Treatment of psychiatric or neurological disorders with parenteral administration of a single effective parenteral dose of a short-acting psychedelic agent

Abstract

The present invention relates to dosage regimens, methods of treatment, delivery devices, or parenteral formulations used to treat psychiatric or neurological disorders in a patient. In particular, the present invention relates to the administration of psychedelic agents.

Description

FIELD OF THE INVENTION

[0001] The present invention relates to dosage regimens, methods of treatment, delivery devices, parenteral formulations, or kits used to treat psychiatric or neurological disorders in patients. In particular, the present invention relates to the administration of psychedelic agents. BACKGROUND OF THE INVENTION

[0002] Classical psychedelics have shown promise preclinically and clinically in the treatment of psychiatric disorders (Carhart-Harris and Goodwin, Neuropsychopharmacology 42, 2105-2113 (2017)). In particular, psilocybin (also known as psilocybin) has shown significant improvements in various depression and anxiety rating scales in randomized, double-blind trials (Griffiths et al. Journal of Psychopharmacology, 30(12), 1181-1197 (2016)). The efficacy of psilocybin has been shown in depression (RL Carhart-Harris et al., Psychopharmacology, 2018, 235, 399-408), end-of-life anxiety (RR Griffiths et al., J. Psychopharmacol., 2016, 30, 12, 1181-1197), addiction (MW Johnson, A. Garcia-Romeu and RR Griffiths, Am. J. Drug Alcohol Abuse, 2017, 43, 1, 55-60), and is currently being investigated for several other mental health disorders rooted in psychologically destructive thought processing patterns (anorexia nervosa: NCT# NCT04052568).

[0003] N,N-dimethyltryptamine (DMT) has also been proposed to have therapeutic value as a short-acting psychedelic. A review of studies on DMT biosynthesis and metabolism in the brain and peripheral tissues, as well as methods and results for DMT detection in body fluids and the brain, is published by SA Barker in Front. Neurosci., 12, 536, 1-17 (2018). Barker et al. suggest that "further characterization of DMT's cellular distribution, receptors, and general biochemistry could lead to more effective pharmaceutical agents and new targets for intervention." D. Nutt et al. (Cell. 2020 Apr 2;181(1):24-28. doi: 10.1016 / j.cell.2020.03.020) suggest the potential therapeutic role of DMT, stating, "However, theoretically, a short-term trip, such as that administered intravenously, could 'shake up' or 'reset' abnormal patterns of brain activity, potentially resulting in some therapeutic effect." Both Barker et al. and Nutt et al. conclude that further research is needed into the role and function of DMT.

[0004] Sanches et al. and Palhano-Fontes et al. reported that a single oral dose of ayahuasca, a natural psychedelic plant beverage, was associated with improvement in depressive symptoms in patients with recurrent major depressive disorder (MDD) or treatment-resistant depression (TRD) (Sanches RF, de Lima Osorio F, dos Santos RG, et al. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: A SPECT study. J Clin Psychopharmacol 2016;36(1):77-81 and Palhano-Fontes F, Barreto D, Onias H, et al. Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychol Med 2019;49(4):655-663). N,N-dimethyltryptamine (DMT) is the primary psychedelic compound found in ayahuasca.

[0005] Good et al. discuss the results of a phase I study investigating the pharmacokinetics of N,N-dimethyltryptamine fumarate in healthy subjects (Good, M., Joel, Z., Benway, T. et al. Pharmacokinetics of N,N-dimethyltryptamine in Humans. Eur J Drug Metab Pharmacokinet 48, 311-327 (2023). https: / / doi.org / 10.1007 / s13318-023-00822-y). This study did not include patients with psychiatric or neurological disorders. D'Souza et al. report "An Exploratory Study of the Dose-Related Safety, Tolerability, and Efficacy of Dimethyltryptamine (DMT) in Healthy Volunteers and with Major Depressive Disorder" (Neuropsychopharmacology (2022) 47:1854-1862). Seven patients with major depressive disorder received two doses of DMT hemifumarate (0.1 mg / kg, then 0.3 mg / kg) at least 48 hours apart. Participants received the DMT intravenously (i.e., bolus injection) over 30–60 seconds.

[0006] Goodwin et al. reported the results of a phase II clinical trial of psilocybin in adults with treatment-resistant depression (N. Engl. J. Med. (2022) 387:1637-1648). Patients received a single oral dose of psilocybin along with psychological support, with treatment sessions lasting 6-8 hours. 20% of patients receiving the 25 mg dose reported a sustained response after 12 weeks.

[0007] WO2022195489 discusses a method of using psychedelics, which involves an initial bolus injection followed by a lower maintenance dose, and WO2022031566 discusses the intravenous administration of DMT.

[0008] Timmermann et al. discuss the results of a clinical trial examining the effects of intravenous DMT in healthy individuals ( Translational Psychiatry (2023) 13:172, published online May 23, 2023).

[0009] Cybin has completed the first phase of a Phase 1 / 2a clinical trial evaluating its deuterated psilocybin compound (CYB003) in healthy participants with and without major depressive disorder (ClinicalTrials.gov Identifier: NCT05385783). In February 2023, Cybin announced that after a single oral dose of CYB003, the psychedelic effects were felt within approximately 15 minutes, with a mean duration of peak effects of approximately 2 hours. This data is based on an interim analysis of CYB003 in healthy volunteers (https: / / cybin.com / cyb003 / ).

[0010] In May 2023, Cybin announced that it was evaluating intravenous administration of its deuterated dimethyltryptamine compound (CYB004) in healthy volunteers. Part C of the Phase 1 CYB004-E trial is a crossover study design evaluating an IV bolus plus infusion regimen of CYB004 in up to two cohorts.

[0011] As interest in the potential uses of psychedelics, such as psilocybin and DMT, in psychiatry grows, so does the need for methods to administer these drugs in a safe and tolerable manner. Summary of the Invention

[0012] In a first aspect, the present invention provides a dosing regimen for administering a short-acting psychedelic agent to a patient for the treatment of a psychiatric or neurological disorder, the regimen comprising administering to the patient (preferably parenterally) a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin (also known as psilocin), deuterated analogues thereof, and pharmaceutically acceptable salts thereof; wherein the administration occurs no more than once in any one, two, three, six, nine, or twelve month period.

[0013] In a second aspect, the present invention provides a method of treating a psychiatric or neurological disorder in a patient, the method comprising administering to the patient (preferably parenterally) a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof, wherein the administration occurs no more than once in any one, two, three, six, nine, or twelve month period.

[0014] In a third aspect, the present invention provides a delivery device for use in treating a psychiatric or neurological disorder in a patient, the delivery device being configured to administer (preferably parenterally) to the patient a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof, wherein the administration occurs no more than once in any one, two, three, six, nine, or twelve month period.

[0015] In a fourth aspect, the present invention provides a parenteral formulation for use in treating a psychiatric or neurological disorder in a patient, said treatment comprising administering to the patient (preferably parenterally) a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof, wherein said administration occurs no more than once in any one, two, three, six, nine, or twelve month period.

[0016] In a fifth aspect, the present invention provides a kit comprising a parenteral formulation for use in treating a psychiatric or neurological disorder in a patient, the parenteral formulation comprising a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof, and further comprising instructions for administration of the parenteral formulation, preferably parenteral administration, indicating that the administration is to occur no more than once in any one, two, three, six, nine, or twelve month period.

[0017] In a sixth aspect, the present invention provides a parenteral formulation comprising a single effective parenteral dose of a short-acting psychedelic agent for use in treating a psychiatric or neurological disorder in a patient, said treatment comprising administering to the patient, preferably parenterally, a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof, wherein said administration occurs no more than once in any one, two, three, six, nine, or twelve month period.

[0018] In a seventh aspect, the present invention provides a parenteral formulation comprising a single effective parenteral dose of a short-acting psychedelic agent for use in treating a psychiatric or neurological disorder in a patient, said treatment comprising administering to the patient, preferably parenterally, a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof, wherein the administration occurs at most once per month, at most once every two months, at most once per three months, at most once per six months, at most once per nine months, or at most once per twelve months.

[0019] In an eighth aspect, the present invention provides a dosing regimen for administering a short-acting psychedelic agent to a patient for the treatment of a psychiatric or neurological disorder, the regimen comprising administering to the patient (preferably parenterally) a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof; wherein the administration occurs at most once per month, at most once every two months, at most once per three months, at most once per six months, at most once per nine months, or at most once per twelve months.

[0020] In a ninth aspect, the present invention provides a method of treating a psychiatric or neurological disorder in a patient, the method comprising administering to the patient (preferably parenterally) a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof, wherein the administration occurs at most once per month, at most once every two months, at most once per three months, at most once per six months, at most once per nine months, or at most once per twelve months.

[0021] In a tenth aspect, the present invention provides a delivery device for use in treating a psychiatric or neurological disorder in a patient, the delivery device configured to administer (preferably parenterally) to the patient a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof, wherein the administration occurs at most once per month, at most once every two months, at most once per three months, at most once per six months, at most once per nine months, or at most once per twelve months.

[0022] In an eleventh aspect, the present invention provides a kit comprising a parenteral formulation for use in treating a psychiatric or neurological disorder in a patient, the parenteral formulation comprising a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof, and further comprising instructions for administration of the parenteral formulation, preferably parenteral administration, instructing the administration to occur at most once per month, at most once every two months, at most once per three months, at most once per six months, at most once per nine months, or at most once per twelve months. [Brief explanation of the drawings]

[0023] [Figure 1]: Study design of NCT04673383, Part B. Figure 1 shows the clinical trial design for NCT04673383, Part B.

[0024] [Figure 2] Percentage of subjects who showed a 50% or greater reduction from baseline. Figure 2 shows the percentage of subjects in Group A (study drug) and Group P (placebo) who achieved a 50% or greater reduction in Montgomery-Asberg Depression Rating Scale (MADRS) scores compared to baseline assessment (weeks 1 and 2 post-dose).

[0025] [Figure 3] Percentage of subjects with MADRS scores of 10 or less. Figure 3 shows the percentage of subjects with a MADRS score of 10 or less for Group A (study drug) and Group P (placebo) (weeks 1 and 2 after administration).

[0026] [Figure 4] Mean MADRS score Figure 4 shows the mean MADRS scores for Group A (study drug) and Group P (placebo) at weeks 1 and 2 after administration.

[0027] [Figure 5] Sustained reduction in mean MADRS score Figure 5 shows the sustained reduction in mean MADRS scores at weeks 1, 2, 4, and 12 after treatment for Group A (study drug) and Group P (placebo).

[0028] [Figure 6] 50% or more reduction from baseline Figure 6 shows the percentage of subjects who achieved a 50% or greater reduction in MADRS scores compared to baseline assessment at weeks 1, 2, 4, and 12 after open-label administration for group PA (placebo, investigational drug) and group AA (investigational drug, investigational drug).

[0029] [Figure 7] MADRS score of 10 or less Figure 7 shows the percentage of subjects with MADRS scores of 10 or less at weeks 1, 2, 4, and 12 after open-label administration for group PA (placebo, investigational drug) and group AA (investigational drug, investigational drug).

[0030] definition Throughout this specification, one or more aspects of the present invention may be combined with one or more features described herein to define separate embodiments of the present invention.

[0031] In the detailed description, reference will be made to a number of terms, which shall be understood to have the meanings set forth below unless the context clearly indicates to the contrary.

[0032] The nomenclature used herein for the psychedelic agents used in the present invention is that commonly used in the art. The compounds described herein may also be referred to by nomenclature in accordance with the International Union of Pure and Applied Chemistry (IUPAC) rules for chemical compounds, specifically the "IUPAC Compendium of Chemical Terminology (Gold Book)" (see AD Jenkins et al., Pure & Appl. Chem., 1996, 68, 2287-2311). For the avoidance of doubt, in the event that the rules of the IUPAC organization conflict with a definition set forth herein, the definition set forth herein shall prevail.

[0033] N,N-Dimethyltryptamine is also known by the IUPAC name: 2-(1H-indol-3-yl)-N,N-dimethylethanamine. 5-Methoxy-N,N-dimethyltryptamine is also known by the IUPAC name: 2-(5-methoxy-1H-indol-3-yl)-N,N-dimethylethanamine. 4-Acetoxy-N,N-dimethyltryptamine is also known by the IUPAC name: [3-[2-(dimethylamino)ethyl]-1H-indol-4-yl]acetate. Psilocybin is also known by the IUPAC name: [3-[2-(dimethylamino)ethyl]-1H-indol-4-yl] dihydrogen phosphate. Psilocin is also known by the IUPAC name: 3-[2-(dimethylamino)ethyl]-1H-indol-4-ol.

[0034] As used herein, the term "deuterated analog" of a psychedelic agent refers to one or more hydrogen atoms in the structure of a psychedelic agent that have been replaced with a deuterium atom, where a deuterium atom is a hydrogen atom to which a neutron has been added. The deuterium substitution may be at one or more of the α and β positions, on a methyl group, on the indole ring, and in certain compounds, at a substituent on the indole ring, e.g., the methoxy group of 5-methoxy-N,N-dimethyltryptamine. In some embodiments, the deuteration may be at the methyl group, the α position, and optionally the β position. Preferably, the deuteration is at the α position.

[0035] When a compound described herein is designated or described as a deuterated analog, the compound is enriched with deuterium (above natural abundance) by an amount that depends on the proportion of deuterium available in the reagent from which the compound is derived. For example, the d6-dimethylamino moiety of a compound of Formula I can be represented by -NR 2 R 3When is -N(CD3)2, it is derived from dimethyl-d7-amine or dimethyl-d6-amine (commonly available as the HCl salt), which are available from commercial chemical suppliers with deuterium purities ranging from 98% to 99%. The resulting purity of deuterium in the resulting d6-dimethylamino substituent is 98% to 99%. This means that, as will be appreciated by those skilled in the art, not all compounds of Formula I (for example) will contain d6-dimethylamino substituents, and some may contain d0-d5 dimethylamino, but the average purity of deuterium will be about 98% to 99%.

[0036] In some embodiments, the psychedelic agent is substituted at the 5-position with methoxy, or at the 4-position with acetoxy or hydroxy, or with monohydrogen phosphate. The term "acetoxy" (often abbreviated as OAc) defines a monovalent group derived from acetic acid by removing a hydrogen atom from the OH moiety. The term "methoxy" (often abbreviated as OMe) defines a monovalent group derived from methanol by removing a hydrogen atom from the OH moiety. The term "hydroxy" (often abbreviated as OH) defines a monovalent group derived from water by removing a hydrogen atom from the HO moiety. The term "monohydrogen phosphate" defines a divalent group of formula HPO4 derived from phosphoric acid by removing protons from two of the three OH moieties, thus having the formula -OP(O)(OH)O - means a substituent of the formula:

[0037] When the 4-position of a dimethyltryptamine compound is substituted with a hydroxyl group, the psychedelic agent is referred to herein as psilocin. When the 4-position of a dimethyltryptamine compound is substituted with a monohydrogen phosphate, this reflects the fact that psilocybin (also known as [3-(2-dimethylaminoethyl)-1H-indol-4-yl]dihydrogen phosphate) in water generally has a monohydrogen phosphate at the 4-position, which is generally understood to be the predominant form due to the estimated pKa values ​​of the two terminal phosphate oxygen atoms of 1.3 and 6.5. Furthermore, it is understood that the monohydrogen phosphate-containing form of psilocybin exists as a zwitterion (i.e., an inner salt) in which the nitrogen atom of the dimethylamino moiety is protonated. Therefore, this form, and psilocybin, are considered salts of dimethyltryptamine compounds substituted with a monohydrogen phosphate at the 4-position.

[0038] For the avoidance of doubt, the 4- and 5-positions, and the α- and β-positions in psychedelics refer to the positions labeled in the structures below (substituents not shown). [ka]

[0039] As used herein, a dose or total dose of a psychedelic agent refers to the dose or total dose as the free base equivalent of the agent.

[0040] As used herein, the terms "parenteral administration" or "parenterally administering" refer to the administration of a dose of a psychedelic agent by a route other than oral administration, either single or multiple doses over a period of time. Parenteral administration is preferably essentially continuous, with the administration period being from about 5 to about 15 minutes. In other embodiments, parenteral administration may involve an initial bolus administration of the psychedelic agent, which is a single dose of the psychedelic agent administered rapidly, typically within about 30 to about 60 seconds, providing an early-onset breakthrough psychedelic experience, followed by essentially continuous administration over a period of about 5 to about 15 minutes. In other embodiments, parenteral administration may involve a bolus administration of the psychedelic agent, which is a single dose of the agent administered rapidly, typically within about 30 to about 60 seconds.

[0041] As used herein, the term "effective amount" refers to a dose sufficient to produce a psychedelic experience (i.e., a period during which the patient experiences one or more intense reactions or emotions, altered states of perception, visual or other sensory hallucinations, spiritual experiences, ego dissolution, and dissociation). Ego dissolution refers to a state in which the boundaries between the individual and the outside world disappear (dissolve). Dissociation refers to a state in which different parts of the brain experience a sense of disconnection, such as a split between mind and body.

[0042] The Mystical Experience Questionnaire (MEQ), specifically designed to address hallucinogen-induced experiences, allows researchers to understand the typically elusive subjective experiences associated with psychedelics. The MEQ consists of 30 questions, and participants are asked to answer each question according to their feelings, thoughts, and experiences during the session. Each item is rated on a scale of 0 to 5 (from 0 = not at all to 5 = highest (better than at any time in my life)). The minimum score is 0 and the maximum score is 150, with higher scores indicating greater mystical experience. The MEQ total score is calculated by averaging the responses to all items. In some embodiments, a "psychedelic experience" is an experience with a percentage score of at least 40% on the Mystical Experience Questionnaire (MEQ), e.g., 40% or more, 45% or more, 50% or more, 55% or more, or 60% or more on the MEQ.

[0043] "Breakthrough psychedelic experience" means an intense and immersive psychedelic experience in which nearly all connection with the real world is lost. In some embodiments, a breakthrough psychedelic experience is one that scores 50% or greater, 55% or greater, or 60% or greater on the MEQ.

[0044] Fast onset refers to a psychedelic experience that peaks less than two minutes after the start of psychedelic administration (e.g., as observed after bolus intravenous or inhalation administration).

[0045] The term "month" as used herein is defined as a period of 30 days, so one month is 30 days, two months is 60 days, three months is 90 days, six months is 180 days, nine months is 270 days, twelve months is 360 days, and so on.

[0046] As used herein, "administration is performed only once in any one-month period" means that there is an interval of at least 30 days between administrations. Similarly, as used herein, "administration is performed only once in any two-month period" means that there is an interval of at least 60 days between administrations, and so on.

[0047] "Doses are administered at most once a month" means that at least one month, or 30 days, elapses between doses. Similarly, "doses are administered at most once every two months" means that at least two months, or 60 days, elapses between doses, and so on.

[0048] As used herein, a reference to the singular form of a noun includes the plural form of that noun (and vice versa), unless the context requires otherwise.

[0049] Throughout this specification, the word "comprise" or variations such as "comprises" or "comprising" will be understood to mean the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of other elements, integers or steps, or other groups of elements, integers or steps. The term "comprising" includes within its scope the terms "consisting only of" or "consisting essentially only of."

[0050] The term "consisting only of" or variations thereof will be understood to mean including the stated elements, integers or steps, or groups of elements, integers or steps, and to the exclusion of other elements, integers or steps, or other groups of elements, integers or steps.

[0051] The term "consisting essentially of" or variations thereof is understood to mean including the recited elements, integers or steps, or group of elements, group of integers or group of steps, and that additional components may be present, but only so long as they do not materially affect the essential characteristics of the embodiment of the invention.

[0052] As used herein, the term "about," when modifying a numerical value or value, refers to a value within ±5% of the specified value. For the avoidance of doubt, when a numerical value or value is specified in the present specification without the term "about," the numerical value or value should be understood according to standard numerical rounding practices according to the number of decimal places. For example, an integer such as 6 is understood to include values ​​equal to or greater than 5.5 and less than 6.5. Similarly, a numerical value specified to one decimal place, such as 5.3, is understood to include values ​​equal to or greater than 5.25 and less than 5.35.

[0053] Where a range of values ​​is provided, the range is inclusive of the endpoints, e.g., the range 20 to 28, or 20-28, includes the values ​​20, 21, 22, 23, 24, 25, 26, 27, and 28, and the range 5 to 15, or 5-15, includes the values ​​5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15.

[0054] As used herein, the term "patient" preferably refers to a mammal. Typically, the mammal is a human, but may also refer to domestic mammals. This term does not include laboratory mammals.

[0055] As used herein, the term "in combination with psychotherapy" refers to the treatment of a psychiatric disorder by psychological means that is augmented by a dosing regimen, treatment method, delivery device, or parenteral formulation for use in the present invention.

[0056] The term "treatment" refers to the therapeutic treatment of a patient to slow or stop the rate of progression of a disorder (disease), or to improve or cure the disorder. Also included is prophylactic treatment of patients with a diagnosed psychiatric or neurological disorder. Such prophylactic treatment, also known as secondary prevention, aims to reduce the effects of the disorder and / or prevent the progression of the disorder through treatment according to the present invention.

[0057] As used herein, the term "improvement" refers to a clinically meaningful reduction in symptom severity over a period of time compared to a baseline assessment, or as assessed by patient-reported outcomes. Improvement may be assessed by patient-reported outcomes or healthcare professional-reported outcomes (such as structured patient interviews or questionnaires). The term "healthcare professional (clinician)" refers to a licensed and / or registered physician or healthcare professional, including therapists, psychiatrists, and psychologists.

[0058] Patient-reported or healthcare professional-reported outcomes may include assessment using a rating scale, including, but not limited to, the following: The Clinical Global Impression (CGI) scale is an observer-rated scale consisting of one or more of three different measures: Severity of Illness (CGI-S), Global Improvement (CGI-I), and Efficacy Index (CGI-E); the Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item diagnostic questionnaire; the 17-item Hamilton Depression Rating Scale (HAMD17); the Beck Depression Inventory-II; the Ruminative Response Scale (RRS-22) is a self-report measure consisting of 22 items and three factors (depression, brooding, and reflection); the Beck Anxiety Inventory (BAI); and the Hamilton Anxiety Scale (HAM-A). Anxiety Scale; State-Trait Anxiety Inventory (STAI); General Anxiety Disorder-7 Assessment (GAD-7); Clinician-Administered Posttraumatic Stress Disorder Scale (CAPS); Yale-Brown Obsessive-Compulsive Scale;a suicidality rating scale, such as the Beck Scale for Suicidal Ideation (BSS), the Columbia-Suicide Severity Rating Scale (C-SSRS), or the suicidal thoughts item of the MADRS for suicidal ideation or the Clinical Global Impression of Severity of Suicidality-Revised (CGI-SS-R) scale. Patient-reported outcomes may include the Beck Depression Inventory (BDI-II); the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF), a 16-item self-administered questionnaire; the EQ-5D-5L descriptive system and EQ VAS; the Patient Global Impression of Severity scale (PGI-S); and / or the Patient Global Impression of Improvement scale (PGI-I). Combinations of rating scales may also be used. Healthcare professional or patient-reported outcomes may include weight gain in anorexia nervosa; frequency of binge-purging episodes in bulimia nervosa; or frequency of binge-eating episodes in binge eating disorder.

[0059] Clinically meaningful reductions in symptom severity are measured according to rating scales or other healthcare professional- or patient-reported outcomes, including:

[0060] On the Clinical Global Impression Scale (CGI), response scores of 0, 1, 2, and 3 typically indicate improvement, with 0, 1, and 2 being desirable.

[0061] Typically, for rating scales such as the Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HAMD), Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), Beck Suicidal Ideation Scale (BSS), Columbia-Suicide Severity Rating Scale (C-SSRS), Hamilton Anxiety Rating Scale (HAM-A), State-Trait Anxiety Inventory (STAI-T), Yale-Brown Obsessions and Compulsions Scale, Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF), EQ-5D-5L Descriptive System and EQ VAS, and Clinician-Administered Posttraumatic Stress Disorder Scale (CAPS), a score reduction of 15% or more compared to baseline is considered an improvement, with 20%, 30%, and preferably 50% reductions considered appropriate. A reduction of less than 15% is not considered clinically meaningful.

[0062] Alternatively, a clinically meaningful reduction in symptom severity may be assessed by a point reduction on a rating scale, such as a reduction of -6 or more points on the MADRS scale, a reduction of 4 or more points on the HAMD-17 scale, or a reduction of 12 or more points on the Beck Depression Inventory-II (BDI-II). Alternatively, a reduction in severity category (e.g., from severe to moderate) may indicate improvement.

[0063] On the Columbia-Suicide Severity Rating Scale (C-SSRS), improvement is typically indicated by a decrease in the number of questions answered "yes" or by a reduction in severity category, for example, from very severe to severe or from severe to moderately severe.

[0064] On the Patient Global Impression of Severity Scale (PGI-S), improvement is typically indicated by a reduction in the patient-rated severity rating, for example, from a rating of 6 (severe) to 4 (moderate).

[0065] On the Patient Global Impression of Improvement (PGI-I) scale, a rating of 3 (slight improvement) or less typically indicates improvement, with a score of 2 (marked improvement) or less being desirable. The PGI-I scale is not assessed relative to baseline assessments, but only post-treatment.

[0066] As used herein, the term "remission" refers to a reduction in the symptoms of a psychiatric or neurological disorder to a level that indicates mild symptoms or that the patient is within the healthy range (i.e., the patient is not experiencing symptoms that indicate a clinical condition). For depressive disorders, remission is usually considered to be a score of 13 or less (preferably 10 or less) on the MADRS rating scale; or 7 or less on the HAMD-17 rating scale; or 19 or less on the Beck Depression Inventory II; or 15 or less on the Beck Anxiety Inventory; or 17 or less on the Hamilton Anxiety Rating Scale; or 15 or less on the Yale-Brown Obsession-Compulsion Scale; or 3 or less on the Patient Global Impression of Severity (PGI-S). Remission is usually considered to be a patient who answers "no" to each question on the Columbia-Suicide Severity Rating Scale (C-SSRS) or scores 10 or less (moderate), preferably 6 or less.

[0067] As used herein, the term "short-acting psychedelic agent" or "short-acting psychedelic" refers to a psychedelic agent that, when parenterally administered, induces a psychedelic experience of a duration of about 3 hours or less, about 2 hours or less, or about 1 hour or less following parenteral administration. Preferably, the duration of the psychedelic experience is about 3 hours or less, or about 2 hours or less, when the psychedelic agent is deuterated. Preferably, the duration of the psychedelic experience is about 2 hours or less, about 1 hour or less, more preferably about 45 minutes or less, and even more preferably about 30 minutes or less, when the psychedelic agent is not deuterated.

[0068] As used herein, "neurological disorder (neurological disease)" refers to a disorder that may be associated with dysfunction in the brain or nervous system and may result in physical and / or psychological symptoms. As used herein, the term "mental disorder (mental illness)" is characterized by a clinically significant impairment in an individual's cognition, emotional regulation, or behavior and is associated with current distress (e.g., painful symptoms) or disability (i.e., impairment in one or more important areas of functioning), or a significantly increased risk of suffering from death, pain, disability, or significant loss of freedom.

[0069] The diagnostic criteria for the psychiatric or neurological disorders referred to herein are set out in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).

[0070] As used herein, the term "psychedelic assisted psychotherapy" is defined as any psychotherapeutic practice provided in conjunction with the administration of a psychedelic therapeutic formulation (e.g., including any dose defined herein). The term "psychedelic assisted psychotherapy" includes assisted therapies that provide patient preparation, psychological support, and therapeutic integration before, during, and after the administration of psychedelics.

[0071] As used herein, the term "obsessive-compulsive disorder (OCD)" is defined by the presence of either obsessions or compulsions (usually both). The symptoms can cause significant functional impairment and / or distress. Obsessions are defined as unwanted, intrusive thoughts, images, or urges that repeatedly invade a person's mind. Compulsions are repetitive behaviors or mental acts that a person feels compelled to perform. OCD typically manifests as one or more obsessions that lead to compulsions. For example, an obsession with germs may lead to a compulsion to clean, or an obsession with food may lead to a compulsion to overeat, undereat, or vomit after eating (i.e., a food obsession may manifest as an eating disorder). Compulsions can be overt and observable, such as checking to see if the door is locked, or covert and unobservable, such as repeating a particular phrase in one's mind. To assess OCD, the Yale-Brown Obsessions and Compulsions Scale (Y-BOCS) may be used.

[0072] As used herein, the term "eating disorder" is defined by severe and persistent disturbances in eating behavior and associated distressing thoughts and feelings. The term "eating disorder" includes anorexia nervosa and bulimia nervosa, binge eating disorder, avoidant-restrictive food intake disorder, other specified eating behavior or eating disorders, pica, and rumination disorder. Evaluation of eating disorders may be performed by assessing weight gain, frequency of binge-purge episodes, and / or frequency of binge eating episodes.

[0073] Eating disorders often co-occur with anxiety disorders and obsessive-compulsive disorders. Neziroglu and Sandler distinguish between OCD and eating disorders: "Patients with eating disorders are primarily concerned about their physical appearance and, as a result, alter their eating patterns in an effort to lose weight. Patients with OCD may restrict their eating for reasons entirely different from body image concerns" (https: / / iocdf.org / expert-opinions / expert-opinion-eating-disorders-and-ocd).

[0074] The term "eating disorders" includes anorexia nervosa, bulimia, and binge eating disorder (BED). Symptoms of anorexia nervosa include eating too little and / or exercising too much in order to lose as much weight as possible. Symptoms of bulimia include eating a lot of food in a very short period of time (i.e., binge eating) and then intentionally making oneself sick, using laxatives, eating too little, and / or exercising too much to prevent weight gain. Symptoms of BED include regularly eating large amounts of food until one is uncomfortably full and feeling upset or guilty as a result.

[0075] As used herein, the term "depressive disorder" includes major depressive disorder, persistent depressive disorder, bipolar disorder, bipolar depression, and end-stage depression.

[0076] As used herein, the term "major depressive disorder" (also referred to as MDD, major depression, or clinical depression) is defined as the presence of five or more of the following symptoms most of the day, nearly every day, for a period of two weeks or more (also referred to herein as a "major depressive episode"): Depressed mood, such as feeling sad, empty, or tearful (in children and teenagers, depressed mood can appear as constant irritability); ·Significantly decreased interest in or pleasure from all or most activities; · Significant weight loss, weight gain, or decreased or increased appetite when not dieting (in children, failure to gain weight as expected); Insomnia or increased need to sleep; · Restlessness or slowness of movement observable by others; Fatigue or loss of energy; · Feelings of worthlessness or excessive or inappropriate guilt; · Poor decision-making or difficulty thinking or concentrating; Recurrent thoughts of death or suicide, or suicide attempts At least one of the symptoms must be either depressed mood or loss of interest or pleasure.

[0077] Persistent depressive disorder, also known as dysthymia, is defined as a patient who exhibits two characteristics: A: Depressed mood most of the time, almost every day, for at least 2 years. Children and adolescents may have an irritable mood that has lasted for at least 1 year. B: When you are depressed, you experience at least two of the following symptoms: Overeating or loss of appetite Excessive sleepiness or sleep disorders Fatigue, loss of energy Low self-esteem · Poor concentration or decision-making ability

[0078] As used herein, the term "treatment-resistant major depressive disorder" refers to MDD that does not respond adequately to treatment with standard therapies.

[0079] As used herein, "bipolar disorder," also known as manic depression, refers to a disorder characterized by abnormal changes in mood, energy, activity level, and ability to carry out daily tasks.

[0080] There are two subcategories of bipolar disorder, both of which involve distinct changes in mood, energy, and activity levels. These moods range from periods of very upbeat, elated, and energetic behavior (known as manic episodes and further defined below) to periods of very sad, down, or hopeless moods (known as depressive episodes). Less severe manic states are called hypomanic episodes.

[0081] Bipolar I disorder: Defined by a manic episode lasting at least 7 days or by manic symptoms severe enough to require immediate hospital treatment. Depressive episodes usually occur as well, usually lasting at least 2 weeks. Mixed depressive episodes (in which both depressive and manic symptoms are present) are also possible.

[0082] Bipolar II disorder: Defined by a pattern of depressive and hypomanic episodes, but without the full-blown manic episodes described above.

[0083] As used herein, "bipolar depression" is defined as an individual experiencing depressive symptoms who has previously experienced or is experiencing concurrent manic episodes but who does not meet the clinical criteria for bipolar disorder.

[0084] Depressive disorders are typically assessed using a rating scale selected from the following: Clinical Global Impression (CGI), Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HAMD-17), Beck Depression Inventory-II, Beck Anxiety Inventory (BAI), suicidality rating scales such as the Beck Scale for Suicidal Ideation (BSS), the Columbia-Suicide Severity Rating Scale (C-SSRS), or the MADRS suicidal ideation item, the Clinical Global Impression of Suicidality Severity Revised (CGI-SS-R), or the Columbia-Suicide Severity Rating Scale (C-SSRS), and combinations of these scales. Depressive disorders may also be assessed using patient-reported outcomes selected from the Beck Depression Inventory-II (BDI-II), the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF), the EQ-5D-5L short answer system and EQ VAS, the Patient Global Impression of Severity Scale (PGI-S), and combinations of these outcome measures.

[0085] Depressive disorders are preferably assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS), Beck Depression Questionnaire-II, Beck Scale for Suicidal Ideation (BSS), Montgomery-Asberg Depression Rating Scale (MADRS), and / or the 17-item Hamilton Depression Rating Scale (HAMD-17).

[0086] The term "anxiety disorder (anxiety disorder)" as used herein includes generalized anxiety disorder, phobia, panic disorder, social anxiety disorder (social phobia) and post-traumatic stress disorder.Anxiety disorder is usually assessed using a rating scale selected from the Beck Anxiety Inventory (BAI), Hamilton Anxiety Scale (HAM-A), State-Trait Anxiety Inventory (STAI-T), Generalized Anxiety Disorder Assessment (GAD-7), and combinations of these scales.Anxiety disorder can also be assessed using patient-reported outcomes, as described above.

[0087] As used in this document, "generalized anxiety disorder" (GAD) refers to a chronic disorder characterized by long-lasting anxiety that is not focused on any particular object or situation. People with GAD experience persistent, nonspecific fear and worry and become excessively concerned with everyday things. GAD is characterized by chronic excessive worry accompanied by three or more of the following symptoms: restlessness, fatigue, difficulty concentrating, irritability, muscle tension, and sleep disturbance.

[0088] A "phobia" is defined as a persistent fear of an object or situation, which the sufferer goes to great lengths to avoid (usually to an extent disproportionate to the actual risk). If the feared object or situation cannot be completely avoided, the sufferer endures it with significant distress and causes significant impairment in social or occupational functioning.

[0089] A patient suffering from "panic disorder" is defined as one who experiences one or more brief attacks of intense fear and anxiety (also called panic attacks), often characterized by trembling, shaking, confusion, dizziness, nausea, and / or difficulty breathing. A panic attack is defined as a sudden feeling of fear or discomfort that peaks in less than 10 minutes.

[0090] "Social anxiety disorder" is defined as an intense fear and avoidance of negative public opinion, public embarrassment, humiliation, or social interactions. Social anxiety often manifests with specific physical symptoms, including blushing, sweating, and difficulty speaking.

[0091] Post-traumatic stress disorder (PTSD) is an anxiety disorder resulting from a traumatic experience. Post-traumatic stress can result from extreme situations such as combat, natural disasters, rape, hostage situations, child abuse, bullying, or serious accidents. Common symptoms include hypervigilance, flashbacks, avoidance behaviors, anxiety, anger, and depression.

[0092] The Clinician Administered Posttraumatic Stress Disorder Scale (CAPS) can be used to assess symptoms of PTSD.

[0093] As used herein, the term "postpartum depression" (PPD) refers to a form of depression experienced by either parent of a newborn. Symptoms typically begin within four weeks of birth and often include extreme sadness, fatigue, anxiety, loss of interest or pleasure in hobbies and activities, irritability, and changes in sleeping or eating patterns.

[0094] As used herein, the term "substance abuse" means a patterned use of a drug in which the user takes the substance in amounts or in ways that are harmful to themselves or others.

[0095] As used herein, the term "gambling disorder" refers to persistent and recurrent problematic gambling behavior that results in clinically significant impairment or distress. This disorder is similar to substance abuse.

[0096] As used herein, the term "avolition disorder" refers to a disorder whose symptoms include a decreased motivation to initiate and carry out voluntary purposeful activity.

[0097] As used herein, the term "breakthrough psychedelic experience" refers to an immersive and intense experience in which nearly all connection to the real world is lost.

[0098] As used herein, a "slow onset breakthrough psychedelic experience" refers to a breakthrough psychedelic experience that peaks at least about 2 minutes, preferably at least about 5 minutes, and more preferably at least about 10 minutes after parenteral administration begins. The peak may occur at different times depending on the method of administration. For example, with intravenous administration, the psychedelic experience may peak at least about 5 minutes, or at least about 10 minutes after administration begins, while with intramuscular administration, the psychedelic experience may peak at least about 20 minutes, or at least about 25 minutes, or at least about 30 minutes after administration begins. DETAILED DESCRIPTION

[0099] The dosing regimens, methods of treatment, delivery devices, parenteral formulations, or kits of the present invention are based on the surprising discovery that significant relief of symptoms of psychiatric and neurological disorders, such as major depressive disorder, can be achieved by administering a single effective dose of a short-acting psychedelic (such as N,N-dimethyltryptamine and deuterated N,N-dimethyltryptamine) to a patient, with the response demonstrated to be sustained even three months after administration.

[0100] Accordingly, a first aspect of the present invention provides, as embodiment 1, a dosing regimen for administering a short-acting psychedelic agent to a patient for the treatment of a psychiatric or neurological disorder, the regimen comprising administering to the patient (preferably parenterally) a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof, wherein the administration occurs no more than once in any one, two, three, six, nine, or twelve month period.

[0101] A second aspect of the present invention provides, as embodiment 2, a method of treating a psychiatric or neurological disorder in a patient, the method comprising administering to the patient (preferably parenterally) a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof, wherein the administration occurs no more than once in any one, two, three, six, nine, or twelve month period.

[0102] A third aspect of the present invention provides, as embodiment 3, a delivery device for use in treating a psychiatric or neurological disorder in a patient, the delivery device configured to administer (preferably parenterally) to the patient a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof, wherein the administration occurs no more than once in any one, two, three, six, nine, or twelve month period.

[0103] A fourth aspect of the present invention provides, as embodiment 4, a parenteral formulation for use in treating a psychiatric or neurological disorder in a patient, said treatment comprising administering to the patient (preferably parenterally) a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof, wherein said administration occurs no more than once in any one, two, three, six, nine, or twelve month period.

[0104] A fifth aspect of the present invention provides, as embodiment 5, a kit comprising a parenteral formulation for use in treating a psychiatric or neurological disorder in a patient, the parenteral formulation comprising a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof, and further comprising instructions for administering the parenteral formulation, preferably parenterally, the instructions indicating that the administration is to occur no more than once in any one, two, three, six, nine, or twelve month period.

[0105] A sixth aspect of the present invention provides, as embodiment 6, a parenteral formulation comprising a single effective parenteral dose of a short-acting psychedelic agent for use in treating a psychiatric or neurological disorder in a patient, said treatment comprising administering to the patient (preferably parenterally) a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof, wherein the administration occurs no more than once in any one, two, three, six, nine, or twelve month period.

[0106] In embodiment 7, the present invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit according to any preceding embodiment, wherein the administration is (i) only once in any one-month, two-month, or three-month period, or (ii) only once in any three-month period. Preferably, the administration is only once in any one-month period.

[0107] In embodiment 8, the present invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit of any preceding embodiment, wherein the administration is performed only once in any six-month period or any nine-month period.

[0108] In embodiment 9, the invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit of any preceding embodiment, wherein the administration is performed only once in any twelve-month period.

[0109] A seventh aspect of the present invention provides, as embodiment 10, a parenteral formulation comprising a single effective parenteral dose of a short-acting psychedelic agent for use in treating a psychiatric or neurological disorder in a patient, said treatment comprising administering to the patient (preferably parenterally) a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof, wherein the administration occurs at most once per month, at most once every two months, at most once per three months, at most once per six months, at most once per nine months, or at most once per twelve months.

[0110] An eighth aspect of the present invention provides, as embodiment 11, a dosing regimen for administering a short-acting psychedelic agent to a patient for the treatment of a psychiatric or neurological disorder, the regimen comprising administering to the patient (preferably parenterally) a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof; wherein the administration occurs at most once per month, at most once every two months, at most once per three months, at most once per six months, at most once per nine months, or at most once per twelve months.

[0111] A ninth aspect of the present invention provides, as embodiment 12, a method of treating a psychiatric or neurological disorder in a patient, the method comprising administering to the patient (preferably parenterally) a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof, wherein the administration occurs at most once per month, at most once every two months, at most once per three months, at most once per six months, at most once per nine months, or at most once per twelve months.

[0112] A tenth aspect of the present invention provides, as embodiment 13, a delivery device for use in treating a psychiatric or neurological disorder in a patient, the delivery device configured to administer (preferably parenterally) to the patient a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof, wherein the administration occurs at most once per month, at most once every two months, at most once per three months, at most once per six months, at most once per nine months, or at most once per twelve months.

[0113] An eleventh aspect of the present invention provides, as embodiment 14, a kit comprising a parenteral formulation for use in treating a psychiatric or neurological disorder in a patient, the parenteral formulation comprising a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogues thereof, and pharmaceutically acceptable salts thereof, and further comprising instructions for administering the parenteral formulation (preferably parenterally), the instructions indicating that the administration is to occur at most once per month, at most once every two months, at most once per three months, at most once per six months, at most once per nine months, or at most once per twelve months.

[0114] In embodiment 15, the present invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit according to any one of embodiments 10 to 14, wherein the administration is (i) at most once per month, or at most once every two months, or at most once per three months, or (ii) at most once per three months. Preferably, the administration is at most once per three months.

[0115] In embodiment 16, the present invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit of any one of embodiments 10 to 15, wherein the administration is performed at most once every six months or at most once every nine months.

[0116] In embodiment 17, the present invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit of any one of embodiments 10 to 16, wherein the administration is performed at most once every 12 months.

[0117] In embodiment 18, the present invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit of any preceding embodiment, further comprising parenterally administering a second single effective dose of a short-acting psychedelic agent within a period of three to twelve months after administration of the first single effective dose.

[0118] In embodiment 19, the present invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit of embodiment 18, further comprising parenterally administering a second single effective dose of a short-acting psychedelic agent within a period of three to nine months after administration of the first single effective dose.

[0119] In embodiment 20, the present invention provides an administration regimen, method of treatment, delivery device, parenteral formulation, or kit according to embodiment 18 or embodiment 19, wherein the administration of the first single effective dose and the second single effective dose is performed only once in any twelve-month period.

[0120] In embodiment 21, the present invention provides an administration regimen, method of treatment, delivery device, parenteral formulation, or kit of embodiment 18 or embodiment 19, wherein the administration of both the first single effective dose and the second single effective dose is performed at most once every twelve months.

[0121] In embodiment 22, the invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit of any preceding embodiment, further comprising the steps and / or instructions of: (i) baseline assessment of patients using rating scales and / or healthcare professional-reported outcomes and / or patient-reported outcomes; (ii) parenteral administration to the patient of a single effective dose of a short-acting psychedelic agent, wherein said psychedelic agent is selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogs thereof, and pharmaceutically acceptable salts thereof; and (iii) Post-administration patient evaluation.

[0122] In embodiment 23, the present invention provides the administration regimen, method of treatment, delivery device, parenteral formulation, or kit of any one of embodiments 1 to 22, further comprising the steps of: (i) A baseline assessment of the patient using a rating scale and / or healthcare professional-reported outcomes and / or patient-reported outcomes prior to parenteral administration to the patient; and (ii) Post-administration patient evaluation following parenteral administration to the patient.

[0123] In embodiment 24, the present invention provides a dosing regimen, a method of treatment, a delivery device, a parenteral formulation, or a kit of embodiment 22 or embodiment 23, wherein the baseline assessment comprises: or by a rating scale selected from the following: Clinical Global Impression (CGI); Montgomery-Asberg Depression Rating Scale (MADRS); Hamilton Depression Rating Scale (HAMD17); Beck Depression Inventory-II; Beck Anxiety Inventory (BAI); Hamilton Anxiety Scale-A (HAM-A); State-Trait Anxiety Inventory (STAI); Clinician-Administered Posttraumatic Stress Disorder Scale (CAPS); Yale-Brown Obsession-Compulsion Scale; Beck Scale for Suicidal Ideation (BSS), Columbia-Suicide Severity Rating Scale (C-SSRS); MADRS Suicidal Thought Item for Suicidal Ideation; Clinical Global Impression-Revised (CGI-SS-R) Scale of Suicidality Severity; Beck Depression Inventory (BDI-II); Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF); EQ-5D-5L Short Answer System and EQ VAS; Patient Global Impression of Severity (PGI-S); and / or Patient Global Impression of Improvement (PGI-I); and combinations thereof; or This is done by assessing body weight, frequency of binge-purging episodes, and / or frequency of binge eating episodes.

[0124] In embodiment 25, the present invention provides the dosing regimen, method of treatment, delivery device, parenteral formulation, or kit of any one of embodiments 22 to 24, wherein the post-administration assessment comprises: The assessment may be performed using a scale selected from the following: Clinical Global Impression (CGI); Montgomery-Asberg Depression Rating Scale (MADRS); Hamilton Depression Rating Scale (HAMD17); Beck Depression Inventory II; Beck Anxiety Inventory (BAI); Hamilton Anxiety Scale (HAM-A); State-Trait Anxiety Inventory (STAI); Generalized Anxiety Disorder Assessment (GAD-7); Clinician-Administered Posttraumatic Stress Disorder Scale (CAPS); Yale-Brown Obsession-Compulsion Scale; Beck Scale of Suicidal Ideation (BSS); Columbia-Suicide Severity Rating Scale (C-SSRS); MADRS Suicidal Thought Item for Suicidal Ideation; Clinical Global Impression-Revised (CGI-SS-R) Scale of Suicidality Severity; Beck Depression Inventory (BDI-II); Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF); EQ-5D-5L Descriptive System and EQ VAS; Patient Global Impression of Severity (PGI-S); Clinical Global Improvement (CGI-I); Patient Global Impression of Improvement (PGI-I); and combinations thereof; or This is done by assessing body weight, frequency of binge-purging episodes, and / or frequency of binge eating episodes.

[0125] In embodiment 26, the present invention provides an administration regimen, a method of treatment, a delivery device, a parenteral formulation, or a kit according to any one of embodiments 22 to 25, wherein the psychiatric or neurological disorder is a depressive disorder, and wherein the baseline and post-administration assessments are performed using a depression rating scale selected from the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Rating Scale (HAMD17), the Beck Depression Inventory-II, and combinations thereof.

[0126] In embodiment 27, the present invention provides a dosing regimen, a method of treatment, a delivery device, a parenteral formulation, or a kit of any preceding embodiment, wherein the parenteral administration comprises: The patient is parenterally administered a dose of the psychedelic agent over an administration period of about 5 minutes to about 15 minutes. Here, parenteral administration is essentially (substantially) continuous. As used herein, "essentially continuous" means that there is no substantial interruption in administration. Optionally, parenteral administration is continuous.

[0127] In embodiment 28, the present invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit of any preceding embodiment, wherein the parenteral administration is selected from the group consisting of intravenous administration, intramuscular administration, subcutaneous administration, intranasal administration, transmucosal administration, sublingual administration, rectal administration, transdermal administration, and inhalation.

[0128] In embodiment 29, the present invention provides a dosing regimen, a method of treatment, a delivery device, a parenteral formulation, or a kit of any preceding embodiment, wherein the parenteral administration is by intravenous infusion, preferably using a syringe pump for intravenous administration.

[0129] In embodiment 30, the present invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit of any preceding embodiment, wherein parenteral administration is by biphasic intravenous infusion.

[0130] In embodiment 31, the present invention provides a dosing regimen, a method of treatment, a delivery device, a parenteral formulation, or a kit according to any one of embodiments 1 to 29, wherein parenteral administration is by monophasic intravenous infusion.

[0131] In embodiment 32, the present invention provides an administration regimen, a method of treatment, a delivery device, a parenteral formulation, or a kit according to any one of embodiments 27 to 31, wherein the administration period is from about 8 minutes to about 12 minutes.

[0132] In embodiment 33, the present invention provides an administration regimen, a method of treatment, a delivery device, a parenteral formulation, or a kit according to any one of embodiments 27 to 31, wherein the administration period is about 9 minutes to about 11 minutes, or about 10 minutes.

[0133] As embodiment 34, the present invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit of any preceding embodiment, wherein the single effective dose of the psychedelic agent is selected from the group consisting of: about 20 mg to about 70 mg of N,N-dimethyltryptamine, a deuterated analog thereof, or a pharmaceutically acceptable salt thereof; about 15 mg to about 30 mg of N,N-dimethyltryptamine, a deuterated analog thereof, or a pharmaceutically acceptable salt thereof; about 10 mg to about 20 mg of N,N-dimethyltryptamine, a deuterated analog thereof, or a pharmaceutically acceptable salt thereof; about 5 mg to about 15 mg of N,N-dimethyltryptamine, a deuterated analog thereof, or a pharmaceutically acceptable salt thereof; About 10 to about 30 mg of 5-methoxy-N,N-dimethyltryptamine, its deuterated analog, or a pharmaceutically acceptable salt thereof. about 1 mg to about 5 mg of psilocybin, a deuterated analog thereof, or a pharmaceutically acceptable salt thereof; about 3 mg to about 15 mg of 4-acetoxy-N,N-dimethyltryptamine, its deuterated analog, or a pharmaceutically acceptable salt thereof; and About 1 mg to about 5 mg, or about 3 mg to about 25 mg of psilocin, its deuterated analog, or a pharmaceutically acceptable salt thereof.

[0134] In embodiment 35, the invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit as described in any preceding embodiment, comprising parenteral administration of a total dose of about 20 mg to about 29 mg of N,N-dimethyltryptamine, a deuterated analogue thereof, or a pharmaceutically acceptable salt thereof.

[0135] In embodiment 36, the invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit as described in any preceding embodiment, comprising parenteral administration of N,N-dimethyltryptamine, its deuterated analogue, or a pharmaceutically acceptable salt thereof in a total dose of about 20 mg to about 23 mg, or about 26 mg to about 29 mg.

[0136]

[0037] In embodiment 37, the present invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit of any preceding embodiment, wherein the psychedelic agent is N,N-dimethyltryptamine, a deuterated analog thereof, or a pharmaceutically acceptable salt thereof, and the total dose is about 7 mg to about 10 mg.

[0137] In embodiment 38, the present invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit according to embodiment 34, wherein the administration is by biphasic intravenous infusion, the psychedelic agent is N,N-dimethyltryptamine, a deuterated analogue thereof, or a pharmaceutically acceptable salt thereof, and the total dose is about 20 mg to about 23 mg, or about 10 mg to about 20 mg.

[0138] In embodiment 39, the present invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit according to embodiment 35, wherein the administration is by monophasic intravenous infusion, the psychedelic agent is N,N-dimethyltryptamine, a deuterated analog thereof, or a pharmaceutically acceptable salt thereof, and the total dose is about 26 to about 29 mg.

[0139] In embodiment 40, the present invention provides an administration regimen, a method of treatment, a delivery device, a parenteral formulation, or a kit according to any one of embodiments 1 to 29 and 32 to 37, wherein the administration is by intramuscular administration.

[0140] In embodiment 41, the present invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit of any preceding embodiment, wherein the psychedelic agent is N,N-dimethyltryptamine, a deuterated analog thereof, or a pharmaceutically acceptable salt thereof, and the total dose is about 20 mg to about 70 mg, preferably about 50 mg to about 70 mg.

[0141] In embodiment 42, the present invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit according to any one of embodiments 1 to 34, and 40, comprising parenteral administration of a total dose of about 1.5 to about 3 mg of psilocybin, a deuterated analogue thereof, or a pharmaceutically acceptable salt thereof, or about 1.5 to about 3 mg of psilocin, a deuterated analogue thereof, or a pharmaceutically acceptable salt thereof.

[0142] In embodiment 43, the present invention provides a dosing regimen, a method of treatment, a delivery device, a parenteral formulation, or a kit according to any preceding embodiment, wherein the psychedelic agent is a compound of Formula I or a pharmaceutically acceptable salt thereof: [ka] During the ceremony, Ra is selected from H, D, —OH, —OAc, and —PO3OH, and Rb is H or D; or Ra is H or D and Rb is selected from H, D, -OMe, and -OCD3; R 2 and R 3 are each independently -C(H z ) selected from 3; and Each H x , H y and H z are each independently selected from protium or deuterium.

[0143] In embodiment 44, the present invention provides a compound comprising R 2 and R 3are each independently selected from —C(H)3 and —C(D)3.

[0144] In embodiment 45, the present invention provides a compound comprising R 2 and R 3 are both -C(H)3 or R 2 and R 3 are both -C(D)3 or R 2 is -C(H)3 and R 3 is -C(D)3.

[0145] In embodiment 46, the present invention provides a method for producing a hydroxyl group comprising: x is H or each H x is D or one H x is H and another H x The dosing regimen, method of treatment, delivery device, parenteral formulation or kit of any one of embodiments 43-45, wherein

[0146] In embodiment 47, the present invention provides a method for producing a hydroxyl group comprising: y is H or each H y is D or one H y is H and another H y

[0049] The dosing regimen, method of treatment, delivery device, parenteral formulation, or kit according to any one of embodiments 43 to 46, wherein each H is D. y is D.

[0147] In embodiment 48, the present invention provides a method for producing a hydroxyl group comprising: x , H y , and H z The dosing regimen, method of treatment, delivery device, parenteral formulation, or kit of any one of embodiments 43-47 and 34, wherein is deuterium.

[0148] In embodiment 49, the present invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit according to any one of embodiments 43 to 48, wherein the psychedelic agent is selected from the group consisting of the following compounds, or pharmaceutically acceptable salts thereof: [ka]

[0149] In embodiment 50, the present invention provides the dosing regimen, method of treatment, delivery device, parenteral formulation, or kit of any one of embodiments 43 to 48, wherein the psychedelic agent is selected from the group consisting of the following compounds or pharmaceutically acceptable salts thereof, and Ra and Rb are as defined in embodiment 43: [ka]

[0150] In embodiment 51, the present invention provides an administration regimen, a method of treatment, a delivery device, a parenteral formulation, or a kit according to any one of embodiments 43 to 48 and 49 to 50, wherein Ra is H or Ra is D.

[0151] In embodiment 52, the present invention provides the dosing regimen, method of treatment, delivery device, parenteral formulation, or kit of any one of embodiments 43-48 and 49-50, wherein Rb is H or Rb is D.

[0152] In embodiment 53, the present invention provides an administration regimen, method of treatment, delivery device, parenteral formulation, or kit according to any one of embodiments 1 to 39 and 41 to 52, wherein parenteral administration comprises intravenous infusion using one or two syringe pumps.

[0153] In embodiment 54, the present invention provides an administration regimen, a method of treatment, a delivery device, a parenteral formulation, or a kit according to any preceding embodiment, wherein the psychiatric or neurological disorder is selected from the group consisting of (i) obsessive-compulsive disorder, (ii) depressive disorder, (iii) anxiety disorder, (iv) substance abuse and gambling disorder, and (v) anorexia disorder. Typically, the disorder is selected from the group consisting of major depressive disorder, treatment-resistant major depressive disorder, postpartum depression, obsessive-compulsive disorder, and eating disorders (such as compulsive eating disorder). Preferably, the psychiatric or neurological disorder is selected from the group consisting of depressive disorder and anxiety disorder.

[0154] In embodiment 55, the invention provides the dosing regimen, method of treatment, delivery device, parenteral formulation, or kit of any preceding embodiment, wherein the psychiatric or neurological disorder is a depressive disorder or an anxiety disorder.

[0155] In embodiment 56, the invention provides the dosing regimen, method of treatment, delivery device, parenteral formulation, or kit of any preceding embodiment, wherein the psychiatric or neurological disorder is major depressive disorder.

[0156] In embodiment 57, the present invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit as described in any preceding embodiment, wherein the duration of the psychedelic experience is about 3 hours or less, or about 2 hours or less, or about 1 hour or less.

[0157] As embodiment 58, the present invention provides a dosing regimen, method of treatment, delivery device, or parenteral formulation of any preceding embodiment, wherein the duration of the psychedelic experience is: about 15 minutes to about 30 minutes, or about 30 minutes to about 90 minutes, when the psychedelic agent is N,N-dimethyltryptamine, a deuterated analog thereof, or a pharmaceutically acceptable salt thereof; or about 15 minutes to about 45 minutes, or about 45 minutes to about 180 minutes, when the psychedelic agent is selected from psilocybin, 4-acetoxy-N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, psilocin, deuterated analogs thereof, or pharmaceutically acceptable salts thereof; or about 20 minutes to about 30 minutes when the psychedelic agent is N,N-dimethyltryptamine or a pharmaceutically acceptable salt thereof; or When the psychedelic agent is a deuterated analog of N,N-dimethyltryptamine or a pharmaceutically acceptable salt thereof, from about 60 minutes to about 90 minutes.

[0158] In embodiment 59, the present invention provides the administration regimen, method of treatment, delivery device, parenteral formulation, or kit of any one of embodiments 1 to 58, wherein: the psychedelic agent is N,N-dimethyltryptamine or a pharmaceutically acceptable salt thereof, and the duration of the psychedelic experience is about 20 minutes to about 30 minutes, preferably about 20 minutes; or The psychedelic agent is a deuterated analog of N,N-dimethyltryptamine or a pharmaceutically acceptable salt thereof, and the duration of the psychedelic experience is about 60 minutes to about 90 minutes.

[0159] In embodiment 60, the present invention provides an administration regimen, method of treatment, delivery device, parenteral formulation, or kit described in any one of embodiments 57 to 59, wherein the duration of the experience is assessed by an attending clinician (preferably a psychiatrist, psychologist, or therapist).

[0160] In embodiment 61, the present invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit according to any preceding embodiment, further comprising the steps and / or instructions of: a. Preparation phase: involves preparing the patient for the psychedelic experience; b. administering: comprising a dosing regimen, method of treatment, or parenteral formulation as described in any preceding embodiment; and c. Integration phase: This involves an interview or discussion conducted by a psychiatrist or therapist with the patient that focuses on the psychedelic experience.

[0161] In embodiment 62, the invention provides the administration regimen, method of treatment, delivery device, parenteral formulation, or kit of any preceding embodiment, wherein treating a psychiatric or neurological disorder in a patient comprises psychedelic-assisted psychotherapy.

[0162] In embodiment 63, the present invention provides a dosing regimen, method of treatment, delivery device, parenteral formulation, or kit as described in any preceding embodiment, wherein a single effective dose is sufficient to achieve a breakthrough psychedelic experience in a patient.

[0163] In embodiment 64, the invention provides the dosing regimen, method of treatment, delivery device, parenteral formulation, or kit of any preceding embodiment, wherein, at baseline assessment, the patient is assessed as having moderate or severe symptoms according to a psychiatric or neurological disorder rating scale.

[0164] In embodiment 65, the present invention provides the administration regimen, method of treatment, delivery device, parenteral formulation, or kit described in embodiment 64, wherein the psychiatric or neurological disorder is a depressive disorder and the rating scale is selected from the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Rating Scale (HAMD-17), the Beck Depression Inventory-II (BDI-II), and combinations thereof.

[0165] As embodiment 66, the present invention provides the dosing regimen, method of treatment, delivery device, parenteral formulation, or kit described in embodiment 65, wherein, at the baseline assessment, the patient is assessed as having a score of 20 or greater on the Montgomery-Asberg Depression Rating Scale, or a score of 17 or greater on the Hamilton Depression Rating Scale (HAMD-17), or a score of 23 or greater on the Beck Depression Inventory-II.

[0166] Psychedelic agents for use in the dosing regimens, methods of treatment, delivery devices, or parenteral formulations for use in the present invention can be prepared according to the synthetic processes described in WO2021 / 089873, US20210395201, WO2022 / 117359, US11242318, US11724985, and US20220202775, the disclosures of which are incorporated herein by reference in their entireties.

[0167] The dose of psychedelic agent for use in the administration regimen, treatment method, delivery device, or parenteral formulation for use in the present invention may preferably be in the form of a pharmaceutically acceptable salt, wherein the salt comprises an acid and the free base of the psychedelic agent, the psychedelic agent being selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, and deuterated analogs thereof. An example of a salt comprising an acid and a dimethyltryptamine compound is N,N-dimethyltryptamine fumarate, the fumarate salt of N,N-dimethyltryptamine. P.H. Stahl and C.G. Wermuth provide an overview of pharmaceutical salts and the acids contained therein in "Handbook of Pharmaceutical Salts: Properties, Selection and Use," Weinheim / Zurich: Wiley-VCH / VHCA, 2002. The acids mentioned in this review are suitable acids for inclusion in the salt formulations.

[0168] For clarity, when the phrase "a psychedelic agent is selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogs thereof, and pharmaceutically acceptable salts thereof" is used, this is meant to include 1) any one of the listed compounds, 2) a pharmaceutically acceptable salt of any one of the listed compounds, 3) a deuterated analog of any one of the listed compounds, and 4) a pharmaceutically acceptable salt of any one of the deuterated analogs of any one of the listed compounds. For example, as a non-limiting example, "psychedelic agent" includes N,N-dimethyltryptamine, a pharmaceutically acceptable salt of N,N-dimethyltryptamine, a deuterated analog of N,N-dimethyltryptamine, or a pharmaceutically acceptable salt of a deuterated analog of N,N-dimethyltryptamine. The same applies to the other listed compounds.

[0169] Preferred psychedelic agents for use in any embodiment of the present invention are selected from the following: N,N-dimethyltryptamine; α-Protio,α-deutero-N,N-dimethyltryptamine; α,α-dideutero-N,N-dimethyltryptamine; α,α,β,β-tetradeutero-N,N-dimethyltryptamine; N,N-di(trideuteromethyl)tryptamine; α-Prothio,α-deutero-N,N-di(trideuteromethyl)tryptamine; α,α-dideutero-N,N-di(trideuteromethyl)tryptamine; α,α,β,β-tetradeutero-N,N-di(trideuteromethyl)tryptamine; 5-Methoxy-N,N-dimethyltryptamine; 5-Methoxy-α-prothio,α-deutero-N,N-dimethyltryptamine; 5-Methoxy-α,α-dideutero-N,N-dimethyltryptamine; 5-Methoxy-α,α,β,β-tetradeutero-N,N-dimethyltryptamine; 5-Methoxy-N,N-di(trideuteromethyl)tryptamine; 5-Methoxy-α-prothio,α-deutero-N,N-di(trideuteromethyl)tryptamine; 5-Methoxy-α,α-dideutero-N,N-di(trideuteromethyl)tryptamine; 5-Methoxy-α,α,β,β-tetradeutero-N,N-di(trideuteromethyl)tryptamine; psilocybin; α-protio,α-deutero-psilocybin; α,α-dideutero-psilocybin; α,α,β,β-tetradeutero-psilocybin; 4-(dihydrogen phosphate)-N,N-di(trideuteromethyl)tryptamine; 4-(dihydrogen phosphate)-α-protio,α-deutero-N,N-di(trideuteromethyl)tryptamine; 4-(dihydrogen phosphate)-α,α-dideutero-N,N-di(trideuteromethyl)tryptamine; 4-(dihydrogen phosphate)-α,α,β,β-tetradeutero-N,N-di(trideuteromethyl)tryptamine; Psilocin; α-Protio,α-Deutero-psilocin; α,α-dideutero-psilocin; α,α,β,β-tetradeutero-syloin; 4-hydroxy-N,N-di(trideuteromethyl)tryptamine; 4-Hydroxy-α-prothio,α-deutero-N,N-di(trideuteromethyl)tryptamine; 4-Hydroxy-α,α-dideutero-N,N-di(trideuteromethyl)tryptamine; 4-hydroxy-α,α,β,β-tetradeutero-N,N-di(trideuteromethyl)tryptamine; and and pharmaceutically acceptable salts thereof.

[0170] The salt may comprise an acid selected from the group consisting of fumaric acid, tartaric acid, citric acid, acetic acid, lactic acid, gluconic acid, 1-hydroxy-2-naphthoic acid, 2,2-dichloroacetic acid, 2-hydroxyethanesulfonic acid, 2-oxoglutaric acid, 4-acetamidobenzoic acid, 4-aminosalicylic acid, adipic acid, ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid, camphoric acid (camphoric acid), camphor-10-sulfonic acid, decanoic acid, hexanoic acid, octanoic acid, carbonic acid, cinnamic acid, cyclamic acid, dodecyl sulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, formic acid, galactosyl esters, methyl ... Lactaric acid, gentisic acid (gentisic acid), glucoheptonic acid, glucuronic acid, glutamic acid, glutaric acid, glycerophosphoric acid, glycolic acid, hippuric acid, hydrobromic acid, hydrochloric acid, isobutyric acid, lactobionic acid, lauric acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, nicotinic acid, nitric acid, oleic acid, oxalic acid, palmitic acid, pamoic acid, phosphoric acid, propionic acid, pyroglutamic acid (-L), salicylic acid, sebacic acid, stearic acid, succinic acid, sulfuric acid, thiocyanic acid, toluenesulfonic acid, undecylenic acid.

[0171] Preferably, the pharmaceutically acceptable salt is selected from fumarate, tartrate, citrate and hydrochloride salts, more preferably the pharmaceutically acceptable salt is fumarate. More preferably, the pharmaceutically acceptable salt of the psychedelic agent is a fumarate salt.

[0172] Parenteral administration routes include intravenous, intramuscular, subcutaneous, nasal, transmucosal, sublingual, rectal, transdermal, and inhalation. Any parenteral route capable of administration over a period of 5 to 15 minutes is suitable for use in the present invention. Parenteral routes capable of bolus administration over a period of less than 5 minutes, or less than 1 minute, are suitable for use in the present invention. Preferred routes of parenteral administration according to any aspect of the present invention are selected from intravenous, intramuscular, subcutaneous, intranasal, transmucosal, and transdermal administration, and inhalation. Intravenous infusion is a particularly preferred route of administration. Intramuscular administration is a particularly preferred route of administration. One skilled in the art will understand that the delivery device for use in the present invention will be selected depending on the route of administration of the psychedelic agent.

[0173] When the parenteral route of administration is intravenous, the delivery device may include an infusion bag or a syringe, and preferably may further include a syringe pump. When two syringe pumps are used to perform intravenous infusion, the syringe pumps may be connected to a single cannula via a three-way tap. When the parenteral route of administration is intramuscular, the delivery device may include a syringe. When the parenteral route of administration is intranasal, the delivery device may include a pump-activated spray means. When the parenteral route is transmucosal, the delivery device may include an oromucosal film. When the parenteral route is transdermal, the delivery device may include a transdermal patch. When the administration route is inhalation, the delivery device may include a metered-dose inhaler, vaporizer, or nebulizer.

[0174] Dosage forms suitable for parenteral administration have a pH of approximately 3 to approximately 9 and, for liquid formulations, an osmolality of approximately 250 to approximately 600 mOsm / kg. I. Usach et al. reported that pH values ​​above 9 are associated with tissue necrosis (cell death within tissue) (Adv. Ther., 36, 2986-2996 (2019)), while pH values ​​below 3 have been reported to cause pain and phlebitis (inflammation of the veins). Osmolality above 600 mOsm / kg has also been reported to cause pain. Usach et al. also recommended that parenteral formulations be formulated as isotonic solutions (osmolality approximately 300 mOsm / kg), with an upper limit of 600 mOsm / kg suggested to minimize pain.

[0175] Osmotic pressure is formally defined as the quotient of the negative natural logarithm of the rational activity of water and the molar mass of water, and is given by the following formula:

number

[0176] As used herein, when a first solution is defined as being isotonic with a second solution, the solutions have the same osmotic pressure. For example, when a formulation is defined as being isotonic with human blood serum, the formulation has the same osmotic pressure as human blood serum. Human blood serum typically has an osmotic pressure of about 275 to about 300 mOsm / kg (L. Hooper et al., BMJ Open, 2015; 5(10): e008846).

[0177] Suitable formulations for injection according to the present invention are described in WO2022 / 043227 and US11406619. Formulations suitable for inhaled administration according to the present invention are described in WO2022 / 117640. Formulations suitable for transdermal administration are described in US20210346347 and US17 / 866,477. Other suitable formulations according to the present invention are described in co-pending patent application US17 / 574,424. The entire disclosure of each of these patent applications is incorporated herein by reference in its entirety.

[0178] In some embodiments, a parenteral formulation for use in the present invention comprises a salt of a psychedelic agent, a base agent, water, and optionally a buffer separate from the salt, wherein the formulation has a pH of about 5 to about 6, a concentration of about 10 mg / ml or more as the free base, and an osmolality of about 250 to about 350 mOsm / Kg; and wherein the formulation contains a dose of an optionally substituted dimethyltryptamine compound in a volume of 5 ml or less.

[0179] The base agent adjusts the pH of the formulation to the required pH range, for example, pH 5 to pH 6. The pH of formulations containing an optionally substituted dimethyltryptamine salt, water, and a buffer is often low, for example, below pH 5, and therefore may require pH adjustment with a base agent. Those skilled in the art can evaluate a suitable base agent for adjusting the pH of the solution without risking decomposition of the optionally substituted dimethyltryptamine salt. The base agent may be sodium hydroxide or potassium hydroxide.

[0180] Parenteral formulations optionally contain a buffer, but this buffer is distinct from the salt; i.e., the buffer is not simply a counterion of the psychedelic agent. For example, if the salt is N,N-dimethyltryptamine fumarate (i.e., the fumarate salt of N,N-dimethyltryptamine), a buffer in excess of the buffering effect provided by the fumarate salt may be required. The term "buffer" is well known in the art and refers to a chemical substance contained in a formulation that resists changes in pH due to the addition of an acid or base to the formulation. As used herein, the term "buffer" refers to a buffering system or buffering agent. In a formulation, a buffer includes a weak acid and its conjugate base. Suitable buffers include acids with pKa values ​​within ±1 of the desired pH of the formulation. For example, if the desired pH of the formulation is about 5.0, suitable buffers include weak acids with pKa values ​​of about 4.0 to about 6.0. If the acid of the buffer has more than one pKa value (i.e., each molecule of the acid can donate more than one proton), at least one of the pKa values ​​must be within the desired pH range for the buffer to be suitable.

[0181] The weak acid and conjugate base of a buffer are in equilibrium with each other. According to Le Châtelier's principle (adding a constraint to a system at equilibrium (e.g., a change in the concentration of a reactant) shifts the equilibrium in a way that counteracts the effect of the constraint), adding an acid or base to a formulation shifts the position of equilibrium in favor of the conjugate base or weak acid, respectively. As a result, the concentration of free protons in the formulation (i.e., pH) remains relatively unchanged.

[0182] Suitable buffer systems include acetate with acetic acid (pKa=4.75); citrate with citric acid (pKa=3.13, 4.76, 6.40); and phosphate with phosphoric acid (pKa=2.14, 7.20, 12.37); or mixtures thereof. pKa values ​​quoted herein are those reported in water at 25°C. Typically, buffers contain only one member of the above pairs, i.e., one acid and its conjugate base.

[0183] In some embodiments, the buffer comprises acetate and acetic acid; citrate and citric acid; or phosphate and phosphoric acid. Sometimes, the buffer comprises acetate and acetic acid; or citrate and citric acid. In some embodiments, the buffer comprises acetate and acetic acid, often sodium acetate and acetic acid, or potassium acetate and acetic acid.

[0184] The concentration of the buffer in the formulation is typically sufficient to resist significant pH change of the formulation when the formulation is stored for two weeks (i.e., the pH typically fluctuates by less than about 0.1 pH units). One skilled in the art can assess and achieve an appropriate buffer concentration. In many cases, the buffer concentration is about 15 mM to about 75 mM, e.g., about 20 mM to about 30 mM. In some embodiments, the buffer concentration is about 25 mM.

[0185] As used herein, the term "buffer" refers to a weak acid or a weak base. Pharmaceutically acceptable buffers, including phosphoric acid, citric acid, acetic acid, phosphates, citrates, and acetates, can be used in the formulations of the present invention. In some embodiments, the buffer comprises sodium phosphate, sodium citrate, or sodium acetate.

[0186] Sometimes, the concentration of the psychedelic agent and any buffer in the formulation results in the desired osmolality. Alternatively, the desired osmolality can be achieved by including one or more tonicity agents in the formulation. Thus, in some embodiments, the formulation further comprises a tonicity agent. As used herein, a tonicity agent is defined as a chemical substance that, when contained within a formulation, increases the osmolality of the formulation. As discussed above, osmolality is the number of osmotically active particles (solute particles) in 1 kg of solution. Therefore, chemical substances that act as solutes when incorporated into a formulation are included within the definition of a tonicity agent.

[0187] In some embodiments, the formulation includes a tonicity agent. The concentration of the tonicity agent depends on the concentration of other components in the formulation, such as the psychedelic agent and buffer. For example, if the formulation without the tonicity agent has an osmolality of about 60 mOsm / Kg, a tonicity of at least about 190 mOsm / Kg would be provided by the tonicity agent (e.g., 95 mM sodium chloride). M.F. Powell, T. Nguyen, and L. Baloian provide a review of excipients suitable for parenteral administration (administration via a route other than the mouth or digestive tract) (PDA J. Pharm. Sci. Technol., 52, 238-311 (1998)). All of the soluble intravenously administrable excipients listed in this review contribute to the osmolality of the formulation and can therefore be considered tonicity agents.

[0188] When used in accordance with the present invention, suitable excipients for use in administering psychedelics may be selected from the group consisting of: ethanol, citric acid, trisodium citrate, benzalkonium chloride, microcrystalline cellulose, sodium carboxymethylcellulose, chlorobutanol, disodium edetate, glycerin, hydrochloric acid, methylparaben, polyethylene glycol, propylene glycol, propylparaben, sodium saccharin, sodium bicarbonate, sodium bisulfate, sodium bisulfite, sodium chloride, sodium hydroxide, sodium metabisulfite, sodium phosphate, sodium citrate, sulfuric acid, trisodium citrate, tromethamine, and mixtures thereof.

[0189] Some excipients may act as cosolvents. Solvents or cosolvents suitable for use in the formulations of the present invention may be selected from ethanol, polyethylene glycol, propylene glycol, and mixtures thereof. In some embodiments, the formulation includes a cosolvent. In some embodiments, the formulation does not include a cosolvent. In particular, when the salt of the optionally substituted dimethyltryptamine compound is a fumarate salt, such as N,N-dimethyltryptamine fumarate or α,α-dideutero-N,N-dimethyltryptamine fumarate, the formulation does not include a cosolvent.

[0190] The onset and end of the psychedelic experience will be assessed by the attending healthcare professional, psychiatrist, or therapist. As used herein, "duration of the psychedelic experience" refers to the time from the start of continuous parenteral administration to the end of the psychedelic experience.

[0191] Therapeutic improvement can be assessed using rating scales commonly used in this field. For patients with depressive disorders such as MDD or TRD, the Montgomery-Asberg Depression Rating Scale (MADRS) or Hamilton Depression Rating Scale (HAMD-17) can be used. Rating scales are used to conduct a baseline assessment before psychedelic administration and again after psychedelic administration (post-dose) to evaluate treatment efficacy. Post-dose assessments are preferably conducted approximately 24 hours to approximately 1 month after psychedelic administration, preferably approximately 1 week, 2 weeks, 3 weeks, and / or 4 weeks after psychedelic administration. Remission is considered when symptoms are reduced to a substantially symptom-free level. Remission may be assessed by a MADRS score of 13 or less (or 10 or less), a HAMD-17 score of 10 or less (preferably 8 or less), or a BDI-II score of 13 or less (preferably 11 or less).

[0192] In some embodiments, the psychedelic agent may be administered as a biphasic intravenous infusion via an intravenous cannula over 6-11 minutes. In some embodiments, the psychedelic agent may be administered as a biphasic intravenous infusion via an intravenous cannula, with each phase comprising a 5 minute infusion. In some embodiments, the psychedelic agent may be administered as a monophasic intravenous infusion over 6-11 minutes (preferably about 10 minutes) via an intravenous cannula. When a biphasic intravenous infusion is used, optionally, syringe pumps are connected to a single cannula via a three-way tap: once the infusion with the first pump is complete, the three-way tap is switched to continue the infusion from the second pump.

[0193] The term "monophasic" intravenous (IV) infusion refers to intravenous infusion administration via one syringe pump, where administration of the psychedelic agent is from one syringe pump. The term "biphasic" intravenous infusion refers to intravenous infusion administration via two syringe pumps, where the first phase involves administration of the psychedelic agent from a first syringe pump, followed by the second phase involves administration of the psychedelic agent from a second syringe pump. A biphasic intravenous infusion is essentially continuous, with no substantial interruption in the infusion to change administration from the first syringe pump to the second syringe pump.

[0194] In some embodiments, the psychedelic agent may be administered intramuscularly.

[0195] In some embodiments, the kit is for treating a psychiatric or neurological disorder in a patient, and the kit includes: a) and b) a) a psychiatric or neurological disorder; a) a container containing a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogs thereof, and pharmaceutically acceptable salts thereof; and b) A label or package insert on or associated with the container that contains instructions for administering the parenteral formulation and specifies that administration is to occur only once within any one-month, two-month, or three-month period. [Example]

[0196] A double-blind, randomized, placebo-controlled study of intravenous administration of DMT fumarate was conducted in patients with major depressive disorder (Clinical Trial Identifier: NCT04673383, Part B). The protocol, as shown in Figure 1, consisted of the following steps: Day 1 -MADRS evaluation by an independent assessor Day 1 Placebo or one dose of DMT fumarate administered by continuous intravenous infusion over an administration period of approximately 10 minutes. -Tolerability assessment after the psychedelic experience. Day 8, Day 14, Day 22 (± 1 day), Day 29 (± 2 days), Day 45 (± 2 days), Day 105 (± 5 days) -MADRS evaluation

[0197] In NCT04673383 Part B, the investigational drug, DMT fumarate (SPL026), was administered according to the present invention. Data for days 8, 14, 22, and 29 are shown in Table 1. Group A received one dose of study drug and was evaluated on days 8 and 14. Group P received placebo on day 1 and was evaluated on days 8 and 14. Group PA received placebo on day 1, one dose of study drug on day 15, and was evaluated on days 22 and 29.

[0198] [Table 1]

[0199] These data demonstrate a clear and rapid mean improvement in symptoms in subjects receiving a single dose of study drug (Groups A and P A) compared with subjects receiving placebo only (Group P). There was a statistically significant difference in the mean change from baseline between Groups A and P of -10.8 points (p=0.002) at Day 8 and -7.4 points (p=0.02) at Day 15. Data showing the percentage of subjects in Groups A and P achieving a 50% or greater reduction in MADRS from baseline and a MADRS score of 10 or less are shown in Figures 2 and 3, respectively.

[0200] Data for days 22, 29, 45, and 105 are shown in Table 2. Group A received one dose of study drug on day 1. Group PA received placebo on day 1 followed by one dose of study drug (open label) on day 15. Group AA received one dose of study drug on day 1 followed by a second dose of study drug (open label) on day 15.

[0201] [Table 2]

[0202] These data demonstrate clear and sustained mean improvement in symptoms from Day 22 through Day 105 in all treatment groups. At Day 105, 50.0% of subjects in Groups PA and A had a 50% or greater reduction in MADRS scores compared to baseline assessment. Additionally, 57% of subjects in Group PA and 50.0% of patients in Group A had a MADRS score of 10 or less (remission). Data showing the mean reduction in MADRS scores are shown in Figure 5. Data showing the percentage of subjects with a 50% or greater reduction in MADRS from baseline and a MADRS score of 10 or less (in Groups AA and PA) at Weeks 1, 2, 4, and 12 after open-label treatment are shown in Figures 6 and 7, respectively. Furthermore, the data surprisingly show that there was no significant difference in improvement between subjects who received two doses of study drug (Group AA) and those who received a single dose (Groups PA and A). This unexpected outcome is commercially beneficial in that a single dose of a therapeutic agent is (at least) less expensive in terms of starting materials, processing, and medical / administrative burden. Furthermore, a single-dose regimen may reduce patient burden and improve patient convenience and compliance.

[0203] The data are presented in Table 3 and show the reduction in severity categories on the MADRS rating scale on days 8 (D8), 14, 29, 45, and 105 for subjects who received placebo on day 1 and a single dose of study drug on day 15 (Group PA).

[0204] [Table 3]

[0205] At Day 45, 62.5% of subjects experienced at least a one-level reduction in symptom severity category on the MADRS scale, and at Day 105, 64.3% experienced at least a one-level reduction. At Day 45, 43.8% of subjects experienced a two- or three-level reduction, and at Day 105, 35.7% experienced a two- or three-level reduction. At Day 105, 28.6% of subjects experienced a two-level reduction from moderate to no symptoms, and at Day 45, 31.3% of subjects also experienced a two-level reduction from moderate to no symptoms. Furthermore, at Day 45, 6.3% of subjects experienced a three-level reduction from severe to no symptoms, and at Day 105, 7.1% of subjects experienced a three-level reduction from severe to no symptoms. These data demonstrate that administration of a psychedelic agent according to the present invention achieved at least a one-level reduction in symptom severity category in a significant proportion of subjects, particularly for those rated as moderate at baseline.

[0206] Analysis of patient-reported depression scores confirmed the MADRS assessments by independent clinical assessors. Improvements in depression scores from baseline (measured by the Beck Depression Inventory (BDI)) were observed at all study time points in patients who received at least one dose of an investigational drug in accordance with the present invention. This included a statistically significant improvement in depressive symptoms at two weeks post-dose (p=0.002 compared to placebo). The efficacy outcomes in the BDI were consistent with the MADRS, further supporting the rapid and sustained therapeutic profile of DMT fumarate administered in accordance with the present invention for the treatment of MDD.

[0207] Indicators assessing anxiety and well-being in patients often adversely affected by depression were also analyzed in this study. After administration of a single dose of the active ingredient according to the present invention (in combination with supportive care), patients showed rapid and sustained improvement in anxiety symptoms measured with the STAI-T (State-Trait Anxiety Inventory-Trait) scale. A statistically significant improvement in anxiety symptoms was observed at 2 weeks post-treatment compared with placebo (p=0.03). After 12 weeks of open-label treatment (Group PA), patients receiving a single dose (Group PA) showed a mean change from baseline (CFB) of -14.2.

[0208] Furthermore, after at least one administration of the active ingredient according to the present invention (in combination with supportive care), a rapid and sustained improvement in well-being (as measured by the Warwick-Edinburgh Mental Well-being Scale [WEMWBS]) was observed. Two weeks after blinded administration of the investigational drug or placebo (Groups A and P), the mean CFB in Group A was 10.1 and in Group P was 0.9.

[0209] Statistical analysis was performed on the MADRS open-label data. A statistically significant difference was observed in the mean total MADRS scores across all open-label study time points for both the PA and AA groups (p<0.05). Further analysis was performed to assess the difference in total MADRS scores between the PA and AA groups using a repeated measures mixed model across all time points for all subjects. No statistical differences (p=ns) were observed between these dosing regimens at any time point up to 12 weeks. This analysis further supports that a single dose of the active ingredient is sufficient to induce a rapid and sustained antidepressant effect. The data are presented in Table 4.

[0210] [Table 4]

Claims

1. 1. A parenteral formulation comprising a short-acting psychedelic agent for use in treating a psychiatric or neurological disorder in a patient, said treatment comprising parenterally administering to the patient a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogs thereof, and pharmaceutically acceptable salts thereof, wherein said administration occurs no more than once in any one, two, three, six, nine, or twelve month period.

2. 2. The parenteral formulation for use according to claim 1, wherein the administration is (i) no more than once in any one, two, or three month period, or (ii) no more than once in any three month period.

3. 10. A parenteral formulation for use according to any preceding claim, wherein said administration occurs only once in any six month or any nine month period.

4. 10. A parenteral formulation for use according to any preceding claim, wherein said administration occurs only once in any twelve month period.

5. 1. A parenteral formulation comprising a single effective parenteral dose of a short-acting psychedelic agent for use in treating a psychiatric or neurological disorder in a patient, comprising: The treatment comprises administering to the patient (preferably parenterally) a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, their deuterated analogs, and their pharmaceutically acceptable salts, wherein the administration occurs at most once per month, or at most once every two months, or at most once per three months, or at most once per six months, or at most once per nine months, or at most once per twelve months in a parenteral formulation.

6. 6. The parenteral formulation for use according to claim 5, wherein the administration is (i) at most once a month, or at most once every two months, or at most once every three months, or (ii) at most once every three months.

7. 7. A parenteral formulation for use according to claim 5 or claim 6, wherein the administration is carried out at most once every six months or at most once every nine months.

8. A parenteral formulation for use according to any one of claims 5 to 7, wherein said administration is carried out at most once every twelve months.

9. A parenteral formulation for use according to any preceding claim, further comprising parenterally administering a second single effective dose of a short-acting psychedelic agent within a period of three to twelve months after administration of the first single effective dose.

10. 10. A parenteral formulation for use as described in claim 9, comprising parenterally administering a second single effective dose of a short-acting psychedelic agent within a period of three to nine months after administration of the first single effective dose.

11. 11. The parenteral formulation for use according to claim 9 or claim 10, wherein the administration of the first single effective dose and the second single effective dose occurs only once in any twelve month period.

12. 11. The parenteral formulation for use according to claim 9 or claim 10, wherein the administration of both the first single effective dose and the second single effective dose occurs at most once every twelve months.

13. 10. A parenteral formulation for use according to any preceding claim, further comprising the steps of: (i) Patient baseline assessment using rating scales and / or healthcare professional-reported outcomes and / or patient-reported outcomes; (ii) parenteral administration to the patient of a single effective dose of a short-acting psychedelic agent, wherein said psychedelic agent is selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogs thereof, and pharmaceutically acceptable salts thereof; and (iii) Post-administration patient evaluation.

14. The parenteral formulation for use according to any one of claims 1 to 12, further comprising the following steps: (i) a baseline assessment of the patient using a rating scale and / or healthcare professional-reported outcomes and / or patient-reported outcomes prior to parenteral administration to the patient; and (ii) Post-administration patient evaluation following parenteral administration to the patient.

15. The baseline assessment is The assessment may be performed using a rating scale selected from the following: Clinical Global Impression (CGI); Montgomery-Asberg Depression Rating Scale (MADRS); Hamilton Depression Rating Scale (HAMD-17); Beck Depression Inventory-II; Beck Anxiety Inventory (BAI); Hamilton Anxiety Scale (HAM-A); State-Trait Anxiety Inventory (STAI); Generalized Anxiety Disorder Assessment (GAD-7); Clinician-Administered Posttraumatic Stress Disorder Scale (CAPS); Yale-Brown Obsessions and Compulsions Scale; Beck Scale for Suicidal Ideation (BSS); Columbia-Suicide Severity Rating Scale (C-SSRS); MADRS Suicidal Thoughts Item for Suicidal Ideation; Clinical Global Impression-Revised (CGI-SS-R) Scale of Suicidality Severity; Beck Depression Inventory-II; Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF); EQ-5D-5L Short Answer System and EQ VAS; Patient Global Impression of Severity Scale (PGI-S); and combinations thereof; or by assessing body weight, frequency of binge-purging episodes, and / or frequency of binge eating episodes; 15. A parenteral formulation for use according to claim 13 or claim 14.

16. Post-administration evaluation: The assessment may be performed using a rating scale selected from the following: Clinical Global Impression (CGI); Montgomery-Asberg Depression Rating Scale (MADRS); Hamilton Depression Rating Scale (HAMD-17); Beck Depression Inventory-II; Beck Anxiety Inventory (BAI); Hamilton Anxiety Scale (HAM-A); State-Trait Anxiety Inventory (STAI); Generalized Anxiety Disorder Assessment (GAD-7); Clinician-Administered Posttraumatic Stress Disorder Scale (CAPS); Yale-Brown Obsessions and Compulsions Scale; Beck Scale for Suicidal Ideation (BSS); Columbia-Suicide Severity Rating Scale (C-SSRS); MADRS Suicidal Thoughts Item for Suicidal Ideation; Clinical Global Impression-Revised (CGI-SS-R) Scale of Suicidality Severity; Beck Depression Inventory-II; Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF); EQ-5D-5L Short Answer System and EQ VAS; Patient Global Impression of Severity (PGI-S); Clinical Global Improvement Scale (CGI-I); Patient Global Impression of Improvement (PGI-I); and combinations thereof; or by assessing body weight, frequency of binge-purging episodes, and / or frequency of binge eating episodes; A parenteral formulation for use according to any one of claims 13 to 15.

17. the psychiatric or neurological disorder is a depressive disorder, and Baseline and post-administration assessments will be performed using depression rating scales selected from the Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HAMD17), Beck Depression Inventory-II, and combinations thereof. A parenteral formulation for use according to any one of claims 13 to 16.

18. the parenteral administration comprises parenterally administering to the patient a dose of the psychedelic agent over an administration period of about 5 minutes to about 15 minutes; 10. A parenteral formulation for use according to any preceding claim, wherein parenteral administration is essentially continuous.

19. 10. The parenteral formulation for use according to any preceding claim, wherein parenteral administration is selected from the group consisting of intravenous administration, intramuscular administration, subcutaneous administration, intranasal administration, transmucosal administration, sublingual administration, rectal administration, transdermal administration, and inhalation.

20. 10. A parenteral formulation for use according to any preceding claim, wherein parenteral administration is by intravenous infusion or by intramuscular administration, preferably intravenous administration is performed using a syringe pump.

21. 10. A parenteral formulation for use according to any preceding claim, wherein parenteral administration is by biphasic intravenous infusion.

22. The parenteral formulation for use according to any one of claims 1 to 20, wherein parenteral administration is by monophasic intravenous infusion.

23. 23. The parenteral formulation for use according to any one of claims 18 to 22, wherein the administration period is from about 8 minutes to about 12 minutes.

24. 23. The parenteral formulation for use according to any one of claims 18 to 22, wherein the administration period is from about 9 minutes to about 11 minutes, or about 10 minutes.

25. 10. The parenteral formulation for use according to any preceding claim, wherein the single effective dose of the psychedelic agent is selected from the group consisting of: about 20 mg to about 70 mg of N,N-dimethyltryptamine, its deuterated analog, and / or a pharmaceutically acceptable salt thereof; about 15 mg to about 30 mg of N,N-dimethyltryptamine, its deuterated analog, and / or a pharmaceutically acceptable salt thereof; about 10 mg to about 20 mg of N,N-dimethyltryptamine, its deuterated analog, and / or a pharmaceutically acceptable salt thereof; about 5 mg to about 15 mg of N,N-dimethyltryptamine, its deuterated analog, and / or a pharmaceutically acceptable salt thereof; About 10 to about 30 mg of 5-methoxy-N,N-dimethyltryptamine, its deuterated analogs, and / or pharmaceutically acceptable salts thereof. about 1 mg to about 5 mg of psilocybin, a deuterated analog thereof, and / or a pharmaceutically acceptable salt thereof; about 3 mg to about 15 mg of 4-acetoxy-N,N-dimethyltryptamine, its deuterated analog, and / or a pharmaceutically acceptable salt thereof; about 1 mg to about 5 mg of psilocin, its deuterated analog, and / or a pharmaceutically acceptable salt thereof; and About 3 mg to about 25 mg of psilocin, its deuterated analog, and / or a pharmaceutically acceptable salt thereof.

26. 10. The parenteral formulation for use according to any preceding claim, comprising parenteral administration of a total dose of about 20 mg to about 29 mg of N,N-dimethyltryptamine, its deuterated analogue, or a pharmaceutically acceptable salt thereof.

27. 10. The parenteral formulation for use according to any preceding claim, comprising parenteral administration of a total dose of about 20 mg to about 23 mg, or about 26 mg to about 29 mg of N,N-dimethyltryptamine, its deuterated analogue, or a pharmaceutically acceptable salt thereof.

28. 10. The parenteral formulation for use according to any preceding claim, wherein the psychedelic agent is N,N-dimethyltryptamine, a deuterated analogue thereof, or a pharmaceutically acceptable salt thereof, and the total dose is from about 7 mg to about 10 mg.

29. 26. The parenteral formulation for use according to claim 25, wherein administration is by biphasic intravenous infusion, the psychedelic agent is N,N-dimethyltryptamine, a deuterated analogue thereof, or a pharmaceutically acceptable salt thereof, and the total dose is from about 20 mg to about 23 mg, or from about 10 mg to about 20 mg.

30. 27. The parenteral formulation for use according to claim 26, wherein administration is by monophasic intravenous infusion, the psychedelic agent is N,N-dimethyltryptamine, a deuterated analogue thereof, or a pharmaceutically acceptable salt thereof, and the total dose is about 26 to about 29 mg.

31. A parenteral formulation for use according to any one of claims 1 to 20 and 23 to 28, wherein administration is by intramuscular administration.

32. 10. The parenteral formulation for use according to any preceding claim, wherein the psychedelic agent is N,N-dimethyltryptamine, a deuterated analogue thereof, or a pharmaceutically acceptable salt thereof, and the total dose is from about 20 mg to about 70 mg.

33. 32. The parenteral formulation for use according to any one of claims 1 to 25 and 31, comprising parenteral administration of a total dose of about 1.5 to about 3 mg of psilocybin, a deuterated analogue thereof, or a pharmaceutically acceptable salt thereof.

34. 10. The parenteral formulation for use according to any preceding claim, wherein the psychedelic agent is a compound of formula I or a pharmaceutically acceptable salt thereof: 【Chemistry 1】 (In the formula, Ra is H, D, -OH, -OAc, and -PO 3 OH, and Rb is H or D; or Ra is H or D, and Rb is H, D, -OMe, and -OCD 3 Selected from: R 2 and R 3 are each independently -C(H z ) 3 selected from; and Each H x , H y and H z are independently selected from protium and deuterium).

35. R 2 and R 3 are each independently -C(H) 3 and -C(D) 3 35. A parenteral formulation for use according to claim 34, selected from:

36. R 2 and R 3 Both are -C(H) 3 or R 2 and R 3 Both are -C(D) 3 or R 2 -C(H) 3 and R 3 -C(D) 3 35. The parenteral formulation for use according to claim 34, wherein

37. Each H x is H or each H x is D or one H x is H and another H x The parenteral formulation for use according to any one of claims 34 to 36, wherein is D.

38. Each H y is H or each H y is D or one H y is H and another H y The parenteral formulation for use according to any one of claims 34 to 37, wherein is D.

39. Each H x , H y , and H z The parenteral formulation for use according to any one of claims 34 to 38, wherein is deuterium.

40. 40. The parenteral formulation for use according to any one of claims 34 to 39, wherein the psychedelic agent is selected from the group consisting of the following compounds, or pharmaceutically acceptable salts thereof, wherein Ra and Rb are as defined in claim 34: 【Chemistry 2】

41. The parenteral formulation for use according to any one of claims 34 to 40, wherein Ra is H or Ra is D.

42. 42. The parenteral formulation for use according to any one of claims 34 to 41, wherein Rb is H or Rb is D.

43. 43. The parenteral formulation for use according to any one of claims 34 to 42, wherein the psychedelic agent is selected from the group consisting of the following compounds or pharmaceutically acceptable salts thereof: 【Transformation 3】

44. 44. The parenteral formulation for use according to any one of claims 1 to 30 and 32 to 43, wherein parenteral administration comprises intravenous infusion by one or two syringe pumps.

45. 10. The parenteral formulation for use according to any preceding claim, wherein the psychiatric or neurological disorder is selected from the group consisting of (i) obsessive-compulsive disorder, (ii) depressive disorder, (iii) anxiety disorder, (iv) substance abuse and gambling disorder, and (v) anorexia disorder, preferably a depressive disorder or an anxiety disorder.

46. 10. The parenteral formulation for use according to any preceding claim, wherein the psychiatric or neurological disorder is a depressive disorder or an anxiety disorder.

47. 10. The parenteral formulation for use according to any preceding claim, wherein the psychiatric or neurological disorder is major depressive disorder.

48. 10. The parenteral formulation for use according to any preceding claim, wherein the duration of the psychedelic experience is about 3 hours or less, or about 2 hours or less, or about 1 hour or less.

49. The duration of the psychedelic experience: about 15 minutes to about 30 minutes, or about 30 minutes to about 90 minutes, when the psychedelic agent is N,N-dimethyltryptamine, a deuterated analog thereof, or a pharmaceutically acceptable salt thereof; or about 15 minutes to about 45 minutes, or about 45 minutes to about 180 minutes, when the psychedelic agent is selected from psilocybin, 4-acetoxy-N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, psilocin, deuterated analogs thereof, or pharmaceutically acceptable salts thereof; or about 20 minutes to about 30 minutes when the psychedelic agent is N,N-dimethyltryptamine or a pharmaceutically acceptable salt thereof; or about 60 minutes to about 90 minutes when the psychedelic agent is a deuterated analog of N,N-dimethyltryptamine or a pharmaceutically acceptable salt thereof; 10. A parenteral formulation for use according to any preceding claim, wherein:

50. the psychedelic agent is N,N-dimethyltryptamine or a pharmaceutically acceptable salt thereof, and the duration of the psychedelic experience is about 20 minutes to about 30 minutes, preferably about 20 minutes; or the psychedelic agent is a deuterated analog of N,N-dimethyltryptamine or a pharmaceutically acceptable salt thereof, and the duration of the psychedelic experience is from about 60 minutes to about 90 minutes; A parenteral formulation for use according to any one of claims 1 to 49.

51. 51. The parenteral formulation for use according to any one of claims 48 to 50, wherein the duration of the experience is assessed by the attending clinician, preferably a psychiatrist, psychologist or therapist.

52. 10. A parenteral formulation for use according to any preceding claim, further comprising the steps of: a. The preparation phase, which involves preparing the patient to undergo a psychedelic experience; b. administering, comprising a parenteral formulation for use according to any preceding claim; and c. An integration phase, involving an interview or discussion focused on the psychedelic experience conducted by a psychiatrist or therapist with the patient.

53. 10. A parenteral formulation for use according to any preceding claim, wherein the treatment of a psychiatric or neurological disorder in a patient comprises psychedelic-assisted psychotherapy.

54. 10. A parenteral formulation for use according to any preceding claim, wherein a single effective dose is sufficient to achieve a breakthrough psychedelic experience in a patient.

55. 10. The parenteral formulation for use according to any preceding claim, wherein the patient is assessed at baseline assessment as having moderate or severe symptoms according to a psychiatric or neurological disorder rating scale.

56. 56. The parenteral formulation for use according to claim 55, wherein the psychiatric or neurological disorder is a depressive disorder and the rating scale is selected from the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Rating Scale (HAMD-17), the Beck Depression Inventory-II (BDI-II), and combinations thereof.

57. 57. The parenteral formulation for use according to claim 56, wherein at baseline assessment, the patient is assessed as having a score of 20 or greater on the Montgomery-Asberg Depression Rating Scale, or a score of 17 or greater on the Hamilton Depression Rating Scale (HAMD-17), or a score of 23 or greater on the Beck Depression Inventory-II.

58. 1. A dosing regimen for administering a short-acting psychedelic agent to a patient for the treatment of a psychiatric or neurological disorder, comprising: A dosing regimen comprising parenterally administering to a patient a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogs thereof, and pharmaceutically acceptable salts thereof, wherein said administration occurs only once in any one, two, three, six, nine, or twelve month period.

59. 1. A method for treating a psychiatric or neurological disorder in a patient, comprising: A method of treatment comprising parenterally administering to a patient a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogs thereof, and pharmaceutically acceptable salts thereof, wherein said administration occurs no more than once in any one, two, three, six, nine, or twelve month period.

60. 1. A delivery device for use in treating a psychiatric or neurological disorder in a patient, comprising: The delivery device is configured to parenterally administer to a patient a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogs thereof, and pharmaceutically acceptable salts thereof, wherein the administration occurs only once in any one, two, three, six, nine, or twelve month period.

61. 1. A kit comprising a parenteral formulation for use in treating a psychiatric or neurological disorder in a patient, comprising: A kit wherein the parenteral formulation comprises a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogs thereof, and pharmaceutically acceptable salts thereof, and further comprises instructions for parenteral administration of the parenteral formulation, the instructions indicating that the administration is to occur no more than once in any one, two, three, six, nine, or twelve month period.

62. 62. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58-61, wherein the administration is (i) administered only once in any one-month, two-month, or three-month period, or (ii) administered only once in any three-month period.

63. 63. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 62, wherein said administration occurs only once in any six month period or any nine month period.

64. 64. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 63, wherein said administration occurs only once in any twelve month period.

65. 1. A dosing regimen for administering a short-acting psychedelic agent to a patient for the treatment of a psychiatric or neurological disorder, comprising: A dosing regimen comprising parenterally administering to a patient a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogs thereof, and pharmaceutically acceptable salts thereof, wherein said administration occurs at most once per month, at most once every two months, at most once per three months, at most once per six months, at most once per nine months, or at most once per twelve months.

66. 1. A method for treating a psychiatric or neurological disorder in a patient, comprising: A method of treatment comprising parenterally administering to a patient a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, their deuterated analogs, and their pharmaceutically acceptable salts, wherein said administration occurs at most once per month, at most once every two months, at most once per three months, at most once per six months, at most once per nine months, or at most once per twelve months.

67. 1. A delivery device for use in treating a psychiatric or neurological disorder in a patient, comprising: The delivery device is configured to parenterally administer to a patient a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogs thereof, and pharmaceutically acceptable salts thereof, wherein the administration occurs at most once per month, at most once every two months, at most once per three months, at most once per six months, at most once per nine months, or at most once per twelve months.

68. 1. A kit comprising a parenteral formulation for use in treating a psychiatric or neurological disorder in a patient, comprising: The parenteral formulation comprises a single effective parenteral dose of a short-acting psychedelic agent selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogs thereof, and pharmaceutically acceptable salts thereof, and further comprises instructions for parenteral administration of the parenteral formulation, the instructions indicating that the administration is to occur at most once per month, at most once every two months, at most once per three months, at most once per six months, at most once per nine months, or at most once per twelve months.

69. 69. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 65 to 68, wherein the administration is (i) at most once per month, or at most once every two months, or at most once per three months, or (ii) at most once per three months.

70. 70. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 65 to 69, wherein said administration occurs at most once every six months, or at most once every nine months.

71. 71. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 65 to 70, wherein said administration occurs at most once every twelve months.

72. 72. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 71, further comprising parenterally administering a second single effective dose of a short-acting psychedelic agent within a period of three to twelve months after administration of the first single effective dose.

73. 73. The dosing regimen, method of treatment, delivery device, or kit of claim 72, comprising parenterally administering a second single effective dose of a short-acting psychedelic agent within a period of three to nine months after administration of the first single effective dose.

74. 74. The dosing regimen, method of treatment, delivery device, or kit of claim 72 or claim 73, wherein the administration of the first single effective dose and the second single effective dose occurs only once in any twelve month period.

75. 74. The dosing regimen, method of treatment, delivery device, or kit of claim 72 or claim 73, wherein the administration of both the first single effective dose and the second single effective dose occurs at most once every twelve months.

76. 76. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 75, further comprising the steps and / or instructions of: (i) Patient baseline assessment using rating scales and / or healthcare professional-reported outcomes and / or patient-reported outcomes; (ii) parenteral administration to the patient of a single effective dose of a short-acting psychedelic agent, wherein said psychedelic agent is selected from N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, psilocybin, psilocin, deuterated analogs thereof, and pharmaceutically acceptable salts thereof; and (iii) Post-administration patient evaluation.

77. 76. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 75, further comprising the steps and / or instructions of: (i) a baseline assessment of the patient using a rating scale and / or healthcare professional-reported outcomes and / or patient-reported outcomes prior to parenteral administration to the patient; and (iii) Post-administration patient evaluation following parenteral administration to the patient.

78. The baseline assessment is The assessment may be performed using a rating scale selected from the following: Clinical Global Impression (CGI); Montgomery-Asberg Depression Rating Scale (MADRS); Hamilton Depression Rating Scale (HAMD-17); Beck Depression Inventory-II; Beck Anxiety Inventory (BAI); Hamilton Anxiety Scale (HAM-A); State-Trait Anxiety Inventory (STAI); Generalized Anxiety Disorder Assessment (GAD-7); Clinician-Administered Posttraumatic Stress Disorder Scale (CAPS); Yale-Brown Obsessions and Compulsions Scale; Beck Scale for Suicidal Ideation (BSS); Columbia-Suicide Severity Rating Scale (C-SSRS); MADRS Suicidal Thoughts Item for Suicidal Ideation; Clinical Global Impression-Revised (CGI-SS-R) Scale of Suicidality Severity; Beck Depression Inventory-II; Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF); EQ-5D-5L Short Answer System and EQ VAS; Patient Global Impression of Severity Scale (PGI-S); and combinations thereof; or by assessing body weight, frequency of binge-purging episodes, and / or frequency of binge eating episodes; 78. The dosing regimen, method of treatment, delivery device, or kit of claim 76 or claim 77.

79. Post-administration evaluation: The assessment may be performed using a rating scale selected from the following: Clinical Global Impression (CGI); Montgomery-Asberg Depression Rating Scale (MADRS); Hamilton Depression Rating Scale (HAMD-17); Beck Depression Inventory-II; Beck Anxiety Inventory (BAI); Hamilton Anxiety Scale (HAM-A); State-Trait Anxiety Inventory (STAI); Generalized Anxiety Disorder Assessment (GAD-7); Clinician-Administered Posttraumatic Stress Disorder Scale (CAPS); Yale-Brown Obsessions and Compulsions Scale; Beck Scale for Suicidal Ideation (BSS); Columbia-Suicide Severity Rating Scale (C-SSRS); MADRS Suicidal Thoughts Item for Suicidal Ideation; Clinical Global Impression-Revised (CGI-SS-R) Scale of Suicidality Severity; Beck Depression Inventory-II; Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF); EQ-5D-5L Short Answer System and EQ VAS; Patient Global Impression of Severity (PGI-S); Clinical Global Improvement Scale (CGI-I); Patient Global Impression of Improvement (PGI-I); and combinations thereof; or 79. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 76 to 78, performed by assessment of body weight, frequency of binge-purging episodes, and / or frequency of binge eating episodes.

80. the psychiatric or neurological disorder is a depressive disorder, and 80. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 76-79, wherein baseline and post-administration assessments are conducted using a depression rating scale selected from the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Rating Scale (HAMD17), the Beck Depression Inventory-II, and combinations thereof.

81. 81. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 80, wherein the parenteral administration comprises parenterally administering a dose of the psychedelic agent to the patient over an administration period of about 5 minutes to about 15 minutes, wherein the parenteral administration is essentially continuous.

82. 82. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58-81, wherein parenteral administration is selected from the group consisting of intravenous administration, intramuscular administration, subcutaneous administration, intranasal administration, transmucosal administration, sublingual administration, rectal administration, transdermal administration, and inhalation.

83. 83. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 82, wherein parenteral administration is by intramuscular administration or by intravenous infusion, preferably intravenous administration is performed using a syringe pump.

84. 84. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 83, wherein parenteral administration is by biphasic intravenous infusion.

85. 84. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 83, wherein parenteral administration is by monophasic intravenous infusion.

86. 86. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 81 to 85, wherein the administration period is from about 8 minutes to about 12 minutes.

87. 86. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 81 to 85, wherein the administration period is from about 9 minutes to about 11 minutes, or about 10 minutes.

88. 88. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58-87, wherein the single effective dose of the psychedelic agent is selected from the group consisting of: about 20 mg to about 70 mg of N,N-dimethyltryptamine, its deuterated analog, and / or a pharmaceutically acceptable salt thereof; about 15 mg to about 30 mg of N,N-dimethyltryptamine, its deuterated analog, and / or a pharmaceutically acceptable salt thereof; about 10 mg to about 20 mg of N,N-dimethyltryptamine, its deuterated analog, and / or a pharmaceutically acceptable salt thereof; about 5 mg to about 15 mg of N,N-dimethyltryptamine, its deuterated analog, and / or a pharmaceutically acceptable salt thereof; about 10 to about 30 mg of 5-methoxy-N,N-dimethyltryptamine, its deuterated analog, and / or a pharmaceutically acceptable salt thereof; about 1 mg to about 5 mg of psilocybin, a deuterated analog thereof, and / or a pharmaceutically acceptable salt thereof; about 3 mg to about 15 mg of 4-acetoxy-N,N-dimethyltryptamine, its deuterated analog, and / or a pharmaceutically acceptable salt thereof; about 1 mg to about 5 mg of psilocin, its deuterated analog, and / or a pharmaceutically acceptable salt thereof; and About 3 mg to about 25 mg of psilocin, its deuterated analog, and / or a pharmaceutically acceptable salt thereof.

89. 89. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58-88, comprising parenteral administration of a total dose of about 20 mg to about 29 mg of N,N-dimethyltryptamine, its deuterated analog, or a pharmaceutically acceptable salt thereof.

90. 90. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58-89, comprising parenteral administration of a total dose of about 20 mg to about 23 mg, or about 26 mg to about 29 mg of N,N-dimethyltryptamine, its deuterated analog, or a pharmaceutically acceptable salt thereof.

91. 91. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 90, wherein the psychedelic agent is N,N-dimethyltryptamine, a deuterated analog thereof, or a pharmaceutically acceptable salt thereof, and the total dose is from about 7 mg to about 10 mg.

92. 89. The dosing regimen, method of treatment, delivery device, or kit of claim 88, wherein administration is by biphasic intravenous infusion, the psychedelic agent is N,N-dimethyltryptamine, a deuterated analog thereof, or a pharmaceutically acceptable salt thereof, and the total dose is from about 20 mg to about 23 mg, or from about 10 mg to about 20 mg.

93. 90. The dosing regimen, method of treatment, delivery device, or kit of claim 89, wherein administration is by monophasic intravenous infusion, the psychedelic agent is N,N-dimethyltryptamine, a deuterated analog thereof, or a pharmaceutically acceptable salt thereof, and the total dose is about 26 to about 29 mg.

94. 92. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58-83 and 86-91, wherein administration is by intramuscular administration.

95. 95. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 94, wherein the psychedelic agent is N,N-dimethyltryptamine, a deuterated analogue thereof, or a pharmaceutically acceptable salt thereof, and the total dose is from about 20 mg to about 70 mg, preferably from about 50 mg to about 70 mg.

96. 95. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58-88 and 94, comprising parenteral administration of a total dose of about 1.5 to about 3 mg of psilocybin, a deuterated analog thereof, or a pharmaceutically acceptable salt thereof.

97. 97. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 96, wherein the psychedelic agent is a compound of formula I or a pharmaceutically acceptable salt thereof: 【Chemistry 4】 (In the formula, Ra is H, D, -OH, -OAc, and -PO 3 OH, and Rb is H or D; or Ra is H or D, and Rb is H, D, -OMe, and -OCD 3 Selected from: R 2 and R 3 are each independently -C(H z ) 3 selected from; and Each H x , H y and H z are independently selected from protium and deuterium).

98. R 2 and R 3 are each independently -C(H) 3 and -C(D) 3 98. The dosing regimen, method of treatment, delivery device, or kit of claim 97, selected from:

99. R 2 and R 3 Both are -C(H) 3 or R 2 and R 3 Both are -C(D) 3 or R 2 -C(H) 3 and R 3 -C(D) 3 98. The dosing regimen, method of treatment, delivery device, or kit of claim 97, wherein

100. Each H x is H or each H x is D or one H x is H and another H x 100. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 97 to 99, wherein

101. Each H y is H or each H y is D or one H y is H and another H y The dosing regimen, method of treatment, delivery device, or kit of any one of claims 97 to 100, wherein

102. Each H x , H y , and H z 102. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 97-101, wherein is deuterium.

103. 103. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 97-102, wherein the psychedelic agent is selected from the group consisting of the following compounds, or pharmaceutically acceptable salts thereof, wherein Ra and Rb are as defined in claim 97: 【Transformation 5】

104. 104. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 97 to 103, wherein Ra is H or Ra is D.

105. 105. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 97-104, wherein Rb is H or Rb is D.

106. 106. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 97-105, wherein the psychedelic agent is selected from the group consisting of the following compounds or pharmaceutically acceptable salts thereof: 【Transformation 6】

107. 107. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58-93 and 95-106, wherein parenteral administration comprises intravenous infusion by one or two syringe pumps.

108. 108. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 107, wherein the psychiatric or neurological disorder is selected from the group consisting of: (i) obsessive-compulsive disorder, (ii) depressive disorder, (iii) anxiety disorder, (iv) substance abuse and gambling disorder, and (v) anmotivation disorder, preferably a depressive disorder or an anxiety disorder.

109. 109. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 108, wherein the psychiatric or neurological disorder is a depressive disorder or an anxiety disorder.

110. 110. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 109, wherein the psychiatric or neurological disorder is major depressive disorder.

111. 111. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 110, wherein the duration of the psychedelic experience is about 3 hours or less, or about 2 hours or less, or about 1 hour or less.

112. The duration of the psychedelic experience: about 15 minutes to about 30 minutes, or about 30 minutes to about 90 minutes, when the psychedelic agent is N,N-dimethyltryptamine, a deuterated analog thereof, or a pharmaceutically acceptable salt thereof; or about 15 minutes to about 45 minutes, or about 45 minutes to about 180 minutes, when the psychedelic agent is selected from psilocybin, 4-acetoxy-N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, psilocin, deuterated analogs thereof, or pharmaceutically acceptable salts thereof; or about 20 minutes to about 30 minutes when the psychedelic agent is N,N-dimethyltryptamine or a pharmaceutically acceptable salt thereof; or about 60 minutes to about 90 minutes when the psychedelic agent is a deuterated analog of N,N-dimethyltryptamine or a pharmaceutically acceptable salt thereof; 112. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 111, wherein

113. the psychedelic agent is N,N-dimethyltryptamine or a pharmaceutically acceptable salt thereof, and the duration of the psychedelic experience is about 20 minutes to about 30 minutes, preferably about 20 minutes; or the psychedelic agent is a deuterated analog of N,N-dimethyltryptamine or a pharmaceutically acceptable salt thereof, and the duration of the psychedelic experience is from about 60 minutes to about 90 minutes; 113. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 57 to 112.

114. 114. The dosing regimen, method of treatment, delivery device, or kit of claim 112 or 113, wherein the duration of the experience is assessed by an attending clinician, preferably a psychiatrist, psychologist, or therapist.

115. 115. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 114, further comprising the steps and / or instructions of: a. The preparation phase, which involves preparing the patient to undergo a psychedelic experience; b. administering, comprising the administration regimen or method of treatment of any preceding claim; and c. An integration phase, involving an interview or discussion focused on the psychedelic experience conducted by a psychiatrist or therapist with the patient.

116. 116. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 115, wherein treating a psychiatric or neurological disorder in a patient comprises psychedelic-assisted psychotherapy.

117. 117. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 116, wherein a single effective dose is sufficient to achieve a breakthrough psychedelic experience in a patient.

118. 118. The dosing regimen, method of treatment, delivery device, or kit of any one of claims 58 to 117, wherein the patient is assessed at baseline assessment as having moderate or severe symptoms according to a psychiatric or neurological disorder rating scale.

119. 119. The dosing regimen, method of treatment, delivery device, or kit of claim 118, wherein the psychiatric or neurological disorder is a depressive disorder and the rating scale is selected from the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Rating Scale (HAMD-17), the Beck Depression Inventory-II (BDI-II), and combinations thereof.

120. 120. The dosing regimen, method of treatment, delivery device, or kit of claim 119, wherein at baseline assessment, the patient is assessed to have a score of 20 or greater on the Montgomery-Asberg Depression Rating Scale, or a score of 17 or greater on the Hamilton Depression Rating Scale (HAMD-17), or a score of 23 or greater on the Beck Depression Inventory-II.

Images