprimary amine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to any one of claims 30 to 33 wherein the threshold value for 5-MIAA is 2000 pg.
36. 36. A 5-methoxy-N, N-dimethylprimary amine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to any one of claims 30 to 33 wherein the threshold value for 5-MIAA is 75 pg.
37. 37. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 1 to 36, wherein the breast feeding is adjusted such that the DID of 5-MeO-DMT per kg of infant body weight is 1 μg/kg/day or less within the first 24 hours of resumption of breast feeding, wherein the adjustment is by selecting the appropriate point in time to resumption of breast feeding, the appropriate number of feeds within the first 24 hours of resumption of breast feeding, aspiration and discard of breast milk during the appropriate period of time, or a combination of these measures.
38. 38. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 1 to 36, wherein the breast feeding is adjusted such that the DID of 5-MeO-DMT per kg of infant body weight is 0.4 μg/kg/day or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting the appropriate point in time for resumption of breast feeding, the appropriate number of feeds within the first 24 hours of resumption of breast feeding, aspiration and discard of breast milk during the appropriate period of time, or a combination of these measures.
39. 39. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 1 to 36, wherein the breast feeding is adjusted such that the DID of 5-MeO-DMT per kg of infant body weight is 0.2 μg/kg/day or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting the appropriate point in time for resumption of breast feeding, the appropriate number of feeds within the first 24 hours of resumption of breast feeding, aspiration and discard of breast milk during the appropriate period of time, or a combination of these measures.
40. 40. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 1 to 39, wherein the breast feeding is adjusted such that the RID of 5-MeO-DMT is 10% or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting the appropriate point in time to resumption of breast feeding, the appropriate number of feeds within the first 24 hours of resumption of breast feeding, sucking and discarding breast milk during the appropriate period of time, or a combination of these measures.
41. 41. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 1 to 39, wherein the breast feeding is adjusted such that the RID of 5-MeO-DMT is 5% or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting the appropriate point in time to resumption of breast feeding, the appropriate number of feeds within the first 24 hours of resumption of breast feeding, sucking and discarding breast milk during the appropriate period of time, or a combination of these measures.
42. 42. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 1 to 39, wherein the breast feeding is adjusted such that the RID of 5-MeO-DMT is 1% or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting the appropriate point in time to resumption of breast feeding, the appropriate number of feeds within the first 24 hours of resumption of breast feeding, sucking and discarding breast milk during the appropriate period of time, or a combination of these measures.
43. 43. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT), or a pharmaceutically acceptable salt thereof, for use according to claims 1 to 42, wherein the breast feeding is adjusted such that the DID of the final metabolite 5-MIAA per kg of infant body weight is 4 μg/kg/day or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting the appropriate point in time for resumption of breast feeding, the appropriate number of feeds within the first 24 hours of resumption of breast feeding, aspiration and discard of breast milk during the appropriate period of time, or a combination of these measures.
44. 44. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT), or a pharmaceutically acceptable salt thereof, for use according to claims 1 to 42, wherein the breast feeding is adjusted such that the DID of the final metabolite 5-MIAA per kg of infant body weight is 2 μg/kg/day or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting the appropriate point in time for resumption of breast feeding, the appropriate number of feeds within the first 24 hours of resumption of breast feeding, aspiration and discard of breast milk during the appropriate period of time, or a combination of these measures.
45. 45. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT), or a pharmaceutically acceptable salt thereof, for use according to claims 1 to 42, wherein the breast feeding is adjusted such that the DID of the final metabolite 5-MIAA per kg of infant body weight is 1 μg/kg/day or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting the appropriate point in time for resumption of breast feeding, the appropriate number of feeds within the first 24 hours of resumption of breast feeding, aspiration and discard of breast milk during the appropriate period of time, or a combination of these measures.
46. 46. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 1 to 45, wherein the breast feeding is adjusted such that the RID of the terminal metabolite 5-MIAA is 4% or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting an appropriate point in time for resumption of breast feeding, an appropriate number of feeds within the first 24 hours of resumption of breast feeding, aspiration and discard of breast milk during an appropriate period of time, or a combination of these measures.
47. 47. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 1 to 45, wherein the breast feeding is adjusted such that the RID of the terminal metabolite 5-MIAA is 2% or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting an appropriate point in time for resumption of breast feeding, an appropriate number of feeds within the first 24 hours of resumption of breast feeding, aspiration and discard of breast milk during an appropriate period of time, or a combination of these measures.
48. 48. The 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use according to claims 1 to 45, wherein the breast feeding is adjusted such that the RID of the terminal metabolite 5-MIAA is 1% or less within the first 24 hours of feeding after resumption of breast feeding, wherein the adjustment is by selecting an appropriate point in time for resumption of breast feeding, an appropriate number of feeds within the first 24 hours of resumption of breast feeding, aspiration and discard of breast milk during an appropriate period of time, or a combination of these measures.
49. 49. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claims 1 to 48, wherein the patient is afflicted with PPD.
50. 50. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 49, wherein the alleviation of symptoms of depression, assessed as a MADRS score of 10 or less, occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.
51. 51. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 50, wherein the alleviation of symptoms of depression, assessed as having a HAM-D score of 7 or less, occurs no later than about 2 hours after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof.
52. 52. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use according to claim 1 to 51, wherein maternal function is improved according to the Barkin maternal function index (BIMF) of maternal-maternal interactions and mental health, which is reflected in improvements in the area of function.
53. 53. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of claim 52, wherein the improvement in cumulative score for the BIMF-scale item reflecting mental health is at least 25% and the improvement in cumulative score for the BIMF-scale item reflecting maternal-maternal interaction is at least 5%.
54. 54. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 52 or 53, wherein an improvement in the MADRS project in lazy, pessimistic ideas, sensory deficit, internal stress, and/or sleep reduction results in an increase in the BIMF scale score reflecting mental health, and an improvement in the MADRS project sensory deficit and internal stress results in an increase in the BIMF scale score reflecting maternal-maternal interaction.
55. 55. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to any one of claims 1 to 54, wherein the patient suffers from a mental or neurological disorder involving one or more symptoms selected from sleep disorders and anxiety, wherein each of these symptoms impairs maternal function.
56. 56. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of claim 55, wherein the patient suffers from a mental or neurological disorder in which anxiety symptoms are involved, and wherein the treatment reduces or eliminates symptoms of anxiety, particularly internal stress.
57. 57. The5-MeO-DMTorapharmaceuticallyacceptablesaltthereofforuseofclaim56,whereinabout2hoursafterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,theclinicalresponseresultingfromtreatmentisreflectedinadecreaseintheHAM-ascoreofatleast50%comparedtothecorrespondingscorepriortotreatment.
58. 58. The5-MeO-DMTorapharmaceuticallyacceptablesaltthereofforuseofclaim56or57,whereinatday1,e.g.,afterabout24hours,afterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,theclinicalresponsecausedbytreatmentisreflectedinadecreaseintheHAM-ascoreofatleast50%comparedtothecorrespondingscorepriortotreatment.
59. 59. The5-MeO-DMTorapharmaceuticallyacceptablesaltthereofforuseofclaims56-58,whereinatday7afterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,theclinicalresponseresultingfromtreatmentisreflectedinadecreaseintheHAM-ascoreofatleast50%comparedtothecorrespondingscorepriortotreatment.
60. 60. The5-MeO-DMTorapharmaceuticallyacceptablesaltthereofforuseofclaims56-59,whereinatday14afterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,theclinicalresponseresultingfromtreatmentisreflectedinadecreaseintheHAM-ascoreofatleast50%comparedtothecorrespondingscorepriortotreatment.
61. 61. The5-MeO-DMTorapharmaceuticallyacceptablesaltthereofforuseofclaims56to60,whereinatday28afterthelastadministrationof5-MeO-DMTorapharmaceuticallyacceptablesaltthereof,theclinicalresponseresultingfromtreatmentisreflectedinadecreaseintheHAM-ascoreofatleast50%comparedtothecorrespondingscorepriortotreatment.
62. 62. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of claim 55 to 61, wherein the patient suffers from a mental or neurological disorder that involves symptoms of a sleep disorder, and wherein treatment reduces or eliminates symptoms of a sleep disorder.
63. 63. The 5-MeO-DMT or pharmaceutically acceptable salt thereof for use according to claim 62, wherein the patient suffers from sleep disorders reflected as a Pittsburgh Sleep Quality Index (PSQI) overall score of >5.
64. 64. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 62 or 63, wherein the treatment reduces or eliminates sleep disorders and the reduction or elimination of sleep disorders is reflected in an improvement in the total score of the Pittsburgh Sleep Quality Index (PSQI) at day 1, e.g., about 24 hours, after the last administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof, wherein the recall period is from the point in time when the acute illusion experience subsides after the last administration to the point in time of evaluation.
65. 65. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of claims 62 to 64, wherein the success of treatment is indicated by a decrease in the PSQI total points.
66. 66. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of claims 62 to 65, wherein the success of the treatment is indicated by a decrease in at least four of the seven component scores of PSQI.
67. 67. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of claims 62 to 66, wherein the success of treatment is indicated by a total decrease in said PSQI to 5 or less.
68. 68. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of claims 62 to 67, wherein the sleep disorder is insomnia.
69. 69. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claims 1-68, wherein the 5-MeO-DMT or salt thereof is administered at a dose or dose regimen that causes the patient to experience a peak fantasy experience.
70. 70. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claims 1-69, wherein a dose of about 2 mg, or about 5mg, or about 8 mg is administered, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.
71. 71. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claims 1 to 69, wherein a dose of about 1 mg, or about 2 mg, or about 3 mg is administered, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.
72. 72. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claims 1-69, wherein a dose of about 2 mg, or about 4 mg, or about 6 mg is administered, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.
73. 73. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claims 1-69, wherein the 5-MeO-DMT or salt thereof is administered in a first dose at a first administration and the 5-MeO-DMT or salt thereof is administered in zero to six subsequent administrations, wherein each subsequent administration uses a higher dose than the previous administration unless the patient experiences a peak fantasy experience.
74. 74. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claims 1-69 or 73, wherein the 5-MeO-DMT is administered at a dose of about 1 mg to about 3mg when administered for the first time, then increases to a dose of about 4mg to about 6 mg when administered for the second time unless the patient has experienced a peak camouflage experience, then increases to a dose of about 7 mg to about 9 mg when administered for the third time unless the patient has experienced a peak camouflage experience, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.
75. 75. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 74, wherein the first dose of 5-MeO-DMT is about 2 mg, the second dose of 5-MeO-DMT is about 5 mg, and the third dose of 5-MeO-DMT is about 8 mg, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.
76. 76. The 5-MeO-DMT for use of claims 1 to 69 or 73, or a pharmaceutically acceptable salt thereof, wherein the 5-MeO-DMT is administered at a dose of about 0.5 mg to about 1.5 mg when administered for the first time, then increases to a dose of about 1.5 mg to about 2.5 mg when administered for the second time unless the patient has experienced a peak vagal experience, then increases to a dose of about 2.5 mg to about 3.5 mg when administered for the third time unless the patient has experienced a peak vagal experience, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.
77. 77. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 76, wherein the first dose of 5-MeO-DMT is about 1 mg, the second dose of 5-MeO-DMT is about 2 mg, and the third dose of 5-MeO-DMT is about 3 mg, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.
78. 78. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claims 1-69 or 73, wherein the 5-MeO-DMT is administered at a dose of about 2 mg to about 3mg when administered for the first time, then increases to a dose of about 4 mg to about 5mg when administered for the second time unless the patient has experienced a peak camouflage experience, then increases to a dose of about 6 mg to about 7.5 mg when administered for the third time unless the patient has experienced a peak camouflage experience, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.
79. 79. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 78, wherein the first dose of 5-MeO-DMT is about 2 mg, the second dose of 5-MeO-DMT is about 4 mg, and the third dose of 5-MeO-DMT is about 6 mg, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.
80. 80. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to claims 73 to 79, wherein the interval between two administrations is not less than 1 hour and not more than 24 hours, such as about 1 to 4 hours, preferably 1 to 2 hours.
81. 81. The method according to claim 1 to 69, wherein the 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt thereof,

    Wherein about 1 mg to about 5 mg doses of 5-MeO-DMT or equimolar amounts of the pharmaceutically acceptable salt are administered in a single dose or in the highest dose in an up-titration regimen involving an administration interval of at least about 1 hour,

    Wherein said 5-MeO-DMT or said pharmaceutically acceptable salt thereof is administered via intravenous, intramuscular, or subcutaneous routes,

    Wherein the patient is advised to temporarily stop breast feeding.
82. 82. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claim 81, wherein a dose of about 1 mg, or about 5 mg is administered, or wherein an equimolar amount of the pharmaceutically acceptable salt is administered in place of 5-MeO-DMT.
83. 83. The 5-MeO-DMT or pharmaceutically acceptable salt thereof for use of claim 82, wherein the 5-MeO-DMT or salt thereof is administered in a first dose at a first administration and the 5-MeO-DMT or salt thereof is administered in zero to six subsequent administrations, wherein each subsequent administration uses a dose higher than the previous administration unless the patient experiences a peak illusive experience.
84. 84. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use according to claim 83, wherein the interval between two administrations is not less than 1 hour and not more than 24 hours, such as about 1 to 4 hours, preferably 1 to 2 hours.
85. 85. The 5-MeO-DMT for use according to any one of claims 69 to 84, or a pharmaceutically acceptable salt thereof, wherein the occurrence of the peak fantasy experience is identified by reaching at least 60% of the highest possible score in each of the four sub-scales (mystery, active emotion, override time and space and self-evident) of the 30 project revised mystery experience questionnaire (MEQ 30), or by reaching at least 60% of the highest possible score of the marine-like borderless (OBN) dimension in the state of consciousness change (ASC) questionnaire, or by reaching at least 75 Peak Experience Scale (PES) total score.
86. 86. The 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, for use of claim 85, wherein the occurrence of peak fantasy experience is identified by reaching a Peak Experience Scale (PES) score of at least 75.
87. 87. The 5-MeO-DMT or a pharmaceutically acceptable salt thereof for use of claims 1-86, wherein the 5-MeO-DMT or a pharmaceutically acceptable salt thereof is administered via intravenous injection.