[go: up one dir, main page]

WO2024229352A2 - Dérivés de tryptamine - Google Patents

Dérivés de tryptamine Download PDF

Info

Publication number
WO2024229352A2
WO2024229352A2 PCT/US2024/027673 US2024027673W WO2024229352A2 WO 2024229352 A2 WO2024229352 A2 WO 2024229352A2 US 2024027673 W US2024027673 W US 2024027673W WO 2024229352 A2 WO2024229352 A2 WO 2024229352A2
Authority
WO
WIPO (PCT)
Prior art keywords
crystalline
meo
hydromaleate
purified
crystalline form
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2024/027673
Other languages
English (en)
Other versions
WO2024229352A3 (fr
Inventor
Andrew R. Chadeayne
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Caamtech Inc
Original Assignee
Caamtech Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Caamtech Inc filed Critical Caamtech Inc
Publication of WO2024229352A2 publication Critical patent/WO2024229352A2/fr
Publication of WO2024229352A3 publication Critical patent/WO2024229352A3/fr
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/02—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
    • C07C57/13—Dicarboxylic acids
    • C07C57/15—Fumaric acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
    • C07D209/16—Tryptamines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Definitions

  • This disclosure relates to 2-(5-methoxy-lH-indol-3-yl)ethan-l-aminium (2E)-3-carboxyprop-2- enoate (5-methoxytryptamrnonium hydrofumarate or 5-MeO-T hydrofumarate), crystalline 5-MeO-T hydrofumarate, and specific crystalline forms thereof, including crystalline form 1 of 5-MeO-T hydrofumarate; to pharmaceutical compositions containing 5-MeO-T hydrofumarate or crystalline 5- MeO-T hydrofumarate, including crystalline form 1 of 5-MeO-T hydrofumarate; and to methods of treatment/therapeutic uses of 5-MeO-T hydrofumarate or crystalline 5-MeO-T hydrofumarate, including crystalline form 1 of 5-MeO-T hydrofumarate.
  • This disclosure further relates to 2-(5-methoxy-lH-indol-3-yl)ethan-l-aminium (2Z)-3- carboxyprop-2-enoate (5-methoxytryptammonium hydromaleate or 5-MeO-T hydromaleate), crystalline 5-MeO-T hydromaleate, and specific crystalline forms thereof, including crystalline form 1 of 5-MeO-T hydromaleate; to pharmaceutical compositions containing 5-MeO-T hydromaleate or crystalline 5-MeO- T hydromaleate, including crystalline form 1 of 5-MeO-T hydromaleate; and to methods of treatment/therapeutic uses of 5-MeO-T hydromaleate or crystalline 5-MeO-T hydromaleate, including crystalline form 1 of 5-MeO-T hydromaleate.
  • This disclosure further relates to bis(2-(5-methoxy-lH-indol-3-yl)ethan-l-aminium) (2R,3S,4R,5S)-2,3,4,5-tetrahydroxyhexanedioate (5-methoxytryptammonium galactarate or 5-MeO-T galactarate), crystalline 5-MeO-T galactarate, and specific crystalline forms thereof, including crystalline form 1 of 5-MeO-T galactarate; to pharmaceutical compositions containing 5-MeO-T galactarate or crystalline 5-MeO-T galactarate, including crystalline form 1 of 5-MeO-T galactarate; and to methods of treatment/therapeutic uses of 5-MeO-T galactarate or crystalline 5-MeO-T galactarate, including crystalline form 1 of 5-MeO-T galactarate.
  • This disclosure further relates to bis(2-(5-methoxy-lH-indol-3-yl)ethan-l-aminium) 2- hydroxybutanedioate (5-methoxytryptammonium malate or 5-MeO-T malate), crystalline 5-MeO-T malate, and specific crystalline forms thereof, including crystalline form 1 of 5-MeO-T malate; to pharmaceutical compositions containing 5-MeO-T malate or crystalline 5-MeO-T malate, including crystalline form 1 of 5-MeO-T malate; and to methods of treatment/therapeutic uses of 5-MeO-T malate or crystalline 5-MeO-T malate, including crystalline form 1 of 5-MeO-T malate.
  • This disclosure further relates to 2-(6-fluoro-lH-indol-3-yl)ethan-l-aminium (2E)-3-carboxyprop- 2-enoate (6-fluorotryptammonium hydromaleate or 6-F-T hydromaleate), crystalline 6-F-T hydromaleate, and specific crystalline forms thereof, including crystalline form 1 of 6-F-T hydromaleate; to pharmaceutical compositions containing 6-F-T hydromaleate or crystalline 6-F-T hydromaleate, including crystalline form 1 of 6-F-T hydromaleate; and to methods of treatment/therapeutic uses of 6- F-T hydromaleate or crystalline 6-F-T hydromaleate, including crystalline form 1 of 6-F-T hydromaleate.
  • 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.
  • API's molecular weight is used to calculate the concentration of compositions comprising that API.
  • 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.
  • This disclosure relates to 2-(5-methoxy-lH-indol-3-yl)ethan-l-aminium (2E)-3-carboxyprop-2- enoate (5-methoxytryptammonium hydrofumarate or 5-MeO-T hydrofumarate), crystalline 5-MeO-T hydrofumarate, and specific crystalline forms thereof.
  • this disclosure pertains to particular crystalline forms of 5-MeO-T hydrofumarate, including crystalline form 1 of 5-MeO-T hydrofumarate.
  • XRPD X-ray powder diffraction
  • This disclosure further relates to 2-(5-methoxy-lH-indol-3-yl)ethan-l-aminium (2Z)-3- carboxyprop-2-enoate (5-methoxytryptammonium hydromaleate or 5-MeO-T hydromaleate), crystalline 5-MeO-T hydromaleate, and specific crystalline forms thereof.
  • this disclosure pertains to particular crystalline forms of 5-MeO-T hydromaleate, including crystalline form 1 of 5-MeO- T hydromaleate.
  • XRPD X-ray powder diffraction
  • This disclosure further relates to bis(2-(5-methoxy-lH-indol-3-yl)ethan-l-aminium)
  • XRPD X-ray powder diffraction
  • This disclosure further relates to bis(2-(5-methoxy-lH-indol-3-yl)ethan-l-aminium) 2- hydroxybutanedioate (5-methoxytryptammonium malate or 5-MeO-T malate), crystalline 5-MeO-T malate, and specific crystalline forms thereof.
  • this disclosure pertains to particular crystalline forms of 5-MeO-T malate, including crystalline form 1 of 5-MeO-T malate.
  • XRPD X-ray powder diffraction
  • This disclosure further relates to 2-(6-fluoro-lH-indol-3-yl)ethan-l-aminium (2E)-3- carboxyprop-2-enoate (6-fluorotryptammonium hydromaleate or 6-F-T hydromaleate), crystalline 6-F-T hydromaleate, and specific crystalline forms thereof.
  • this disclosure pertains to particular crystalline forms of 6-F-T hydromaleate, including crystalline form 1 of 6-F-T hydromaleate.
  • XRPD X-ray powder diffraction
  • the disclosure further relates to a composition
  • a composition comprising 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, or specific crystalline forms thereof, such as crystalline form 1 of 5- MeO-T hydrofumarate, and at least one excipient.
  • the disclosure further relates to a composition
  • a composition comprising 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5- MeO-T hydromaleate, and at least one excipient.
  • the disclosure further relates to a composition
  • a composition comprising 5-MeOT galactarate, crystalline 5-MeOT galactarate, or specific crystalline forms thereof, such as crystalline form 1 of 5- MeOT galactarate, and at least one excipient.
  • the disclosure further relates to a composition
  • a composition comprising 5-MeO-T malate, crystalline 5-MeO-T malate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T malate, and at least one excipient.
  • the disclosure further relates to a composition
  • a composition comprising 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 6-F-T hydromaleate, and at least one excipient.
  • the disclosure also provides a composition comprising 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5- MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5- MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate, 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
  • 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 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT alactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5- MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate, or a composition according to this disclosure.
  • 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 5- MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO- T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-M
  • 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.).
  • 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.
  • 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.
  • identifying a person in need of treatment comprises performing a psychiatric evaluation.
  • identifying a person in need of treatment comprises performing a blood test. In one embodiment, identifying a person in need of treatment comprises determining whether a person has a compulsive disorder. In one embodiment, identifying a person in need of treatment comprises self-identifying as having a compulsive disorder.
  • FIG. 1 shows the molecular structure of crystalline form 1 of 5-MeO-T hydrofumarate.
  • FIG. 2 shows the molecular structure of crystalline form 1 of 5-MeO-T hydromaleate.
  • FIG. 3 shows the molecular structure of crystalline form 1 of 5-MeOT galactarate.
  • FIG. 4 shows the molecular structure of crystalline form 1 of 5-MeO-T malate.
  • FIG. 5 shows the molecular structure of crystalline form 1 of 6-F-T hydromaleate.
  • FIG. 6 shows the unit cell of crystalline form 1 of 5-MeO-T hydrofumarate along the a- axis.
  • FIG. 7 shows the unit cell of crystalline form 1 of 5-MeO-T hydromaleate along the a- axis.
  • FIG. 8 shows the unit cell of crystalline form 1 of 5-MeOT galactarate along the a-axis.
  • FIG. 9 shows the unit cell of crystalline form 1 of 5-MeO-T malate along the a-axis.
  • FIG. 10 shows the unit cell of crystalline form 1 of 6-F-T hydromaleate along the b-axis.
  • FIG. 11 shows the 2:1 ratio of crystalline form 1 of 5-MeOT galactarate as a dimer.
  • FIG. 12 shows the 2:1 ratio of crystalline form 1 of 5-MeO-T malate as a dimer.
  • FIG. 13 shows the simulated X-ray powder diffraction pattern (XRPD) for crystalline form 1 of 5-MeO-T hydrofumarate.
  • FIG. 14 shows the simulated X-ray powder diffraction pattern (XRPD) for crystalline form
  • FIG. 15 shows the simulated X-ray powder diffraction pattern (XRPD) for crystalline form
  • FIG. 16 shows the simulated X-ray powder diffraction pattern (XRPD) for crystalline form 1 of 5-MeO-T malate.
  • FIG. 17 shows the simulated X-ray powder diffraction pattern (XRPD) for crystalline form
  • This disclosure relates to 2-(5-methoxy-lH-indol-3-yl)ethan-l-aminium (2E)-3- carboxyprop-2-enoate (5-methoxytryptammonium hydrofumarate or 5-MeO-T hydrofumarate), crystalline 5-MeO-T hydrofumarate, 2-(5-methoxy-lH-indol-3-yl)ethan-l-aminium (2Z)-3-carboxyprop-2- enoate (5-methoxytryptammonium hydromaleate or 5-MeO-T hydromaleate), crystalline 5-MeO-T hydromaleate, bis(2-(5-methoxy-lH-indol-3-yl)ethan-l-aminium) (2R, 3S,4R,5S)-2, 3,4,5- tetrahydroxyhexanedioate (5-methoxytryptammonium galactarate or 5-MeO-
  • 5-MeO-T hydrofumarate has the following chemical formula:
  • 5-MeO-T hydromaleate has the following chemical formula:
  • 5-MeOT galactarate has the following chemical formula:
  • 5-MeO-T malate has the following chemical formula:
  • 6-F-T hydromaleate has the following chemical formula:
  • 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate according to the disclosure, and the methods and the compositions are used to treat inflammation and/or pain by administering a therapeutically effective dose of 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrof
  • Methods of the disclosure also relate to the administration of a therapeutically effective amount of 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5- MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate to prevent or treat a disease or condition, such as those discussed below for a subject in need of treatment.
  • 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5- MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate 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 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO- T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate 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).
  • depression depression
  • psychotic disorder schizophrenia
  • schizophreniform disorder acute schizophrenic episode
  • 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5- MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate 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 5-MeO-T hydrofumarate, crystalline 5- MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO- T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate.
  • a brain disorder
  • 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5- MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate 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, s
  • 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 5- MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO- T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate including the exemplary embodiments discussed above.
  • 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5- MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate 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 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate of the disclosure, including the exemplary embodiments discussed herein.
  • treatable "pain” includes nociceptive, neuropathic, and mix-type.
  • a method of the disclosure may reduce or alleviate the symptoms associated with inflammation, including but not limited to treating localized manifestation of inflammation characterized by acute or chronic swelling, pain, redness, increased temperature, or loss of function in some cases.
  • a method of the disclosure may reduce or alleviate the symptoms of pain regardless of the cause of the pain, including but not limited to reducing pain of varying severity, i.e., mild, moderate and severe pain, acute pain and chronic pain.
  • a method of the disclosure is effective in treating joint pain, muscle pain, tendon pain, burn pain, and pain caused by inflammation such as rheumatoid arthritis.
  • Skeletal or muscular diseases or conditions which may be treated include but are not limited to musculoskeletal sprains, musculoskeletal strains, tendinopathy, peripheral radiculopathy, osteoarthritis, joint degenerative disease, polymyalgia rheumatica, juvenile arthritis, gout, ankylosing spondylitis, psoriatic arthritis, systemic lupus erythematosus, costochondritis, tendonitis, bursitis, such as the common lateral epicondylitis (tennis elbow), medial epicondylitis (pitchers elbow) and trochanteric bursitis, temporomandibular joint syndrome, and fibromyalgia.
  • 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5- MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate of the disclosure may be used to modulate activity of a mitogen-activated protein kinase (MAPK), comprising administering a composition of the invention.
  • MPK mitogen-activated protein kinase
  • MAPKs provide a wide-ranging signaling cascade that allow cells to quickly respond to biotic and abiotic stimuli.
  • exemplary MAPKs include, but are not limited to, Tropomyosin Receptor Kinase A (TrkA), P38- alpha, and c-Jun N-Terminal Kinase 3 (JNK3).
  • TrkA is a high affinity catalytic receptor of nerve growth factor (NGF) protein. TrkA regulates NGF response, influencing neuronal differentiation and outgrowth as well as programmed cell death.
  • NGF nerve growth factor
  • p38-alpha is involved with the regulation of pro-inflammatory cytokines, including TNF-a.
  • JNK3 is a neuronalspecific 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.
  • modulating activity of a mitogen-activated protein kinase refers to changing, manipulating, and/or adjusting the activity of a mitogen-activated protein kinase.
  • modulating the activity of a MAPK can influence neural health, neurogenesis, neural growth and differentiation, and neurodegenerative diseases.
  • 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5- MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate of the disclosure may be used to modulate neurogenesis, comprising administering a composition of the invention.
  • neurogenesis refers to changing, manipulating, and/or adjusting the growth and development of neural tissue.
  • neurogenesis comprises adult neurogenesis, in which new neural stem cells are generated from neural stem cells in an adult animal.
  • modulating neurogenesis comprises increasing and/or enhancing the rate at which new neural tissue is developed.
  • 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5- MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate of the disclosure may be used to modulate neurite outgrowth, comprising administering a composition of the invention.
  • modulating neurite outgrowth refers to changing, manipulating, and/or adjusting the growth and development of neural projections, or "neurites.”
  • neurogenesis comprises modulating the growth of new neurites, the number of neurites per neuron, and/or neurite length.
  • modulating neurite outgrowth comprises increasing and/or enhancing the rate and/or length at which neurites develop.
  • 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5- MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate 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.
  • the disclosure may be used to prevent
  • 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5- MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate of the disclosure may be used to prevent and/or treat women's health disorders including, but not limited to, menstrual cramping, dysmenorrhea, posthysterectomy pain, vaginal or vulvar vestibule mucosa disorder, menopaus
  • compositions comprising an effective amount of 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO- T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate and an excipient (e.g., a pharmaceutically-acceptable excipient).
  • an excipient e.g., a pharmaceutically-acceptable excipient
  • the disclosure also relates to pharmaceutical compositions comprising a therapeutically effective amount of 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5- MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate and a pharmaceutically acceptable excipient (also known as a pharmaceutically acceptable carrier).
  • a pharmaceutically acceptable excipient also known as a pharmaceutically acceptable carrier
  • 5-MeO-T hydrofumarate, crystalline 5- MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO- T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate 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.
  • a composition or a pharmaceutical composition of the disclosure may be in any form which contains 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5- MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate.
  • 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 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5- MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate of the disclosure and, for example, 99% to 1% by weight of at least
  • the composition may be between about 5% and about 75% by weight of 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO- T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate of the disclosure, with the rest being at least one suitable pharmaceutically acceptable excipient or at least one other adjuvant, as discussed below.
  • 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.
  • 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO- T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate 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.
  • this disclosure provides a composition
  • a composition comprising: a first component comprising 5-MeO-T hydrofumarate, crystalline 5- MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO- T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate 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
  • compositions When used in such compositions as a first component comprising 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO- T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate 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 cann
  • compositions having as a first component 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5- MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate 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
  • 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.
  • 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.
  • the term “purified” means separated from other materials, such as plant or fungal material, e.g., protein, chitin, cellulose, or water.
  • the term “purified” refers to a compound substantially free of other materials.
  • the term “purified” refers to a compound that is substantially free from a second tryptamine compound.
  • the term “purified” refers to a compound substantially free from histidine.
  • the term “purified” refers to a compound substantially free from a biological material, such as mold, fungus, plant matter, or bacteria.
  • the term “purified” refers to a compound substantially free from a paralytic.
  • 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.
  • a "purified" psilocybin derivative is partially or completely isolated from other psilocybin derivatives present in a source material, such as a psilocybin-containing mushroom.
  • "purified" baeocystin is substantially free from psilocybin and/or psilocin.
  • psilocybin mushroom extracts aka crude extracts or fruit body extracts
  • traditional psilocybin mushroom extracts would be expected to contain an unpredictable and varying amount of psilocybin, psilocin, baeocystin, norbaeocystin, salts thereof, or combinations thereof.
  • 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.
  • cannabidiol cannabidiol
  • CBD cannabidiol
  • the term "purified" refers to a compound or composition that has been crystallized.
  • 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.
  • the term "purified" refers to a compound or composition that has been distilled.
  • the term “purified” refers to a compound or composition that has been sublimed.
  • 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.
  • the term "purified” refers to a compound that is between 80-100% pure.
  • the term “purified” refers to a compound that is between 90-100% pure.
  • the term “purified” refers to a compound that is between 95-100% pure.
  • the term "purified" refers to a compound that is between 99-100% pure.
  • the term "purified" refers to a compound that is between 99.9- 100% pure.
  • a serotonergic drug refers to a compound that binds to, blocks, or otherwise influences
  • 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.
  • a pharmaceutical formulation of the disclosure may comprise, consist essentially of, or consist of (a) 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5- MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate of the disclosure and (b) at least one second active compound selected from a serotonergic drug, a purified psilocybin derivative, a purified cannabinoi
  • Exemplary molar ratios of 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate 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
  • a pharmaceutical formulation of the disclosure may comprise a composition containing
  • 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.
  • composition containing 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO- T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate 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.
  • the disclosure provides a pharmaceutical formulation comprising as (a) 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO- T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate of the disclosure and at least one second component selected from (a) a purified psilocybin derivative, (b) a purified cannabinoid, and (c) a purified terpen
  • 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.
  • 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.
  • serotonergic drugs include the following molecules, including any salts, solvates, or polymorphs thereof: 6-allyl-N,N-diethyl-NL; N,N-dibutyl-T; N,N-diethyl-T; N,N-diisopropyl-T; 5-methyoxy-alpha-methyl-T; N,N- dimethyl-T; 2,alpha-dimethyl-T; alpha, N-dimethyl-T; N,N-dipropyl-T; N-ethyl-N-isopropyl-T; alpha-ethyl- T; 6-N,N-Triethyl-NL; 3,4-dihydro-7-methoxy-l-methyl-C; 7-methyoxy-l-methyl-C; N,N-dibutyl-4- hydroxy-T; N,N-diethyl-4-hydroxy-T; N,N-diisopropyl-4-hydroxy-T;
  • 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, phene
  • 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 [082]-[0110] US 2019/0142851 Al as well as the disclosed exemplary embodiments, incorporated here by reference.
  • compositions disclosed herein comprise one or more purified psilocybin derivatives chosen from: [3-(2-dimethylaminoethyl)-lH-indol-4-yl] dihydrogen phosphate; 4- hydroxytryptamine; 4-hydroxy-N,N-dimethyltryptamine; [3-(2-methylaminoethyl)-lH-indol-4-yl] dihydrogen phosphate; 4-hydroxy-N-methyltryptamine; [3-(aminoethyl)-lH-indol-4-yl] dihydrogen phosphate; [3-(2-trimethylaminoethyl)-lH-indol-4-yl] dihydrogen phosphate; and 4-hydroxy-N,N,N- trimethyltryptamine.
  • purified psilocybin derivatives chosen from: [3-(2-dimethylaminoethyl)-lH-indol-4-y
  • 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.
  • 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
  • the purified cannabinoid is chosen from THC, THCA, THCV, THCVA, CBC, CBCA, CBCV, CBCVA, CBD, CBDA, CBDV, CBVD, CBDVA, CBG, CBGA, CBGV, or CBGVA.
  • Exemplary terpenes include but are not limited to the terpenes described in paragraphs
  • 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, eth
  • 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.
  • adrenergic drug refers to a compound that binds, blocks, or otherwise influences (e.g., via an allosteric reaction) activity at an adrenergic receptor.
  • an adrenergic drug binds to an adrenergic receptor.
  • an adrenergic drug indirectly affects an adrenergic receptor, e.g., via interactions affecting the reactivity of other molecules at the adrenergic receptor.
  • an adrenergic drug is an agonist, e.g., a compound activating an adrenergic receptor.
  • an adrenergic drug is an antagonist, e.g., a compound binding but not activating an adrenergic receptor, e.g., blocking a receptor.
  • an adrenergic drug is an effector molecule, e.g., a compound binding to an enzyme for allosteric regulation.
  • an adrenergic drug acts (either directly or indirectly) at more than one type of receptor (e.g., 5HT, dopamine, adrenergic, acetylcholine, etc.).
  • 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.
  • 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.
  • 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.
  • a dopaminergic drug binds to a dopamine receptor.
  • a dopaminergic drug indirectly affects a dopamine receptor, e.g., via interactions affecting the reactivity of other molecules at the dopamine receptor.
  • a dopaminergic drug is an agonist, e.g., a compound activating a dopamine receptor.
  • a dopaminergic drug is an antagonist, e.g., a compound binding but not activating a dopamine receptor, e.g., blocking a receptor.
  • a dopaminergic drug is an effector molecule, e.g., a compound binding to an enzyme for allosteric regulation.
  • a dopaminergic drug acts (either directly or indirectly) at more than one type of receptor (e.g., 5HT, dopamine, adrenergic, acetylcholine, etc.).
  • a dopaminergic drug is a dopamine transporter inhibitor.
  • a dopaminergic drug is a vesicular monoamine transporter inhibitor.
  • 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.
  • a MAOI refers to a compound that blocks the actions of monoamine oxidase enzymes.
  • a MAOI inhibits the activity of one or both monoamine oxidase A and monoamine oxidase B.
  • a MAOI is a reversible inhibitor of monoamine oxidase A.
  • a MAOI is a drug chosen from isocarboxazid, phenelzine, or tranylcypromine.
  • a MAOI is
  • the compositions and methods disclosed herein include one or more purified erinacine molecules.
  • the compositions and methods disclosed herein comprise purified erinacine A.
  • the compositions and methods disclosed herein comprise erinacine B.
  • the compositions and methods disclosed herein comprise erinacine C.
  • the compositions and methods disclosed herein comprise erinacine D.
  • the compositions and methods disclosed herein comprise erinacine E.
  • the compositions and methods disclosed herein comprise erinacine F.
  • the compositions and methods disclosed herein comprise erinacine G.
  • the compositions and methods disclosed herein comprise erinacine H.
  • 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. [0089] 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.
  • 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.
  • 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5- MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate of the disclosure may be any one of the exemplary embodiments described above including the crystalline forms as disclosed herein.
  • 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO- T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate of the disclosure may be any one of the exemplary embodiments described above including the crystalline forms as disclosed herein.
  • An "effective amount” or a "therapeutically effective amount” of 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO- T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5-MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromaleate 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
  • 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.
  • 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 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5- MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F
  • 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.
  • a solid dosage form 5-MeO-T hydrofumarate, crystalline 5-MeO-T hydrofumarate, 5-MeO-T hydromaleate, crystalline 5-MeO-T hydromaleate, 5-MeOT galactarate, crystalline 5-MeOT galactarate, 5-MeO-T malate, crystalline 5-MeO-T malate, 6-F-T hydromaleate, crystalline 6-F-T hydromaleate, or specific crystalline forms thereof, such as crystalline form 1 of 5-MeO-T hydrofumarate, crystalline form 1 of 5- MeO-T hydromaleate, crystalline form 1 of 5-MeOT galactarate, crystalline form 1 of 5-MeO-T malate, and crystalline form 1 of 6-F-T hydromale
  • the dosage forms may also comprise buffering agents.
  • the excipient is not water.
  • the excipient is not a solvent (e.g., EtOH, diethyl ether, ethyl acetate, or hydrocarbonbased solvents (e.g., hexanes).
  • 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.
  • Excipients or pharmaceutically acceptable adjuvants known in the pharmaceutical formulation art may also be used in the pharmaceutical compositions of the disclosure.
  • microorganisms 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.
  • a pharmaceutical composition of the disclosure may also contain minor amounts of auxiliary substances such as wetting or emulsifying agents, pH buffering agents, antioxidants, and the like, such as, for example, citric acid, sorbitan monolaurate, triethanolamine oleate, butylated hydroxytoluene, etc.
  • auxiliary substances such as wetting or emulsifying agents, pH buffering agents, antioxidants, and the like, such as, for example, citric acid, sorbitan monolaurate, triethanolamine oleate, butylated hydroxytoluene, etc.
  • 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.
  • 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.
  • 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.
  • Solid dosage forms for oral administration which includes capsules, tablets, pills, powders, and granules, may be used.
  • the active compound may be mixed with at least one inert, pharmaceutically acceptable excipient (also known as a pharmaceutically acceptable carrier).
  • administration may be, for example, orally, buccally, nasally, parenterally (intravenous, intramuscular, or subcutaneous), topically, transdermally, i ntra agi nally, 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.
  • E5. A composition comprising 5-methoxytryptammonium hydrofumarate according to
  • E6 A composition comprising crystalline 5-methoxytryptammonium hydrofumarate according to any one of E2-E4 and an excipient.
  • E7 A composition comprising 5-methoxytryptammonium hydrofumarate according to
  • El as a first component and a second component selected from at least one of (a) a serotonergic drug, (b) a purified psilocybin derivative, (c) a purified cannabinoid, (d) a purified terpene, (e) an adrenergic drug, (f) a dopaminergic drug, (g) a monoamine oxidase inhibitor, (h) a purified erinacine, and (i) a purified hericenone. [00108] E8.
  • a composition comprising crystalline 5-methoxytryptammonium hydrofumarate according to any one of E2-E4 as a first component and a second component selected from at least one of (a) a serotonergic drug, (b) a purified psilocybin derivative, (c) a purified cannabinoid, (d) a purified terpene, (e) an adrenergic drug, (f) a dopaminergic drug, (g) a monoamine oxidase inhibitor, (h) a purified erinacine, and (i) a purified hericenone.
  • 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 5- methoxytryptammonium hydrofumarate according to El.
  • 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 5- methoxytryptammonium hydrofumarate according to any one of E2-E4.
  • Ell. A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a composition according to E5 or E7.
  • E12 A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a composition according to E6 or E8.
  • E13 A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a therapeutically effective amount of 5- methoxytryptammonium hydrofumarate according to El.
  • E14 A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a therapeutically effective amount of crystalline 5- methoxytryptammonium hydrofumarate according to any one of E2-E4.
  • E15 A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a composition according to E5 or E7.
  • E16 A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a composition according to E6 or E8.
  • E17 2-(5-methoxy-lH-indol-3-yl)ethan-l-aminium (2Z)-3-carboxyprop-2-enoate (5- methoxytryptammonium hydromaleate).
  • E18 Crystalline 2-(5-methoxy-lH-indol-3-yl)ethan-l-aminium (2Z)-3-carboxyprop-2- enoate (5-methoxytryptammonium hydromaleate).
  • E22 A composition comprising crystalline 5-methoxytryptammonium hydromaleate according to any one of E18-E20 and an excipient.
  • E23 A composition comprising 5-methoxytryptammonium hydromaleate according to
  • E17 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.
  • E24 A composition comprising crystalline 5-methoxytryptammonium hydromaleate according to any one of E18-E20 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.
  • E25 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 5- methoxytryptammonium hydromaleate according to E17.
  • E26 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 5- methoxytryptammonium hydromaleate according to any one of E18-E2O.
  • E27 A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a composition according to E21 or E23.
  • E28 A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a composition according to E22 or E24.
  • E29 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 5- methoxytryptammonium hydromaleate according to E17.
  • E30 A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a therapeutically effective amount of crystalline 5- methoxytryptammonium hydromaleate according to any one of E18-E20.
  • E31 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 E21 or E23.
  • E32 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 E22 or E24.
  • E33 Bis(2-(5-methoxy-lH-indol-3-yl)ethan-l-aminium) (2R, 3S,4R,5S)-2, 3,4,5- tetrahydroxyhexanedioate (5-methoxytryptammonium galactarate).
  • E34 Crystalline bis(2-(5-methoxy-lH-indol-3-yl)ethan-l-aminium) (2R, 3S,4R,5S)-2, 3,4,5- tetrahydroxyhexanedioate (5-methoxytryptammonium galactarate).
  • Y 90°; an X-ray powder diffraction pattern substantially similar to FIG. 15; or an X-ray powder diffraction pattern characterized by at least two peaks selected from 6.5, 10.1, and 11.6 °26 ⁇ 0.2 °20.
  • E37 A composition comprising 5-methoxytryptammonium galactarate according to E33 and an excipient.
  • E38 A composition comprising crystalline 5-methoxytryptammonium galactarate according to any one of E34-E36 and an excipient.
  • a composition comprising 5-methoxytryptammonium galactarate according to E33 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.
  • E40 A composition comprising crystalline 5-methoxytryptammonium galactarate according to any one of E34-E36 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.
  • E41 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 5- methoxytryptammonium galactarate according to E33.
  • E42 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 5- methoxytryptammonium galactarate according to any one of E34-E36.
  • E43 A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a composition according to E37 or E39.
  • E44 A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a composition according to E38 or E40.
  • E45 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 5- methoxytryptammonium galactarate according to E33.
  • E46 A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a therapeutically effective amount of crystalline 5- methoxytryptammonium galactarate according to any one of E34-E36.
  • E47 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 E37 or E39.
  • E48 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 E38 or E40.
  • E50 Crystalline bis(2-(5-methoxy-lH-indol-3-yl)ethan-l-aminium) 2- hydroxybutanedioate (5-methoxytryptammonium malate).
  • E51 Crystalline form 1 of bis(2-(5-methoxy-lH-indol-3-yl)ethan-l-aminium) 2- hydroxybutanedioate (5-methoxytryptammonium malate).
  • E53 A composition comprising 5-methoxytryptammonium malate according to E49 and an excipient.
  • E54 A composition comprising crystalline 5-methoxytryptammonium malate according to any one of E50-E52 and an excipient.
  • a composition comprising 5-methoxytryptammonium malate according to E49 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.
  • E56 A composition comprising crystalline 5-methoxytryptammonium malate according to any one of E50-E52 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.
  • E57 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 5- methoxytryptammonium malate according to E49.
  • E58 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 5- methoxytryptammonium malate according to any one of E50-E52.
  • E59 A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a composition according to E53 or E55.
  • E60 A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a composition according to E54 or E56.
  • E61 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 5- methoxytryptammonium malate according to E49.
  • E62 A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a therapeutically effective amount of crystalline 5- methoxytryptammonium malate according to any one of E50-E52.
  • E63 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 E53 or E55.
  • E64 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 E54 or E56.
  • E65 2-(6-fluoro-lH-indol-3-yl)ethan-l-aminium (2E)-3-carboxyprop-2-enoate (6- fluorotryptammonium hydromaleate).
  • E69 A composition comprising 6-fluorotryptammonium hydromaleate according to E65 and an excipient.
  • E70 A composition comprising crystalline 6-fluorotryptammonium hydromaleate according to any one of E66-E68 and an excipient.
  • E71 A composition comprising 6-fluorotryptammonium hydromaleate according to E65 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.
  • E72 A composition comprising crystalline 6-fluorotryptammonium hydromaleate according to any one of E66-E68 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.
  • E73 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 6- fluorotryptammonium hydromaleate according to E65.
  • E74 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 6- fluorotryptammonium hydromaleate according to any one of E66-E68.
  • E75 A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a composition according to E69 or E71.
  • E76 A method of preventing or treating a psychological disorder comprising the step of: administering to a subject in need thereof a composition according to E70 or E72.
  • E77 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 6- fluorotryptammonium hydromaleate according to E65.
  • E78 A method of preventing or treating inflammation and/or pain comprising the step of: administering to a subject in need thereof a therapeutically effective amount of crystalline 6- fluorotryptammonium hydromaleate according to any one of E66-E68.
  • E79 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 E69 or E71.
  • E80 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 E70 or E72.
  • FIG. 1 shows the molecular structure of crystalline form 1 of 5-MeO-T hydrofumarate, showing the atomic labeling.
  • FIG. 2 shows the molecular structure of crystalline form 1 of 5-MeO-T hydromaleate, showing the atomic labeling.
  • FIG. 3 shows the molecular structure of crystalline form 1 of 5-MeOT galactarate, showing the atomic labeling.
  • FIG. 4 shows the molecular structure of crystalline form 1 of 5-MeO-T malate, showing the atomic labeling.
  • FIG. 5 shows the molecular structure of crystalline form 1 of 6-F-T hydromaleate, showing the atomic labeling.
  • FIG. 6 shows the unit cell of crystalline form 1 of 5-MeO-T hydrofumarate along the a- axis.
  • FIG. 7 shows the unit cell of crystalline form 1 of 5-MeO-T hydromaleate along the a- axis.
  • FIG. 8 shows the unit cell of crystalline form 1 of 5-MeOT galactarate along the a-axis.
  • FIG. 9 shows the unit cell of crystalline form 1 of 5-MeO-T malate along the a-axis.
  • FIG. 10 shows the unit cell of crystalline form 1 of 6-F-T hydromaleate along the b-axis.
  • FIG. 11 shows the 2:1 ratio of crystalline form 1 of 5-MeOT galactarate as a dimer.
  • FIG. 12 shows the 2:1 ratio of crystalline form 1 of 5-MeO-T malate as a dimer.
  • FIG. 13 shows a simulated X-ray powder diffraction pattern (XRPD) for crystalline form 1 of 5-MeO-T hydrofumarate generated from its single crystal data.
  • Table 4 lists the angles, °20 ⁇ O.2°20, and d-spacing of the peaks identified in the experimental XRPD pattern of FIG. 13. The entire list of peaks, or a subset thereof, may be sufficient to characterize the cocrystal.
  • the cocrystal may be characterized by at least two peaks selected from the peaks at 6.9, 11.3, and 13.3 °20 ⁇ O.2°20 or their corresponding d-spacing as well as by an XRPD pattern substantially similar to FIG. 13.
  • FIG. 14 shows a simulated X-ray powder diffraction pattern (XRPD) for crystalline form 1 of 5-MeO-T hydromaleate generated from its single crystal data.
  • Table 5 lists the angles, °20 ⁇ O.2°20, and d-spacing of the peaks identified in the experimental XRPD pattern of FIG. 14. The entire list of peaks, or a subset thereof, may be sufficient to characterize the cocrystal.
  • the cocrystal may be characterized by at least two peaks selected from the peaks at 12.5, 15.5, and 17.1 °20 ⁇ O.2°20 or their corresponding d-spacing as well as by an XRPD pattern substantially similar to FIG. 14.
  • FIG. 15 shows a simulated X-ray powder diffraction pattern (XRPD) for crystalline form 1 of 5-MeOT galactarate generated from its single crystal data.
  • XRPD simulated X-ray powder diffraction pattern
  • Table 6 lists the angles, °20 ⁇ O.2°20, and d-spacing of the peaks identified in the experimental XRPD pattern of FIG. 15. The entire list of peaks, or a subset thereof, may be sufficient to characterize the cocrystal.
  • the cocrystal may be characterized by at least two peaks selected from the peaks at 6.5, 10.1, and 11.6 °20 ⁇ O.2°20 or their corresponding d-spacing as well as by an XRPD pattern substantially similar to FIG. 15.
  • FIG. 16 shows a simulated X-ray powder diffraction pattern (XRPD) for crystalline form 1 of 5-MeO-T malate generated from its single crystal data.
  • Table 7 lists the angles, °29 ⁇ O.2°20, and d- spacing of the peaks identified in the experimental XRPD pattern of FIG. 16. The entire list of peaks, or a subset thereof, may be sufficient to characterize the cocrystal.
  • the cocrystal may be characterized by at least two peaks selected from the peaks at 6.2, 13.9, and 15.3 °20 ⁇ O.2°20 or their corresponding d-spacing as well as by an XRPD pattern substantially similar to FIG. 16.
  • FIG. 17 shows a simulated X-ray powder diffraction pattern (XRPD) for crystalline form 1 of 6-F-T hydromaleate generated from its single crystal data.
  • Table 8 lists the angles, °20 ⁇ O.2°20, and d- spacing of the peaks identified in the experimental XRPD pattern of FIG. 17. The entire list of peaks, or a subset thereof, may be sufficient to characterize the cocrystal.
  • the cocrystal may be characterized by at least two peaks selected from the peaks at 8.9, 11.3, and 14.2 °20 + O.2°20 or their corresponding d-spacing as well as by an XRPD pattern substantially similar to FIG. 17.

Landscapes

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

Abstract

La présente divulgation concerne du 2-(5-méthoxy-1H-indol-3-yl)éthan-1-aminium (2E)-3-carboxyprop-2-énoate (hydrofumarate de 5-méthoxytryptammonium ou hydrofumarate de 5-MeO-T), de l'hydrofumarate de 5-MeO-T cristallin, du 2-(5-méthoxy-1H-indol-3-yl)éthan-1-aminium (2Z)-3-carboxyprop-2-énoate (hydromaléate de 5-méthoxytryptammonium ou hydromaléate de 5-MeO-T), de l'hydromaléate de 5-MeO-T cristallin, du bis(2-(5-méthoxy-1H-indol-3-yl)éthan-1-aminium) (2R, 3S,4R,5S)-2,3,4,5-tétrahydroxyhexanedioate (galactarate de 5-méthoxytryptammonium ou galactarate de 5-MeO-T), du galactarate de 5-MeO-T cristallin, du bis(2-(5-méthoxy-1H-indol-3-yl)éthan-1-aminium) 2-hydroxybutanedioate (malate de 5-méthoxytryptammonium ou malate de 5-MeO-T), du malate de 5-MeO-T cristallin, du 2-(6-fluoro-1H-indol- 3-yl)éthan-1-aminium (2E)-3-carboxyprop-2-énoate (hydromaléate de 6-fluorotryptammonium ou hydromaléate de 6-F-T), de l'hydromaléate de 6-F-T cristallin, et des formes cristallines spécifiques associées, telles que la forme cristalline 1 d'hydrofumarate de 5-MeO-T, la forme cristalline 1 d'hydromaléate de 5-MeO-T, la forme cristalline 1 de galactarate de 5-MeO-T, la forme cristalline 1 de malate de 5-MeO-T, et la forme cristalline 1 d'hydromaléate de 6-F-T, des compositions les contenant, et des procédés de traitement les utilisant.
PCT/US2024/027673 2023-05-04 2024-05-03 Dérivés de tryptamine Pending WO2024229352A2 (fr)

Applications Claiming Priority (10)

Application Number Priority Date Filing Date Title
US202363500087P 2023-05-04 2023-05-04
US63/500,087 2023-05-04
US202363502999P 2023-05-18 2023-05-18
US63/502,999 2023-05-18
US202363516907P 2023-08-01 2023-08-01
US202363516905P 2023-08-01 2023-08-01
US63/516,905 2023-08-01
US63/516,907 2023-08-01
US202363518140P 2023-08-08 2023-08-08
US63/518,140 2023-08-08

Publications (2)

Publication Number Publication Date
WO2024229352A2 true WO2024229352A2 (fr) 2024-11-07
WO2024229352A3 WO2024229352A3 (fr) 2024-12-12

Family

ID=93333477

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2024/027673 Pending WO2024229352A2 (fr) 2023-05-04 2024-05-03 Dérivés de tryptamine

Country Status (1)

Country Link
WO (1) WO2024229352A2 (fr)

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG11201901449XA (en) * 2016-08-23 2019-03-28 Neurim Pharmaceuticals 1991 Ltd Method for treating pruritus and/or itch
AU2020386445A1 (en) * 2019-11-19 2022-06-02 Paul Edward Stamets Tryptamine compositions for enhancing neurite outgrowth

Also Published As

Publication number Publication date
WO2024229352A3 (fr) 2024-12-12

Similar Documents

Publication Publication Date Title
US20240409513A1 (en) Crystalline tryptamine compounds
AU2022408191B2 (en) Psilocybin derivatives
WO2024138007A2 (fr) Dérivés de tryptamine
AU2023254841A1 (en) Tryptamine derivatives
AU2023288538A1 (en) Tryptamine derivatives
WO2023225678A2 (fr) Dérivés de tryptamine
WO2024229352A2 (fr) Dérivés de tryptamine
US20250257033A1 (en) Methyl substituted quaternary tryptamine derivatives
WO2024040158A2 (fr) Dérivés de tryptamine
WO2025049837A1 (fr) Galactarate de tryptammonium
WO2024206109A1 (fr) Dérivés de tryptamine
WO2025042934A1 (fr) Fumarate de 5-méthyl-n-isopropyltryptammonium
WO2024178051A2 (fr) Dérivés de tryptamine
WO2025049835A1 (fr) Hydrofumarate de 5-chlorotryptammonium
WO2025250900A1 (fr) Hydroglutarate de 4-hydroxy-n, n-diisopropyltryptaminium
WO2025049675A1 (fr) 5-méthoxy-tryptammonium glutarate
WO2025049512A1 (fr) Hydromaléate de 5-méthyl-n-isopropyltryptammonium
WO2025042937A1 (fr) Hydrophtalate de 5-méthoxytryptammonium
WO2025049672A1 (fr) 5-méthyl-n-isopropyltryptamine
WO2025042938A1 (fr) Chlorure de 4-benzyloxy-n-méthyl-n-isopropyltryptammonium
WO2025043059A1 (fr) 4-méthoxy-n-méthyl-n-cyclopropyltryptamine
WO2025043056A1 (fr) Chlorure de 4-méthoxy-n,n-diisopropyltryptammonium
WO2025043053A1 (fr) Chlorure de 4-méthoxy-n,n-dicyclopropyltryptammonium
AU2023255767A1 (en) Crystalline quaternary salts of 4-substituted tryptamines
WO2024097944A2 (fr) Dérivés de tryptamine

Legal Events

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

Ref document number: 24800667

Country of ref document: EP

Kind code of ref document: A2