Psilacetin salts

Abstract

This disclosure relates to crystalline psilacetin salts, to pharmaceutical compositions containing the crystalline psilacetin salts, and to methods of treatment / therapeutic uses of the crystalline psilacetin salts. In particular, the disclosure relates to a crystalline psilacetin monotartrate form 1 salt, a crystalline psilacetin monotartrate form 2 salt, a crystalline psilacetin hemitartrate form 1 salt, a crystalline psilacetin hemitartrate form 2 salt, a crystalline psilacetin monosuccinate salt, and a crystalline psilacetin hemisuccinate salt.

Description

PSILACETIN SALTSCross-Reference to Related Applications

[0001] This application claims priority to U.S. Provisional Application No. 63 / 588,335, filed on October 6, 2023; the disclosure of which is incorporated herein by reference.Technical Field

[0002] This disclosure relates to crystalline psilacetin salts, to pharmaceutical compositions containing the crystalline psilacetin salts, and to methods of treatment / therapeutic uses of the crystalline psilacetin salts.Background of the Invention

[0003] 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

[0004] The disclosure relates to crystalline psilacetin salts. In particular, the disclosure relates to a crystalline psilacetin monotartrate form 1 salt, a crystalline psilacetin monotartrate form 2 salt, a crystalline psilacetin hemitartrate form 1 salt, a crystalline psilacetin hemitartrate form 2 salt, a crystalline psilacetin monosuccinate salt, and a crystalline psilacetin hemisuccinate salt.

[0005] The disclosure further relates to a composition comprising crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetinmonosuccinate salt, or crystalline psilacetin hemisuccinate salt, according to the disclosure, and at least one excipient.

[0006] The disclosure also provides a composition comprising crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt, according to the disclosure, 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.

[0007] 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 crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt, according to the disclosure, or a composition according to this disclosure.

[0008] 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 crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt, according to the disclosure, and to administering a pharmaceutical composition or a composition according to the invention.

[0009] 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 oneembodiment, 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 overlaid XRPD profiles of psilacetin monotartrate (lower XRPD profile) and psilacetin hemitartrate (upper XRPD profile).

[0011] FIG. 2 shows the overlaid XRPD profiles of psilacetin monosuccinate (lower XRPD profile) and psilacetin hemisuccinate (upper XRPD profile).

[0012] FIG. 3 shows the overlaid XRPD profiles of psilacetin monotartrate form 2 (lower XRPD profile) and psilacetin monotartrate form 1 (upper XRPD profile).

[0013] FIG. 4 shows the overlaid XRPD profiles of the succinic acid, 1 to 1 stoichiometry (upper XRPD profile) and the succinic acid, 1 to 2 stoichiometry (lower XRPD profile).

[0014] FIG. 5 shows the overlaid XRPD profiles of psilacetin hemitartrate form 2 (lower XRPD profile) and psilacetin hemitartrate form 1 (upper XRPD profile).

[0015] FIG. 6 shows the overlaid XRPD profiles of samples of the L-tartaric acid, 1 to 1 stoichiometry from the scaled-up samples (upper XRPD profile) and the L-tartaric acid, 1 to 1 stoichiometry sample from Panel #3 (lower XRPD profile).

[0016] FIG. 7 shows the XRPD profile for psilacetin.

[0017] FIG. 8 shows the1H NMR spectrum of psilacetin, acquired in methanol-d4.

[0018] FIG. 9 shows the DSC profile of psilacetin.

[0019] FIG. 10 shows the TGA profile of psilacetin.

[0020] FIG. 11A and FIG. 11B show the Polarized Light Microscopy (PLM) images of psilacetin at 4x magnification.

[0021] FIG. 12 shows the XRPD profile of psilacetin monotartrate form 1.

[0022] FIG. 13 shows the1H NMR spectrum of psilacetin monotartrate form 1 acquired in methanol-d4.

[0023] FIG. 14 shows the DSC profile of psilacetin monotartrate form 1.

[0024] FIG. 15 shows the TGA profile of psilacetin monotartrate form 1.

[0025] FIG. 16 shows the PLM microscopy images of psilacetin monotartrate form 1, at lOx magnification.

[0026] FIG. 17 shows the XRPD profile of psilacetin hemitartrate form 1.

[0027] FIG. 18 shows the1H NMR spectrum of psilacetin hemitartrate form 1 acquired in methanol-d4.

[0028] FIG. 19 shows the DSC profile of psilacetin hemitartrate form 1.

[0029] FIG. 20 shows the TGA profile of psilacetin hemitartrate form 1.

[0030] FIG. 21A and FIG. 21B show the PLM images taken under both normal and cross polarized light of psilacetin hemitartrate form 1 at lOx magnification.

[0031] FIG. 22 shows the XRPD profile of psilacetin monosuccinate.

[0032] FIG. 23 shows the1H NMR spectrum of psilacetin monosuccinate acquired in methanol-d4.

[0033] FIG. 24A and FIG. 24B show the PLM images taken under both normal and cross polarized light of psilacetin monosuccinate at lOx magnification.

[0034] FIG. 25 shows the XRPD profile of psilacetin hemisuccinate.

[0035] FIG. 26 shows the1H NMR spectrum of psilacetin hemisuccinate acquired in methanol-d4.

[0036] FIG. 1 shows the DSC profile of psilacetin hemisuccinate.

[0037] FIG. 28 shows the TGA profile of psilacetin hemisuccinate.

[0038] FIG. 29A and FIG. 29B show PLM images taken under both normal and cross polarized light of psilacetin hemisuccinate at lOx magnification.

[0039] FIG. 30 shows the XRPD profile of psilacetin monotartrate form 2.

[0040] FIG. 31 shows the DSC profile of the psilacetin monotartrate form 2 sample obtained from Panel #3.

[0041] FIG. 32 shows the TGA profile of psilacetin monotartrate form 2.

[0042] FIG. 33 shows the XRPD profile of psilacetin hemitartrate form 2.

[0043] FIG. 34 shows the1H NMR spectrum of psilacetin hemitartrate form 2.

[0044] FIG. 35 shows the TGA profile of psilacetin hemitartrate form 2.

[0045] FIG. 36 shows the XRPD profile of the psilacetin hydrochloric acid sample as an amorphous solid.

[0046] FIG. 37 shows the TGA profile of the psilacetin hydrochloric acid sample.

[0047] FIG. 38 shows the XRPD profile of the psilacetin hydrobromic acid sample as an amorphous solid.

[0048] FIG. 39 shows the XRPD profile of psilacetin monotartrate form 1 (bottom XRPD profile) overlaid with psilacetin (middle XRPD profile) and tartaric acid (top XRPD profile).

[0049] FIG. 40 shows the XRPD profile of psilacetin hemitartrate form 1 (bottom XRPD profile) overlaid with psilacetin (middle XRPD profile) and tartaric acid (top XRPD profile).

[0050] FIG. 41 shows the XRPD profile of psilacetin monosuccinate (bottom XRPD profile) overlaid with psilacetin (middle XRPD profile) and succinic acid (top XRPD profile).

[0051] FIG. 42 shows the XRPD profile of psilacetin hemisuccinate (bottom XRPD profile) overlaid with psilacetin (middle XRPD profile) and succinic acid (top XRPD profile).

[0052] FIG. 43 shows the XRPD profile of the succinic acid, 1 to 1 stoichiometry sample obtainedfrom Panel #3 (lower XRPD profile) overlaid with that of the psilacetin hemisuccinate sample obtained from Panel #2 (upper XRPD profile).

[0053] FIG. 44 shows the XRPD profile of the succinic acid, 1 to 2 stoichiometry sample obtained from Panel #3 (lower XRPD profile) overlaid with that of the psilacetin hemisuccinate sample obtained from Panel #2 (upper XRPD profile).

[0054] FIG. 45 shows the XRPD profile of the scaled-up L-tartaric acid, 1 to 1 stoichiometry sample (upper XRPD profile) overlaid with that of the psilacetin monotartrate form 2 sample obtained from Panel #3 (lower XRPD profile).

[0055] FIG. 46 shows the1H NMR spectrum of the scaled-up psilacetin monotartrate form 2 sample acquired in methanol-d4.

[0056] FIG. 47 shows the DSC profile of the scaled-up psilacetin monotartrate form 2 sample.

[0057] FIG. 48 shows the XRPD profile of the scaled-up succinic acid, 1 to 1 stoichiometry sample(upper XRPD profile) overlaid with that of the scaled-up succinic acid, 1 to 2 stoichiometry sample (lower XRPD profile).

[0058] FIG. 49 shows the XRPD profile of the scaled-up succinic acid, 1 to 2 stoichiometry sample (lower XRPD profile) overlaid with that of the psilacetin hemisuccinate sample obtained from Panel #2.Detailed Description

[0059] The disclosure relates to crystalline psilacetin salts. In particular, the disclosure relates to a crystalline psilacetin monotartrate form 1 salt, a crystalline psilacetin monotartrate form 2 salt, a crystalline psilacetin hemitartrate form 1 salt, a crystalline psilacetin hemitartrate form 2 salt, a crystalline psilacetin monosuccinate salt, and a crystalline psilacetin hemisuccinate salt; to pharmaceutical compositions containing crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt according to the disclosure. The therapeutic uses of crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt according to the disclosure are described below as well as compositions containing them. Crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, and crystalline psilacetin hemisuccinate salt, and some exemplary methods used to characterize them are described below.

[0060] The crystalline psilacetin salts, their preparation, and their characterization are described below and shown in the figures.

[0061] Methods of Treatment and Therapeutic Uses

[0062] Crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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 crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt of the disclosure. In one embodiment, crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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 crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt of the disclosure.

[0063] Methods of the disclosure also relate to the administration of a therapeutically effective amount of crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt to prevent or treat a disease or condition, such as those discussed below for a subject in need of treatment. Crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt may be administered neat or as a composition comprising crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt as discussed below.

[0064] Crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt,crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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 crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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).

[0065] Crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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 crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt.

[0066] Crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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 crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt including the exemplary embodiments discussed above.

[0067] Crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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 crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt of the disclosure, including the exemplary embodiments discussed herein. Generally speaking, treatable "pain" includes nociceptive, neuropathic, and mixtype. 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.

[0068] Crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt of the disclosure may be used to modulate activity of a mitogen-activated protein kinase (MAPK), comprisingadministering a composition of the invention. MAPKs provide a wide-ranging signaling cascade that allows 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.

[0069] 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.

[0070] Crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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.

[0071] Crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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.

[0072] Crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt,crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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.

[0073] Crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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.

[0074] Compositions

[0075] The disclosure also relates to compositions comprising an effective amount of crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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 crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt and a pharmaceutically acceptable excipient (also known as a pharmaceutically acceptable carrier). As discussed above, crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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.

[0076] A composition or a pharmaceutical composition of the disclosure may be in any form which contains crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt. 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 crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt,crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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 crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt of the disclosure, with the rest being at least one suitable pharmaceutically acceptable excipient or at least one other adjuvant, as discussed below.

[0077] 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, crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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 crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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.

[0078] When used in such compositions as a first component comprising crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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 particularembodiments of the invention. Compositions having as a first component crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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 crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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.

[0079] 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.

[0080] 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" traditionallyrefers 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.

[0081] In one embodiment, the term "purified" refers to a compound or composition that has been crystallized.

[0082] 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.

[0083] In one embodiment, the term "purified" refers to a compound or composition that has been distilled.

[0084] In one embodiment, the term "purified" refers to a compound or composition that has been sublimed.

[0085] 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.

[0086] In one embodiment, the term "purified" refers to a compound that is between 80-100% pure.

[0087] In one embodiment, the term "purified" refers to a compound that is between 90-100% pure.

[0088] In one embodiment, the term "purified" refers to a compound that is between 95-100% pure.

[0089] In one embodiment, the term "purified" refers to a compound that is between 99-100% pure.

[0090] In one embodiment, the term "purified" refers to a compound that is between 99.9-100% pure.

[0091] 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.

[0092] A pharmaceutical formulation of the disclosure may comprise, consist essentially of, or consist of (a) crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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, crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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 crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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.

[0093] A pharmaceutical formulation of the disclosure may comprise a composition containing crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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 crystalline psilacetin monotartrateform 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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) crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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.

[0094] 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-a llyl-N,N-diethyl-N L; 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, -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.

[0095] 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-di methyltryptamine; [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.

[0096] 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-tetra hydrocannabinol (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.

[0097] 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, beta-mercaptoethanol, 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.Y1

[0098] 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.).

[0099] 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.

[0100] 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.).

[0101] 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.

[0102] 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 P-carboline, pinoline, harmane, harmine, harmaline, harmalol, tetrahydroharmine, 9-methyl- -carboline, or 3- carboxy-tetrahydronon harman.

[0103] 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.

[0104] 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.

[0105] Exemplary compositions of crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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. Crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt of the disclosure may be any one of the exemplary embodiments described above including the crystalline forms as disclosed herein.Table 1

[0106] Exemplary pharmaceutical compositions of crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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 crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt to the second compound are shown in Table 2. Crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt of the disclosure may be any one of the exemplary embodiments described above including the crystalline forms as disclosed herein.Table 2

[0107] An "effective amount" or a "therapeutically effective amount" of crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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. Crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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.

[0108] 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 crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetinhemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt of the disclosure, or produce undesirable biological effects or otherwise interact in a deleterious manner with any other component(s) of the pharmaceutical composition.

[0109] 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, crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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 hydrocarbon-based 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.

[0110] 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, pHbuffering agents, antioxidants, and the like, such as, for example, citric acid, sorbitan monolaurate, triethanolamine oleate, butylated hydroxytoluene, etc.

[0111] 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.

[0112] 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.

[0113] 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).

[0114] Administration of crystalline psilacetin monotartrate form 1 salt, crystalline psilacetin monotartrate form 2 salt, crystalline psilacetin hemitartrate form 1 salt, crystalline psilacetin hemitartrate form 2 salt, crystalline psilacetin monosuccinate salt, or crystalline psilacetin hemisuccinate salt 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.

[0115] Exemplary Embodiments of the Invention

[0116] El. A crystalline psilacetin salt selected from the group consisting of a crystalline psilacetin monotartrate form 1 salt, a crystalline psilacetin monotartrate form 2 salt, a crystalline psilacetin hemitartrate form 1 salt, a crystalline psilacetin hemitartrate form 2 salt, a crystalline psilacetin monosuccinate salt, and a crystalline psilacetin hemisuccinate salt.

[0117] E2. The crystalline psilacetin salt of El, wherein the crystalline psilacetin salt is crystalline psilacetin monotartrate form 1 salt.

[0118] E3. The crystalline psilacetin salt of E2, characterized by at least one of: an X-ray diffraction pattern substantially similar to FIG. 12; or an X-ray diffraction pattern characterized by at least two peaks selected from 7.1, 12.2, and 14.2 °26 ± 0.2 °26.

[0119] E4. The crystalline psilacetin salt of El, wherein the crystalline psilacetin salt is crystalline psilacetin monotartrate form 2 salt.

[0120] E5. The crystalline psilacetin salt of E4, characterized by at least one of: an X-ray diffraction pattern substantially similar to FIG. 30; or an X-ray diffraction pattern characterized by at least two peaks selected from 16.1, 17.4, and 22.6 °26 ± 0.2 °26.

[0121] E6. The crystalline psilacetin salt of El, wherein the crystalline psilacetin salt is crystalline psilacetin hemitartrate form 1 salt.

[0122] E7. The crystalline psilacetin salt of E6, characterized by at least one of: an X-ray diffraction pattern substantially similar to FIG. 17; or an X-ray diffraction pattern characterized by at least two peaks selected from 5.2, 13.4, and15.1 °26 ± 0.2 °26.

[0123] E8. The crystalline psilacetin salt of El, wherein the crystalline psilacetin salt is crystalline psilacetin hemitartrate form 2 salt.

[0124] E9. The crystalline psilacetin salt of E8, characterized by at least one of: an X-ray diffraction pattern substantially similar to FIG. 33; or an X-ray diffraction pattern characterized by at least two peaks selected from 13.4, 15.1, and24.2 °26 ± 0.2 °26.

[0125] E10. The crystalline psilacetin salt of El, wherein the crystalline psilacetin salt is crystalline psilacetin monosuccinate salt.

[0126] Ell. The crystalline psilacetin salt of E10, characterized by at least one of: an X-ray diffraction pattern substantially similar to FIG. 22; or an X-ray diffraction pattern characterized by at least two peaks selected from 12.7, 17.3, and 18.5 °26 ± 0.2 °26.

[0127] E12. The crystalline psilacetin salt of El, wherein the crystalline psilacetin salt is crystalline psilacetin hemisuccinate salt.

[0128] E13. The crystalline psilacetin salt of E12, characterized by at least one of: an X-ray diffraction pattern substantially similar to FIG. 25; oran X-ray diffraction pattern characterized by at least two peaks selected from 7.8, 17.1, and 21.3 °20 ± 0.2 °20.

[0129] E14. A composition comprising a crystalline psilacetin salt according to any one of E1-E13 and an excipient.

[0130] E15. A composition comprising a crystalline psilacetin salt according to any one of E1-E13 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.

[0131] E16. 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 a crystalline psilacetin salt according to any one of E1-E13.

[0132] E17. A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a composition according to E14 or E15.

[0133] E18. 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 a crystalline psilacetin salt according to any one of E1-E13.

[0134] E19. 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 E14 or E15.Examples

[0135] Salt Screen- Summary

[0136] Psilacetin hemifumarate was supplied by Aptuit OXF as a crystalline solid. A salt release was performed on the supplied material to obtain the native API for the salt screening activities described below. The salt release was performed by pH adjustment, in conjunction with consecutive extractions by dichloromethane. Psilacetin presented as a crystalline powder by X-ray powder diffraction (XRPD), that had solidified from an oily phase on standing, under sub-ambient conditions (2 to 6 °C). The native API was demonstrated to be chemically stable under these conditions, evident by the no de-acetylation observed by liquid chromatography-mass spectrometry (LC-MS) up to 5 days. The native API is psilacetin (C14H18N2O2; molecular weight: 246.31 gmol1). The chemical formula of psilacetin is shown below:

[0137] A focused salt screen was performed, limited to 9 acids at relevant stoichiometry. The acids were selected based on desirable properties and experience with structurally similar molecules.

[0138] The screen was structured across 3 distinct panels, to maximize the potential for successful salification hits under different conditions. The panels are listed below:• Panel #1 performed in 2-propanol / water (1 / 1, v / v)• Panel #2 in 100% acetone• Panel #3 in 100% acetonitrile

[0139] The reaction scheme for the salification of psilacetin is shown below:

[0140] Unsuccessful samples were treated with tert-butylmethylether to promote crystallization of the salts. The solvent system selected for Panel #1 was based upon conditions successfully used in the production campaign of psilacetin hemifumarate. The solvent selection for Panels #2 and #3 was guided by an informal qualitative solubility assessment carried out on psilacetin in 14 ICH class 2 and 3 solvents.

[0141] No solids were isolated from Panel #1, and this was accompanied by significant decomposition of the API, via de-acetylation, monitored by LC-MS. A total of four salt versions of psilacetin were identified across Panels #2 and #3, while polymorphism was evident in some cases:• Psilacetin monotartrate- form 1 and form 2;• Psilacetin monosuccinate;• Psilacetin hemitartrate- form 1 and form 2; and• Psilacetin hemisuccinate.

[0142] Experimental

[0143] X-Ray Powder Diffraction (XRPD)

[0144] XRPD analysis was carried out using a Bruker D2 Phaser powder diffractometer equipped with a LynxEye detector. The specimens underwent minimum preparation but, if necessary, were lightly milled in a pestle and mortar before acquisition. The specimens were located at the center of a silicon sample holder within a 5 mm pocket (ca. 5 to 10 mg). The samples were continuously spun during data collection and scanned using a step size of 0.02 ° 2-theta (26) between the range of 4 ° to 40 ° 2-theta or 5 ° to 60 ° 2-theta. Data were acquired using either 3-minute or 10-minute acquisition methods. Bruker Diffrac.Suite was used to process the data.

[0145] 1H Nuclear Magnetic Resonance (NMR)

[0146] XH NMR spectra were acquired using a Bruker 400 MHz spectrometer and data were processed using Topspin. Samples were prepared in Methanol-cLj at typical concentrations of 10 toNMR w / w assay and calibrated to the corresponding nondeuterated solvent residual at 2.50 ppm.

[0147] NMR Assay

[0148] Assays (w / w) of API by1H NMR spectroscopy were measured by the project chemist using Topspin. Internal standard 2, 3, 5, 6-tetrachlorinitrobenzene (TCNB, ca. 20 mg, F.W. 260.89) were dissolved in Methanol-d4and theNMR spectrum was acquired using an extended relaxation method.

[0149] Differential Scanning Calorimetry (DSC)

[0150] A Mettler Toledo DSC 3 instrument was used for the thermal analysis with STARe™ software. The analysis was conducted in closed, pierced, aluminum pans (40 pl), under nitrogen and sample sizes ranged from 1 to 10 mg. Typical analysis method was 20 to 250 °C at 10 °C / minute.

[0151] Thermogravimetric Analysis (TGA)

[0152] A Mettler Toledo TCA-2 instrument was used to measure the weight loss as a function of temperature from 25 to 500 ° C. The scan rate was typically 5 or 10 ° C per minute. Experiments and analysis were carried out using the STARe™ software. The analysis was conducted in 100 pl open aluminum pans, under nitrogen and sample sizes ranged from 1 to 10 mg.

[0153] Liquid Chromatography-Mass Spectrometry (LC-MS)

[0154] Routine LC-MS data were collected using the Agilent 1260 Infinity II interfaced with 1260Infinity II DAD HS and Agilent series 1260 Infinity II binary pump. The instrument used a single quadrupole I nfi nity Lad MSD. The instrument was calibrated up to 2000 Da.

[0155] LC-MS method parameters:• Inj. Vol: 5 pl• Detection: UV @ 254 nm• Mobile Phase A: Acetonitrile + 0.1 % TFA / HZO 95:5• Mobile Phase B: Acetonitrile + 0.05 % THA / HZ) 5:95• The time versus each mobile phase is shown in Table 3.Table 3• Flow rate: 1 ml / min• Column temperature: 30 °C• Run time: 12 minutes

[0156] General Procedures

[0157] Salt Release of Psilacetin Hemifumarate

[0158] Psilacetin hemifumarate (1.01 g, 1.0 wt.) was charged to a vessel and dichloromethane (15.0 ml, 15.0 vol.) was added. The mixture was allowed to stir at 3.0 to 7.0 °C for 40 minutes.Potassium hydrogen carbonate (20% w / w aqueous, 17.0 ml, 17.0 vol.) was added in small aliquots until the pH was measured at 8.54 (ATC) maintaining the temperature 3.0 to 10.0 °C. The biphasic mixture was transferred to a separatory funnel and the organic layer retained. The aqueous phase was treated with dichloromethane (5 vol.) and stirred at 3.0 to 10.0 °C for 15 minutes and the organic layer retained. A second extraction was then performed as detailed. The organic layer was dried with anhydrous sodium sulphate (0.5 wt.) before the mixture was filtered by suction filtration and the funnel maintained under a steady nitrogen flow. The filtrates were dried in a rotary evaporator to afford a dense oil. The product was stored at 2 to 8 °C and eventually crystallized. The product psilacetin was characterized by XRPD, LC-MS, andJH NMR to confirm the absence of fumaric acid and verify the molecular integrity.

[0159] Panel #1: Salt Screen in 2-propanol / water

[0160] An initial salt screen was carried out using the binary solvent mixture 2-propanol / water (1 / 1). The solvent system selected from it was found to be an effective crystallization solvent during the development of psilacetin hemifumarate. A total of 9 acid agents were screened, in theappropriate acid stoichiometries, as seen in Table 4.Table 4 List of Acid Counterions Screened in Panel #1

[0161] No solids were isolated from the panel after allowing the samples to stand undisturbed under sub-ambient conditions.

[0162] Solution volumes were gradually reduced to two-thirds and one-half of their original volume, to encourage crystallization. LC-MS analysis revealed most samples underwent significant decomposition via de-acetylation.

[0163] Following the unsuccessful panel, a qualitative solubility screen was performed and used to guide solvent selection for the subsequent salt screen panels.

[0164] Salt Screen of Psilacetin (Panel #1)

[0165] Portions of API (100.0 mg, 1.0 wt.) were charged to separate vials. The relevant acid (1.1 eq.) was added to the appropriate vial and the binary solvent mixture 2-propanol / water (0.50 ml, 5.0 vol.) was charged to all vials. The suspensions were stirred until dissolution was achieved. Once dissolved, the solutions were left to cool down and stand undisturbed under sub-ambient conditions for several days. No crystallization was observed. The samples were reduced in volume by 50% under a steady flow of nitrogen and left to stand under sub-ambient conditions for 24 hours. The remaining solvent was fully evaporated under nitrogen, at which time, most samples showed signs of de-acetylation by LC-MS.

[0166] Informal Solubility Assessment of Psilacetin

[0167] Psilacetin (40.0 mg, 1.0 wt.) was charged to separate vials. The relevant solvent (0.22 ml, 5.0 vol) was added to the separate vial and the suspensions were stirred at 20 °C until dissolution was observed. If dissolution was not observed, the samples were first stirred at 40 °C, then refluxedand if no dissolution was achieved, more solvent (0.22 ml, 5 vol) was added and the cycle repeated starting at 20 °C up to maximum of 15 vol total solvent. Where appropriate, material which crystallized after dissolution, was analyzed by XRPD.

[0168] Panel #2: Salt Screen in Acetone

[0169] A second panel was set up using acetone as the crystallization solvent, identified from an informal solubility assessment carried out on the native API. The same selection of acids was screened as in Panel #1, except for citric acid at 1 to 2 and 1 to 3 stoichiometries to conserve material, as seen in Table 5.Table 5 List of Acid Counterions Screened in Panel #2

[0170] Solids were isolated from the following samples in Panel #2:• L-tartaric acid, 1 to 1 stoichiometry• L-tartaric acid, 1 to 2 stoichiometry• Succinic acid, 1 to 1 stoichiometry• Succinic acid, 1 to 2 stoichiometry

[0171] All four samples showed unique XRPD patterns from the wet pellet, with the dried pellets matching the wet, suggesting no phase conversions after drying.

[0172] XH NMR confirmed that samples isolated from mono- input stoichiometries yielded the mono- salt version of the API, whereas samples with hemi- input stoichiometry yielded the hemi-salt versions.

[0173] FIG. 1 shows the overlaid XRPD profiles of psilacetin monotartrate (lower XRPD profile) and psilacetin hemitartrate (upper XRPD profile). The two patterns do not match, as expected from different salt versions.

[0174] FIG. 2 shows the overlaid XRPD profiles of psilacetin monosuccinate (lower XRPD profile)and psilacetin hemisuccinate (upper XRPD profile). The two patterns do not match, as expected from different salt versions.

[0175] All experiments that remained in solution were allowed to evaporate to dryness before being treated with tert-butylmethylether. This second round of treatment yielded solid products:• Hydrochloric acid• Hydrobromic acid

[0176] Once isolated and analyzed by XRPD, the crude solids were consistent with amorphous patterns.

[0177] Panel #3: Salt Screen in Acetonitrile

[0178] To maximize the potential for successful hits, a third panel, analogous to the second, was set up using acetonitrile as the crystallization solvent, again identified from the informal solubility assessment carried out on the native API. The same selection of acids was screened as in Panel #2, as seen in Table 6.Table 6 List of Acid Counterions Screened in Panel #3

[0179] Solids were isolated from the following samples in Panel #3:• Succinic acid, 1 to 1 stoichiometry• Succinic acid, 1 to 2 stoichiometry

[0180] Both samples exhibited congruent XRPD patterns, that matched that obtained from psilacetin hemisuccinate. Insufficient material was obtained from the sample from succinic acid, 1 to 1 stoichiometry. In the succinic acid, 1 to 2 stoichiometry sample the dried pellet matched the wet pellet, thus, suggesting no phase conversions occurred on drying.

[0181] These results hinted towards the fact that hemi-stoichiometry salification of succinic acid may be preferred over the mono-salification. A proposed mechanism for the formation of the hemisuccinate version from the succinic acid, 1 to 1 stoichiometry sample was via reproportionation into the preferred hemi-succinate and non-ionized succinic acid salt version, following initial monosalification, as seen in Equation 1.Psilacetin monosuccinate -> psilacetin hemisuccinate + 0.5 succinic acid Equation 1: Hypothesized reproportionation mechanism of psilacetin monosuccinate into psilacetin hemisuccinate

[0182] All samples which were unsuccessful in yielding solids were allowed to evaporate to dryness before being treated with tert-butylmethylether. The treatment yielded solid products:• L-tartaric acid, 1 to 1 stoichiometry• L-tartaric acid, 1 to 2 stoichiometry

[0183] Only the L-tartaric acid, 1 to 1 stoichiometry sample was characterized due to the limited about of the L-tartaric acid, 1 to 2 stoichiometry sample.

[0184] The solids from the L-tartaric acid, 1 to 1 stoichiometry sample were characterized by XRPD and the resulting pattern did not match any of the previously characterized phases from Panel #2, though it did show some resemblance with that of psilacetin monotartrate.NMR analysis revealed that the stoichiometry was equivalent to the mono-, hinting towards a different phase of psilacetin monotartrate, assigned form 2.

[0185] FIG. 3 shows the overlaid XRPD profiles of psilacetin monotartrate form 2 (lower XRPD profile) and psilacetin monotartrate form 1 (upper XRPD profile).

[0186] Salt Screen of Psilacetin (Panels #2 and #3)

[0187] A stock solution of psilacetin (360.0 mg, 12.0 wt.) was prepared in the appropriate solvent (acetone or acetonitrile, 1.8 ml, 60.0 vol.). The stock API solution was aliquoted to all vials (5.0 vol, i.e., 30.0 mg). The relevant acid (1.2 eq., or 0.6 eq. for 1:2 stoichiometries) was added to the appropriate vial and the mixtures were stirred at 20 °C for at least 24 hours. The samples were then allowed to stand undisturbed at 2 to 8 °C for a further 24 hours. After crystallization was judged complete, the products were isolated by centrifugation and the pellets were dried at 40 °C under reduced pressure. Products from the crystallization (wet and dry) were initially analyzed by XRPD (9- minute method), further analysis of certain products were performed by NMR, DSC, and TGA, if the diffraction pattern indicated differences.

[0188] Scale Up of Identified Psilacetin Salts

[0189] To generate more material to complete characterization on all identified salt versions, a further experiment was performed on a slightly increased scale. Four samples were prepared with the intention of replicating the four salt versions identified in Panel #2, as seen in Table 7. Acetone was used to maintain the conditions analogous to those of Panel #2.Table 7 List of Scaled Up Samples

[0190] A stock solution of psilacetin (240.0 mg, 4.0 wt.) was prepared in acetone (1.2 ml, 20.0 vol.). The stock API solution was aliquoted to all vials (5.0 vol, i.e., 60.0 mg). The relevant acid (1.2 eq. or 0.6 eq.) was added to the appropriate vial and the mixtures were stirred at 20 °C for 72 hours. The samples were then allowed to stand undisturbed at 2 to 8 °C for a further 24 hours. After crystallization was judged complete, the products were isolated by centrifugation and the pellets were dried at 40 °C under reduced pressure. Products from the crystallization (wet and dry) were initially analyzed by XRPD (9-minute method), further analyzed of certain products were performed by1H NMR, DSC, and TGA.

[0191] Solids were isolated for each sample and analyzed by XRPD. Both succinic acid samples yielded psilacetin hemisuccinate, with psilacetin monosuccinate not being observed at all. This reinforced the hypothesis made during Panel #3 with regard to the hemi succinate salt version being favored over the mono-stoichiometry.

[0192] The L-tartaric acid, 1 to 1 stoichiometry sample was analyzed by XRPD and appeared to be congruent with the pattern arising from psilacetin monotartrate form 2 isolated in Panel #3.

[0193] A previously unobserved pattern was identified from the L-tartaric acid, 1 to 2 stoichiometry sample, showing similarities with the XRPD profile of psilacetin hemitartrate.1H NMR analysis confirmed the stoichiometry consistent with psilacetin hemitartrate. This was assigned form 2.

[0194] FIG. 4 shows the overlaid XRPD profiles of the succinic acid, 1 to 1 stoichiometry (upper XRPD profile) and the succinic acid, 1 to 2 stoichiometry (lower XRPD profile). The two patterns are congruent with that of psilacetin hemisuccinate isolated in Panel #2 of the salt screen.

[0195] FIG. 5 shows the overlaid XRPD profiles of psilacetin hemitartrate form 2 (lower XRPD profile) and psilacetin hemitartrate form 1 (upper XRPD profile).

[0196] FIG. 6 shows the overlaid XRPD profiles of samples of the L-tartaric acid, 1 to 1 stoichiometry from the scaled-up samples (upper XRPD profile) and the L-tartaric acid, 1 to 1 stoichiometry sample from Panel #3 (lower XRPD profile). The two patterns are congruent and represent psilacetin monotartrate form 2.

[0197] Salt Screen- Characterization

[0198] NMR spectroscopy was performed to confirm the identity of the API and measure residual solvent content.

[0199] LC-MS was performed to confirm chemical purity of the API.

[0200] Solid state physical characterization of the API included:Differential Scanning Calorimetry (DSC) analysis to provide an evaluation of transition activity, solvent release, melt and decomposition events; modulated DSC, applied where necessary, to deconvolute complex thermal transitions.Thermogravimetric Analysis (TGA) analysis to align weight loss transition activity with key thermal events, observed by DSC.1H NMR spectroscopy performed on thermally treated specimens, extracted after key thermal events- to confirm the chemical identity was consistent with the input (where relevant).Optical microscopy performed under a cross-polarized filter, to provide an informal assessment of the present of optically amorphous material, non-homogeneity and approximate particle population dimensions.

[0201] Qualitative solubility assessment against a panel of common solvents to guide solvent selection for subsequent screens.

[0202] Focused Salt Screen

[0203] The panel of counter-ions were screened based on the molecular structure of the API and the calculated pKa(cpKa). Once crystalline products were generated, the analysis and physical characterizations were performed and completed by additional analysis where necessary.

[0204] Qualitative Solubility Assessment

[0205] The approximate solubility of psilacetin was determined in 14 ICH class 2 and 3 solvents at 20 °C, 40 °C, and reflux. The solutions were inspected after cooling to determine if crystallization occurred on standing at room temperature (15 to 25 °C), or under sub-ambient conditions (2 to 6 °C).

[0206] The findings of the solubility screen enabled a selection of appropriate sub-set of solvents in which psilacetin was freely soluble and were used in Panels #2 and #3 salt screens.

[0207] Psilacetin exhibited good solubility at 5 vol., 20 °C in acetone, acetonitrile, dichloromethane, chlorobenzene, 2-propanol, and methylethyl ketone. All other solvents were unsuccessful at solubilizing the native API across all temperatures and volume iterations.

[0208] No crystallization was observed from the solubilized samples on standing at room temperature (15 to 25 °C), or under sub-ambient conditions (2 to 6°C). The results from the informal qualitative solubility assessment of psilacetin are shown in Table 8.Table 8 Results from informal qualitative solubility assessment of Psilacetin

[0209] Results- Psilacetin

[0210] Psilacetin hemifumarate was the test salt release of the supplied batch; it was used as the input for salt screen Panels #1 and #2; and it was used as the input for salt screen Panel #3. The results of the salt screen of psilacetin are found in Table 9 below.Table 9

[0211] FIG. 7 shows the XRPD profile for psilacetin.

[0212] Table 10 shows the peak angle data of psilacetin.Table 10

[0213] FIG. 8 shows the1H NMR spectrum of psilacetin, acquired in methanol-d4.

[0214] FIG. 9 shows the DSC profile of psilacetin.

[0215] FIG. 10 shows the TGA profile of psilacetin.

[0216] LC-MS was performed on psilacetin.

[0217] FIG. 11A and FIG. 11B show the Polarized Light Microscopy (PLM) images of psilacetin at 4x magnification.

[0218] Results- Psilacetin Monotartrate (Form 1)

[0219] Psilacetin monotartrate (form 1) was isolated from salt screen Panel #2 (acetone). The results of the salt screen of psilacetin monotartrate (form 1) are found in Table 11 below.Table 11

[0220] FIG. 12 shows the XRPD profile of psilacetin monotartrate form 1.

[0221] Table 12 shows the peak angle data of psilacetin monotartrate form 1 from the peaks identified in the XRPD pattern of FIG. 12. The entire list of peaks, or a subset thereof, may be sufficient to characterize the crystalline salt. For example, the crystalline salt may be characterized by at least two peaks selected from the peaks at 7.1, 12.2, and 14.2°20 ± O.2°20 or their corresponding d-spacing as well as by an XRPD pattern substantially similar to FIG. 12.Table 12

[0222] FIG. 13 shows the1H NMR spectrum of psilacetin monotartrate form 1 acquired in methanol-d4.

[0223] FIG. 14 shows the DSC profile of psilacetin monotartrate form 1.

[0224] FIG. 15 shows the TGA profile of psilacetin monotartrate form 1.

[0225] LC-MS was performed on psilacetin monotartrate form 1.

[0226] FIG. 16 shows the PLM microscopy images of psilacetin monotartrate form 1, at lOx magnification.

[0227] Results- Psilacetin Hemitartrate (Form 1)

[0228] Psilacetin hemitartrate (form 1) was isolated from salt screen Panel #2 (acetone). The results of the salt screen of psilacetin hemitartrate (form 1) are found in Table 13 below.Table 13

[0229] FIG. 17 shows the XRPD profile of psilacetin hemitartrate form 1.

[0230] Table 14 shows the peak angle data of psilacetin hemitartrate form 1 from the peaks identified in the XRPD pattern of FIG. 17. The entire list of peaks, or a subset thereof, may be sufficient to characterize the crystalline salt. For example, the crystalline salt may be characterized by at least two peaks selected from the peaks at 5.2, 13.4, and 15.1°20 ± O.2°20 or their corresponding d-spacing as well as by an XRPD pattern substantially similar to FIG. 17.Table 14

[0231] FIG. 18 shows the1H NMR spectrum of psilacetin hemitartrate form 1 acquired in methanol-d4.

[0232] FIG. 19 shows the DSC profile of psilacetin hemitartrate form 1.

[0233] FIG. 20 shows the TGA profile of psilacetin hemitartrate form 1.

[0234] LC-MS was performed on psilacetin hemitartrate form 1.

[0235] FIG. 21A and FIG. 21B show the PLM images taken under both normal and cross polarized light of psilacetin hemitartrate form 1 at lOx magnification.

[0236] Results- Psilacetin Monosuccinate

[0237] Psilacetin monosuccinate was isolated from salt screen Panel #2 (acetone). The results ofthe salt screen of psilacetin monosuccinate are found in Table 15 below.Table 15

[0238] FIG. 22 shows the XRPD profile of psilacetin monosuccinate.

[0239] Table 16 shows the peak angle data of psilacetin monosuccinate from the peaks identified in the XRPD pattern of FIG. 22. The entire list of peaks, or a subset thereof, may be sufficient to characterize the crystalline salt. For example, the crystalline salt may be characterized by at least two peaks selected from the peaks at 12.7, 17.3, and 18.5°29 ± O.2°20 or their corresponding d- spacing as well as by an XRPD pattern substantially similar to FIG. 22.Table 16

[0240] FIG. 23 shows the1H NMR spectrum of psilacetin monosuccinate acquired in methanol-da.

[0241] LC-MS was performed on psilacetin monosuccinate.

[0242] FIG. 24A and FIG. 24B show the PLM images taken under both normal and cross polarized light of psilacetin monosuccinate at lOx magnification.

[0243] Results- Psilacetin Hemisuccinate

[0244] Psilacetin hemisuccinate was isolated from salt screen Panel #2 (acetone); from salt screen Panel #3 (acetonitrile); and from salt screen scale up (acetone). The results of the salt screen of psilacetin hemisuccinate are found in Table 17 below.Table 17

[0245] FIG. 25 shows the XRPD profile of psilacetin hemisuccinate.

[0246] Table 18 shows the peak angle data of psilacetin hemisuccinate from the peaks identified in the XRPD pattern of FIG. 25. The entire list of peaks, or a subset thereof, may be sufficient to characterize the crystalline salt. For example, the crystalline salt may be characterized by at least two peaks selected from the peaks at 7.8, 17.1, and 21.3°26 ± O.2°20 or their corresponding d- spacing as well as by an XRPD pattern substantially similar to FIG. 25.Table 18

[0247] FIG. 26 shows the1H NMR spectrum of psilacetin hemisuccinate acquired in methanol-d4.

[0248] FIG. 27 shows the DSC profile of psilacetin hemisuccinate.

[0249] FIG. 28 shows the TGA profile of psilacetin hemisuccinate.

[0250] LC-MS was performed on psilacetin hemisuccinate.

[0251] FIG. 29A and FIG. 29B show PLM images taken under both normal and cross polarized light of psilacetin hemisuccinate at lOx magnification.

[0252] Results- Psilacetin Monotartrate (Form 2)

[0253] FIG. 30 shows the XRPD profile of psilacetin monotartrate form 2.

[0254] Table 19 shows the peak angle data of psilacetin monotartrate form 2 from the peaks identified in the XRPD pattern of FIG. 30. The entire list of peaks, or a subset thereof, may be sufficient to characterize the crystalline salt. For example, the crystalline salt may be characterized by at least two peaks selected from the peaks at 16.1, 17.4, and 22.6°26 ± 0.2°29 or their corresponding d-spacing as well as by an XRPD pattern substantially similar to FIG. 30.Table 19

[0255] FIG. 31 shows the DSC profile of the psilacetin monotartrate form 2 sample obtained from Panel #3.

[0256] FIG. 32 shows the TGA profile of psilacetin monotartrate form 2.

[0257] LC-MS was performed on psilacetin monotartrate form 2.

[0258] Results- Psilacetin hemitartrate (Form 2)

[0259] FIG. 33 shows the XRPD profile of psilacetin hemitartrate form 2.

[0260] Table 20 shows the peak angle data of psilacetin hemitartrate form 2 from the peaks identified in the XRPD pattern of FIG. 33. The entire list of peaks, or a subset thereof, may be sufficient to characterize the crystalline salt. For example, the crystalline salt may be characterized by at least two peaks selected from the peaks at 13.4, 15.1, and 24.2°20 ± O.2°20 or their corresponding d-spacing as well as by an XRPD pattern substantially similar to FIG. 33.Table 20

[0261] FIG. 34 shows the1H NMR spectrum of psilacetin hemitartrate form 2.

[0262] FIG. 35 shows the TGA profile of psilacetin hemitartrate form 2.

[0263] LC-MS was performed on psilacetin hemitartrate form 2.

[0264] Experimental Results

[0265] FIG. 36 shows the XRPD profile of the psilacetin hydrochloric acid sample as an amorphous solid.

[0266] FIG. 37 shows the TGA profile of the psilacetin hydrochloric acid sample.

[0267] FIG. 38 shows the XRPD profile of the psilacetin hydrobromic acid sample as an amorphous solid.

[0268] FIG. 39 shows the XRPD profile of psilacetin monotartrate form 1 (bottom XRPD profile) overlaid with psilacetin (middle XRPD profile) and tartaric acid (top XRPD profile).

[0269] FIG. 40 shows the XRPD profile of psilacetin hemitartrate form 1 (bottom XRPD profile) overlaid with psilacetin (middle XRPD profile) and tartaric acid (top XRPD profile).

[0270] FIG. 41 shows the XRPD profile of psilacetin monosuccinate (bottom XRPD profile) overlaid with psilacetin (middle XRPD profile) and succinic acid (top XRPD profile).

[0271] FIG. 42 shows the XRPD profile of psilacetin hemisuccinate (bottom XRPD profile) overlaid with psilacetin (middle XRPD profile) and succinic acid (top XRPD profile).

[0272] FIG. 43 shows the XRPD profile of the succinic acid, 1 to 1 stoichiometry sample obtained from Panel #3 (lower XRPD profile) overlaid with that of the psilacetin hemisuccinate sample obtained from Panel #2 (upper XRPD profile).

[0273] FIG. 44 shows the XRPD profile of the succinic acid, 1 to 2 stoichiometry sample obtained from Panel #3 (lower XRPD profile) overlaid with that of the psilacetin hemisuccinate sample obtained from Panel #2 (upper XRPD profile).

[0274] FIG. 45 shows the XRPD profile of the scaled-up L-tartaric acid, 1 to 1 stoichiometry sample (upper XRPD profile) overlaid with that of the psilacetin monotartrate form 2 sample obtained from Panel #3 (lower XRPD profile).

[0275] FIG. 46 shows the1H NMR spectrum of the scaled-up psilacetin monotartrate form 2 sample acquired in methanol-d4.

[0276] FIG. 47 shows the DSC profile of the scaled-up psilacetin monotartrate form 2 sample.

[0277] FIG. 48 shows the XRPD profile of the scaled-up succinic acid, 1 to 1 stoichiometry sample (upper XRPD profile) overlaid with that of the scaled-up succinic acid, 1 to 2 stoichiometry sample (lower XRPD profile).

[0278] FIG. 49 shows the XRPD profile of the scaled-up succinic acid, 1 to 2 stoichiometry sample (lower XRPD profile) overlaid with that of the psilacetin hemisuccinate sample obtained from Panel #2.

[0279] Conclusions

[0280] Four salt versions of the API were identified from the salt screen activities performed on psilacetin:• Psilacetin monotartrate;• Psilacetin monosuccinate;• Psilacetin hemitartrate; and• Psilacetin hemisuccinate.

[0281] Polymorphism was evident in both psilacetin monotartrate and psilacetin hemitartrate, with two different forms (assigned form 1 and form 2, respectively) being identified for each of the two salt versions. No evidence of polymorphism was observed at this stage for psilacetin hemisuccinate and psilacetin monosuccinate, although it cannot be excluded from the limited work performed as part of the salt screen. Further work could be conducted as part of polymorph screen to establish whether the tartaric acid salts exhibit greater degrees of polymorphism.

[0282] Psilacetin hemisuccinate was found to crystalize from samples with both mono- and hemi- input stoichiometries of the acid, suggesting that the psilacetin hemisuccinate salt version is more thermodynamically favored over psilacetin monosuccinate.

[0283] Acetone was identified as a preferred crystallization solvent over acetonitrile. Water presence within the solvent system appeared to impair crystallization, as observed from Panel #1 of the salt screen.

Claims

The claimed invention is:

1. A crystalline psilacetin salt selected from the group consisting of a crystalline psilacetin monotartrate form 1 salt, a crystalline psilacetin monotartrate form 2 salt, a crystalline psilacetin hemitartrate form 1 salt, a crystalline psilacetin hemitartrate form 2 salt, a crystalline psilacetin monosuccinate salt, and a crystalline psilacetin hemisuccinate salt.

2. The crystalline psilacetin salt of claim 1, wherein the crystalline psilacetin salt is crystalline psilacetin monotartrate form 1 salt.

3. The crystalline psilacetin salt of claim 2, characterized by at least one of: an X-ray diffraction pattern substantially similar to FIG. 12; or an X-ray diffraction pattern characterized by at least two peaks selected from 7.1, 12.2, and 14.2 °20 ± 0.2 °20.

4. The crystalline psilacetin salt of claim 1, wherein the crystalline psilacetin salt is crystalline psilacetin monotartrate form 2 salt.

5. The crystalline psilacetin salt of claim 4, characterized by at least one of: an X-ray diffraction pattern substantially similar to FIG. 30; or an X-ray diffraction pattern characterized by at least two peaks selected from 16.1, 17.4, and 22.6 °20 ± 0.2 °20.

6. The crystalline psilacetin salt of claim 1, wherein the crystalline psilacetin salt is crystalline psilacetin hemitartrate form 1 salt.

7. The crystalline psilacetin salt of claim 6, characterized by at least one of: an X-ray diffraction pattern substantially similar to FIG. 17; or an X-ray diffraction pattern characterized by at least two peaks selected from 5.2, 13.4, and 15.1 °20 ± 0.2 °20.

8. The crystalline psilacetin salt of claim 1, wherein the crystalline psilacetin salt is crystalline psilacetin hemitartrate form 2 salt.

9. The crystalline psilacetin salt of claim 8, characterized by at least one of:an X-ray diffraction pattern substantially similar to FIG. 33; or an X-ray diffraction pattern characterized by at least two peaks selected from 13.4, 15.1, and24.2 °20 ± 0.2 °20.

10. The crystalline psilacetin salt of claim 1, wherein the crystalline psilacetin salt is crystalline psilacetin monosuccinate salt.

11. The crystalline psilacetin salt of claim 10, characterized by at least one of: an X-ray diffraction pattern substantially similar to FIG. 22; or an X-ray diffraction pattern characterized by at least two peaks selected from 12.7, 17.3, and 18.5 °20 ± 0.2 °20.

12. The crystalline psilacetin salt of claim 1, wherein the crystalline psilacetin salt is crystalline psilacetin hemisuccinate salt.

13. The crystalline psilacetin salt of claim 12, characterized by at least one of: an X-ray diffraction pattern substantially similar to FIG. 25; or an X-ray diffraction pattern characterized by at least two peaks selected from 7.8, 17.1, and21.3 °20 ± 0.2 °20.

14. A composition comprising a crystalline psilacetin salt according to any one of claims 1-13 and an excipient.

15. A composition comprising a crystalline psilacetin salt according to any one of claims 1-13 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.

16. 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 a crystalline psilacetin salt according to any one of claims 1-13.

17. 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 14.

18. 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 15.

19. 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 a crystalline psilacetin salt according to any one of claims 1-13.

20. 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 14.

21. 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 15.

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