WO2025043053A1 - 4-methoxy-n,n-dicyclopropyltryptammonium chloride - Google Patents

Abstract

The disclosure relates to N-cyclopropyl-N-[2-(4-methoxy-1H-indol-3-yl)ethyl]cyclopropanaminium chloride (4-methoxy-N,N-dicyclopropyltryptammonium chloride), crystalline 4-methoxy-N,N- dicyclopropyltryptammonium chloride, and specific crystalline forms thereof, including crystalline form 1 of 4-methoxy-N,N-dicyclopropyltryptammonium chloride, to compositions containing the same, and to methods of treatment using them.

Description

4-METHOXY-N,/V-DICYCLOPROPYLTRYPTAMMONIUM CHLORIDE

Cross-Reference to Related Applications

[001] This application claims priority to U.S. Provisional Application No. 63/578,258, filed on August 23, 2023; the disclosure of which is incorporated herein by reference.

Technical Field

[002] This disclosure relates to N-cyclopropyl-N-[2-(4-methoxy-lH-indol-3- yl)ethyl]cyclopropanaminium chloride (4-methoxy-A/,M-dicyclopropyltryptammonium chloride or 4- MeO-DcPT chloride), crystalline 4-MeO-DcPT chloride, and specific crystalline forms thereof, including crystalline form 1 of 4-MeO-DcPT chloride; to pharmaceutical compositions containing 4-MeO-DcPT chloride or crystalline 4-MeO-DcPT chloride, including crystalline form 1 of 4-MeO-DcPT chloride; and to methods of treatment/therapeutic uses of 4-MeO-DcPT chloride or crystalline 4-MeO-DcPT chloride, including crystalline form 1 of 4-MeO-DcPT chloride.

Background of the Invention

[003] Obtaining specific salts or crystalline forms of an active pharmaceutical ingredient (API) is extremely useful in drug development. It permits better characterization of the drug candidate's chemical and physical properties. Crystalline forms often have better chemical and physical properties than the API in its amorphous state. Such crystalline forms may possess more favorable pharmaceutical and pharmacological properties or be easier to process. Additionally, preparing a crystalline API and solving its crystal structure provides the gold standard for chemical characterization and determining the molecular formula (and molecular weight) of the API. Accordingly, preparing a crystalline form with an accompanying crystal structure thereof prevents potential ambiguities and/or inaccuracies in the API's molecular weight. This is important because the API's molecular weight is used to calculate the concentration of compositions comprising that API. Thus, inaccuracies in molecular weight may lead to errors in the calculations pertaining to dosing, potency, toxicity, etc. in all downstream in vitro and in vivo assays that correlated the concentration of the API with a measured property. Accordingly, there remains a need to obtain and characterize crystalline forms of APIs, such as tryptamines and other psychedelic drug compounds. Summary of the Invention

[004] This disclosure relates to N-cyclopropyl-N-[2-(4-methoxy-lH-indol-3- yl)ethyl]cyclopropanaminium chloride (4-methoxy-A/,/\/-dicyclopropyltryptammonium chloride or 4- MeO-DcPT chloride), crystalline 4-MeO-DcPT chloride, and specific crystalline forms thereof. In one embodiment, this disclosure pertains to particular crystalline forms of 4-MeO-DcPT chloride, including crystalline form 1 of 4-MeO-DcPT chloride. In one embodiment, crystalline form 1 of 4-MeO-DcPT chloride is characterized by at least one of: a monoclinic, C2/c space group at a temperature of about 300(2) K; unit cell dimensions a = 19.2681(19) A, b = 7.1763(6) A, c = 24.519(2) A, a = 90°, 0 = 104.629(4)°, and y = 90°; an X-ray powder diffraction (XRPD) pattern substantially similar to FIG. 3; and an X-ray powder diffraction pattern characterized by at least two peaks selected from 9.5, 14.6, and 22.5 °20 ± 0.2 °20.

[005] The disclosure further relates to a composition comprising 4-MeO-DcPT chloride, crystalline 4- MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, and at least one excipient.

[006] The disclosure also provides a composition comprising 4-MeO-DcPT chloride, crystalline 4- MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, as a first component and a second component selected from at least one of (a) a serotonergic drug, (b) a purified psilocybin derivative, (c) a purified cannabinoid, (d) a purified terpene, (e) an adrenergic drug, (f) a dopaminergic drug, (g) a monoamine oxidase inhibitor, (h) a purified erinacine, and (i) a purified hericenone; and at least one excipient.

[007] The disclosure also relates to a method of preventing or treating a psychological disorder comprising the step of administering to a subject in need thereof a therapeutically effective amount of 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, or a composition according to this disclosure.

[008] The disclosure further relates to a method of preventing or treating inflammation and/or pain, preventing or treating a neurological disorder, modulating activity of a mitogen-activated protein kinase (MAPK), modulating neurogenesis, or modulating neurite outgrowth comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of 4-MeO- DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, and to administering a pharmaceutical composition or a composition according to the invention. [009] As used herein, the term "a subject in need thereof" refers to a person requiring a composition to treat a particular disease or condition (e.g., inflammation, pain, a psychological disorder, modulating activity at a receptor, etc.). In one embodiment, the "subject in need thereof" may be identified by analyzing, diagnosing, and/or determining whether the person (or subject) requires the composition for treatment of a particular disease or condition. In one embodiment, identifying a person in need of treatment comprises diagnosing a person with a medical condition, e.g., a neurological disorder, a chemical imbalance, a hereditary condition, etc. In one embodiment, identifying a person in need of treatment comprises performing a psychiatric evaluation. In one embodiment, identifying a person in need of treatment comprises performing a blood test. In one embodiment, identifying a person in need of treatment comprises determining whether a person has a compulsive disorder. In one embodiment, identifying a person in need of treatment comprises self-identifying as having a compulsive disorder.

Description of the Figures

[0010] FIG. 1 shows the molecular structure of crystalline form 1 of 4-methoxy-/V,A/- dicyclopropyltryptammonium chloride.

[0011] FIG. 2 shows the unit cell of crystalline form 1 of 4-methoxy-A/,A/-dicyclopropyltryptammonium chloride along the b-axis.

[0012] FIG. 3 shows the simulated X-ray powder diffraction pattern (XRPD) for crystalline form 1 of 4- methoxy-/V,A/-dicyclopropyltryptammonium chloride.

Detailed Description

[0013] Compounds

[0014] This disclosure relates to N-cyclopropyl-N-[2-(4-methoxy-lH-indol-3- yl)ethyl]cyclopropanaminium chloride (4-methoxy-A/,/\/-dicyclopropyltryptammonium chloride or 4- MeO-DcPT chloride), crystalline 4-MeO-DcPT chloride, and specific crystalline forms thereof, including crystalline form 1 of 4-MeO-DcPT chloride, and to compositions containing 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4- MeO-DcPT chloride, according to the disclosure. The therapeutic uses of 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4- MeO-DcPT chloride, according to the disclosure are described below as well as compositions containing it. 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, and some exemplary methods used to characterize it are described below. [0015] 4-MeO-DcPT chloride has the following chemical formula:

[0016] Methods of Treatment and Therapeutic Uses

[0017] 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, according to the disclosure, and the methods and the compositions (e.g., pharmaceutical compositions) are used to regulate the activity of a neurotransmitter receptor by administering a therapeutically effective dose of 4-MeO-DcPT chloride, crystalline 4-MeO- DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure. In one embodiment, 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, according to the disclosure, and the methods and the compositions (e.g., pharmaceutical compositions) are used to treat inflammation and/or pain by administering a therapeutically effective dose of 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4- MeO-DcPT chloride, of the disclosure.

[0018] Methods of the disclosure also relate to the administration of a therapeutically effective amount of 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, to prevent or treat a disease or condition, such as those discussed below for a subject in need of treatment. 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, may be administered neat or as a composition comprising 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, as discussed below. [0019] 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure may be used to prevent and/or treat a psychological disorder. The disclosure provides a method for preventing and/or treating a psychological disorder by administering to a subject in need thereof a therapeutically effective amount of 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure, including the exemplary embodiments discussed herein. The psychological disorder may be chosen from: depression; psychotic disorder; schizophrenia; schizophreniform disorder (acute schizophrenic episode); schizoaffective disorder; bipolar I disorder (mania, manic disorder, manic-depressive psychosis); bipolar II disorder; major depressive disorder; major depressive disorder with psychotic feature (psychotic depression); delusional disorders (paranoia); shared psychotic disorder (shared paranoia disorder); brief psychotic disorder (other and unspecified reactive psychosis); psychotic disorder not otherwise specified (unspecified psychosis); paranoid personality disorder; schizoid personality disorder; schizotypal personality disorder; anxiety disorder; social anxiety disorder; substance-induced anxiety disorder; selective mutism; panic disorder; panic attacks; agoraphobia; attention deficit syndrome; post-traumatic stress disorder (PTSD); premenstrual dysphoric disorder (PMDD); and premenstrual syndrome (PMS).

[0020] 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure may be used to prevent and/or treat a brain disorder. The disclosure provides a method for preventing and/or treating a brain disorder (e.g., Huntington's disease, Alzheimer's disease, dementia, and Parkinson's disease) by administering to a subject in need thereof a therapeutically effective amount of 4-MeO-DcPT chloride, crystalline 4-MeO- DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride. [0021] 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure may be used to prevent and/or treat developmental disorders, delirium, dementia, amnestic disorders and other cognitive disorders, psychiatric disorders due to a somatic condition, drug-related disorders, schizophrenia and other psychotic disorders, mood disorders, anxiety disorders, somatoform disorders, factitious disorders, dissociative disorders, eating disorders, sleep disorders, impulse control disorders, adjustment disorders, or personality disorders. The disclosure provides a method for preventing and/or treating these disorders by administering to a subject in need thereof a therapeutically effective amount of 4- MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, including the exemplary embodiments discussed above. [0022] 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure may be used to prevent and/or treat inflammation and/or pain, such as for example inflammation and/or pain associated with inflammatory skeletal or muscular diseases or conditions. The disclosure provides a method for preventing and/or treating an inflammation and/or pain by administering to a subject in need thereof a therapeutically effective amount of 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure, including the exemplary embodiments discussed herein. Generally speaking, treatable "pain" includes nociceptive, neuropathic, and mix-type. A method of the disclosure may reduce or alleviate the symptoms associated with inflammation, including but not limited to treating localized manifestation of inflammation characterized by acute or chronic swelling, pain, redness, increased temperature, or loss of function in some cases. A method of the disclosure may reduce or alleviate the symptoms of pain regardless of the cause of the pain, including but not limited to reducing pain of varying severity, i.e., mild, moderate and severe pain, acute pain and chronic pain. A method of the disclosure is effective in treating joint pain, muscle pain, tendon pain, burn pain, and pain caused by inflammation such as rheumatoid arthritis. Skeletal or muscular diseases or conditions which may be treated include but are not limited to musculoskeletal sprains, musculoskeletal strains, tendinopathy, peripheral radiculopathy, osteoarthritis, joint degenerative disease, polymyalgia rheumatica, juvenile arthritis, gout, ankylosing spondylitis, psoriatic arthritis, systemic lupus erythematosus, costochondritis, tendonitis, bursitis, such as the common lateral epicondylitis (tennis elbow), medial epicondylitis (pitchers elbow) and trochanteric bursitis, temporomandibular joint syndrome, and fibromyalgia.

[0023] 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure may be used to modulate activity of a mitogen-activated protein kinase (MAPK), comprising administering a composition of the invention. MAPKs provide a wide-ranging signaling cascade that allow cells to quickly respond to biotic and abiotic stimuli. Exemplary MAPKs include, but are not limited to, Tropomyosin Receptor Kinase A (TrkA), P38- alpha, and c-Jun N-Terminal Kinase 3 (JNK3). TrkA is a high affinity catalytic receptor of nerve growth factor (NGF) protein. TrkA regulates NGF response, influencing neuronal differentiation and outgrowth as well as programmed cell death. p38-alpha is involved with the regulation of pro-inflammatory cytokines, including TNF-a. In the central nervous system, p38-alpha regulates neuronal death and neurite degeneration, and it is a common target of Alzheimer's disease therapies. JNK3 is a neuronal- specific protein isoform of the JNKs. It is involved with the regulation of apoptosis. JNK3 also plays a role in modulating the response of cytokines, growth factors, and oxidative stress.

[0024] As used herein, the term "modulating activity of a mitogen-activated protein kinase" refers to changing, manipulating, and/or adjusting the activity of a mitogen-activated protein kinase. In one embodiment, modulating the activity of a MAPK can influence neural health, neurogenesis, neural growth and differentiation, and neurodegenerative diseases.

[0025] 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure may be used to modulate neurogenesis, comprising administering a composition of the invention. As used herein, the term "modulating neurogenesis" refers to changing, manipulating, and/or adjusting the growth and development of neural tissue. In one embodiment, neurogenesis comprises adult neurogenesis, in which new neural stem cells are generated from neural stem cells in an adult animal. In one embodiment, modulating neurogenesis comprises increasing and/or enhancing the rate at which new neural tissue is developed.

[0026] 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure may be used to modulate neurite outgrowth, comprising administering a composition of the invention. As used herein, the term "modulating neurite outgrowth" refers to changing, manipulating, and/or adjusting the growth and development of neural projections, or "neurites." In one embodiment, neurogenesis comprises modulating the growth of new neurites, the number of neurites per neuron, and/or neurite length. In one embodiment, modulating neurite outgrowth comprises increasing and/or enhancing the rate and/or length at which neurites develop.

[0027] 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure may be used to prevent and/or treat sexual health disorders including, but not limited to, hypoactive sexual desire disorder, hyperactive sexual desire disorder, orgasmic disorder, arousal disorder, vaginismus, and dyspareunia. In some embodiments, the disorder is a male sexual dysfunction disorder. In some embodiments, the disorder is a female sexual dysfunction disorder.

[0028] 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure may be used to prevent and/or treat women's health disorders including, but not limited to, menstrual cramping, dysmenorrhea, post- hysterectomy pain, vaginal or vulvar vestibule mucosa disorder, menopausal-related disorders, vaginal atrophy, or vulvar vestibulitis.

[0029] Compositions

[0030] The disclosure also relates to compositions comprising an effective amount of 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, and an excipient (e.g., a pharmaceutically-acceptable excipient). In another embodiment, the disclosure also relates to pharmaceutical compositions comprising a therapeutically effective amount of 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, and a pharmaceutically acceptable excipient (also known as a pharmaceutically acceptable carrier). As discussed above, 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4- MeO-DcPT chloride, of the disclosure may be, for example, therapeutically useful to prevent and/or treat the psychological disorders, brain disorders, pain, and inflammation as well as the other disorders described herein.

[0031] A composition or a pharmaceutical composition of the disclosure may be in any form which contains 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride. The composition may be, for example, a tablet, capsule, liquid suspension, injectable, topical, or transdermal. The compositions generally contain, for example, about 1% to about 99% by weight of 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure and, for example, 99% to 1% by weight of at least one suitable pharmaceutically acceptable excipient. In one embodiment, the composition may be between about 5% and about 75% by weight of 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure, with the rest being at least one suitable pharmaceutically acceptable excipient or at least one other adjuvant, as discussed below.

[0032] Published US applications US 2018/0221396 Al and US 2019/0142851 Al disclose compositions comprising a combination of a first purified psilocybin derivative with a second purified psilocybin derivative, with one or two purified cannabinoids or with a purified terpene. Various ratios of these components in the composition are also disclosed. The disclosures of US 2018/0221396 Al and US 2019/0142851 Al are incorporated herein by reference. According to this disclosure, 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure may be used as the "first purified psilocybin derivative" in the compositions described in US 2018/0221396 Al and US 2019/0142851 Al. Accordingly, this disclosure provides a composition comprising: a first component comprising 4-MeO-DcPT chloride, crystalline 4- MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure; at least one second component selected from at least one of (a) a serotonergic drug, (b) a purified psilocybin derivative, (c) a purified cannabinoid, and (d) a purified terpene; and at least one pharmaceutically-acceptable excipient or at least one other adjuvant. Such a composition may be a pharmaceutical composition wherein the components are present individually in therapeutically effective amounts or by combination in a therapeutically effective amount to treat a disease, disorder, or condition as described herein.

[0033] When used in such compositions as a first component comprising 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4- MeO-DcPT chloride, of the disclosure with a second component selected from at least one of (a) a serotonergic drug, (b) a purified psilocybin derivative, (c) a purified cannabinoid, and (d) a purified terpene, the compositions represent particular embodiments of the invention. Compositions having as a first component 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure with a second component selected from at least one of (e) an adrenergic drug, (f) a dopaminergic drug, (g) a monoamine oxidase inhibitor, (h) a purified erinacine, and (i) a purified hericenone represent additional particular embodiments of the invention represented by the compositions having 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, according to the disclosure. In some embodiments, the first and second components can be administered at the same time (e.g., together in the same composition), or at separate times over the course of treating a patient in need thereof. Such a composition may be a pharmaceutical composition wherein the components are present individually in therapeutically effective amounts or by combination in a therapeutically effective amount to treat a disease, disorder, or condition as described herein.

[0034] Within the context of this disclosure, the term "purified" means separated from other materials, such as plant or fungal material, e.g., protein, chitin, cellulose, or water. In one embodiment, the term "purified" refers to a compound substantially free of other materials. In one embodiment, the term "purified" refers to a compound that is substantially free from a second tryptamine compound. In one embodiment, the term "purified" refers to a compound substantially free from histidine. In one embodiment, the term "purified" refers to a compound substantially free from a biological material, such as mold, fungus, plant matter, or bacteria. In one embodiment, the term "purified" refers to a compound substantially free from a paralytic.

[0035] In one embodiment, the term "purified" refers to a compound which has been separated from other compounds that are typically co-extracted when the purified compound is extracted from a naturally occurring organism. In one embodiment, a "purified" psilocybin derivative is partially or completely isolated from other psilocybin derivatives present in a source material, such as a psilocybin- containing mushroom. In one example, "purified" baeocystin is substantially free from psilocybin and/or psilocin. By contrast, traditional psilocybin mushroom extracts (aka crude extracts or fruit body extracts) would be expected to contain an unpredictable and varying amount of psilocybin, psilocin, baeocystin, norbaeocystin, salts thereof, or combinations thereof. Other examples of unpurified psilocybin derivatives would include mycelium containing psilocybin derivatives and/or naturally occurring fungal material such as biological material and/or structural material such as chitin. Similarly, the term "cannabis extracts" or "cannabinoid extracts" traditionally refers to whole plants (aka crude or full spectrum extracts) which have not been subjected to further purification to eliminate unwanted molecules that naturally occur in the cannabis plant. For example, a "cannabis extract comprising cannabidiol" could be expected to include cannabidiol (aka "CBD") and also varying amounts of other compounds, including cannabinoids, terpenes, and other biological material.

[0036] In one embodiment, the term "purified" refers to a compound or composition that has been crystallized.

[0037] In one embodiment, the term "purified" refers to a compound or composition that has been chromatographed, for example by gas chromatography, liquid chromatography (e.g., LC, HPLC, etc.), etc. [0038] In one embodiment, the term "purified" refers to a compound or composition that has been distilled.

[0039] In one embodiment, the term "purified" refers to a compound or composition that has been sublimed.

[0040] In one embodiment, the term "purified" refers to a compound or composition that has been subject to two or more steps chosen from crystallization, chromatography, distillation, or sublimation. [0041] In one embodiment, the term "purified" refers to a compound that is between 80-100% pure.

[0042] In one embodiment, the term "purified" refers to a compound that is between 90-100% pure.

[0043] In one embodiment, the term "purified" refers to a compound that is between 95-100% pure.

[0044] In one embodiment, the term "purified" refers to a compound that is between 99-100% pure. [0045] In one embodiment, the term "purified" refers to a compound that is between 99.9-100% pure.

[0046] A serotonergic drug refers to a compound that binds to, blocks, or otherwise influences (e.g., via an allosteric reaction) activity at a serotonin receptor as described in paragraphs [0245]-[0253] of US 2018/0221396 Al and [0305]-[0311] US 2019/0142851 Al as well as the disclosed exemplary embodiments. Exemplary psilocybin derivatives include but are not limited to psilocybin itself and the psilocybin derivatives described in paragraphs [0081]-[0109] of US 2018/0221396 Al and [0082]-[0110] US 2019/0142851 Al as well as the disclosed exemplary embodiments. Exemplary cannabinoids include but are not limited to the cannabinoids described in paragraphs [0111]-[0145] of US 2018/0221396 Al and [0112]-[0146] US 2019/0142851 Al as well as the disclosed exemplary embodiments. Exemplary terpenes include but are not limited to the terpenes described in paragraphs [0160]-[0238] of US 2018/0221396 Al and [0161]-[0300] US 2019/0142851 Al as well as the disclosed exemplary embodiments.

[0047] A pharmaceutical formulation of the disclosure may comprise, consist essentially of, or consist of (a) 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure and (b) at least one second active compound selected from a serotonergic drug, a purified psilocybin derivative, a purified cannabinoid, a purified terpene, an adrenergic drug, a dopaminergic drug, a monoamine oxidase inhibitor, a purified erinacine, and a purified hericenone, and (c) a pharmaceutically acceptable excipient. In some embodiments, 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, and the second active compound(s) are each present in a therapeutically effective amount using purposefully engineered and unnaturally occurring molar ratios. Exemplary molar ratios of 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure to the second active compound in a composition of the disclosure include but are not limited to from about 0.1:100 to about 100:0.1, from about 1:100 to about 100:1, from about 1:50 to about 50:1, from about 1:25 to about 25:1, from about 1:20 to about 20:1, from about 1:10 to about 10:1, from about 1:5 to about 5:1, from about 1:2 to about 2:1 or may be about 1:1.

[0048] A pharmaceutical formulation of the disclosure may comprise a composition containing 4- MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure and a serotonergic drug, a purified psilocybin derivative, a purified cannabinoid, or a purified terpene, each present in a therapeutically effective amount using purposefully engineered and unnaturally occurring molar ratios. Published US applications US 2018/0221396 Al and US 2019/0142851 Al disclose compositions comprising a combination of a purified psilocybin derivative with a second purified psilocybin derivative, with one or two purified cannabinoids or with a purified terpene. According to this disclosure composition containing 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride of the disclosure may be used in place of a "purified psilocybin derivative" in the compositions described in US 2018/0221396 Al and US 2019/0142851 Al. Accordingly, the disclosure provides a pharmaceutical formulation comprising as (a) 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure and at least one second component selected from (a) a purified psilocybin derivative, (b) a purified cannabinoid, and (c) a purified terpene; and at least one pharmaceutically-acceptable excipient or at least one other adjuvant, as described herein. Such a composition may be a pharmaceutical composition wherein the components are present individually in therapeutically effective amounts or by combination in a therapeutically effective amount to treat a disease, disorder, or condition as described herein.

[0049] A serotonergic drug refers to a compound that binds to, blocks, or otherwise influences (e.g., via an allosteric reaction) activity at a serotonin receptor as described in paragraphs [0245]-[0253] of US 2018/0221396 Al and [0305]-[0311] US 2019/0142851 Al as well as the disclosed exemplary embodiments. Some exemplary serotonergic drugs include SSRIs and SNRIs. Some examples of specific serotonergic drugs include the following molecules, including any salts, solvates, or polymorphs thereof: 6-allyl-N,N-diethyl-NL; N,N-dibutyl-T; N,N-diethyl-T; N,N-diisopropyl-T; 5-methyoxy-alpha-methyl-T; N,N- dimethyl-T; 2,alpha-dimethyl-T; alpha, N-dimethyl-T; N,N-dipropyl-T; N-ethyl-N-isopropyl-T; alpha-ethyl- T; 6-N,N-Triethyl-NL; 3,4-dihydro-7-methoxy-l-methyl-C; 7-methyoxy-l-methyl-C; N,N-dibutyl-4- hydroxy-T; N,N-diethyl-4-hydroxy-T; N,N-diisopropyl-4-hydroxy-T; N,N-dimethyl-4-hydroxy-T; N,N- dimethyl-5-hydroxy-T; N, N-dipropyl-4-hydroxy-T; N-ethyl-4-hydroxy-N-methyl-T; 4-hydroxy-N-isopropyl- N-methyl-T; 4-hydroxy-N-methyl-N-propyl-T; 4-hydroxy-N,N-tetramethylene-T; ibogaine; N,N-diethyl-L; N-butyl-N-methyl-T; N,N-diisopropyl-4,5-methylenedioxy-T; N,N-diisopropyl-5,6-methylenedioxy-T; N,N- dimethyl-4,5-methylenedioxy-T; N,N-dimethyl-5,6-methylenedioxy-T; N-isopropyl-N-methyl-5,6- methylenedioxy-T; N,N-diethyl-2-methyl-T; 2-N,N-trimethyl-T; N-acetyl-5-methoxy-T; N,N-diethyl-5- methoxy-T; N,N-diisopropyl-5-methoxy-T; 5-methoxy-N, N-dimethyl-T; N-isopropyl-4-methoxy-N-methyl- T; N-isopropyl-5-methoxy-N-methyl-T; 5,6-dimethoxy-N-isopropyl-N-methyl-T; 5-methoxy-N-methyl-T; 5-methoxy-N, N-tetramethylene-T; 6-methoxy-l-methyl-l,2,3,4-tetrahydro-C; 5-methoxy-2-N,N- trimethyl-T; N,N-dimethyl-5-methylthio-T; N-isopropyl-N-methyl-T; alpha-methyl-T; N-ethyl-T; N-methyl- T; 6-propyl-N L; N,N-tetramethylene-T; tryptamine; 7-methoxy-l-methyl-l,2,3,4-tetrahydro-C; and alpha, N-dimethyl-5-methoxy-T. For additional information regarding these compounds see Shulgin, A. T., & Shulgin, A. (2016). Tihkal: The Continuation. Berkeley, Calif.: Transform Press. In one embodiment, a serotonergic drug is chosen from alprazolam, amphetamine, aripiprazole, azapirone, a barbiturate, bromazepam, bupropion, buspirone, a cannabinoid, chlordiazepoxide, citalopram, clonazepam, clorazepate, dextromethorphan, diazepam, duloxetine, escitalopram, fluoxetine, flurazepam, fluvoxamine, lorazepam, lysergic acid diethylamide, lysergamide, 3,4- methylenedioxymethamphetamine, milnacipran, mirtazapine, naratriptan, paroxetine, pethidine, phenethylamine, psicaine, oxazepam, reboxetine, serenic, serotonin, sertraline, temazepam, tramadol, triazolam, a tryptamine, venlafaxine, vortioxetine, and/or derivatives thereof. In an exemplary embodiment, the serotonergic drug is 3,4-methylenedioxymethamphetamine.

[0050] Exemplary psilocybin derivatives include but are not limited to psilocybin itself and the psilocybin derivatives described in paragraphs [0081]-[0109] of US 2018/0221396 Al and [0082]-[0110] US 2019/0142851 Al as well as the disclosed exemplary embodiments, incorporated here by reference. In one embodiment, the compositions disclosed herein comprise one or more purified psilocybin derivatives chosen from: [3-(2-dimethylaminoethyl)-lH-indol-4-yl] dihydrogen phosphate; 4- hydroxytryptamine; 4-hydroxy-N,N-dimethyltryptamine; [3-(2-methylaminoethyl)-lH-indol-4-yl] dihydrogen phosphate; 4-hydroxy-N-methyltryptamine; [3-(aminoethyl)-lH-indol-4-yl] dihydrogen phosphate; [3-(2-trimethylaminoethyl)-lH-indol-4-yl] dihydrogen phosphate; and 4-hydroxy-N,N,N- trimethyltryptamine.

[0051] Exemplary cannabinoids include but are not limited to the cannabinoids described in paragraphs [0111]-[0145] of US 2018/0221396 Al and [0112]-[0146] US 2019/0142851 Al as well as the disclosed exemplary embodiments. Examples of cannabinoids within the context of this disclosure include the following molecules: cannabichromene (CBC); cannabichromenic acid (CBCA); cannabichromevarin (CBCV); cannabichromevarinic acid (CBCVA); cannabicyclol (CBL); cannabicyclolic acid (CBLA); cannabicyclovarin (CBLV); cannabidiol (CBD); cannabidiol monomethylether (CBDM); cannabidiolic acid (CBDA); cannabidiorcol (CBD-C1); cannabidivarin (CBDV); cannabidivarinic acid (CBDVA); cannabielsoic acid B (CBEA-B); cannabielsoin (CBE); cannabielsoin acid A (CBEA-A); cannabigerol (CBG); cannabigerol monomethylether (CBGM); cannabigerolic acid (CBGA); cannabigerolic acid monomethylether (CBGAM); cannabigerovarin (CBGV); cannabigerovarinic acid (CBGVA); cannabinodiol (CBND); cannabinodivarin (CBVD); cannabinol (CBN); cannabinol methylether (CBNM); cannabinol-C2 (CBN-C2); cannabinol-C4 (CBN-C4); cannabinolic acid (CBNA); cannabiorcol (CBN-C1); cannabivarin (CBV); cannabitriol (CBT); cannabitriolvarin (CBTV); 10-ethoxy-9-hydroxy-delta-6a- tetrahydrocannabinol; cannabicitran (CBTC); cannabiripsol (CBR); 8,9-dihydroxy-delta-6a- tetrahydrocannabinol; delta-8-tetrahydrocannabinol (A8-THC); delta-8-tetrahydrocannabinolic acid (A8- THCA); delta-9-tetrahydrocannabinol (THC); delta-9-tetrahydrocannabinol-C4 (THC-C4); delta-9- tetrahydrocannabinolic acid A (THCA-A); delta-9-tetrahydrocannabinolic acid B (THCA-B); delta-9- tetrahydrocannabinolic acid-C4 (THCA-C4); delta-9-tetrahydrocannabiorcol (THC-C1); delta-9- tetrahydrocannabiorcolic acid (THCA-C1); delta-9-tetrahydrocannabivarin (THCV); delta-9- tetrahydrocannabivarinic acid (THCVA); 10-oxo-delta-6a-tetrahydrocannabinol (OTHC); cannabichromanon (CBCF); cannabifuran (CBF); cannabiglendol; delta-9-cis-tetrahydrocannabinol (cis- THC); trihydroxy-delta-9-tetrahydrocannabinol (triOH-THC); dehydrocannabifuran (DCBF); and 3, 4,5,6- tetrahydro-7-hydroxy-alpha-alpha-2-trimethyl-9-n-propyl-2,6-methano-2H-l-benzoxocin-5-methanol. In one embodiment, the purified cannabinoid is chosen from THC, THCA, THCV, THCVA, CBC, CBCA, CBCV, CBCVA, CBD, CBDA, CBDV, CBVD, CBDVA, CBG, CBGA, CBGV, or CBGVA.

[0052] Exemplary terpenes include but are not limited to the terpenes described in paragraphs [0160]-[0238] of US 2018/0221396 Al and [0161]-[0300] US 2019/0142851 Al as well as the disclosed exemplary embodiments. In one embodiment, a purified terpene is chosen from acetanisole, acetyl cedrene, anethole, anisole, benzaldehyde, bornyl acetate, borneol, cadinene, cafestol, caffeic acid, camphene, camphor, capsaicin, carene, carotene, carvacrol, carvone, caryophyllene, caryophyllene, caryophyllene oxide, cedrene, cedrene epoxide, cecanal, cedrol, cembrene, cinnamaldehyde, cinnamic acid, citronellal, citronellol, cymene, eicosane, elemene, estragole, ethyl acetate, ethyl cinnamate, ethyl maltol, eucalyptol/l,8-cineole, eudesmol, eugenol, euphol, farnesene, farnesol, fenchone, geraniol, geranyl acetate, guaia-l(10),ll-diene, guaiacol, guaiol, guaiene, gurjunene, herniarin, hexanaldehyde, hexanoic acid, humulene, ionone, ipsdienol, isoamyl acetate, isoamyl alcohol, isoamyl formate, isoborneol, isomyrcenol, isoprene, isopulegol, isovaleric acid, lavandulol, limonene, gamma-linolenic acid, linalool, longifolene, lycopene, menthol, methyl butyrate, 3-mercapto-2-methylpentanal, betamercaptoethanol, mercaptoacetic acid, methyl salicylate, methylbutenol, methyl-2-methylvalerate, methyl thiobutyrate, myrcene, gamma-muurolene, nepetalactone, nerol, nerolidol, neryl acetate, nonanaldehyde, nonanoic acid, ocimene, octanal, octanoic acid, pentyl butyrate, phellandrene, phenylacetaldehyde, phenylacetic acid, phenylethanethiol, phytol, pinene, propanethiol, pristimerin, pulegone, retinol, rutin, sabinene, squalene, taxadiene, terpineol, terpine-4-ol, terpinolene, thujone, thymol, umbelliferone, undecanal, verdoxan, or vanillin. In one embodiment, a purified terpene is chosen from bornyl acetate, alpha-bisabolol, borneol, camphene, camphor, carene, caryophyllene, cedrene, cymene, elemene, eucalyptol, eudesmol, farnesene, fenchol, geraniol, guaiacol, humulene, isoborneol, limonene, linalool, menthol, myrcene, nerolidol, ocimene, phellandrene, phytol, pinene, pulegone, sabinene, terpineol, terpinolene, or valencene.

[0053] As used herein, the term "adrenergic drug" refers to a compound that binds, blocks, or otherwise influences (e.g., via an allosteric reaction) activity at an adrenergic receptor. In one embodiment, an adrenergic drug binds to an adrenergic receptor. In one embodiment, an adrenergic drug indirectly affects an adrenergic receptor, e.g., via interactions affecting the reactivity of other molecules at the adrenergic receptor. In one embodiment, an adrenergic drug is an agonist, e.g., a compound activating an adrenergic receptor. In one embodiment, an adrenergic drug is an antagonist, e.g., a compound binding but not activating an adrenergic receptor, e.g., blocking a receptor. In one embodiment, an adrenergic drug is an effector molecule, e.g., a compound binding to an enzyme for allosteric regulation. In one embodiment, an adrenergic drug acts (either directly or indirectly) at more than one type of receptor (e.g., 5HT, dopamine, adrenergic, acetylcholine, etc.).

[0054] In one embodiment, an adrenergic drug is an antidepressant. In one embodiment, an adrenergic drug is a norepinephrine transporter inhibitor. In one embodiment, an adrenergic drug is a vesicular monoamine transporter inhibitor. In one embodiment, an adrenergic drug is chosen from adrenaline, agmatine, amoxapine, aptazapine, atomoxetine, bupropion, clonidine, doxepin, duloxetine, esmirtazpine, mianserin, ketanserin, mirabegron, mirtazapine, norepinephrine, phentolamine, phenylephrine, piperoxan, reserpine, ritodrine, setiptiline, tesofensine, timolol, trazodone, trimipramine, or xylazine.

[0055] As used herein, the term "dopaminergic drug" refers to a compound that binds, blocks, or otherwise influences (e.g., via an allosteric reaction) activity at a dopamine receptor. In one embodiment, a dopaminergic drug binds to a dopamine receptor. In one embodiment, a dopaminergic drug indirectly affects a dopamine receptor, e.g., via interactions affecting the reactivity of other molecules at the dopamine receptor. In one embodiment, a dopaminergic drug is an agonist, e.g., a compound activating a dopamine receptor. In one embodiment, a dopaminergic drug is an antagonist, e.g., a compound binding but not activating a dopamine receptor, e.g., blocking a receptor. In one embodiment, a dopaminergic drug is an effector molecule, e.g., a compound binding to an enzyme for allosteric regulation. In one embodiment, a dopaminergic drug acts (either directly or indirectly) at more than one type of receptor (e.g., 5HT, dopamine, adrenergic, acetylcholine, etc.). [0056] In one embodiment, a dopaminergic drug is a dopamine transporter inhibitor. In one embodiment, a dopaminergic drug is a vesicular monoamine transporter inhibitor. In one embodiment, a dopaminergic drug is chosen from amineptine, apomorphine, benzylpiperazine, bromocriptine, cabergoline, chlorpromazine, clozapine, dihydrexidine, domperidone, dopamine, fluphenazine, haloperidol, ketamine, loxapine, methamphetamine, olanzapine, pemoline, perphenazine, pergolide, phencyclidine, phenethylamine, phenmetrazine, pimozide, piribedil, a psychostimulant, reserpine, risperidone, ropinirole, tetrabenazine, or thioridazine.

[0057] As used herein, the term "monoamine oxidase inhibitor" (MAOI) refers to a compound that blocks the actions of monoamine oxidase enzymes. In one embodiment, a MAOI inhibits the activity of one or both monoamine oxidase A and monoamine oxidase B. In one embodiment a MAOI is a reversible inhibitor of monoamine oxidase A. In one embodiment a MAOI is a drug chosen from isocarboxazid, phenelzine, or tranylcypromine. In one embodiment, a MAOI is -carboline, pinoline, harmane, harmine, harmaline, harmalol, tetrahydroharmine, 9-methyl-P-carboline, or 3-carboxy- tetrahydrononharman.

[0058] In one embodiment, the compositions and methods disclosed herein include one or more purified erinacine molecules. In one embodiment, the compositions and methods disclosed herein comprise purified erinacine A. In one embodiment, the compositions and methods disclosed herein comprise erinacine B. In one embodiment, the compositions and methods disclosed herein comprise erinacine C. In one embodiment, the compositions and methods disclosed herein comprise erinacine D. In one embodiment, the compositions and methods disclosed herein comprise erinacine E. In one embodiment, the compositions and methods disclosed herein comprise erinacine F. In one embodiment, the compositions and methods disclosed herein comprise erinacine G. In one embodiment, the compositions and methods disclosed herein comprise erinacine H. In one embodiment, the compositions and methods disclosed herein comprise erinacine I. In one embodiment, the compositions and methods disclosed herein comprise erinacine J. In one embodiment, the compositions and methods disclosed herein comprise erinacine K In one embodiment, the compositions and methods disclosed herein comprise erinacine P. In one embodiment, the compositions and methods disclosed herein comprise erinacine Q. In one embodiment, the compositions and methods disclosed herein comprise erinacine R. In one embodiment, the compositions and methods disclosed herein comprise erinacine S.

[0059] In one embodiment, the compositions and methods disclosed herein include one or more purified hericenone molecules. In one embodiment, the compositions and methods disclosed herein comprise purified hericenone A. In one embodiment, the compositions and methods disclosed herein comprise purified hericenone B. In one embodiment, the compositions and methods disclosed herein comprise purified hericenone C. In one embodiment, the compositions and methods disclosed herein comprise purified hericenone D. In one embodiment, the compositions and methods disclosed herein comprise purified hericenone E. In one embodiment, the compositions and methods disclosed herein comprise purified hericenone F. In one embodiment, the compositions and methods disclosed herein comprise purified hericenone G. In one embodiment, the compositions and methods disclosed herein comprise purified hericenone H.

[0060] Exemplary compositions of 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure and a second compound selected from a serotonergic drug, a purified psilocybin derivative, a purified cannabinoid, a purified terpene, an adrenergic drug, a dopaminergic drug, a monoamine oxidase inhibitor, a purified erinacine, and a purified hericenone in exemplary molar ratios are shown in Table 1. 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure may be any one of the exemplary embodiments described above including the crystalline forms as disclosed herein.

Table 1

[0061] Exemplary pharmaceutical compositions of 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure and a second compound selected from a serotonergic drug, a purified psilocybin derivative, a purified cannabinoid, a purified terpene, an adrenergic drug, a dopaminergic drug, a monoamine oxidase inhibitor, a purified erinacine, and a purified hericenone and an excipient with exemplary molar ratios of 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, to the second compound are shown in Table 2. 4- MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure may be any one of the exemplary embodiments described above including the crystalline forms as disclosed herein.

Table 2

[0062] An "effective amount" or a "therapeutically effective amount" of 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4- MeO-DcPT chloride, of the disclosure is generally in the range of about 0.1 to about 100 mg daily (oral dose), of about 0.1 to about 50 mg daily (oral dose), of about 0.25 to about 25 mg daily (oral dose), of about 0.1 to about 5 mg daily (oral dose), or of about 0.5 to about 2.5 mg daily (oral dose). The actual amount required for treatment of any particular patient may depend upon a variety of factors including, for example, the disease being treated and its severity; the specific pharmaceutical composition employed; the age, body weight, general health, sex, and diet of the patient; the mode of administration; the time of administration; the route of administration; and the rate of excretion; the duration of the treatment; any drugs used in combination or coincidental with the specific compound employed; and other such factors well known in the medical arts. These factors are discussed in Goodman and Gilman's "The Pharmacological Basis of Therapeutics," Tenth Edition, A. Gilman, J. Hardman and L. Limbird, eds., McGraw-Hill Press, 155-173 (2001), which is incorporated herein by reference. 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure and pharmaceutical compositions containing it may be used in combination with other agents that are generally administered to a patient being treated for psychological and other disorders discussed above. They may also be co-formulated with one or more of such agents in a single pharmaceutical composition.

[0063] Depending on the type of pharmaceutical composition, the pharmaceutically acceptable carrier may be chosen from any one or a combination of carriers known in the art. The choice of the pharmaceutically acceptable carrier depends upon the pharmaceutical form and the desired method of administration to be used. Exemplary carriers include those that do not substantially alter the structure or activity of 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure, or produce undesirable biological effects or otherwise interact in a deleterious manner with any other component(s) of the pharmaceutical composition.

[0064] The pharmaceutical compositions of the disclosure may be prepared by methods know in the pharmaceutical formulation art, for example, see Remington's Pharmaceutical Sciences, 18th Ed., (Mack Publishing Company, Easton, Pa., 1990), which is incorporated herein by reference. In a solid dosage form, 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure may be admixed with at least one pharmaceutically acceptable excipient such as, for example, sodium citrate or dicalcium phosphate or (a) fillers or extenders, such as, for example, starches, lactose, sucrose, glucose, mannitol, and silicic acid, (b) binders, such as, for example, cellulose derivatives, starch, alginates, gelatin, polyvinylpyrrolidone, sucrose, and gum acacia, (c) humectants, such as, for example, glycerol, (d) disintegrating agents, such as, for example, agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, croscarmellose sodium, complex silicates, and sodium carbonate, (e) solution retarders, such as, for example, paraffin, (f) absorption accelerators, such as, for example, quaternary ammonium compounds, (g) wetting agents, such as, for example, cetyl alcohol, and glycerol monostearate, magnesium stearate and the like, (h) adsorbents, such as, for example, kaolin and bentonite, and (i) lubricants, such as, for example, talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, or mixtures thereof. In the case of capsules, tablets, and pills, the dosage forms may also comprise buffering agents. In some embodiments, the excipient is not water. In some embodiments, the excipient is not a solvent (e.g., EtOH, diethyl ether, ethyl acetate, or hydrocarbonbased solvents (e.g., hexanes). In some embodiments, the dosage form is substantially free of water and/or solvents, for example less than about 5% water by mass, less than 2% water by mass, less than 1% water by mass, less than 0.5% water by mass, or less than 0.1% water by mass.

[0065] Excipients or pharmaceutically acceptable adjuvants known in the pharmaceutical formulation art may also be used in the pharmaceutical compositions of the disclosure. These include, but are not limited to, preserving, wetting, suspending, sweetening, flavoring, perfuming, emulsifying, and dispensing agents. Prevention of the action of microorganisms may be ensured by inclusion of various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, and the like. It may also be desirable to include isotonic agents, for example, sugars, sodium chloride, and the like. If desired, a pharmaceutical composition of the disclosure may also contain minor amounts of auxiliary substances such as wetting or emulsifying agents, pH buffering agents, antioxidants, and the like, such as, for example, citric acid, sorbitan monolaurate, triethanolamine oleate, butylated hydroxytoluene, etc.

[0066] Solid dosage forms as described above may be prepared with coatings and shells, such as enteric coatings and others well known in the art. They may contain pacifying agents and can also be of such composition that they release the active compound or compounds in a certain part of the intestinal tract in a delayed manner. Non-limiting examples of embedded compositions that may be used are polymeric substances and waxes. The active compounds may also be in microencapsulated form, if appropriate, with one or more of the above-mentioned excipients.

[0067] Suspensions, in addition to the active compounds, may contain suspending agents, such as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, or mixtures of these substances, and the like.

[0068] Solid dosage forms for oral administration, which includes capsules, tablets, pills, powders, and granules, may be used. In such solid dosage forms, the active compound may be mixed with at least one inert, pharmaceutically acceptable excipient (also known as a pharmaceutically acceptable carrier).

[0069] Administration of 4-MeO-DcPT chloride, crystalline 4-MeO-DcPT chloride, or specific crystalline forms thereof, such as crystalline form 1 of 4-MeO-DcPT chloride, of the disclosure in pure form or in an appropriate pharmaceutical composition may be carried out via any of the accepted modes of administration or agents for serving similar utilities. Thus, administration may be, for example, orally, buccally, nasally, parenterally (intravenous, intramuscular, or subcutaneous), topically, transdermally, intravaginally, intravesically, or intrasystemically, in the form of solid, semi-solid, lyophilized powder, or liquid dosage forms, such as, for example, tablets, suppositories, pills, soft elastic and hard gelatin capsules, powders, solutions, suspensions, or aerosols, or the like, such as, for example, in unit dosage forms suitable for simple administration of precise dosages. One route of administration may be oral administration, using a convenient daily dosage regimen that can be adjusted according to the degree of severity of the disease-state to be treated.

[0070] Exemplary Embodiments of the Invention

[0071] El. N-cyclopropyl-N-[2-(4-methoxy-lH-indol-3-yl)ethyl]cyclopropanaminium chloride (4- methoxy-A/,A/-dicyclopropyltryptammonium chloride).

[0072] E2. Crystalline N-cyclopropyl-N-[2-(4-methoxy-lH-indol-3-yl)ethyl]cyclopropanaminium chloride (4-methoxy-/V,/V-dicyclopropyltryptammonium chloride).

[0073] E3. Crystalline form 1 of N-cyclopropyl-N-[2-(4-methoxy-lH-indol-3- yl)ethyl]cyclopropanaminium chloride (4-methoxy-A/,/V-dicyclopropyltryptammonium chloride).

[0074] E4. Crystalline form 1 of 4-methoxy-/V,/\/-dicyclopropyltryptammonium chloride according to

E3, characterized by at least one of: a monoclinic crystal system at a temperature of about 300 K; a C2/c space group at a temperature of about 300 K; unit cell dimensions a = 19.2681(19) A, b = 7.1763(6) A, c = 24.519(2) A, a = 90°, = 104.629(4)°, and y = 90°; an X-ray powder diffraction pattern substantially similar to FIG. 3; or an X-ray powder diffraction pattern characterized by at least two peaks selected from 9.5, 14.6, and 22.5 °20 ± 0.2 °20.

[0075] E5. A composition comprising 4-methoxy-/V,/V-dicyclopropyltryptammonium chloride according to El and an excipient.

[0076] E6. A composition comprising crystalline 4-methoxy-/V,A/-dicyclopropyltryptammonium chloride according to any one of E2-E4 and an excipient.

[0077] E7. A composition comprising 4-methoxy-/V,A/-dicyclopropyltryptammonium chloride according to El as a first component and a second component selected from at least one of (a) a serotonergic drug, (b) a purified psilocybin derivative, (c) a purified cannabinoid, (d) a purified terpene, (e) an adrenergic drug, (f) a dopaminergic drug, (g) a monoamine oxidase inhibitor, (h) a purified erinacine, and (i) a purified hericenone.

[0078] E8. A composition comprising crystalline 4-methoxy-/V,A/-dicyclopropyltryptammonium chloride according to any one of E2-E4 as a first component and a second component selected from at least one of (a) a serotonergic drug, (b) a purified psilocybin derivative, (c) a purified cannabinoid, (d) a purified terpene, (e) an adrenergic drug, (f) a dopaminergic drug, (g) a monoamine oxidase inhibitor, (h) a purified erinacine, and (i) a purified hericenone.

[0079] E9. A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a therapeutically effective amount of 4-methoxy-/V,/\/- dicyclopropyltryptammonium chloride according to El.

[0080] E10. A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a therapeutically effective amount of crystalline 4- methoxy-A/,A/-dicyclopropyltryptammonium chloride according to any one of E2-E4.

[0081] Ell. A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a composition according to E5 or E7.

[0082] E12. A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a composition according to E6 or E8.

[0083] E13. A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a therapeutically effective amount of 4-methoxy-/V,/\/- dicyclopropyltryptammonium chloride according to El. [0084] E14. A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a therapeutically effective amount of crystalline 4- methoxy-A/,A/-dicyclopropyltryptammonium chloride according to any one of E2-E4.

[0085] E15. A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a composition according to E5 or E7.

[0086] E16. A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a composition according to E6 or E8.

Examples

[0087] The preparation and characterization of crystalline form 1 of N-cyclopropyl-N-[2-(4-methoxy- lH-indol-3-yl)ethyl]cyclopropanaminium chloride (4-methoxy-/V,A/-dicyclopropyltryptammonium chloride or 4-MeO-DcPT chloride) is described below.

[0088] Single Crystal X-Ray Diffraction (SCXRD) Characterization: Data were collected on a Bruker D8 Venture CMOS Diffractometer equipped with an Oxford Cryosystems Cryostream cooling device and using Mo Ka radiation. Structures were solved using the Bruker SHELXTL program and refined with the SHELXTL program as part of the Bruker SHELXTL suite, or 0LEX2 software. Unless otherwise stated, hydrogen atoms attached to carbon were placed geometrically and allowed to refine with a riding isotropic displacement parameter. Hydrogen atoms attached to a heteroatom were located in a difference Fourier synthesis and were allowed to refine freely with an isotropic displacement parameter.

[0089] Preparation and Characterization of Crystalline form 1 of 4-methoxy-A/,/\/- dicyclopropyltryptammonium chloride

[0090] Synthesis

[0091] To an ice bath cooled solution of 4-methoxy-lH-indole (2 g) in diethyl ether (85 mL) was added oxalylchloride (3.4 g) dropwise. The mixture was stirred for 4 hours maintaining the cooling, and added into a mixture of ethanol (25 mL) and triethylamine (6.9 g) dropwise under ice bath cooling. The mixture was warmed to room temperature and allowed to stir overnight. The mixture was then diluted with dichloromethane and washed with water. The organic phase was dried over sodium sulfate and solvent was removed in vacuo. The resulting residue was purified by silica gel chromatography (pet. ether/ethyl acetate) to afford ethyl-2-(4-methoxy-lH-indol-3-yl)-2-oxoacetate as a yellow solid (1.1 g, 35% yield).

[0092] This solid (1.1 g) was dissolved in tetrahydrofuran (21 mL) and a slurry of lithium aluminum hydride (538 mg) in tetra hydrofuran (14 mL) was added dropwise under ice bath cooling. The mixture was then heated at reflux overnight. The mixture was cooled in an ice bath, quenched with water, and filtered. The solid was washed with tetrahydrofuran, and the combined filtrates were concentrated under reduced pressure. The residue was purified by silica gel chromatography (petroleum ether/ethyl acetate) to afford 2-(4-methoxy-lH-indol-3-yl)ethan-l-ol as a yellow solid (590 mg, 70 % yield).

[0093] This solid (590 mg) was dissolved in methylene chloride (12 mL) and triphenylphosphine (1.1 g) and carbon tetrabromide (1.4 g) were added. The mixture was stirred at room temperature for 1.5 hours. Solvent was removed in vacuo, and the resulting residue was purified by silica gel chromatography (petroleum ether/ethyl acetate) to afford 3-(2-bromoethyl)-4-methoxy-lH-indole as a white solid (848 mg, 99% yield).

[0094] 200 mg of this solid was dissolved in /V,A/-dimethylformamide (6 mL), and cesium carbonate

(1.3 g), potassium iodide (13 mg) and dicyclopropylamine hydrochloride (211 mg) were added. The mixture was heated at 80 degrees overnight. The mixture was quenched with water, extracted with methylene chloride, washed with water and brine, and the organic layer was dried over sodium sulfate. Solvent was removed in vacuo, and the residue was purified by silica gel chromatography (methylene chloride/methanol (3.5 M ammonia)) to afford 4-methoxy-N,N-dicyclopropyltryptamine (4-MeO-DcPT) as a yellow solid (50 mg, 23% yield).

[0095] To a solution of 4-MeO-DcPT (228 mg) in methylene chloride (4 mL) was added IM hydrochloric acid in ethanol (1.26 mL). The mixture was stirred for 30 minutes and solvent was removed in vacuo. The residue was washed with diethyl ether and dried under reduced pressure to afford the chloride salt as a white solid (207 mg).

[0096] Crystallization

[0097] Single crystals suitable for X-ray diffraction studies were grown from the slow evaporation of an acetone/water solution.

[0098] Single Crystal Characterization

[0099] The single crystal data and structure refinement parameters for the crystalline form 1 structure of 4-MeO-DcPT chloride are reported in Table 3, below.

Table 3

[00100] FIG. 1 shows the molecular structure of crystalline form 1 of 4-MeO-DcPT chloride, showing the atomic labeling. [00101] FIG. 2 shows the unit cell of crystalline form 1 of 4-MeO-DcPT chloride along the b-axis.

[00102] Simulated Powder X-ray Diffraction (PXRD) Pattern

[00103] FIG. 3 shows a simulated X-ray powder diffraction pattern (XRPD) for crystalline form 1 of 4-MeO-DcPT chloride generated from its single crystal data. Table 4 lists the angles, °20 ± O.2°20, and d- spacing of the peaks identified in the experimental XRPD pattern of FIG. 3. The entire list of peaks, or a subset thereof, may be sufficient to characterize the cocrystal. For example, the cocrystal may be characterized by at least two peaks selected from the peaks at 9.5, 14.6, and 22.5 °20 + O.2°20 or their corresponding d-spacing as well as by an XRPD pattern substantially similar to FIG. 3.

Table 4: Crystalline form 1 of 4-MeO-DcPT

References

Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.

Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.

Claims

The claimed invention is:

1. N-cyclopropyl-N-[2-(4-methoxy-lH-indol-3-yl)ethyl]cyclopropanarniniurn chloride (4-methoxy-A/,/V- dicyclopropyltryptammonium chloride).

2. Crystalline N-cyclopropyl-N-[2-(4-methoxy-lH-indol-3-yl)ethyl]cyclopropanaminium chloride (4- rnethoxy-/V,A/-dicyclopropyltryptammoniurn chloride).

3. Crystalline form 1 of N-cyclopropyl-N-[2-(4-methoxy-lH-indol-3-yl)ethyl]cyclopropanaminium chloride (4-rnethoxy-/V,/V-dicyclopropyltryptammonium chloride).

4. Crystalline form 1 of 4-methoxy-A/,/V-dicyclopropyltryptammonium chloride according to claim 3, characterized by at least one of: a monoclinic crystal system at a temperature of about 300 K; a C2/c space group at a temperature of about 300 K; unit cell dimensions a = 19.2681(19) A, b = 7.1763(6) A, c = 24.519(2) A, a = 90°, = 104.629(4)°, and y = 90°; an X-ray powder diffraction pattern substantially similar to FIG. 3; or an X-ray powder diffraction pattern characterized by at least two peaks selected from 9.5, 14.6, and 22.5 °20 ± 0.2 °20.

5. A composition comprising 4-methoxy-A/,A/-dicyclopropyltryptammonium chloride according to claim 1 and an excipient.

6. A composition comprising crystalline 4-methoxy-/V,/\/-dicyclopropyltryptammonium chloride according to any one of claims 2-4 and an excipient.

7. A composition comprising 4-methoxy-A/,A/-dicyclopropyltryptammonium chloride according to claim 1 as a first component and a second component selected from at least one of (a) a serotonergic drug, (b) a purified psilocybin derivative, (c) a purified cannabinoid, (d) a purified terpene, (e) an adrenergic drug, (f) a dopaminergic drug, (g) a monoamine oxidase inhibitor, (h) a purified erinacine, and (i) a purified hericenone.

8. A composition comprising crystalline 4-methoxy-/V,A/-dicyclopropyltryptammonium chloride according to any one of claims 2-4 as a first component and a second component selected from at least one of (a) a serotonergic drug, (b) a purified psilocybin derivative, (c) a purified cannabinoid, (d) a purified terpene, (e) an adrenergic drug, (f) a dopaminergic drug, (g) a monoamine oxidase inhibitor, (h) a purified erinacine, and (i) a purified hericenone.

9. A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a therapeutically effective amount of 4-methoxy-A/,/V- dicyclopropyltryptammonium chloride according to claim 1.

10. A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a therapeutically effective amount of crystalline 4- methoxy-A/,A/-dicyclopropyltryptammonium chloride according to any one of claims 2-4.

11. A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a composition according to claim 5 or claim 7.

12. A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a composition according to claim 6.

13. A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a composition according to claim 8.

14. A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a therapeutically effective amount of 4-methoxy-/V,/\/- dicyclopropyltryptammonium chloride according to claim 1.

15. A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a therapeutically effective amount of crystalline 4- methoxy-A/,A/-dicyclopropyltryptammonium chloride according to any one of claims 2-4.

16. A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a composition according to claim 5 or claim 7.

17. A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a composition according to claim 6.

18. A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a composition according to claim 8.