# US 2025/0082607 A2 · Methods of treating disorders with a psilocybin analog > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2025/0082607 A2 - Document ID: US20250082607A2 - Status: Published application - Kind: A2 - Application number: 18/588,132 - Filed: 2024-02-27 - Published: 2025-03-13 - Earliest claimed: 2023-02-27 - Assignees: Cybin IRL Limited - Applicants: Cybin IRL Limited - Inventors: Alex Nivorozhkin; Michael Palfreyman; Pradip M. Pathare; Kenneth L. Avery; Mohammed I. Shukoor; Michael E. Morgan; Joan M. Krakowsky; Amir Inamdar; Pradeep J. Nathan; Sebastian Krempien - Web page: https://patentgrep.com/patent/US20250082607A2 ## CPC - A61K 31/4045: Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 25/24: Antidepressants - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present disclosure relates generally to methods of treating various diseases, disorders, and conditions, such as depressive disorders (e.g., Major Depressive Disorder (MDD)), substance use disorders, anxiety disorders, eating disorders, pain, and headache disorders via administration of deuterated psilocin and pharmaceutically acceptable salts, polymorphs, or solvates thereof. ## Claims ### Claim 1 A method of treating a depressive disorder in a subject in need thereof, comprising administering orally to the subject about 8 mg to about 16 mg (free base equivalence) of a compound of Formula (I-3) or a pharmaceutically acceptable salt, polymorph, or solvate thereof. ### Claim 2 (depends on 1) The method of claim 1, comprising administering about 12 mg to about 16 mg (free base equivalence) of the compound of Formula (I-3), or a pharmaceutically acceptable salt, polymorph, or solvate thereof, to the subject. ### Claim 3 (depends on 1) The method of claim 1, comprising administering about 12 mg (free base equivalence) of the compound of Formula (I-3), or a pharmaceutically acceptable salt, polymorph, or solvate thereof, to the subject. ### Claim 4 (depends on 1) The method of claim 1, comprising administering about 14 mg (free base equivalence) of the compound of Formula (I-3), or a pharmaceutically acceptable salt, polymorph, or solvate thereof, to the subject. ### Claim 5 (depends on 1) The method of claim 1, comprising administering about 16 mg (free base equivalence) of the compound of Formula (I-3), or a pharmaceutically acceptable salt, polymorph, or solvate thereof, to the subject. ### Claim 6 (depends on 1) The method of claim 1, wherein a pharmaceutically acceptable salt of the compound of Formula (I-3) is administered. ### Claim 7 (depends on 6) The method of claim 6, wherein the pharmaceutically acceptable salt of the compound of Formula (I-3) is selected from the group consisting of a benzenesulfonate, a tartrate, a hemi-fumarate, an acetate, a citrate, a malonate, a fumarate, a succinate, an oxalate, a benzoate, a salicylate, an ascorbate, a hydrochloride, a maleate, a malate, a methanesulfonate, a toluenesulfonate, a glucuronate, and a glutarate salt, of the compound of Formula (I-3). ### Claim 8 (depends on 6) The method of claim 6, wherein the pharmaceutically acceptable salt of the compound of Formula (I-3) is a benzenesulfonate salt of the compound of Formula (I-3). ### Claim 9 (depends on 8) The method of claim 8, wherein the benzenesulfonate salt of the compound of Formula (I-3) is a crystalline benzenesulfonate salt (I-3a), characterized by an X-ray powder diffraction pattern containing at least three characteristic peaks selected from 7.023, 7.767, 11.822, 12.550, 12.860, 13.994, 15.521, 18.436, 19.503, 20.760, 21.070, 22.007, 22.745, 23.340, 24.187, 25.532, 26.880, 27.856, 28.163, 31.267, 33.024, 35.030, 36.835, 39.312, 40.545, and 40.988 °2θ (±0.2° 2θ). ### Claim 10 (depends on 6) The method of claim 6, wherein the pharmaceutically acceptable salt of the compound of Formula (I-3) is a tartrate salt of the compound of Formula (I-3). ### Claim 11 (depends on 10) The method of claim 10, wherein the tartrate salt of the compound of Formula (I-3) is a crystalline tartrate salt (I-3b), characterized by an X-ray powder diffraction pattern containing at least three characteristic peaks selected from 6.732, 12.708, 13.470, 14.774, 15.921, 16.268, 17.295, 18.869, 20.079, 20.208, 20.877, 21.894, 22.657, 23.491, 23.702, 24.636, 24.882, 25.569, 26.685, 27.060, 27.502, 28.179, 28.597, 29.035, 29.257, 29.527, 31.017, 31.527, 32.059, 32.307, 33.012, 34.024, 34.388, 34.905, 35.361, 36.183, 37.372, 37.764, 38.657, and 41.049 °2θ (±0.2° 2θ). ### Claim 12 (depends on 6) The method of claim 6, wherein the pharmaceutically acceptable salt of the compound of Formula (I-3) is a hemi-fumarate salt of the compound of Formula (I-3). ### Claim 13 (depends on 12) The method of claim 12, wherein the hemi-fumarate salt of the compound of Formula (I-3) is a crystalline hemi-fumarate salt (I-3c), characterized by an X-ray powder diffraction pattern containing at least three characteristic peaks selected from 9.713, 11.209, 11.605, 12.338, 12.852, 13.718, 15.117, 16.066, 16.627, 19.026, 19.427, 20.108, 21.068, 21.335, 21.837, 22.429, 23.262, 23.478, 23.900, 24.720, 25.318, 27.912, 28.532, 29.565, 30.457°, 32.698, 34.155, 37.910, 39.566, and 40.999 °2θ (±0.2° 2θ). ### Claim 14 (depends on 6) The method of claim 6, wherein the pharmaceutically acceptable salt of the compound of Formula (I-3) is a citrate salt of the compound of Formula (I-3). ### Claim 15 (depends on 14) The method of claim 14, wherein the citrate salt (I-3e) is amorphous by X-ray powder diffraction. ### Claim 16 (depends on 6) The method of claim 6, wherein the pharmaceutically acceptable salt of the compound of Formula (I-3) is a benzoate salt of the compound of Formula (I-3). ### Claim 17 (depends on 16) The method of claim 16, wherein the benzoate salt of the compound of Formula (I-3) is a crystalline benzoate salt (I-3j), characterized by an X-ray powder diffraction pattern containing at least three characteristic peaks selected from 9.486, 11.006, 12.379, 13.428, 14.608, 15.446, 16.389, 18.247, 18.977, 19.346, 19.831, 20.868, 21.447, 22.860, 23.878, 24.944, 25.737, 26.144, 26.341, 26.990°, 27.708, 28.595, 30.048, 30.763, 31.127, 31.839, 32.800, 34.460, 35.444, 37.725, and 38.597 °2θ (±0.2° 2θ). ### Claim 18 (depends on 1) The method of claim 1, wherein the depressive disorder is major depressive disorder (MDD). ### Claim 19 (depends on 18) The method of claim 18, wherein, prior to treatment, the subject has been diagnosed with moderate to severe major depressive disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). ### Claim 20 (depends on 1) The method of claim 1, wherein, prior to treatment, the subject has scored greater than or equal to 21 on the Montgomery-Åsberg Depression Scale (MADRS). ### Claim 21 (depends on 1) The method of claim 1, wherein a first dose and a second dose, each being about 8 mg to about 16 mg (free base equivalence) of the compound of Formula (I-3), or a pharmaceutically acceptable salt, polymorph, or solvate thereof, are administered to the subject one to four weeks apart (±3 days). ### Claim 22 (depends on 1) The method of claim 1, wherein a first dose and a second dose, each being about 8 mg to about 16 mg (free base equivalence) of the compound of Formula (I-3), or a pharmaceutically acceptable salt, polymorph, or solvate thereof, are administered to the subject three weeks apart (±3 days). ### Claim 23 (depends on 1) The method of claim 1, wherein the subject is taking antidepressant medication as part of ongoing treatment and the method is used as adjunctive therapy. ### Claim 24 A pharmaceutical composition, comprising: about 8 mg to about 16 mg (free base equivalence) of a compound of Formula (I-3) or a pharmaceutically acceptable salt, polymorph, or solvate thereof; and a pharmaceutically acceptable vehicle. ### Claim 25 (depends on 24) The pharmaceutical composition of claim 24, wherein the pharmaceutical composition comprises about 12 mg to about 16 mg (free base equivalence) of the compound of Formula (I-3), or a pharmaceutically acceptable salt, polymorph, or solvate thereof. ### Claim 26 (depends on 24) The pharmaceutical composition of claim 24, wherein the pharmaceutical composition comprises about 12 mg (free base equivalence) of the compound of Formula (I-3), or a pharmaceutically acceptable salt, polymorph, or solvate thereof. ### Claim 27 (depends on 24) The pharmaceutical composition of claim 24, wherein the pharmaceutical composition comprises about 14 mg (free base equivalence) of the compound of Formula (I-3), or a pharmaceutically acceptable salt, polymorph, or solvate thereof. ### Claim 28 (depends on 24) The pharmaceutical composition of claim 24, wherein the pharmaceutical composition comprises about 16 mg (free base equivalence) of the compound of Formula (I-3), or a pharmaceutically acceptable salt, polymorph, or solvate thereof. ### Claim 29 (depends on 24) The pharmaceutical composition of claim 24, wherein the pharmaceutical composition comprises a pharmaceutically acceptable salt of the compound of Formula (I-3). ### Claim 30 (depends on 29) The pharmaceutical composition of claim 29, wherein the pharmaceutically acceptable salt of the compound of Formula (I-3) is selected from the group consisting of a benzenesulfonate, a tartrate, a hemi-fumarate, an acetate, a citrate, a malonate, a fumarate, a succinate, an oxalate, a benzoate, a salicylate, an ascorbate, a hydrochloride, a maleate, a malate, a methanesulfonate, a toluenesulfonate, a glucuronate, and a glutarate salt, of the compound of Formula (I-3). ### Claim 31 (depends on 29) The pharmaceutical composition of claim 29, wherein the pharmaceutically acceptable salt of the compound of Formula (I-3) is a benzenesulfonate salt of the compound of Formula (I-3). ### Claim 32 (depends on 31) The pharmaceutical composition of claim 31, wherein the benzenesulfonate salt of the compound of Formula (I-3) is a crystalline benzenesulfonate salt (I-3a), characterized by an X-ray powder diffraction pattern containing at least three characteristic peaks selected from 7.023, 7.767, 11.822, 12.550, 12.860, 13.994, 15.521, 18.436, 19.503, 20.760, 21.070, 22.007, 22.745, 23.340, 24.187, 25.532, 26.880, 27.856, 28.163, 31.267, 33.024, 35.030, 36.835, 39.312, 40.545, and 40.988 °2θ (±0.2° 2θ). ### Claim 33 (depends on 29) The pharmaceutical composition of claim 29, wherein the pharmaceutically acceptable salt of the compound of Formula (I-3) is a tartrate salt of the compound of Formula (I-3). ### Claim 34 (depends on 33) The pharmaceutical composition of claim 33, wherein the tartrate salt of the compound of Formula (I-3) is a crystalline tartrate salt (I-3b), characterized by an X-ray powder diffraction pattern containing at least three characteristic peaks selected from 6.732, 12.708, 13.470, 14.774, 15.921, 16.268, 17.295, 18.869, 20.079, 20.208, 20.877, 21.894, 22.657, 23.491, 23.702, 24.636, 24.882, 25.569, 26.685, 27.060, 27.502, 28.179, 28.597, 29.035, 29.257, 29.527, 31.017, 31.527, 32.059, 32.307, 33.012, 34.024, 34.388, 34.905, 35.361, 36.183, 37.372, 37.764, 38.657, and 41.049 °2θ (±0.2° 2θ). ### Claim 35 (depends on 29) The pharmaceutical composition of claim 29, wherein the pharmaceutically acceptable salt of the compound of Formula (I-3) is a hemi-fumarate salt of the compound of Formula (I-3). ### Claim 36 (depends on 35) The pharmaceutical composition of claim 35, wherein the hemi-fumarate salt of the compound of Formula (I-3) is a crystalline hemi-fumarate salt (I-3c), characterized by an X-ray powder diffraction pattern containing at least three characteristic peaks selected from 9.713, 11.209, 11.605, 12.338, 12.852, 13.718, 15.117, 16.066, 16.627, 19.026, 19.427, 20.108, 21.068, 21.335, 21.837, 22.429, 23.262, 23.478, 23.900, 24.720, 25.318, 27.912, 28.532, 29.565, 30.457°, 32.698, 34.155, 37.910, 39.566, and 40.999°2θ (±0.2° 2θ). ### Claim 37 (depends on 29) The pharmaceutical composition of claim 29, wherein the pharmaceutically acceptable salt of the compound of Formula (I-3) is a citrate salt of the compound of Formula (I-3). ### Claim 38 (depends on 37) The pharmaceutical composition of claim 37, wherein the citrate salt (I-3e) is amorphous by X-ray powder diffraction. ### Claim 39 (depends on 29) The pharmaceutical composition of claim 29, wherein the pharmaceutically acceptable salt of the compound of Formula (I-3) is a benzoate salt of the compound of Formula (I-3). ### Claim 40 (depends on 39) The pharmaceutical composition of claim 39, wherein the benzoate salt of the compound of Formula (I-3) is a crystalline benzoate salt (I-3j), characterized by an X-ray powder diffraction pattern containing at least three characteristic peaks selected from 9.486, 11.006, 12.379, 13.428, 14.608, 15.446, 16.389, 18.247, 18.977, 19.346, 19.831, 20.868, 21.447, 22.860, 23.878, 24.944, 25.737, 26.144, 26.341, 26.990°, 27.708, 28.595, 30.048, 30.763, 31.127, 31.839, 32.800, 34.460, 35.444, 37.725, and 38.597°2θ (±0.2° 2θ). ### Claim 41 (depends on 24) The pharmaceutical composition of claim 24, wherein the pharmaceutically acceptable vehicle comprises an organic acid agent. ### Claim 42 (depends on 41) The pharmaceutical composition of claim 41, wherein the organic acid agent is citric acid. ### Claim 43 (depends on 41) The pharmaceutical composition of claim 41, wherein the organic acid agent is present in the pharmaceutical composition in an amount of at least 2% by weight and up to 10% by weight, based on a total weight of the pharmaceutical composition (on a dry basis). ### Claim 44 (depends on 24) The pharmaceutical composition of claim 24, wherein the pharmaceutical composition is in a solid dosage form. ### Claim 45 (depends on 44) The pharmaceutical composition of claim 44, wherein the solid dosage form is a solid dosage form adapted for oral administration. ### Claim 46 (depends on 44) The pharmaceutical composition of claim 44, wherein the solid dosage form is a powder in capsule dosage form. ### Claim 47 (depends on 24) The pharmaceutical composition of claim 24, wherein the pharmaceutical composition is an oral liquid dosage form. ### Claim 48 (depends on 24) A method of treating a depressive disorder in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of claim 24. ### Claim 49 (depends on 48) The method of claim 48, wherein the pharmaceutical composition is administered orally to the subject. ### Claim 50 (depends on 48) The method of claim 48, wherein the pharmaceutical composition is administered by reconstituting the pharmaceutical composition in solid dosage form in a pharmaceutically acceptable aqueous medium to form an oral liquid dosage form, followed by administering orally to the subject the oral liquid dosage form. ### Claim 51 (depends on 48) The method of claim 48, wherein the depressive disorder is major depressive disorder (MDD). ### Claim 52 (depends on 51) The method of claim 51, wherein, prior to treatment, the subject has been diagnosed with moderate to severe major depressive disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). ### Claim 53 (depends on 48) The method of claim 48, wherein, prior to treatment, the subject has scored greater than or equal to 21 on the Montgomery-Åsberg Depression Scale (MADRS). ### Claim 54 (depends on 48) The method of claim 48, wherein a first dose and a second dose of the pharmaceutical composition, each comprising about 8 mg to about 16 mg (free base equivalence) of the compound of Formula (I-3), or a pharmaceutically acceptable salt, polymorph, or solvate thereof, are administered to the subject one to four weeks apart (±3 days). ### Claim 55 (depends on 48) The method of claim 48, wherein a first dose and a second dose of the pharmaceutical composition, each comprising about 8 mg to about 16 mg (free base equivalence) of the compound of Formula (I-3), or a pharmaceutically acceptable salt, polymorph, or solvate thereof, are administered to the subject three weeks apart (±3 days). ### Claim 56 (depends on 48) The method of claim 48, wherein the subject is taking antidepressant medication as part of ongoing treatment and the method is used as adjunctive therapy. ### Claim 57 An adjunctive therapy method for treating a depressive disorder in a subject taking an antidepressant medication as part of ongoing treatment, the adjunctive therapy method comprising administering to the subject about 8 mg to about 16 mg (free base equivalence) of a compound of Formula (I-3) or a pharmaceutically acceptable salt, polymorph, or solvate thereof. ### Claim 58 (depends on 57) The adjunctive therapy method of claim 57, wherein the depressive disorder is major depressive disorder (MDD). ### Claim 59 (depends on 58) The adjunctive therapy method of claim 58, wherein, prior to the adjunctive therapy, the subject has been diagnosed with moderate to severe major depressive disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). ### Claim 60 (depends on 57) The adjunctive therapy method of claim 57, wherein, prior to the adjunctive therapy, the subject has scored greater than or equal to 21 on the Montgomery-Åsberg Depression Scale (MADRS). ### Claim 61 (depends on 57) The adjunctive therapy method of claim 57, wherein a first dose and a second dose, each being about 8 mg to about 16 mg (free base equivalence) of the compound of Formula (I-3), or a pharmaceutically acceptable salt, polymorph, or solvate thereof, are administered to the subject one to four weeks apart (±3 days). ### Claim 62 (depends on 57) The adjunctive therapy method of claim 57, wherein a first dose and a second dose, each being about 8 mg to about 16 mg (free base equivalence) of the compound of Formula (I-3), or a pharmaceutically acceptable salt, polymorph, or solvate thereof, are administered to the subject three weeks apart (±3 days). ### Claim 63 (depends on 57) The adjunctive therapy method of claim 57, wherein the antidepressant medication is a selective serotonin reuptake inhibitor (SSRI), a serotonin and noradrenaline reuptake inhibitor (SNRI), or a combination thereof. ### Claim 64 (depends on 57) The adjunctive therapy method of claim 57, wherein the compound of Formula (I-3), or a pharmaceutically acceptable salt, polymorph, or solvate thereof, is administered orally to the subject. ### Claim 65 A method of treating major depressive disorder (MDD) in a subject in need thereof, comprising administering orally to the subject a capsule comprising about 8 mg to about 16 mg (free base equivalence) of a benzenesulfonate salt of a compound of Formula (I-3) ### Claim 66 A method of treating major depressive disorder (MDD) in a subject in need thereof, comprising administering orally to the subject an oral liquid dosage form comprising: (i) about 8 mg to about 16 mg (free base equivalence) of a compound of Formula (I-3) or a pharmaceutically acceptable salt, polymorph, or solvate thereof; and (ii) a pharmaceutically acceptable aqueous medium.