[go: up one dir, main page]

WO2025000092A1 - Traitement à base d'ibogaïne - Google Patents

Traitement à base d'ibogaïne Download PDF

Info

Publication number
WO2025000092A1
WO2025000092A1 PCT/CA2024/050863 CA2024050863W WO2025000092A1 WO 2025000092 A1 WO2025000092 A1 WO 2025000092A1 CA 2024050863 W CA2024050863 W CA 2024050863W WO 2025000092 A1 WO2025000092 A1 WO 2025000092A1
Authority
WO
WIPO (PCT)
Prior art keywords
method defined
component
administered
dose
ibogaine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/CA2024/050863
Other languages
English (en)
Inventor
Jose INZUNZA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ambio Life Sciences Inc
Original Assignee
Ambio Life Sciences Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ambio Life Sciences Inc filed Critical Ambio Life Sciences Inc
Publication of WO2025000092A1 publication Critical patent/WO2025000092A1/fr
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/191—Carboxylic acids, e.g. valproic acid having two or more hydroxy groups, e.g. gluconic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A61K31/51—Thiamines, e.g. vitamin B1
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7016—Disaccharides, e.g. lactose, lactulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials
    • A61K31/765—Polymers containing oxygen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents

Definitions

  • the present invention relates to ibogaine treatment. More particularly, the present invention relates to ibogaine treament using a safety protocol that obviates or mitigates deleterious side effects associated with ibogaine treatment.
  • Ibogaine is a naturally occurring, psychoactive indole alkaloid derived from the root bark of the African shrub Tabernanthe iboga. In West Central Africa, low dosages of Tabernanthe iboga root bark have been employed by indigenous people against fatigue, hunger and thirst. Higher dosages are used for initiation rituals during religious ceremonies. Ibogaine ingestion can lead to intense visions with closed eyes reminding of a waking dream, often accompanied by a vivid recall of autobiographical visual memories (Alper, K.R.; Stajic, M.; Gill, J.R. Fatalities Temporally Associated with the Ingestion of Ibogaine. J. Forensic. Sci. 2012, 57, 398-412 (Alper et al.)).
  • ibogaine interacts with neurotransmitter transporters, opioid receptors, sigma receptors, glutamate receptors, and nicotinic receptors in low micromolar concentrations (Alper, K.R. Ibogaine: A review. Alkaloids Chem. Biol. 2001, 56. 1-38 (Alper)).
  • ibogaine-treated rodents exhibit attenuated opioid withdrawal symptoms, and diminished self-administration of a variety of drugs of abuse including opioids, cocaine, nicotine, and alcohol (Glick, S.D.; Maisonneuve, I.S. Mechanisms of antiaddictive actions of ibogaine. Ann. N. Y. Acad. Sci. 1998, 844, 214-226).
  • Anecdotal evidence suggests that ibogaine is also anti-addictive in humans.
  • ibogaine is administered to treat drug dependence, typically as single one-time dose (Alper, ibid)
  • patients commonly report sustained resolution of the withdrawal syndromes within 12-18 h, and a reduction in drug craving for prolonged time periods up to several weeks (Brown, T.K. Ibogaine in the treatment of substance dependence. Curr. Drug Abuse Rev. 2013, 6, 3-16).
  • Ibogaine s complex pharmacology entails a considerable potential to generate adverse effects. Besides potential neurotoxic actions at dosages outside of the normal therapeutic range (e.g., Alper, ibid), ibogaine also affects the cardiovascular system, and, there are reports of mortality and morbidity that are temporally associated with the administration of the alkaloid (Xaver Koenig, X; Hilber, K. The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation. Molecules 2015, 20, 2208-2228; Table 1). The first published report of fatalities temporally associated with ibogaine noted a total of 19 cases that occurred between 1998 and 2008 (Alper et al., ibid), 11 of which occurred prior to 2006.
  • ibogaine research has focused predominantly on its potential as a treatment for substance use disorders (SUDs) (Brown, T. K. & Alper, K. Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes. Am. J. Drug Alcohol Abuse 44, 24-36 (2016)).
  • SUDs substance use disorders
  • Some studies of ibogaine for SUDs also have noted improvements in selfreported measures of mood (Noller, G. E., Frampton, C. M. & Yazar-Klosinski, B. Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study. Am. J. Drug Alcohol Abuse 44, 37-46 (2018)).
  • SOF are deployed at a greater pace and to higher intensity combat than conventional military, exposing them to greater allostatic load and risk of injury, including from blast exposure (Garcia, A. et al. Neurobehavioral Symptoms in U.S. Special Operations Forces in Rehabilitation After Traumatic Brain Injury: A TBI Model Systems Study. Mil. Med. 187, 1412-1421 (2022)).
  • This has been proposed to result in a unique pattern of physical, cognitive, behavioral, psychiatric, and endocrine-related problems that negatively impact ongoing functioning across several domains (Frueh, B. C. et al. “Operator syndrome”: A unique constellation of medical and behavioral health-care needs of military special operation forces. Int. J.
  • the present invention provides a method of treatment of a patient undergoing ibogaine therapy, wherein the method comprises further administering a combination of: (a) a magnesium compound, (b) lactulose or an analog thereof, (c) sodium lactate or an analog thereof, and (d) dextrose or an analog thereof.
  • an effective amount is meant the amount of a required to ameliorate the symptoms of a disease relative to an untreated patient.
  • the effective amount of active compound(s) used to practice the present invention for therapeutic treatment of a disease varies depending upon the manner of administration, the age, body weight, and general health of the subject. Ultimately, the attending physician or veterinarian will decide the appropriate amount and dosage regimen. Such amount is referred to as an "effective" amount.
  • Ranges provided herein are understood to be shorthand for all of the values within the range.
  • a range of 1 to 50 is understood to include any number, combination of numbers, or sub-range from the group consisting 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50.
  • treat refers to reducing or ameliorating a disorder and/or symptoms associated therewith. It will be appreciated that, although not precluded, treating a disorder or condition does not require that the disorder, condition or symptoms associated therewith be completely eliminated.
  • the term "about” is understood as within a range of normal tolerance in the art, for example within 2 standard deviations of the mean. About can be understood as within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1 %, 0.5%, 0.1%, 0.05%, or 0.01% of the stated value. Unless otherwise clear from context, all numerical values provided herein are modified by the term about.
  • the method includes the step of administering to the mammal a therapeutic amount of an amount of ibogaine, an ibogaine analog, or extractions and purifications of alkaloids found in Tabernanthe iboga, alone or together, sufficient to treat the disease or disorder or symptom thereof, under conditions such that the disease or disorder is treated.
  • Identifying a subject in need of such treatment can be in the judgment of a subject or a health care professional and can be subjective (e.g., opinion) or objective (e.g., measurable by a test or diagnostic method).
  • the therapeutic methods of the invention in general comprise administration of a therapeutically effective amount of the compounds herein, such as a compound of the formulae herein to a subject (e.g., animal, human) in need thereof, including a mammal, particularly a human.
  • a subject e.g., animal, human
  • Such treatment will be suitably administered to subjects, particularly humans, suffering from, having, susceptible to, or at risk for a disease, disorder, or symptom thereof.
  • Determination of those subjects "at risk” can be made by any objective or subjective determination by a diagnostic test or opinion of a subject or health care provider (e.g. genetic test, enzyme or protein marker, Marker (as defined herein), family history, and the like).
  • a diagnostic test or opinion of a subject or health care provider e.g. genetic test, enzyme or protein marker, Marker (as defined herein), family history, and the like.
  • the invention provides a method of monitoring treatment progress.
  • the method includes the step of determining a level of diagnostic marker (Marker) (e.g., any target delineated herein modulated by a compound herein, a protein or indicator thereof, etc.) or diagnostic measurement (e.g., screen, assay) in a subject suffering from or susceptible to a disorder or symptoms thereof associated with multiple sclerosis, traumatic brain injury, substance use disorder or behavioural addiction, etc. in which the subject has been administered a therapeutic amount of a compound herein sufficient to treat the disease or symptoms thereof.
  • the level of Marker determined in the method can be compared to known levels of Marker in either healthy normal controls or in other afflicted patients to establish the subject's disease status.
  • a second level of Marker in the subject is determined at a time point later than the determination of the first level, and the two levels are compared to monitor the course of disease or the efficacy of the therapy.
  • a pre-treatment level of Marker in the subject is determined prior to beginning treatment according to this invention; this pre-treatment level of Marker can then be compared to the level of Marker in the subject after the treatment commences, to determine the efficacy of the treatment.
  • the invention further relates to methods for treatment and/or prevention of multiple sclerosis, traumatic brain injury, some neuropathic pain conditions, other neurodegenerative disorders, mental health disorders, substance use or behavior disorders and/or other disease/disorder affecting the nervous system (e.g. central, peripheral) or muscle including symptoms thereof, in a subject in need thereof using the compounds and compositions described herein.
  • Subject within the scope of the present invention is a mammal, such as a human or a veterinary animal, exhibiting symptoms and/or suffering from, or diagnosed with, diseases/disorders described herein.
  • veterinary animal refers to any animal cared for, or attended to by, a veterinarian, and includes companion (pet) animals and livestock animals, for example, a cat, a dog, and a horse (e.g., a race horse).
  • mice, rats, rabbits, nonhuman primates, such as monkeys are also within the scope of the invention (e.g. experimental allergic encephalomyelitis (EAE)).
  • EAE experimental allergic encephalomyelitis
  • multiple sclerosis is used as per the accepted textbook definition in the field (Handbook of Multiple Sclerosis. 3rd Edition. Edited by Stuart D. Cook. Marcel Dekker, Inc., 2001). Diagnostic criteria used to identify a subject with multiple sclerosis would be apparent to a person of skill in the art. For example, a skilled individual would appreciate that clinically defined multiple sclerosis is based on two attacks of neurological dysfunction separated in time and space. More recent diagnostic criteria for MS include the presence of characteristic areas on cranial or cervical magnetic resonance imaging (MRI).
  • MRI magnetic resonance imaging
  • multiple sclerosis frequently begins in young adulthood with episodic attacks of neurological dysfunction - e.g., visual loss, sensory alterations, motor weakness, ataxia, etc. These subjects are within the scope of the present invention.
  • neurological dysfunction e.g., visual loss, sensory alterations, motor weakness, ataxia, etc.
  • myelin that forms a sheath-like covering around nerve axons and enhances electrochemical signaling in the central nervous system.
  • protein components include, but are not limited to, myelin basic protein, proteolipid protein and myelin oligodendrocyte glycoprotein.
  • Common symptoms of multiple sclerosis and other diseases/disorders affecting nerves and muscles include, but are not limited to, weakness, muscle stiffness, pain, which can be burning, throbbing, aching, imbalance, asthenia or fatigue, depression, visual disturbances or loss, headache, loss of bowel or bladder control, ataxia of gait or limb movements, difficulty walking, difficulty with coordinated movements of the upper extremities, cognitive dysfunction, loss or aberrant sensation, muscle cramps or spasms, among others. Subjects exhibiting these symptoms are within the scope of the present invention.
  • Relapses of multiple sclerosis are discrete occurrences of a subtype of multiple sclerosis known as relapsing remitting multiple sclerosis (RRMS) and occur less often in secondary progressive multiple sclerosis (SPMS).
  • RRMS relapsing remitting multiple sclerosis
  • SPMS secondary progressive multiple sclerosis
  • a "relapse" is defined as the onset of new or worsening neurological symptoms usually lasting at least 48 hours in the absence of any precipitating factor, such as fever orinfection. Subjects suffering from relapses or RRMS are within the scope of the present invention.
  • the goal of treatment of relapses is to stop the autoimmune process associated with the relapse and/or to prevent or minimize residual neurological damage associated with incomplete remission, which occurs in a high percentage of patients.
  • CPMS relapsing remitting phase
  • PPMS primary progressive multiple sclerosis
  • SPMS neurodegenerative disease 2019
  • CPMS and PPMS respond poorly to current drug treatment.
  • Subjects with CPMS and PPMS are also within the scope of the invention.
  • Ibogaine has been used as a botanical preparation from the root bark of Tabernathe iboga for over 100 years in various forms, including as a crude preparation, as a total alkaloid extract, as a purified total alkaloid extract, as a complete botanical drug, and as isolated ibogaine, which was marketed in France until about 1970. More recently, semi-synthetic ibogaine has been produced from voacangine or other similar alkaloids (Dickinson, J. Iboga Root: Dynamics of Iboga’s African Origins and Modem Medical Use. Journal of the American Botanical Council 2016, 109, 48-57,). Synthetic ibogaine and iboga analogs can be produced by various means.
  • ibogaine exhibits stimulant and hallucinogenic properties, and in addition, can induce temporary ataxia and tremors.
  • ibogaine causes these side effects in a majority of patients receiving treatment.
  • ibogaine is classified as a Schedule I controlled substance.
  • the use of ibogaine in humans is complicated by the fact that the ranges in the prior art are exceptionally broad (0.01 to 1000 mg/kg body weight). Furthermore, the ranges generally used to treat addiction (e.g., 13 mg/kg to 20 mg/kg) cause hallucinations and may be fatal. Lotsof and Wachtel, Manual for Ibogaine Therapy: Screening, Safety, Monitoring & Aftercare (2d revision, 2003), accessed at www.ibogaine.desk.nl/manual.html; Hoelen, et al. New Engl. J. Med. 360(3), 308 (2009), which is incorporated herein by reference in its entirety for all of its methods, compositions and teachings. See also the Clinical Guidelines for Ibogaine Assisted Detoxification: https://ibogaineguidelines.com.
  • Ibogaine is isolated from Tabernanth iboga, a shrub endemic to Central Africa, particularly Gabon (Dickinson, ibid). In some cases, ibogaine mixtures contain the other alkaloids found in Tabernanthe iboga, such as ibogamine, ibogaline, tabemanthine, coronoradine, voacangine, etc. Ibogaine, these other alkaloids, and iboga analogs can also be semi-synthesized or synthesized using known methods. See, e.g., Buchi, et al. (1966), J.
  • ibogaine refers to ibogaine, ibogaine derivative, or a pharmaceutically acceptable salt and/or solvate thereof. It may also refer to an ibogaine mixture, such as a botanical extraction of Taberntanthe iboga, or other alkaloids found present in it, including ibogamine, ibogaline, tabemanthine, coronoradine, voacangine, etc.
  • the dose of ibogaine is selected from a dosing range (adjusted by patient body weight) of from about 2 to about 50 mg/kg, from about 3 to about 40 mg/kg, preferably from about 4 to about 30 mg/kg, preferably from about 5 to about 28 mg/kg, preferably from about 6 to about 24 mg/kg.
  • one or more booster dosages of 50-600 mg can be provided 12 hours or more before or after initial dosage in order to boost levels of noribogaine. This can be preferable in cases where the patient either felt less effect than desired from the medicine, or where dosing was interrupted for tolerability.
  • the equivalent or greater than a single flood dose over a period of time can be provided for patients with high sensitivity or tolerability issues, and achieve similar or greater saturation of ibogaine, and its metabolite noribogaine.
  • Ibogaine dosages are calculated by weight, and in a preferred embodiment dosages over 6 mg/kg are divided into several dosages, between 2-5 dosages, which are administered within a 30-to-240-minute window in order to evaluate onset of effects and make adjustments for a desired therapeutic effect.
  • the present invention relates to combining ibogaine treatment with a specific combination of other ingredients to suprisingly obviate or mitigate deleterious side effects associated with ibogaine (alone) treatment. More specifically, present invention relates to combining ibogaine treatment with a combination of the following components: (i) lacutulose or an analog thereof; (ii) magnesium or an analog thereof; and (iii) dextrose or an analog thereof.
  • Lactulose is an osmotic laxative used mainly to treat constipation and, in higher doses, hepatic encephalopathy. Generally, as a sugar, it is not metabolized in the body, so it reaches the colon intact, where it attracts water and promotes bowel movement.
  • Lactulose is commercially available under the following brand names EnuloseTM, GenerlacTM, ConstuloseTM and KristaloseTM.
  • the preferred dose is from about 5 g to about 40 gram per day, preferably from about 7 g to about 30 g per day, preferably from about 10 to about 20 g per day.
  • children e.g., less than 16 years of age
  • the dose depends on the age of the child and will usually be lower than the adult dose.
  • an additional dosage can be administered after at least 6 or 8 hours.
  • Polyethylene glycol (MiraLAX, Glycolax): this is a type of laxative that works by drawing water into the colon, similar to lactulose. It is often used to treat occasional constipation.
  • the preferred dose is from about 10 g to about 25 g, preferably from about 12 g to about 20g, preferably from about 15 g to about 20 g, preferably 17 g. It is preferred to administer the compound as an oral dosage form.
  • Lactitol (Pizensy): This is a sugar alcohol used to treat chronic idiopathic constipation in adults.
  • the preferred dose is from about 0.2 g/kg/day to about 1.0 g/kg/day, preferably from about 0.3 g/kg/day to about 0.8 g/kg/day, preferably from about 0.5 g/kg/day to about 0.7 g/kg/day. It is preferred to administer the compound as an oral dosage form.
  • Magnesium hydroxide (Milk of MagnesiaTM).
  • the preferred dose is from about 10 mL to about 80 mL per day, preferably from about 20 mL to about 70 mL per day, preferably from about 30 mL to about 60 mL per day. It is preferred to administer the doses in divided amounts.
  • Sorbitol is from about 10 mL to about 200 mL per day as a 70% solution, preferably from about 20 mL to about 180 mL per day as a 70% solution, preferably from about 30 mL to about 150 mL per day as a 70% solution.
  • Glycerin suppositories The preferred dose is one suppository inserted into the rectum.
  • ColaceTM The preferred dose is from abou 100 mg to about 500 mg administered orally.
  • SurfakTM The preferred dose is 320 mg to 500 mg administered orally.
  • DulcolaxTM Oral stimulants (DulcolaxTM) [0075] DulcolaxTM: The preferred dose is from about 5 mg to about 10 mg.
  • magnesium intake is associated with a lower risk of hypertension and heart disease. It is believed it can help regulate heart rhythm and is often given to people who have suffered a heart attack to reduce the risk of arrhythmia (irregular heartbeat).
  • Magnesium can be administered intravenously (IV) in a healthcare setting for a variety of reasons, such as severe magnesium deficiency, eclampsia and pre-eclampsia during pregnancy, acute asthma attack, arrhythmia or migraine.
  • magnesium preparations are preferably administered intravenously.
  • Magnesium sulfate This is the most commonly used form of intravenous magnesium. It is used for electrolyte balance, as prophylaxis to ibogaine-assisted treatment and certain cardiac arrhythmias.
  • the preferred dose is from about 0.2 g to about 3.0 g, preferably from about 0.5 g to about 2 g, preferably 1 g.
  • Magnesium Glycinate Known to be easily absorbed and gentle on the stomach, magnesium glycinate is commonly used to correct magnesium deficiencies and may also help reduce symptoms of depression, anxiety and insomnia.
  • the preferred daily dose is from about 100 mg to about 1000 mg, preferably from about 200 mg to about 700 mg, preferably from about 300 mg to about 500 mg. It is preferred to administer the compound as an oral dosage form.
  • Magnesium L-threonate This form of magnesium is believed to be effective in crossing the blood-brain barrier and therefore may benefit cognitive functions.
  • the preferred daily dose is from about 0.5 g to about 3.0, preferably from about 0.7 g to about 2.5 g, preferably from about 1.0 g to about 2.0 g. It is preferred to administer the compound as an oral dosage form.
  • Magnesium malate This form of magnesium is commonly used in people suffering from fatigue or fibromyalgia, as malate is a substrate in the cellular energy cycle.
  • the preferred daily dose is from about 100 mg to about 1000 mg, preferably from about 150 mg to about 700 mg, preferably from about 200 mg to about 500 mg. It is preferred to administer the compound as an oral dosage form.
  • Magnesium taurate This form combines magnesium and the amino acid taurine to potentially contribute to cardiovascular health.
  • the preferred daily dose is from about 50 mg to about 1000 mg, preferably from about 75 mg to about 700 mg, preferably from about 100 mg to about 500 mg. It is preferred to administer the compound as an oral dosage form.
  • Dextrose also known as glucose
  • glucose is a simple form of sugar that the body uses for energy.
  • Intravenous dextrose is a common way to deliver glucose directly into the bloodstream to treat and prevent hypoglycemia, or low blood sugar levels, especially in a hospital setting.
  • dextrose may be administered via a number of non-limiting routes/modes of administration, for example:
  • D5W 5% dextrose in water, consisting of 278 mmol/L dextrose
  • D5NS 5% dextrose in normal saline
  • normal saline 0.9% w/v NaCl
  • D5LR 5% dextrose in Ringer's Lactate solution
  • the preferred dose is from about 0.1 g to about 3.0, preferably from about 0.3 g to about 2.5 g, preferably from about 0.5 g to about 2.0 g.
  • the dose is administered intravenously.
  • the safety protocol further comprises administration of thiamine hydrochloride and analogs thereof.
  • a prodrug of thiamine is use.
  • the prodrug is benfotiamine which is a synthetic S-acyl derivative of thiamine. It is converted to thiamine in the body and is better absorbed than normal thiamine, making it potentially useful in the treatment of certain medical conditions such as diabetic neuropathy.
  • the preferred dose is from about 10 mg to about 500 mg, preferably from about 25 mg to about 350 mg, preferably from about 50 mg to about 200 mg.
  • the dose is administered intravenously.
  • a synthetic derivative of thiamin is used.
  • the synthetic derivative is sulbutiamine which is a synthetic derivative of thiamine capable of more easily crossing the blood-brain barrier. This gives it potential as a treatment for fatigue and certain neurodegenerative conditions.
  • the preferred dose is from about 100 mg to about 1000 mg, preferably from about 200 mg to about 600 mg, preferably from about 300 mg to about 500 mg, preferably 400 mg. It is preferred to administer the compound as an oral dosage form.
  • the synthetic derivative is fursultiamine (thiamine tetrahydrofurfuryl disulfide) which has been used in the treatment of chronic fatigue and other conditions.
  • the preferred dose is from about 100 mg to about 1000 mg, preferably from about 200 mg to about 600 mg, preferably from about 300 mg to about 500 mg, preferably 400 mg.
  • the dose is administered intravenously.
  • a natural derivative of thiamin is used.
  • the natural derivative is allithiamine which is a natural derivative of thiamine found in garlic and onions. It is also better absorbed than regular thiamine.
  • the preferred dose is from about 10 mg to about 500 mg, preferably from about 25 mg to about 350 mg, preferably from about 50 mg to about 200 mg.
  • the dose is administered intravenously.
  • the safety protocol further comprises administration of riboflavin and analogs thereof.
  • Riboflavin also known as vitamin B2
  • riboflavin is administered in the form of riboflavin 5'phosphate sodium.
  • the preferred dose is from about 2 mg/mL to about 100 mg/mL.
  • the dose is administered intravenously or intramuscularly.
  • the safety protocol further comprises administration of nicotinamide and analogs thereof.
  • nicotinamide is used in the form of nicotinamide riboside.
  • Nicotinamide riboside is precursor of nicotinamide adenine dinucleotide (NAD+), a crucial coenzyme involved in many metabolic and cellular processes. Nicotinamide riboside is being studied for its potential to increase NAD+ levels and thus improve a number of health outcomes related to aging, brain health, heart health, etc.
  • the preferred dose is from about 500 mg to about 3000 mg, preferably from about 750 mg to about 2500 mg, preferably from about 1000 mg to about 2000 mg. Preferably, the dose is administered intravenously.
  • nicotinamide is used in the form of nicotinamide mononucleotide.
  • Nicotinamide mononucleotide is another precursor of NAD+. Nicotinamide mononucleotide is used by cells to produce NAD+, and its potential to delay aging, improve energy metabolism and promote brain health is being investigated.
  • the safety protocol further comprises administration of pyridoxal and analogs thereof.
  • pyridoxal is used in the form of pyridoxamine which is another natural form of vitamin B6. It is converted to pyridoxal 5'-phosphate in the body.
  • pyridoxal is used in the form of pyridoxal 5'- phosphate which is the biologically active form of vitamin B6. It acts as a coenzyme in a wide range of enzymatic reactions, particularly those involving amino acid metabolism.
  • pyridoxal is used in the form of pyridoxine 5'- phosphate.
  • Pyridoxine 5'-phosphate is another phosphorylated form of vitamin B6, but is not as biologically active as pyridoxal 5'-phosphate.
  • pyridoxal is used in the form of pyridoxal hydrochloride. This is a form of pyridoxine that is often used in vitamin B6 supplements.
  • pyridoxal is used in the form of 4-deoxypyridoxine and 4'-deoxypyridoxine. These are synthetic vitamin B6 antagonists that are often used in research to induce vitamin B6 deficiency in laboratory animals.
  • pyridoxal is used in the form of cycloserine which is a drug used to treat tuberculosis that acts as a structural analog of pyridoxal. It inhibits enzymes that require pyridoxal 5'-phosphate as a coenzyme.
  • the preferred dose is from about 2 g to about 10 g, preferably from about 3 g to about 8 g, preferably from about 4 g to about 6 g, preferably 5 g.
  • the dose is administered intravenously.
  • Exclusion criteria included history of a neurological disorder (excluding sequelae of TBI); history of any psychotic symptoms or disorders; being at risk for suicidal behavior during the study in the judgement of the investigator; having a significant clinical abnormality on screening physical exam that could affect safety or study integrity; recent or concurrent participation in another study with a drug or device; history of cardiovascular, liver, or kidney problems; pregnancy; or, any other condition that would affect the individual’s ability to safely participate.
  • Racial/ethnic identity was determined by the participants using classification terms provided by the researchers. Classification terms were: American Indian or Alaska Native; Asian; Black or African American; Native Hawaiian or Other Pacific Islander; White; Hispanic or Latino (ethnicity); Not Hispanic or Latino (ethnicity).
  • Gender was determined by the participants using classification terms provided by the researchers. Classification terms were: “male”, “female”, or “other”.
  • Procedure [0119] Upon arrival at the clinic, participants were assessed by the clinic’s medical staff including bloodwork, electrocardiogram, and urinalysis. Group preparatory and ceremonial activities took place. Day 2 involved additional group preparatory activities and an 8-hour fast prior to the treatment, which began on the evening of Day 2 and continued through Day 3. Integration activities occurred on Day 4, and participants returned to the United States on the evening of Day 5.
  • Medical staff were onsite at a ratio of at least 1 staff per 2 patients throughout treatment for monitoring and management, but no specific coaching or psychological support was provided during treatment.
  • blood pressure and pulse oximetry were monitored three times a day, and QTc was monitored via continuous 5-lead ECG.
  • QTc was monitored via continuous 5-lead ECG.
  • a 4 mg/kg booster dose was provided 12 hours after the initial dose given insufficient treatment intensity/duration as judged by clinic personnel; medical monitoring was extended accordingly.
  • Alper describes therapeutic dosing of ibogaine typically leading to three sequential stages beginning approximately one to three hours post-ingestion: “acute” (-4- 8hrs), “evaluative” ( ⁇ 8-20hrs), and “residual” ( ⁇ 24-72hrs). Dreamlike states of consciousness begin during the acute stage, usually with closed eyes. Participants were able to visually orient themselves in the room as needed during their experiences. This acute stage leads into contemplation of the experiences from the previous stage. The residual stage involves reintegration with the environment as any lingering effects resolve.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Toxicology (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un procédé de traitement d'un patient subissant une thérapie à base d'ibogaïne, le procédé comprenant en outre l'administration d'une combinaison de : (a) un composé de magnésium, (b) du lactulose ou un analogue de celui-ci, (c) du lactate de sodium ou un analogue de celui-ci, et (d) du dextrose ou un analogue de celui-ci.
PCT/CA2024/050863 2023-06-28 2024-06-27 Traitement à base d'ibogaïne Pending WO2025000092A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202363523774P 2023-06-28 2023-06-28
US63/523,774 2023-06-28

Publications (1)

Publication Number Publication Date
WO2025000092A1 true WO2025000092A1 (fr) 2025-01-02

Family

ID=93936515

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CA2024/050863 Pending WO2025000092A1 (fr) 2023-06-28 2024-06-27 Traitement à base d'ibogaïne

Country Status (1)

Country Link
WO (1) WO2025000092A1 (fr)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5925634A (en) * 1989-10-20 1999-07-20 Washington University Use of ibogaine for treating neuropathic pain
WO2015134405A1 (fr) * 2014-03-03 2015-09-11 Demerx, Inc. Utilisations therapeutiques de l'ibogaïne et composes associes
US20150258114A1 (en) * 2014-03-13 2015-09-17 Demerx, Inc. Methods for acute and long-term treatment of substance abuse using ibogaine
US20170368073A1 (en) * 2014-03-13 2017-12-28 Demerx, Inc. Use of ibogaine and derivatives thereof for the treatment of pain
US20210029634A1 (en) * 2019-07-25 2021-01-28 Sensata Technologies, Inc. Communication between a wheel unit sensor and a master controller
WO2022003675A1 (fr) * 2020-07-01 2022-01-06 Psyrx Ltd. Compositions et procédés pour traiter des troubles psychiatriques ou des symptômes de ceux-ci

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5925634A (en) * 1989-10-20 1999-07-20 Washington University Use of ibogaine for treating neuropathic pain
WO2015134405A1 (fr) * 2014-03-03 2015-09-11 Demerx, Inc. Utilisations therapeutiques de l'ibogaïne et composes associes
US20150258114A1 (en) * 2014-03-13 2015-09-17 Demerx, Inc. Methods for acute and long-term treatment of substance abuse using ibogaine
US20170368073A1 (en) * 2014-03-13 2017-12-28 Demerx, Inc. Use of ibogaine and derivatives thereof for the treatment of pain
US20210029634A1 (en) * 2019-07-25 2021-01-28 Sensata Technologies, Inc. Communication between a wheel unit sensor and a master controller
WO2022003675A1 (fr) * 2020-07-01 2022-01-06 Psyrx Ltd. Compositions et procédés pour traiter des troubles psychiatriques ou des symptômes de ceux-ci

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BRODY DAVID L., SIDDIQI SHAN H.: "An ancient psychedelic for traumatic brain injury", NATURE MEDICINE, NATURE PUBLISHING GROUP US, NEW YORK, vol. 30, no. 2, 1 February 2024 (2024-02-01), New York, pages 342 - 343, XP093258379, ISSN: 1078-8956, DOI: 10.1038/s41591-023-02759-w *
DICKINSON JONATHAN E., INZUNZA JOSE ADALBERTO DOMINGUEZ, PEREZ-VILLA LILIANA, MILLAR TREVOR G., PUSHPARAJ ABHIRAM P.: "Case report: Ibogaine reduced severe neuropathic pain associated with a case of brachial plexus nerve root avulsion", FRONTIERS IN PAIN RESEARCH, vol. 4, XP093258381, ISSN: 2673-561X, DOI: 10.3389/fpain.2023.1256396 *

Similar Documents

Publication Publication Date Title
TWI326214B (en) Pharmaceutical compositions comprising dextromethorphan and quinidine for the treatment of neurological disorders
JP2008513491A (ja) 自閉症、強迫神経症、および衝動性の治療のためのメマンチン（ナメンダ）の使用
JP6137833B2 (ja) 脱髄性および他の神経系疾患を患っている患者における神経認知的および／または神経精神医学的障害を改善するための４−アミノピリジンの使用
KR20250034521A (ko) 실조증을 치료하기 위한 릴루졸 전구약물의 용도
Carter Anterior ischemic optic neuropathy and stroke with use of PDE-5 inhibitors for erectile dysfunction: cause or coincidence?
US20150051191A1 (en) Treatment of alcoholism using ibudilast
KR20170131543A (ko) 근위축성 측삭 경화증을 치료하기 위한 비오틴
US20230000799A1 (en) Effects of mescaline and of mescaline analogs (scalines) to assist psychotherapy
EP3448431A1 (fr) Agonistes hautement sélectifs pour le sous-type du récepteur de l'adénosine a3 pour la prévention et le traitement de troubles neurodégénératifs
EP1534289B2 (fr) Antagonistes du recepteur a2a de l'adenosine destines au traitement du syndrome des jambes sans repos ou du myoclonus nocturne
WO2025000092A1 (fr) Traitement à base d'ibogaïne
Janssen Does ritanserin, a potent serotonin-S2 antagonist, restore energetic functions during the night?
Schrader et al. Response to sequential administration of clomipramine and lithium carbonate in treatment-resistant depression
US11660279B2 (en) Therapeutic agents for treating restless leg syndrome
EP3454853B1 (fr) Traitement de l'alcoolisme et de la dépression avec de l'ibudilast
Cho et al. Acute Heart Failure after Oral Intake of Liquid Nicotine
CN101203225A (zh) 使用选择性氯离子通道调节剂治疗酒精和/或兴奋剂物质滥用
Wei et al. Stereotypy in the psychiatric symptoms of catatonia
WO2024254701A1 (fr) Ibogaïne pour le traitement de la sclérose en plaques
EP3763380A1 (fr) Méthode de traitement d'encéphalopathie
WO2025227053A1 (fr) Compositions de modulateurs allostériques positifs du récepteur nmda et leurs méthodes d'utilisation
CA2526458A1 (fr) Utilisation therapeutique supplementaire du zolpidem
JPH0737387B2 (ja) 神経系症状の処置剤
Wang et al. Current diagnosis and management of children with vasovagal syncope
TW202440106A (zh) 用於治療勃起障礙之化合物

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24829681

Country of ref document: EP

Kind code of ref document: A1