[go: up one dir, main page]

WO2025068714A1 - Compositions pharmaceutiques comprenant de la 5-méthoxy-n,n-diméthyltryptamine (5-meo-dmt) - Google Patents

Compositions pharmaceutiques comprenant de la 5-méthoxy-n,n-diméthyltryptamine (5-meo-dmt) Download PDF

Info

Publication number
WO2025068714A1
WO2025068714A1 PCT/GB2024/052500 GB2024052500W WO2025068714A1 WO 2025068714 A1 WO2025068714 A1 WO 2025068714A1 GB 2024052500 W GB2024052500 W GB 2024052500W WO 2025068714 A1 WO2025068714 A1 WO 2025068714A1
Authority
WO
WIPO (PCT)
Prior art keywords
dmt
meo
composition
patient
subject
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/GB2024/052500
Other languages
English (en)
Inventor
Cosmo FEILDING-MELLEN
Timothy Mason
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Beckley Psytech Ltd
Original Assignee
Beckley Psytech Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GBGB2314911.5A external-priority patent/GB202314911D0/en
Priority claimed from GBGB2403419.1A external-priority patent/GB202403419D0/en
Priority claimed from GBGB2403721.0A external-priority patent/GB202403721D0/en
Priority claimed from GBGB2405965.1A external-priority patent/GB202405965D0/en
Application filed by Beckley Psytech Ltd filed Critical Beckley Psytech Ltd
Publication of WO2025068714A1 publication Critical patent/WO2025068714A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0043—Nose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/32—Alcohol-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/36—Opioid-abuse

Definitions

  • compositions comprising 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)
  • This invention relates to dosage regimens of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), compositions of 5-MeO-DMT and uses thereof.
  • 5-MeO-DMT 5-methoxy-N,N-dimethyltryptamine
  • 5-MeO-DMT benzoate is the benzoate salt of the pharmacologically active compound of the tryptamine class, 5-MeO-DMT, and has the following structure:
  • 5-MeO-DMT a tryptamine alkaloid, is a short-acting serotonergic psychedelic that was first synthesised in 1936.
  • 5-MeO-DMT has been found in a large number of plants and has also been identified as the primary psychoactive component of the parotid gland venom of Incilius alvarius (formerly Bufo alvarius), the Sonoran Desert toad.
  • 5-MeO-DMT has been detected in blood, urine, and cerebrospinal fluid; however, its physiological role is unknown and more research is needed to definitively determine if 5-MeO-DMT is endogenously produced in humans.
  • 5-MeO-DMT is a serotonin (5-HT) receptor agonist with affinity to a variety of serotonin receptors. Its highest binding affinity is for the 5-HTIA receptor, with a 300-1000-fold higher selectivity compared with the 5-HT2A receptor.
  • the behavioural effects and safety margins of 5-MeO-DMT have been best characterised in rodents.
  • 5-MeO-DMT is rapidly metabolised by monoamine oxidase enzymes in the gut and liver, and is orally inactive. It is therefore usually administered parenterally through smoking or inhalation of vapour, or less commonly via intravenous, intramuscular, rectal, sublingual, or intranasal applications.
  • 5-MeO-DMT induces profound alterations in consciousness including mystical experiences, has minimal visual effects and higher rates of ego-dissolution compared to other psychedelics.
  • Data mainly derived from psilocybin and LSD studies, suggests that a profound psychedelic effect might be a necessary precursor for psychiatric efficacy of psychedelics, suggesting that 5-MeO-DMT, given at the right dose could be a beneficial alternative to current psychedelics in clinical development.
  • 5-MeO-DMT has a rapid onset and short duration of action, which might reduce the duration of treatment sessions and thus resource utilisation.
  • a rapid and sustained treatment of treatment resistant depression/major depressive disorder comprising the administration of 10 mg of 5- MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof.
  • the terms “approximately” and “about” generally should be understood to encompass ⁇ 5% of a specified amount or value.
  • a pharmaceutical composition comprising 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and one or more pharmaceutically acceptable carriers or excipients, wherein the composition comprises a dosage amount of 10 mg 5-MeO-DMT.
  • the composition is formulated for intranasal administration. In an embodiment, the composition is formulated as a dry powder. In an embodiment, the composition is formulated as a spray dried dry powder. In an embodiment, the composition comprises 5-MeO-DMT benzoate. In an embodiment, the composition comprises 5-MeO-DMT hydrochloride. In an embodiment, the composition comprises 5-MeO- DMT hydrobromide. In an embodiment, the composition comprises 5-MeO-DMT oxalate. In an embodiment, the 5-MeO-DMT is in crystalline form. In an embodiment, the composition is in crystalline form.
  • the composition comprises crystalline 5-MeO-DMT benzoate as characterised by one or more peaks in an XRPD diffractogram at 17.5, 17.7 and 21.O°20 ⁇ O.1°20 as measured using an x-ray wavelength of 1.5406 A.
  • the composition comprises crystalline 5-MeO-DMT hydrochloride as characterised by one or more peaks in an XRPD diffractogram at 9.2, 12.2, 14.1, 15.0, 18.5 and 19.5° ⁇ O.1°20 as measured using an x-ray wavelength of 1.5406 A.
  • the composition comprises crystalline 5- MeO-DMT hydrobromide as characterised by one or more peaks in an XRPD diffractogram at 14.6, 16.8, 20.8, 24.3, 24.9 and 27.5°20 ⁇ O.1°20 as measured using an x-ray wavelength of 1.5406 A.
  • the composition comprises crystalline 5-MeO-DMT oxalate as characterised by one or more peaks in an XRPD diffractogram at 13.0, 19.9 and 26.O°20 ⁇ O.1°20 as measured using an x-ray wavelength of 1.5406 A.
  • the composition comprises one or more of: chitosan, chitosan derivatives, fJ-cyclodextrin, Clostridium perfringens enterotoxin, zonula occludens toxin (ZOT), human neutrophil elastase inhibitor (ER143), sodium taurocholate, sodium deoxycholate sodium, sodium lauryl sulphate, glycodeoxycholate, palmitic acid, palmitoleic acid, stearic acid, oleyl acid, oleyl alcohol, capric acid sodium salt, DHA, EPA, dipalmitoyl phosphatidyl choline, soybean lecithin, lysophosphatidylcholine, dodecyl maltoside, tetradecyl maltoside, EDTA, lactose, cellulose, and citric acid.
  • ZOT zonula occludens toxin
  • ER143 human neutrophil elastase inhibitor
  • the composition comprises one or more of: mucoadhesive enhancer, penetrating enhancer, cationic polymers, cyclodextrins, Tight Junction Modulators, enzyme inhibitors, surfactants, chelators, and polysaccharides.
  • the composition is for use in a method of treatment of depression/major depressive disorder.
  • the composition is for use in a method of treatment of depression/major depressive disorder.
  • the composition is for use in a method of treatment of depression/major depressive disorder.
  • the composition is for use in a method of treatment of depression/major depressive disorder.
  • an intranasal dry powder pharmaceutical composition comprising 5- methoxy-N,N-dimethyltryptamine (5-MeO-DMT) benzoate and one or more pharmaceutically acceptable carriers or excipients, wherein the composition comprises a dosage amount of 10 mg 5-MeO-DMT, for use in a method of treatment.
  • the composition is for use in a method of treatment of depression/major depressive disorder.
  • the composition is for use in a method of treatment of treatment-resistant depression/major depressive disorder. In an embodiment, the composition is for use in a method of treatment of substance misuse disorder. In an embodiment, the composition is for use in a method of treatment of alcohol use disorder.
  • a method of treatment wherein a mystical experience is produced in a patient in need thereof by administration of a 10 mg dosage amount of 5-MeO-DMT.
  • 5- MeO-DMT is provided for use in the treatment of a mental health condition/disease, wherein 10 mg of 5-MeO- DMT is administered in a single intranasal dose.
  • the mental health condition/disease is depression/major depressive disorder.
  • the composition comprises a salt of 5-MeO-DMT. In an embodiment, the composition comprises a crystalline salt of 5-MeO-DMT. In an embodiment, there is provided a crystalline form of 5-MeO- DMT hydrobromide. In an embodiment, there is provided a crystalline form of 5-MeO-DMT hydrobromide, characterised by one or more peaks in an XRPD diffractogram at 14.6, 16.8, 20.8, 24.3, 24.9 and 27.5°20 ⁇ O.1°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • a crystalline form of 5-MeO-DMT phosphate characterised by one or more peaks in an XRPD diffractogram at 12.9, 20.4 and 23.1°20 ⁇ O.1°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • a crystalline form of 5-MeO-DMT fumarate characterised by one or more peaks in an XRPD diffractogram at 13.0, 16.3 and 22.1°20 ⁇ O.1°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • a crystalline form of 5-MeO-DMT oxalate characterised by one or more peaks in an XRPD diffractogram at 13.0, 19.9 and 26.O°20 ⁇ O.1°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • a crystalline form of 5-MeO-DMT tartrate characterised by one or more peaks in an XRPD diffractogram at 18.3, 18.6, and 2O.7°20 ⁇ O.1°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • a crystalline form of 5-MeO-DMT benzenesulfonate characterised by one or more peaks in an XRPD diffractogram at 9.5, 21.2, and 23.6°20 ⁇ O.1°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • a crystalline form of 5-MeO-DMT tosylate characterised by one or more peaks in an XRPD diffractogram at 19.3, 23.6 and 24.1 °20 ⁇ O.1°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • a crystalline form of 5-MeO-DMT glycolate characterised by one or more peaks in an XRPD diffractogram at 20.2, 21.1 and 23.4°20 ⁇ O.1°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • a crystalline form of 5-MeO-DMT ketoglutarate characterised by one or more peaks in an XRPD diffractogram at 14.4, 18.2 and 2O.9°20 ⁇ O.1°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • a crystalline form of 5- MeO-DMT malate characterised by one or more peaks in an XRPD diffractogram at 18.3, 18.7 and 18.9°20 ⁇ O.1°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • a crystalline form of 5-MeO-DMT saccharinate characterised by one or more peaks in an XRPD diffractogram at 8.7, 15.2 and 2O.9°20 ⁇ O.1°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • a crystalline form of 5-MeO-DMT hydrochloride characterised by one or more peaks in an XRPD diffractogram at 9.2° ⁇ 0.1°, 12.2° ⁇ 0.1°, 14.1° ⁇ 0.1°, 15.0° ⁇ 0.1°, 18.5° ⁇ 0.1°, and 19.5° ⁇ O.1°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • a crystalline form of 5-MeO-DMT benzoate characterised by one or more peaks in an XRPD diffractogram at 17.5, 17.7 and 21.O°20 ⁇ O.1°20 as measured using an x-ray wavelength of 1.5406 A.
  • the composition is formulated as a powder which is suitable for administration by inhalation/insufflation via a medicament dispenser selected from a reservoir dry powder inhaler, a unit-dose dry powder inhaler, a pre-metered multi-dose dry powder inhaler, a nasal inhaler or a pressurised metered dose inhaler.
  • the powder comprises particles, the particles having a median diameter of less than 2000 pm, 1000 pm, 500 pm, 250 pm, 100 pm, 50 pm, or 1 pm.
  • the powder comprises particles, the particles having a median diameter of greater than 500 pm, 250 pm, 100 pm, 50 pm, 1 pm or 0.5 pm.
  • the nature of the powder can be adjusted to suit needs. For example, if being made for nasal inhalation, then the particles may be adjusted to be much finer than if the powder is going to be formulated into a gelatine capsule, or differently again if it is going to be compacted into a tablet.
  • the 5-MeO-DMT salt is amorphous or crystalline. In an embodiment, the 5-MeO-DMT salt is in a polymorphic crystalline form.
  • the dosage amount is the equivalent amount of the free base delivered when the salt is taken. So 100 mg dosage amount of 5-MeO-DMT corresponds to 117 mg of the hydrochloride salt (i.e. both providing the same molar amount of the active substance).
  • the greater mass of the salt needed is due to the larger formula weight of the hydrogen chloride salt (i.e. 218.3 g/mol for the free base as compared to 254.8 g/mol for the salt).
  • the deuterated or triturated version of 5-MeO-DMT also considered within the scope of the invention, a slight increase in mass can be expected due to the increased formula weight of these isotopic compounds.
  • X mg of a 5-MeO-DMT salt refers to the dosage amount of said salt which equates to X mg of the 5-MeO-DMT freebase. Therefore, a pharmaceutical composition comprising 12 mg 5-MeO-DMT benzoate refers to a pharmaceutical composition comprising 18.7 mg 5-MeO-DMT benzoate which equates to 12 mg of 5-MeO-DMT freebase. In an embodiment, there is provided the use of about 15.59 mg 5-MeO-DMT benzoate, or a pharmaceutical composition, thereof.
  • compositions comprise one or more pharmaceutically acceptable carriers or excipients.
  • the composition comprises one or more pharmaceutically acceptable carriers or excipients.
  • the composition comprises one or more of: mucoadhesive enhancer, penetrating enhancer, cationic polymers, cyclodextrins, Tight Junction Modulators, enzyme inhibitors, surfactants, chelators, and polysaccharides.
  • the composition comprises one or more of: chitosan, chitosan derivatives (such as N,N,N-trimethyl chitosan (TMC), n-propyl-(QuatPropyl), n-butyl-(QuatButyl) and n-hexyl (QuatHexyl)-
  • TMC N,N,N-trimethyl chitosan
  • TMC N,N,N-trimethyl chitosan
  • n-butyl-(QuatButyl) and n-hexyl (QuatHexyl
  • composition disclosed herein is for use as a medicament. In an embodiment the composition disclosed herein is for use in a method of treatment of a human or animal patient/subject by therapy. In an embodiment the composition comprises a dosage amount of 5-MeO-DMT in the range of 0.05 mg to 100 mg. In an embodiment the composition comprises a dosage amount of 5-MeO-DMT in the range of
  • the composition comprises a dosage amount of 5-MeO-DMT in the range of 0.5 mg to 25 mg. In an embodiment the composition comprises a dosage amount of 5-MeO-DMT in the range of 0.5 mg to 10 mg. In an embodiment the composition comprises a dosage amount of 5-MeO-DMT in the range of 1 mg to 10 mg. In an embodiment the composition comprises a dosage amount of 5-MeO-DMT in the range of 1 mg to 8 mg. In an embodiment the composition comprises a dosage amount of 5-MeO-DMT in the range of 3 mg to 15 mg. In an embodiment the composition comprises a dosage amount of 5-MeO-DMT in the range of 0.005 mg to 100 mg.
  • the composition comprises a dosage amount of 5-MeO- DMT in the range of 0.001 mg to 100 mg. In an embodiment the composition comprises a dosage amount of 5- MeO-DMT in the range of 0.0005 mg to 100 mg.
  • the level of the active agent can be adjusted as required by need for example to suit a certain patient group (e.g. the elderly) or the conditions being treated.
  • a pharmaceutical composition comprising 10-12 mg of 5-MeO-DMT.
  • a pharmaceutical composition capable of producing a complete mystical experience wherein said composition comprises 10-12 mg 5-MeO-DMT.
  • the 5-MeO-DMT is present as the benzoate salt.
  • the composition is for intranasal delivery.
  • the composition is a dry powder.
  • a pharmaceutical composition comprising: i) particles of 5-methoxy-N,N- dimethyltryptamine (5-MeO-DMT), or pharmaceutically acceptable salts or derivatives thereof; and ii) a pH-sensitive polymer, wherein the particles are nanoparticles or microparticles; and wherein the particles are encapsulated in the pH-sensitive polymer.
  • a pharmaceutically acceptable composition comprising 5-MeO-DMT, wherein administration of said composition to a patient/subject produces in said patient/subject a blood plasma Cmax (ng/mL) of about 4-39, of about 5-35 or of about 6-29.
  • administration of said composition to a patient/subject produces in said patient/subject a Tmax (h) of about 0.05-0.5, of about 0.06-0.3 or of about 0.1- 0.25. In an embodiment, administration of said composition to a patient/subject produces in said patient/subject a ti/2 (h) of about 0.1-0.55, of about 0.2-0.5 or of about 0.25-0.44. In an embodiment, administration of said composition to a patient/subject produces in said patient/subject a AUCiast (h*ng/mL) of about 1.0-22, of about 1.2-20 or of about 1.5-18.5.
  • administration of said composition to a patient/subject produces in said patient/subject a AUCmt (h*ng/mL) of about 1.5-27, of about 1.7-25 or of about 1.9-24.
  • Cmax may refer to the maximum concentration (e.g., maximum blood plasma concentration) of a compound, as the result of the administration of a composition comprising the compound.
  • Tmax may refer to the time required for the concentration of the compound to reach Cmax, after the administration of the composition
  • ti/2 e.g., half-life
  • halve e.g., reach half of the Cmax
  • AUCiast may refer to an area under a curve representing plasma concentration as a function of time. The area may include the last measured plasma concentration. AUCmt may refer to an area under a curve representing plasma concentration as a function of time, extrapolated to where time approaches infinity.
  • the composition comprises 5-MeO-DMT benzoate. In an embodiment, the 5-MeO-DMT is present as the benzoate salt. In an embodiment, the 5-MeO-DMT composition is a composition for intranasal administration. In an embodiment, the 5-MeO-DMT composition is an intranasal composition. In an embodiment, the composition comprises 1-12 mg of 5-MeO-DMT benzoate.
  • the composition comprises 1 mg of 5-MeO-DMT benzoate, wherein intranasal administration of said composition to a patient/subject produces in said patient/subject one or more of: a Cmax (ng/mL) of about 4-8, of about 5-7 or of about 6; a Tmax (h) of about 0.05-0.2, of about 0.06-0.15 or of about 0.1; a ti/2 (h) of about 0.1-0.4, of about 0.2-0.3 or of about 0.25; a AUCiast (h*ng/mL) of about 1.0-1.8, of about 1.2-1.6 or of about 1.5; or a AUCmt (h*ng/mL) of about 1.5-2.3, of about 1.7-2.0 or of about 1.9.
  • a Cmax ng/mL
  • Tmax of about 0.05-0.2, of about 0.06-0.15 or of about 0.1
  • a ti/2 (h) of about 0.1-0.4 of about 0.2-0.3 or of about 0.
  • the composition comprises 4 mg of 5-MeO-DMT benzoate, wherein intranasal administration of said composition to a patient/subject produces in said patient/subject one or more of: a Cmax (ng/mL) of about 3-13, of about 7-11 or of about 9; a Tmax (h) of about 0.03-0.2, of about 0.09-0.16 or of about 0.12; a ti/2 (h) of about 0.27-0.53, of about 0.30-0.45 or of about 0.37; a AUCiast (h*ng/mL) of about 1.9-7.2, of about 3.5-5.5 or of about 4.5; or a AUCint (h*ng/mL) of about 2.4-7.4, of about 3.5-6.5 or of about 5.
  • the composition comprises 8 mg of 5-MeO-DMT benzoate, wherein intranasal administration of said composition to a patient/subject produces in said patient/subject one or more of: a Cmax (ng/mL) of about 16.4-30.9, of about 19-25 or of about 22; a Tmax (h) of about 0.1-0.27, of about 0.1-0.22 or of about 0.17; a ti/2 (h) of about 0.21-0.37, of about 0.25-0.35 or of about 0.30; a AUCiast (h*ng/mL) of about 9.25- 17.23, of about 11-15 or of about 13.1; or a AUCmt (h*ng/mL) of about 9.42-18.7, of about 11-16 or of about
  • the composition comprises 10 mg of 5-MeO-DMT benzoate, wherein intranasal administration of said composition to a patient/subject produces in said patient/subject one or more of: a Cmax (ng/mL) of about 10.4-46.4, of about 25-39 or of about 32; a Tmax (h) of about 0.03-0.27, of about 0.1-0.22 or of about 0.14; a ti/2 (h) of about 0.24-0.59, of about 0.29-0.47 or of about 0.38; a AUCiast (h*ng/mL) of about 9.37- 20.41, of about 13-18 or of about 15.4; or a AUCmt (h*ng/mL) of about 9.42-18.7, of about 11-16 or of about
  • the composition comprises 12 mg of 5-MeO-DMT benzoate, wherein intranasal administration of said composition to a patient/subject produces in said patient/subject one or more of: a Cmax (ng/mL) of about 20.9-39, of about 25-35 or of about 29; a Tmax (h) of about 0.17-0.5, of about 0.2-0.3 or of about 0.25; a ti/2 (h) of about 0.28-0.55, of about 0.40-0.50 or of about 0.44; a AUCiast (h*ng/mL) of about 14.45-22, of about 16-20 or of about 18.5; or a AUCmt (h*ng/mL) of about 19.10-27, of about 22-25 or of about
  • the composition is a dry powder composition.
  • the composition comprises one or more pharmaceutically acceptable carriers or excipients.
  • the composition comprises one or more of: HPMC, carbomers, xanthan gum, carrageenan, copolymers of methyl vinyl ether and maleic anhydride (PVM/MA), hydroxypropyl cellulose (HPC) or sodium carboxymethylcellulose (Na-CMC).
  • the composition comprises one or more of chitosan, chitosan derivatives (such as N,N,N-trimethyl chitosan (TMC), n-propyl-(QuatPropyl), n-butyl-(QuatButyl) and n-hexyl (QuatHexyl)-N,N-dimethyl chitosan, chitosan chloride), fJ-cyclodextrin, Clostridium perfringens enterotoxin, zonula occludens toxin (ZOT), human neutrophil elastase inhibitor (ER143), sodium taurocholate, sodium deoxycholate sodium, sodium lauryl sulphate, glycodeoxycholate, palmitic acid, palmitoleic acid, stearic acid, oleyl acid, oleyl alcohol, capric acid sodium salt, DHA, EPA, dipalmitoyl phosphatidyl choline, soybean levodo
  • the 5-MeO-DMT is present as crystalline 5-MeO-DMT benzoate as characterised by peaks in an XRPD diffractogram at 17.5, 17.7 and 21.O°20 ⁇ O.1°20.
  • a pharmaceutically acceptable dry powder intranasal composition comprising 1-12 mg of 5-MeO-DMT benzoate and HPMC.
  • intranasal administration of the composition to a patient/subject produces in said patient/subject one or more of: a Cmax (ng/mL) of about 4- 39, of about 5-35 or of about 6-29; a Tmax (h) of about 0.05-0.5, of about 0.06-0.3 or of about 0.1-0.25; a ti/2 (h) of about 0.1-0.55, of about 0.2-0.5 or of about 0.25-0.44; a AUCiast (h*ng/mL) of about 1.0-22, of about 1.2-20 or of about 1.5-18.5; or a AUCmt (h*ng/mL) of about 1.5-27, of about 1.7-25 or of about 1.9-23.9.
  • the use of the composition for the treatment or prevention of a disease or condition is depression/major depressive disorder or treatment-resistant depression/major depressive disorder.
  • the formulation of 5-MeO-DMT benzoate is provided.
  • a pharmaceutically acceptable composition comprising 5-MeO-DMT (hereafter '5-MeO-DMT composition') comprising 1 mg 5-MeO-DMT benzoate wherein intranasal administration of said composition to a patient/subject produces in said patient/subject one or more of: a Cmax (ng/mL) of about 4-8, of about 5-7 or about 6; a Tmax (h) of about 0.05-0.2, of about 0.06-0.15 or about 0.1; a ti/2 (h) of about 0.1-0.4, of about 0.2-0.3 or about 0.25; a AUCiast (h*ng/mL) of about 1.0-1.8, of about 1.2-1.6 or about 1.5; or a AUCint (h*ng/mL) of about 1.5-2.3, of about 1.7-2.0 or about 1.9.
  • a Cmax ng/mL
  • Tmax of about 0.05-0.2, of about 0.06-0.15 or about 0.1
  • a 5-MeO-DMT composition comprising 2.5 mg 5-MeO-DMT benzoate wherein intranasal administration of said composition to a patient/subject produces in said patient/subject one or more of: a Cmax (ng/mL) of about 4-12, of about 6-10 or about 8; a Tmax (h) of about 0.1-0.3, of about 0.15-0.25 or about 0.18; a ti/2 (h) of about 0.1-0.4, of about 0.20-0.35 or about 0.32; a AUCiast (h*ng/mL) of about 2.3-6.5, of about 3.0- 4.4 or about 3.8; or a AUCmt (h*ng/mL) of about 2.9-6.8, of about 3.5-5.5 or about 4.4.
  • a 5-MeO-DMT composition comprising 4 mg 5-MeO-DMT benzoate wherein intranasal administration of said composition to a patient/subject produces in said patient/subject one or more of: a Cmax (ng/mL) of about 3-13, of about 7-11 or about 9; a Tmax (h) of about 0.03-0.2, of about 0.09-0.16 or about 0.12; a ti/2 (h) of about 0.27-0.53, of about 0.30-0.45 or about 0.37; a AUCiast (h*ng/mL) of about 1.9-7.2, of about 3.5-5.5 or about 4.5; or a AUCmt (h*ng/mL) of about 2.4-7.4, of about 3.5-6.5 or about 5.
  • a 5-MeO-DMT composition comprising 6 mg 5-MeO-DMT benzoate wherein intranasal administration of said composition to a patient/subject produces in said patient/subject one or more of: a Cmax (ng/mL) of about 7.7-19.3, of about 12.5-17 or about 15; a Tmax (h) of about 0.07-0.27, of about 0.1-0.2 or about 0.15; a ti/2 (h) of about 0.32-0.42, of about 0.35-0.4 or about 0.37; a AUCiast (h*ng/mL) of about 4.6-12, of about 6-10 or about 8; or a AUCmt (h*ng/mL) of about 8.6-11, of about 9-10.5 or about 9.8.
  • a 5-MeO-DMT composition comprising 8 mg 5-MeO-DMT benzoate wherein intranasal administration of said composition to a patient/subject produces in said patient/subject one or more of: a Cmax (ng/mL) of about 16.4-30.9, of about 19-25 or about 22; a Tmax (h) of about 0.1-0.27, of about 0.1-0.22 or about 0.17; a ti/2 (h) of about 0.21-0.37, of about 0.25-0.35 or about 0.30; a AUCiast (h*ng/mL) of about 9.25-17.23, of about 11-15 or about 13.1; or a AUCmt (h*ng/mL) of about 9.42-18.7, of about 11-16 or about 13.9.
  • a 5-MeO-DMT composition comprising 10 mg 5-MeO-DMT benzoate wherein intranasal administration of said composition to a patient/subject produces in said patient/subject one or more of: a Cmax (ng/mL) of about 10.4-46.4, of about 25-39 or about 32; a Tmax (h) of about 0.03-0.27, of about 0.1-0.22 or about 0.14; a ti/2 (h) of about 0.24-0.59, of about 0.29-0.47 or about 0.38; a AUCiast (h*ng/mL) of about 9.37-20.41, of about 13-18 or about 15.4; or a AUCmt (h*ng/mL) of about 9.42-18.7, of about 11-16 or about 13.9.
  • a 5-MeO-DMT composition comprising 12 mg 5-MeO-DMT benzoate wherein intranasal administration of said composition to a patient/subject produces in said patient/subject one or more of: a Cmax (ng/mL) of about 20.9-38.6, of about 25-35 or about 29; a Tmax (h) of about 0.17-0.5, of about 0.2-0.3 or about 0.25; a ti/2 (h) of about 0.28-0.55, of about 0.40-0.50 or about 0.44; a AUCiast (h*ng/mL) of about 14.45-22.23, of about 16-20 or about 18.5; or a AUCmt (h*ng/mL) of about 19.10-27.15, of about 22- 25 or about 23.9.
  • a 5-MeO-DMT composition comprising 1-12 mg 5-MeO-DMT benzoate wherein intranasal administration of said composition to a patient/subject produces in said patient/subject one or more of: a Cmax (ng/mL) of about 4-38.6, of about 5-35 or about 6-29; a Tmax (h) of about 0.05-0.5, of about 0.06-0.3 or about 0.1-0.25; a ti/2 (h) of about 0.1-0.55, of about 0.2-0.5 or about 0.25-0.44; a AUCiast (h*ng/mL) of about 1.0-22.23, of about 1.2-20 or about 1.5-18.5; or a AUCmt (h*ng/mL) of about 1.5-27.15, of about 1.7-25 or about 1.9-23.9.
  • the composition produces in a subject, per each 10 mg of 5-MeO-DMT present in the composition, one or more of: a Cmax (ng/mL) of about 10.4-46.4, of about 25-39 or about 32; a Tmax (h) of about 0.03-0.27, of about 0.1-0.22 or about 0.14; a ti/2 (h) of about 0.24-0.59, of about 0.29-0.47 or about 0.38; a AUCiast (h*ng/mL) of about 9.37-20.41, of about 13-18 or about 15.4; or a AUCmt (h*ng/mL) of about 9.42-18.7, of about 11-16 or about 13.9.
  • the 5-MeO-DMT composition comprises a mucoadhesive.
  • the 5-MeO- DMT composition comprises one or more of: HPMC, carbomers, xanthan gum, carrageenan, copolymers of methyl vinyl ether and maleic anhydride (PVM/MA), hydroxypropyl cellulose (HPC) or sodium carboxymethylcellulose (Na-CMC).
  • PVM/MA methyl vinyl ether and maleic anhydride
  • HPC hydroxypropyl cellulose
  • Na-CMC sodium carboxymethylcellulose
  • the 5-MeO-DMT composition comprises HPMC.
  • the 5-MeO-DMT composition comprises crystalline 5-MeO-DMT benzoate, as described subsequently or previously.
  • composition disclosed herein is for use as a medicament.
  • a composition as described previously or subsequently for the treatment of a disease or condition there is provided use of a composition as described previously or subsequently for the treatment of a disease or condition.
  • the disease or condition is depression/major depressive disorder. In an embodiment, the disease or condition is treatment-resistant depression/major depressive disorder. In an embodiment, the disease or condition is: conditions caused by dysfunctions of the central nervous system, conditions caused by dysfunctions of the peripheral nervous system, conditions benefiting from sleep regulation (such as insomnia), conditions benefiting from analgesics (such as chronic pain), migraines, trigeminal autonomic cephalgias (such as short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT), and shortlasting neuralgiform headaches with cranial autonomic symptoms (SUNA)), conditions benefiting from neurogenesis (such as stroke, traumatic brain injury, Parkinson's dementia), conditions benefiting from antiinflammatory treatment, depression/major depressive disorder, treatment resistant depression/major depressive disorder, anxiety, substance use disorder, addictive disorder, gambling disorder, eating disorders, obsessive-compulsive disorders, or body dysmorphic disorders, optionally the condition is SUNCT and/or SUNA
  • the method of use is a method of treatment.
  • the method of treatment is a method of treatment of more than one of the above conditions, for example, the method of treatment may be a method of treatment of depression/major depressive disorder and anxiety.
  • the composition is administered one or more times a year. In an embodiment the composition is administered one or more times a month. In an embodiment the composition is administered one or more times a week. In an embodiment the composition is administered one or more times a day. In an embodiment the composition is administered at such a frequency as to avoid tachyphylaxis. In an embodiment the composition is administered together with a complementary treatment and/or with a further active agent.
  • the further active agent is a psychedelic compound, optionally a tryptamine.
  • the further active agent is lysergic acid diethylamide (LSD), psilocybin, psilocin or a prodrug thereof.
  • the further active agent is an antidepressant compound.
  • the further active agent is selected from an SSRI, SNRI, TCA or other antidepressant compounds.
  • the further active agent is selected from Citalopram (Celexa, Cipramil), Escitalopram (Lexapro, Cipralex), Fluoxetine (Prozac, Sarafem), Fluvoxamine (Luvox, Faverin), Paroxetine (Paxil, Seroxat), Sertraline (Zoloft, Lustral), Desvenlafaxine (Pristiq), Duloxetine (Cymbalta), Levomilnacipran (Fetzima), Milnacipran (Ixel, Savella), Venlafaxine (Effexor), Vilazodone (Viibryd), Vortioxetine (Trintellix), Nefazodone (Dutonin, Nefadar, Serzone), Trazodone (Desyrel), Reboxetine (Edronax), Teniloxazine (Lucelan, Metatone), Viloxazine (Vivalan), Bupropion (Wellbutrin), Ami
  • the further active agent is selected from Celexa (citalopram), Cymbalta (duloxetine), Effexor (venlafaxine), Lexapro (escitalopram), Luvox (fluvoxamine), Paxil (paroxetine), Prozac (fluoxetine), Remeron (mirtazapine), Savella (milnacipran), Trintellix (vortioxetine), Vestra (reboxetine), Viibryd (vilazodone), Wellbutrin (bupropion), Zoloft (sertraline).
  • one or more disorders or conditions in the patient have previously failed to be treated with one or more of the above treatments.
  • a method optionally a rapid and durable method, of improving one or more of: sexual functioning, anxiety, anhedonia, cognition and/or overall quality of life, in a patient in need thereof.
  • the improvement is assessed by one or more of: the Arizona Sexual Experiences Scale, the 7-item Generalised Anxiety Disorder Assessment (GAD-7), difference in self-reported anhedonia symptoms, assessed by Snaith-Hamilton Pleasure Scale (SHAPS), the Cognitive Test Battery, Patient Global Impression of Change and/or improvement in self-reported quality of life, assessed by EuroQoL- 5 Dimension-5 Level (EQ-5D-5L).
  • a method optionally a rapid and durable method, of treating a patient in need thereof, wherein the patient is aged 18 to 75 years old.
  • the patient has at least moderate major depressive disorder (MDD), (single or recurrent episode as informed by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5] criteria; if single episode, duration of >3 months and ⁇ 2 years) based on medical records, clinical assessment, and documented completion of the version 7.0.2 Mini International Neuropsychiatric Interview (MINI).
  • MDD major depressive disorder
  • DSM-5 Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5] criteria; if single episode, duration of >3 months and ⁇ 2 years
  • MINI Mini International Neuropsychiatric Interview
  • the patient is diagnosed with TRD defined as failure to respond to an adequate dose and duration of at least 2 pharmacological treatments, in the current episode, based on the MGH ATRQ assessment.
  • augmentation with an add-on treatment counts as a second treatment.
  • the patient has not failed more than 5 prior pharmacological treatments in the current episode.
  • psychotherapy is not counted towards treatment failure.
  • the patient has a Hamilton Depression Rating Scale (HDRS) (17 item) score >19 at baseline/prior to treatment.
  • the patient has a CGI-S >4 at baseline/prior to treatment.
  • the patient does not have a current or past history of schizophrenia, post- traumatic stress disorder, psychotic disorder including psychotic depression, bipolar disorder, delusional disorder, schizoaffective disorder, or any other severe psychiatric disorder.
  • the patient does not have a current or past history of schizophrenia, post-traumatic stress disorder, psychotic disorder including psychotic depression, bipolar disorder, delusional disorder, schizoaffective disorder, or any other severe psychiatric disorder as assessed by medical history and a structured clinical interview (MINI).
  • the patient does not have a current personality disorders: Cluster A (paranoid, schizoid, schizotypal), Cluster B (antisocial, borderline, histrionic, narcissistic), or Cluster C (avoidant, dependent, - obsessive compulsive).
  • the patient does not have a current personality disorders: Cluster A (paranoid, schizoid, schizotypal), Cluster B (antisocial, borderline, histrionic, narcissistic), or Cluster C (avoidant, dependent, -obsessive compulsive) assessed via McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD), MINI, and clinical judgement.
  • the patient does not have a first-degree family history of schizophrenia, bipolar disorder, delusional disorder, or schizoaffective disorder.
  • the patient does not have current (within the last year) alcohol or substance use disorder (other than caffeine or nicotine).
  • the patient does not have current (within the last year) alcohol or substance use disorder (other than caffeine or nicotine) according to DSM-5 and assessed by the MINI.
  • the patient has not at any time been unresponsive to ketamine or esketamine.
  • the patient has not at any time been unresponsive to an adequate course of treatment with electroconvulsive therapy (ECT).
  • ECT electroconvulsive therapy
  • the patient has not at any time been unresponsive to an adequate course of treatment with electroconvulsive therapy (ECT) defined as at least 7 treatments with unilateral/bilateral ECT, or has received vagal nerve stimulation or has received deep brain stimulation.
  • the patient has not had suicidal ideation with some intent to act within 12 months prior to treatment.
  • the patient has not had suicidal ideation with some intent to act within 12 months prior to treatment, based on the C-SSRS, corresponding to a response of "Yes" on Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) for suicidal ideation on the C-SSRS, or any suicidal behavior prior to treatment.
  • the patient has not attempted suicide and/or any other self-injurious behaviour within 12 months prior to treatment.
  • the patient does not have a history of any medical condition that could make receiving a sympathomimetic drug harmful because of transient and marked increases in blood pressure and heart rate.
  • the patient does not have atherosclerotic cardiovascular disease, obstructive coronary artery disease, myocardial infarction, hospitalisation for unstable angina, stroke, hospitalisation for transient ischemic attacks, known aortic or cerebral aneurysm or revascularization procedure within 12 months prior to treatment.
  • the patient does not have significant valvular heart disease, history of hospitalisation for heart failure and/or history of hospitalisation for atrial or ventricular arrhythmias.
  • the patient does not have a history of uncontrolled hypertension despite antihypertensive therapy and/or any past history of a hospital admission for hypertension.
  • the patient does not have controlled hypertension on antihypertensive therapy with repeated clinic seated or semi-recumbent systolic blood pressure >130 mmHg or diastolic blood pressure > 80 mmHg. In an embodiment, the patient does not have repeated clinic seated or semi-recumbent systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg. In an embodiment, the patient does not have one or more of hypo/hyperthyroidism with abnormal thyroid stimulating hormone values, uncontrolled or insulin dependent diabetes with HbAlc >8, renal failure with Creatinine Clearance ⁇ 45 mL/min.
  • the patient does not have any seizure disorder and/or any seizure within 2 years of treatment. In an embodiment, the patient does not have any clinically significant results on ECG or a Q.T interval corrected using Fridericia's formula (QTcF) >450 msec for males or >470 msec for females prior to treatment. In an embodiment, the patient does not have any history of intolerance to 5-MeO-DMT or related compounds. In an embodiment, the patient does not have any nasal obstruction, blockage, or symptoms of congestion at the time of treatment. In an embodiment, the patient is not a female patient who is pregnant, lactating, or of childbearing potential who is not willing or able to use adequate forms of contraception during treatment.
  • QTcF Fridericia's formula
  • the patient is not a male patient who is not willing or able to use adequate forms of contraception during treatment.
  • the patient does not have a personal or family history of malignant hyperthermia.
  • the patient has discontinued one or more of the following at least 5 half-lives prior to treatment: Medications that antagonise the serotonin 2A receptor, Medications with serotonergic activity (e.g., SSRIs, SNRIs, efavirenz, lithium), Tramadol, Opioids, Antiviral Medications, St. John's Wort, Medications that inhibit UGT1A9 or UGT1A10 enzymes, Monoamine Oxidase Inhibitors (MAOIs) and/or Medications that inhibit aldehyde or alcohol dehydrogenase.
  • Medications that antagonise the serotonin 2A receptor Medications with serotonergic activity (e.g., SSRIs, SNRIs, efavirenz, lithium), Tramado
  • the patient does not inhale during the administration.
  • 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11% of the 5-MeO-DMT of the present pharmaceutical compositions reaches the turbinates.
  • the plasma exposure is between 1-46 ng/mL, between 5-40 ng/mL, between 10-35 ng/mL, or between 25-32 ng/mL.
  • the plasma exposure is at least 25 ng/mL.
  • the licensed physician overseeing the administration to the patient uses the plasma exposure to adjust dosing.
  • the subsequent dose received by a patient is 12 mg of 5-MeO-DMT if the plasma exposure was less than 25 ng/mL at the 10 mg dose.
  • the pharmaceutical composition is for use in a method of treating depression in a patient/subject in need thereof, wherein the method comprises: a) measuring the patient/subject's blood pressure a first time; b) administering to the patient/subject 10 mg of 5-MeO-DMT; c) measuring the patient/subject's blood pressure a second time; d) discharging the patient/subject if the patient/subject's blood pressure at the second time is about the same as the patient/subject 's blood pressure at the first time, wherein the patient/subject is discharged within 90 minutes of step (b).
  • the pharmaceutical composition is for use in a method of treating depression in a patient/subject in need thereof, wherein the method comprises: a) measuring the patient/subject's blood pressure a first time; b) administering to the patient/subject 10 mg of 5-MeO-DMT intranasally; c) measuring the patient/subject's blood pressure a second time; d) discharging the patient/subject if the patient/subject's blood pressure at the second time is about the same as the patient/subject 's blood pressure at the first time, wherein the patient/subject is discharged within 90 minutes of step (b).
  • the pharmaceutical composition is for use in a method of treating treatment-resistant depression in a patient/subject in need thereof, wherein the method comprises: a) measuring the patient/subject's blood pressure a first time; b) administering to the patient/subject 10 mg of 5-MeO-DMT; c) measuring the patient/subject's blood pressure a second time; d) discharging the patient/subject if the patient/subject's blood pressure at the second time is about the same as the patient/subject 's blood pressure at the first time, wherein the patient/subject is discharged within 90 minutes of step (b).
  • the pharmaceutical composition is for use in a method of treating treatment-resistant depression in a patient/subject in need thereof, wherein the method comprises: a) measuring the patient/subject's blood pressure a first time; b) administering to the patient/subject 10 mg of 5-MeO-DMT intranasally; c) measuring the patient/subject's blood pressure a second time; d) discharging the patient/subject if the patient/subject's blood pressure at the second time is about the same as the patient/subject 's blood pressure at the first time, wherein the patient/subject is discharged within 90 minutes of step (b).
  • the pharmaceutical composition is for use in a method of treating depression in a patient/subject in need thereof, wherein the method comprises: a) measuring the patient/subject's blood pressure; b) administering to the patient/subject 10 mg of 5-MeO-DMT if the patient/subject's systolic blood pressure is less than 130 mmHg and/or subject's diastolic blood pressure is less than 80 mmHg.
  • the pharmaceutical composition is for use in a method of treating depression in a patient/subject in need thereof, wherein the method comprises: c) measuring the patient/subject's blood pressure; d) intranasally administering to the patient/subject 10 mg of 5-MeO-DMT if the patient/subject's systolic blood pressure is less than 130 mmHg and/or subject's diastolic blood pressure is less than 80 mmHg.
  • the pharmaceutical composition is for use in a method of treating treatment-resistant depression in a patient/subject in need thereof, wherein the method comprises: a) measuring the patient/subject's blood pressure; b) administering to the patient/subject 10 mg of 5-MeO-DMT if the patient/subject's systolic blood pressure is less than 130 mmHg and/or subject's diastolic blood pressure is less than 80 mmHg.
  • the pharmaceutical composition is for use in a method of treating treatment-resistant depression in a patient/subject in need thereof, wherein the method comprises: a) measuring the patient/subject's blood pressure; b) intranasally administering to the patient/subject 10 mg of 5-MeO-DMT if the patient/subject's systolic blood pressure is less than 130 mmHg and/or subject's diastolic blood pressure is less than 80 mmHg.
  • the pharmaceutical composition is for use in a method of treating depression in a patient/subject in need thereof, wherein the method comprises: a) administering to the patient/subject a first dose of 10 mg of 5-MeO-DMT; b) monitoring the patient/subject for relapse of one or more depressive symptoms; c) administering to the patient/subject a second dose of 5-MeO-DMT, wherein the second dose is administered at least 28 days after the first dose is administered to the patient/subject.
  • the pharmaceutical composition is for use in a method of treating depression in a patient/subject in need thereof, wherein the method comprises: a) administering to the patient/subject a first dose of 10 mg of 5-MeO-DMT intranasally; b) monitoring the patient/subject for relapse of one or more depressive symptoms; c) administering to the patient/subject a second dose of 5-MeO-DMT intranasally, wherein the second dose is administered at least 28 days after the first dose is administered to the patient/subject.
  • the pharmaceutical composition is for use in a method of treating treatment-resistant depression in a patient/subject in need thereof, wherein the method comprises: a) administering to the patient/subject a first dose of 10 mg of 5-MeO-DMT; b) monitoring the patient/subject for relapse of one or more depressive symptoms; c) administering to the patient/subject a second dose of 5-MeO-DMT, wherein the second dose is administered at least 28 days after the first dose is administered to the patient/subject.
  • the pharmaceutical composition is for use in a method of treating treatment-resistant depression in a patient/subject in need thereof, wherein the method comprises: a) administering to the patient/subject a first dose of 10 mg of 5-MeO-DMT intranasally; b) monitoring the patient/subject for relapse of one or more depressive symptoms; c) administering to the patient/subject a second dose of 5-MeO-DMT intranasally, wherein the second dose is administered at least 28 days after the first dose is administered to the patient/subject.
  • Figure 1 is a schematic of a one-step synthesis of 5-MeO-DMT from the reaction of 4-methoxyphenylhydrazine hydrochloride with (N,N)-dimethylamino)butanal dimethyl acetal.
  • Figure 2 is a schematic of a three-step synthesis of 5-MeO-DMT.
  • the first step involves the reaction of 5- methoxyindole with oxalyl chloride.
  • the resultant product is aminated with dimethylamine and then is reduced with lithium aluminium hydride.
  • Figure 3 is a schematic route for the formation of a powder form of 5-MeO-DMT using a spray drying process.
  • FIG. 4 is an overview of the slug mucosal irritation (SMI) test.
  • A First 15 minute contact period between slug and test item.
  • B Slug is transferred onto a wet paper towel in a new Petri dish for 1 hour.
  • C Second 15 minute contact period between slug and test item.
  • D Slug is transferred onto a wet paper towel in a new Petri dish for 1 hour.
  • E Third 15 minute contact period between slug and test item.
  • Figure 5 is a graph showing that the benzoate salt of 5-MeO-DMT has higher permeation compared with the hydrochloride salt, as per the experiment detailed in Example 7.
  • Figure 6 is an XRPD diffractogram of 5-MeO-DMT benzoate prior to particle size reduction.
  • Figure 7 is an XRPD diffractogram of 5-MeO-DMT benzoate following particle size reduction.
  • Figure 8 is an XRPD diffractogram of Figures 6 and 7 overlaid on one another.
  • Figure 9 is a graph showing the mean (+/- SD) 5-MeO-DMT (BPL003) plasma linear concentration-time plot.
  • Figure 10 is a graph showing the mean (+/- SD) 5-MeO-DMT (BPL003) plasma log concentration-time plot.
  • Figure 11 is a graph showing the mean (+/- SD) 5-MeO-DMT (BPL002) plasma linear concentration-time plot.
  • Figure 12 is a graph showing the mean (+/- SD) 5-MeO-DMT (BPL002) plasma log concentration-time plot.
  • Figure 13 shows Forced Swim Test results, Time Immobile, for 5-MeO-DMT benzoate at 0.5, 1.0, or 1.5 mg/kg doses, vehicle and imipramine.
  • Figure 14 shows Forced Swim Test results, Latency to Immobility, for 5-MeO-DMT benzoate at 0.5, 1.0, or 1.5 mg/kg doses, vehicle and imipramine.
  • Figure 15 shows a Dynamic Vapour Sorption (DVS) isotherm for 5-MeO-DMT benzoate.
  • Figure 16 shows a DVS isotherm of 5-MeO-DMT hydrochloride (lot 20/20/126-FP).
  • Figure 17 shows a DVS isotherm of 5-MeO-DMT hydrochloride (lot 20/45/006-FP).
  • Figure 18 shows mean ( ⁇ SD) plasma concentration-time curves of 5-MeO-DMT.
  • Figure 19 shows mean ( ⁇ SEM) subjective intensity ratings after single closes of placebo or 8 mg, 10 mg and 12 mg BPL-003 (SEM, Standard error of the mean).
  • Figure 20 shows mean ( ⁇ SEM) MEQ-30 scores after single doses of placebo or 8 mg, 10 mg and 12 mg BPL-003 (MEQ-30, Mystical Experience Questionnaire; SEM, Standard error of the mean. Dotted line indicates a meaningful threshold of >3).
  • Figure 21 shows the mean change from baseline in MADRS total score over time (per protocol population) from a Phase Ila clinical trial of BPL-003 (5-MeO-DMT benzoate).
  • Figure 22 shows the particle size distribution of a 5-MeO-DMT SDD as Bulk Material (Red) and ExDevice (Green).
  • Figure 23 shows the nasal deposition profile for a 5-MeO-DMT SDD delivered via an active delivery nasal delivery device.
  • Figure 24 shows the nasal deposition profile for a 5-MeO-DMT SDD delivered via a passive delivery nasal delivery device.
  • Step 1 Add methyl tert-butyl ether (MTBE) (15 vol) into the reaction vessel and cool to -20 to -30°C, before adding oxalyl chloride (1.5 eq), maintaining the temperature at no more than -20°C. Add a solution of 5- methoxyindole (1.0 eq) in THF (1 vol) to the reaction vessel, maintaining the temperature at no more than - 20°C. Allow the reaction to warm to 0-5°C and stir for at least 1 hour, ensuring that no more than 2% of the starting material indole remains.
  • MTBE methyl tert-butyl ether
  • Step 2 Add the compound obtained in step 1 (1.0 eq) to a reaction vessel together with dimethylamine hydrochloride (3.0 eq) and methanol (2 vol). Add 25% NaOMe in methanol (3.5 eq), to the reaction maintaining the temperature at no more than 30°C. Warm to and stir for no less than 5 hours, ensuring that no more than 0.5% of the starting material from step 1 remains. Adjust the temperature to 0-5°C over no less than 2 hours, then add water (5 vol) over no less than 1 hour while stirring at 0-5°C for no less than 1 hour.
  • Step 3 Add the compound obtained in step 2 (1.0 eq) to a reaction vessel. Add IM Li Al H4 in THF (1.5 eq) in THF (8 vol) to the reaction maintaining no more than 40°C. Heat at reflux for no less than 4 hours ensuring that no more than 2% of the starting material from step 2 remains.
  • Isopropyl acetate (IPAc) (15.8 vol) was added to the solids obtained above and the temperature was raised to about 73°C until the solid dissolved. The solution was allowed to cool to 0-5°C over 2 hours and this temperature was maintained for 1 hour with stirring. The resultant benzoate salt was filtered and vacuum dried at room temperature. Yield 68%.
  • the benzoate salt of 5-MeO-DMT has improved characteristics over the common hydrochloride salt, including reduced mucosal irritation, increased epithelial permeability and increased stability.
  • 5-MeO-DMT benzoate is a white to off white solid powder, soluble in water at >50 mg/ml with a pH of 7-8 at 50 mg/ml and a pKa of 9.71.
  • Spray drying a solution containing the substance(s) of interest (e.g. 5-MeO-DMT, or the salt, thereof inclusive of any excipients).
  • This can be done via an atomizing nozzle such as with rotary atomizers, pressure atomizers, twin fluid nozzles, ultrasonic atomizers, and four-fluid nozzles. This is done so as to form droplets capable of generating co-formed particles in the desired particle size range.
  • a ProCepT spray dryer is used. In an embodiment, a ProCepT spray dryer with an ultrasonic nozzle is used.
  • the Slug Mucosal Irritation (SMI) assay was initially developed at the Laboratory of Pharmaceutical Technology (UGent) to predict the mucosal irritation potency of pharmaceutical formulations and ingredients.
  • the test utilises the terrestrial slug Arion lusitanicus.
  • the body wall of the slugs is a mucosal surface composed of different layers.
  • the outer single-layered columnar epithelium that contains cells with cilia, cells with microvilli and mucus secreting cells covers the subepithelial connective tissue. Slugs that are placed on an irritating substance will produce mucus. Additionally tissue damage can be induced which results in the release of proteins and enzymes from the mucosal surface.
  • the test was validated using reference chemicals for eye irritation (ECETOC eye reference data bank).
  • ECETOC eye reference data bank reference chemicals for eye irritation
  • These studies have shown that the SMI assay can be used as an alternative to the in vivo eye irritation tests.
  • a multi-center prevalidation study with four participating laboratories showed that the SMI assay is a relevant, easily transferable and reproducible alternative to predict the eye irritation potency of chemicals.
  • the purpose of this assay was to assess the stinging, itching or burning potential of the test item(s) defined below. Using the objective values obtained for the mucus production the stinging, itching or burning potential of the test item(s) can be estimated by means of the prediction model that is composed of four categories (no, mild, moderate and severe).
  • Test System Slugs (Arion lusitanicus); 3 slugs per treatment group.
  • the parental slugs of Arion lusitanicus collected in local gardens along Gent and Aalter (Belgium) are bred in the laboratory in an acclimatised room (18-20°C).
  • the slugs are housed in plastic containers and fed with lettuce, cucumber, carrots and commercial dog food.
  • Test Design A single study was performed. Treatment time was 15 minutes three times on the same day.
  • Slugs weighing between 3 and 6 g were isolated from the cultures two days before the start of an experiment. The body wall was inspected carefully for evidence of macroscopic injuries. Only slugs with clear tubercles and with a foot surface that shows no evidence of injuries were used for testing purposes. The slugs were placed in a plastic box lined with paper towel moistened with PBS and were kept at 18 - 20°C. Daily the body wall of the slugs was wetted with 300 pl PBS using a micropipette.
  • the stinging, itching or burning potency of the test item(s), was evaluated by placing 3 slugs per treatment group 3 times a day on 100 pL of test item in a Petri dish for 15 ⁇ 1 min. After each 15-min contact period the slugs were transferred for 60 min into a fresh Petri dish on paper towel moistened with 1 mL PBS to prevent desiccation. An overview of this can be seen in Figure 4.
  • the amount of mucus produced during each contact period was measured by weighing the Petri dishes with the test item before and after each 15-min contact period.
  • the mucus production was expressed as % of the body weight.
  • the slugs were weighed before and after each 15-min contact.
  • test results were based upon the total amount of mucus production during 3 repeated contact periods with the test item.
  • the mucus production was expressed in % of the body weight by dividing the weight of the mucus produced during each contact period by the body weight of the slug before the start of that contact period. The total mucus was calculated for each slug and then the mean per treatment group was calculated. The classification prediction model shown in the Table below was used to classify the compounds. Cut-off values for classification - potency for nasal mucosal discomfort
  • the negative control should be classified as causing no stinging, itching and burning (Total mucus production ⁇ 5.5%) the positive control item should be classified as causing severe stinging, itching and burning (Total mucus production > 17.5%)
  • NC negative control
  • PC positive control
  • BAC benzalkonium chloride
  • the average amount of mucus produced during each 15-min contact period and total mucus production (total MP) is presented in the Table above. According to the classification prediction model of the SMI test, the negative control (untreated slugs) did not induce reactions in the slugs (mean total MP ⁇ 5.5%).
  • the positive control on the other hand (DDWM/SLS 80/20) induced a high mucus production during each contact period (mean total MP > 17.5%) resulting in a classification as severe stinging, itching, and burning (SIB) reactions. The acceptance criteria were met and the experiment was considered valid.
  • test items can be ranked according to increasing total mucus production: sodium acetate (10% w/v) ⁇ sodium citrate (10% w/v) ⁇ disodium fumarate (10% w/v) ⁇ sodium phosphate (10% w/v).
  • NC negative control
  • PC positive control
  • BAC benzalkonium chloride
  • 5-MeO-DMT as a freebase compound is known to be highly irritating to the mucosal lining; therefore, it is commonly prepared as a salt for insufflation.
  • the hydrochloride (HCI) salt of 5-MeO-DMT is most commonly used due to ease of crystallisation. However, it is known that the HCI salt of 5-MeO-DMT is still quite irritating to the mucosal lining.
  • the 5-MeO-DMT benzoate produced 'mild' irritation compared to the 5-MeO-DMT HCI which scored as 'moderate' on testing.
  • less 5-MeO-DMT benzoate salt may be needed by inhalation to provide the same benefit as the HCI salt and the benzoate salt is less irritating, and so provides a synergistic benefit. Smaller amounts of compound also make inhalation easier to accomplish.
  • the XRPD pattern of 5-MeO-DMT benzoate salt was acquired before and following particle size reduction with a mortar and pestle. This reduced the intensity of dominant diffractions and revealed that the XRPD pattern of the benzoate salt was prone to preferred orientation prior to particle size reduction, which is a function of the habit and particle size of the material.
  • XRPD patterns of the benzoate salt prior to and following particle size reduction can be seen in Figures 6 and 7 respectively.
  • the XRPD patterns of the benzoate salt prior to and following particle size reduction overlaid on one another can be seen in Figure 8.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 17.5, 17.7 and 21.O°20 ⁇ O.1°20.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 17.5, 17.7 and 21.O°20 ⁇ O.2°20.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 17.5, 17.7 and 21.O°20 ⁇ O.3°20.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 17.5, 17.7 and 21.O°20 ⁇ O.1°20 as measured by x- ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 17.5, 17.7 and 21.O°20 ⁇ O.2°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 17.5, 17.7 and 21.O°20 ⁇ O.3°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 17.5, 17.7, 21.0 and 25.3°20 ⁇ O.1°20.
  • crystalline 5-MeO- DMT benzoate characterised by peaks in an XRPD diffractogram at 17.5, 17.7, 21.0 and 25.3°20 ⁇ O.2°20.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 17.5, 17.7, 21.0 and 25.3°20 ⁇ O.3°20.
  • crystalline 5-MeO- DMT benzoate characterised by peaks in an XRPD diffractogram at 17.5, 17.7, 21.0 and 25.3°20 ⁇ O.1°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 17.5, 17.7, 21.0 and 25.3°20 ⁇ O.2°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 17.5, 17.7, 21.0 and 25.3°20 ⁇ O.3°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 9.0, 11.5, 14.5, 16.5, 17.5, 17.7, 18.5, 21.0, 22.7, 24.7 and 25.3°20 ⁇ O.1°20.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 9.0, 11.5, 14.5, 16.5, 17.5, 17.7, 18.5, 21.0, 22.7, 24.7 and 25.3°20 ⁇ O.2°20.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 9.0, 11.5, 14.5, 16.5, 17.5, 17.7, 18.5, 21.0, 22.7, 24.7 and 25.3°20 ⁇ O.3°20.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 9.0,
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 9.0, 11.5, 14.5, 16.5, 17.5, 17.7, 18.5, 21.0, 22.7, 24.7 and 25.3°20 ⁇ O.2°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 9.0, 11.5, 14.5, 16.5, 17.5, 17.7, 18.5, 21.0, 22.7, 24.7 and 25.3°20 ⁇ O.3°20 as measured by x- ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 9.0, 11.5, 14.5, 16.3, 16.5, 17.5,
  • crystalline 5-MeO- DMT benzoate characterised by peaks in an XRPD diffractogram at 9.0, 11.5, 14.5, 16.3, 16.5, 17.5, 17.7, 18.5, 21.0, 22.7, 24.7, 25.3 and 3O.5°20 ⁇ O.2°20.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 9.0, 11.5, 14.5, 16.3, 16.5, 17.5, 17.7, 18.5, 21.0, 22.7, 24.7, 25.3 and 3O.5°20 ⁇ O.3°20.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 9.0, 11.5, 14.5, 16.3, 16.5, 17.5, 17.7, 18.5, 21.0, 22.7, 24.7, 25.3 and 3O.5°20 ⁇ O.1°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 9.0, 11.5, 14.5, 16.3, 16.5, 17.5, 17.7, 18.5, 21.0, 22.7, 24.7, 25.3 and 3O.5°20 ⁇ O.2°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram at 9.0, 11.5, 14.5, 16.3, 16.5, 17.5, 17.7, 18.5, 21.0, 22.7, 24.7, 25.3 and 3O.5°20 ⁇ O.3°20 as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 A.
  • crystalline 5-MeO-DMT benzoate characterised by peaks in an XRPD diffractogram as substantially illustrated in Figures 6, 7 or 8.
  • Example 9 Spray drying parameters
  • composition of 5-MeO-DMT benzoate which is a dry powder.
  • this composition is presented in a single dose nasal applicator.
  • 5-MeO-DMT benzoate and HMPC input solutions are made up using sterile water and left to stir until fully dissolved.
  • the spray drying parameters used to produce a dry powder of 5-MeO-DMT benzoate and HPMC are selected from those set out in the Table below:
  • Example 10 A double-blind, randomised, Phase 1, single ascending dose study to evaluate the safety, tolerability and pharmacokinetic profile of intranasal 5-MeO-DMT benzoate (BPL-003) in healthy subjects
  • BPL-003 intranasal 5- MeO-DMT benzoate
  • the mean Cmax was 29 ng/mL for the 12 mg dosage.
  • the mean Tmax was 9.5 minutes whilst the mean half-life (ti/2) was 21 minutes.
  • Bufotenin the O-demethylated metabolite of 5-MeO-DMT, was only detected at very low levels at the 6 mg dose level after the 16 minutes time point.
  • Participants were screened within 56 days before their dose of the trial drug. All participants had 2 psychedelic preparatory visits (one online and one in-person) with a trained psychedelic monitor before being dosed (Day - 7 and Day -3) to prepare the participant for trial drug administration, provide information about 5-MeO-DMT and to establish rapport between the participant and the monitor.
  • Participants were at site from the day before dosing until the morning after dosing.
  • An indwelling intravenous catheter was inserted before trial drug administration, for the collection of PK samples.
  • a nurse and one psychedelic monitor were present in the room, to provide non-directive support and reassurance for participants.
  • dosing took place in a calm, decorated room and a prepared playlist with relaxing music was playing.
  • participants were instructed to do breathing exercises before dosing.
  • participant's psychedelic experience For up to 90 minutes post-dose, participants and the psychedelic monitor rated overall subjective drug intensity. After dosing, participants had a one-to-one guided interview with an independent researcher to discuss their psychedelic experience. Psychometric scales were administered to provide quantitative measures of the participant's psychedelic experience after the interview. All participants had their individual psychological wellbeing, including measures of suicidality, assessed by the trial psychiatrist before discharge from the ward.
  • Participants had an integration visit 2 days after dosing to discuss their experience on a one-to-one basis with the psychedelic monitor.
  • the session could either be done on the ward or conducted via video call, if deemed acceptable by the psychedelic monitor.
  • Trial Drug BPL-003 or matching placebo were administered as a single intranasal spray into 1 nostril by a trained member of the research team (usually a registered nurse), in the presence of a psychedelic monitor, using the Aptar Unidose dry powder delivery device.
  • TEAEs treatment-emergent adverse events
  • CCGs electrocardiograms
  • C-SSRS Columbia-Suicide Severity Rating Scale
  • HPPD Hallucinogen Persisting Perception Disorder
  • Post Traumatic Stress Disorder can be caused by a traumatic experience and was assessed at follow-up via a checklist for DSM-5 (PCL-5) scores.
  • the PCL-5 is a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. Subjects rate each item from 0 (not at all) to 4 (extremely) to indicate the degree to which they have been affected by that symptom over the past month.
  • Plasma and urine 5-MeO-DMT and bufotenine concentrations were quantified in a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. Blood samples were taken pre-dose (dosing day) and at 0.5, 2, 4, 6, 10, and 16 minutes, and 0.5, 1, 1.5, 4, and 24-hours post-dose. Urine samples were collected continuously from 0-6 hours post-dose.
  • LC-MS/MS liquid chromatography-tandem mass spectrometry
  • Urine PK parameters included the amount of unchanged drug excreted in urine at time t (Aet), fraction of administered drug excreted unchanged in urine (fe ), and renal clearance of drug from plasma (CLR), as well as metabolite Aet and CLR.
  • SDI Subjective Drug Intensity
  • the intensity of BPL-003 subjective effects were rated by the participant and psychedelic monitor using the SDI, a Likert Scale of 0-10, where 0 was 'definitely no effect' and 10 was 'the strongest effect imaginable for 5- MeO-DMT'.
  • the assessment was performed every 2 minutes for up to 90 minutes post-dose, and if the trial participants were not responsive, the psychedelic monitor would assess the rating to be 10.
  • the MEQ-30 is a 30-item questionnaire to evaluate mystical experiences, with subdomains to measure mystical, positive mood, transcendence, and ineffability factors. Participants rated the degree to which they experienced each of the 30 phenomena using the following scale: 0 (none; not at all), 1 (so slight cannot decide), 2 (slight), 3 (moderate), 4 (strong [equivalent in degree to any other strong experience]) or 5 (extreme [more than any other time in my life and stronger than 4]). Means were calculated for each subdomain and a total overall score. The % of participants experiencing a "complete mystical experience" in each dose cohort was assessed by calculating the number of participants that scored 3 and above (>60% of the attainable value) in all of the four subdomains of the MEQ-30.
  • CEQ Challenging Experience Questionnaire
  • AA African American
  • BMI body mass index
  • N number of participants
  • SD standard deviation.
  • composition comprising 10 mg 5-MeO-DMT wherein said composition has an improved side effect profile.
  • pharmaceutical composition comprising 10 mg 5-MeO-DMT wherein said composition has an improved tolerability profile.
  • Post-dose heart rate above the reference range were recorded in 1 (7.7%) participants after placebo and 12 (38.7%) participants after BPL-OO3.
  • Post-dose diastolic blood pressures above the reference range were recorded in 1 (7.7%) participants after placebo (93 mmHg) and 15 (62.5%) participants after BPL-OO3 (ranging 91-109 mmHg).
  • Post-dose systolic blood pressures above the reference range were recorded in 4 (30.8%) participants after placebo (range 146-155 mmHg) and 14 (45.2%) participants after BPL-003 (range 141-181 mmHg).
  • Systolic blood pressure over time and the peak post-dose systolic blood pressure can be seen in the Tables below.
  • BPL-OO3 was rapidly absorbed, with a median Tmax of 4 to 15 minutes post-dose across all dose levels. Elimination of 5-MeO-DMT was rapid across all dose levels. Arithmetic mean t% ranged from 15 to 27 minutes across dose levels. Plasma 5-MeO-DMT concentrations were below the limit of detection by 4 hours after administration in all subjects. Variability between participants was generally low to moderate, where all participants in a group had quantifiable 5-MeO-DMT plasma concentrations.
  • Urinary PK parameters for 5-MeO-DMT are summarised in the Table above. Urine concentrations of 5-MeO- DMT were BLQ in most participants after 1 mg BPL-003, and in a few participants after higher doses of BPL- 003.
  • Urine excretion of 5-MeO-DMT appeared negligible.
  • the arithmetic mean fraction of 5-MeO-DMT excreted unchanged (fe- F) at 6 hours post-dose ranged between 0.06% to 0.38% across dose levels. Due to the low levels of 5-MeO-DMT detected in urine, PK parameters derived were highly variable.
  • Urine levels of bufotenine were all BLQ ( ⁇ 0.5 ng/mL).
  • composition comprising 10 mg 5-MeO-DMT wherein said composition has an improved side effect profile and produces a complete mystical experience.
  • pharmaceutical composition comprising 10 mg 5-MeO-DMT wherein said composition has an improved tolerability profile and produces a complete mystical experience.
  • 5-MeO-DMT has a unique profile that, in addition to the activation of the 5-HT2A receptor, also shows a preferential receptor affinity to the 5-HT1A receptor.
  • One of the objectives of this study was to identify and explore a well-tolerated dose of BPL-003 that would reliably elicit profound mystical experiences in most trial participants, to evaluate whether progression into patient studies was appropriate.
  • a dose range of 10 to 12 mg was found to meet this requirement, with 60% of participants experiencing a complete mystical experience and/or ego dissolution events. The elicitation of full mystical experiences is thought to be an encouraging indicator for future therapeutic efficacy.
  • Psychedelic effects increased with BPL-003 dose, with a rapid onset of profound psychedelic effects that were short (45-90min) in duration.
  • the results of this single ascending dose study indicates that doses between 8-12 mg of BPL-003 are suitable for further pharmaceutical development in neuropsychiatric conditions with high unmet medical need, in particular the 10 mg dose which exhibited a particularly desirable side effect profile.
  • Example 11 A double-blind, randomised, Phase 1, single ascending dose study to evaluate the safety, tolerability and pharmacokinetic profile of intranasal 5-MeO-DMT HCI (BPL-002) in healthy subjects
  • BPL-002 A single ascending dose study to evaluate the safety, tolerability and pharmacokinetic profile of intranasal 5- MeO-DMT HCI (BPL-002) was performed.
  • BPL-002 comprises 5-MeO-DMT HCI, HPMC, water for injection (WFI) and a sodium hydroxide solution to adjust pH.
  • An initial stock solution of 0.5% w/w HPMC was prepared using sterile water for injection which was further diluted with sterile water for injection to approximately 90% of the final weight required.
  • the required amount of drug substance (70 mg/ml or 140 mg/ml Freebase) was then dissolved in an aliquot of the 0.5% w/w HPMC stock solution with stirring and the pH of the active stock solution was then adjusted to 6.00 +/- 0.25 by adding sodium hydroxide (0.1 M solution). The IPC measurement was taken to ensure the pH is adjusted within the accepted range before making up to the final weight with sterile water for injection The concentration of the HPMC in the final solution was 0.1% w/w.
  • Placebo solutions of 0.1% w/w HPMC were made up by dissolving the required amount of HPMC in sterile water for injection (approximately 90% of final weight) and adjusted for pH 5.75 +/- 0.25 if necessary by the addition of sodium hydroxide solution (0.05 M). The in process check measurement was taken to ensure the pH is adjusted within the accepted range before making up to the final weight with sterile water for injection. The concentration of the HPMC in the final solution was 0.1% w/w.
  • mice Male CD-I mice from Charles River Laboratories (St. Constant, Quebec, Canada) served as test subjects in this study. Animals generally weighed 25-30 g at the time of testing.
  • mice received the appropriate dose of vehicle, test article, or positive control (treatments summarised above). Following the appropriate pretreatment time, animals were gently placed into tall glass cylinders filled with water (20-25°C). After a period of vigorous activity, each mouse adopted a characteristic immobile posture which is readily identifiable. The swim test involves scoring the duration of immobility. Over a 6-minute test session, the latency to first immobility is recorded (in seconds). The duration of immobility (in seconds) during the last 4 minutes of the test is also measured. Activity or inactivity from 0-2 minutes is not recorded.
  • Latency to immobility vehicle: 95.5 ⁇ 4.6 seconds - 5-MeO-DMT benzoate 121.8 ⁇ 22.0 seconds (0.5 mg/kg), 120.9 ⁇ 13.3 seconds (1.5 mg/kg), 85.0 ⁇ 9.5 seconds (5 mg/kg), imipramine 268.6 ⁇ 30.3 second, Figure 14).
  • Example 13 Dynamic Vapour Sorption (DVS) comparison of 5-MeO-DMT benzoate and HCI
  • the DVS profile for 5-MeO-DMT benzoate salt revealed reversible water uptake/loss over the humidity range and no hysteresis.
  • the water uptake/loss from 0 to 90% was gradual and amounted to a maximum of ca 0.20% and was a consequence of wetting of the solid.
  • the DVS isotherm can be seen in Figure 15.
  • the DVS isotherm of a 5-MeO-DMT Hydrochloride, lot 20/20/126-FP (Figure 16) was found to undergo significant moisture uptake upon the first sorption cycle from 70%RH. Approximately 23% w/w uptake is observed between 70-80% RH, whereas less than 0.3% w/w moisture uptake from 0-70% RH was observed. A further 20% w/w moisture uptake is observed up to and when held at 90% RH before commencement of the second desorption cycle. Subsequent sorption and desorption cycles follow a similar profile with some observed hysteresis between operations that do not match the original desorption step. These return to ca. 6- 9% w/w above the minimum mass recorded at 0% RH, which indicates significant retention of moisture. Upon completion of the DVS cycle, the input material was noted to have been completely deliquesced.
  • a modified DVS isotherm of lot 20/45/006-FP (the same crystalline version) was undertaken to examine material behaviour from 60% RH and above.
  • DVS provides a versatile and sensitive technique for evaluating the stability of pharmaceutical formulations.
  • the DVS profiles show that the stability of the benzoate salt of 5-MeO-DMT is significantly higher than that of the hydrochloride salt and is therefore a more promising salt for development as a pharmaceutical composition.
  • the physical surroundings of the participant/patient/subject are of high importance in the character of many psychedelic experiences.
  • the space should be private, meaning that there should be no chance of intrusion by others. Ideally, sound from outside (e.g. the hallway, the street, etc.) will be minimal.
  • the dosing sessions should take place in rooms that feel like a living room or den rather than a clinical setting. Artwork, plants, flowers, soft furniture, soft lighting, and related decor should be employed in creating a cosy and relaxing aesthetic. Artwork with any specific religious iconography, ideological connotation, or tendency to evoke negative emotions should be avoided.
  • the dosing room may also provide comfortable furniture for the participant and the therapists, who may sit on either side of the participant.
  • the room should shield the participant from sights and sounds of the world beyond the room, and the participant should not have any cause for concern of observation or interruption by anyone other than the therapists.
  • the space may also contain: The tools for safety procedures and medical devices necessary to respond in the unlikely event of a medical complication. The participant should be made aware of these procedures and the equipment, but as much as possible they should be hidden from view.
  • Audio and video-recording equipment If allowed in the study protocol the participant will have already consented to being recorded, and should be made aware of the equipment, but it should be placed to be as unobtrusive as possible. Participants may request the cessation of recording at any time.
  • the space may be large enough to accommodate chairs for two therapists, the stereo equipment and cabinet for storage of the participant's belongings and any extra supplies the therapists may need during the day.
  • the space may accommodate a bed or couch on which the participant can either sit up or lie down with a comfortable surroundings of pillows.
  • the space may be at least 100 2 feet or 10 2 metres so that participants do not feel cramped or too physically close to therapists. Participants should have room to explore a variety of positions including sitting on the floor or stretching their bodies without restriction. A bathroom should be either accessible directly from the session room or nearby.
  • 5-MeO-DMT sessions may use a pre-set playlist of nature sounds for creating a calm atmosphere. These nature sounds are considered to be a background element, helping drown out any noise from outside the room, and keep the participant focused on their experience. Participants are not instructed to listen to the sounds in any particular way, but may be asked to focus on it as a way of grounding their senses and relaxing before or after a session.
  • Medication discontinuation can be challenging for participants. Participants are to have discontinued all contraindicated medications and completed washout periods prior to Prep-1 with the therapist.
  • the study team members, including the therapist, may provide supportive check-in calls with the participant prior to this, as- needed during the washout period, but should not start Prep-1 until washout is complete and the participant confirms intention to continue with the therapy.
  • This treatment model includes three, 60-90 minute preparatory sessions with the therapist. These take place 7 days, 4 days, and 1 day before the 5-MeO-DMT session. Preparatory sessions are designed to take place via telemedicine, but can be in-person if possible.
  • the therapist will spend some of the preparation session time getting to know the participant.
  • the therapist may ask open-ended questions about:
  • the therapist should be listening for how the participant talks about themselves and their relationship to their depression/major depressive disorder, how they relate to the therapist and study environment, and stay attuned to establishing a sense of trust and rapport with the participant.
  • Clinical impressions of difficulty forming a trusting relationship with the therapist or any other clinical factors that could interfere with the participants' ability to engage in the treatment should be noted and discussed with the study team.
  • the therapist may learn more of the participant that could be reasons for study exclusion. Establishing the role of the therapist
  • the therapist should explain the therapeutic model used in this research study to the participant in the first preparation session.
  • the explanation should include:
  • Therapists may advise participants to take caution around posting about their experience on social media so as not to elicit excessive public commentary. Inadequate social support or use of social media in a way that may be disruptive to the therapeutic process may be discussed and resolved prior to 5-MeO-DMT administration.
  • the therapist should explain that on the day of the session that a member of the research team will enter the room briefly to administer the study drug.
  • the therapist should explain the participant positioning, e.g. they will be in a seated position on the bed or couch, that the research team member will insert the nasal spray device in one nostril, and that they will be asked to allow the therapist to assist them in lying down on the bed or couch immediately afterward.
  • Session procedures including boundaries, use of touch, safety, etc.
  • the therapist will explain the process of the session.
  • the session is contained by the timing of the dosing and the physical environment of the dosing room. It begins when the participant enters the room and engages with the therapist in the Session Opening. Session Opening is a formal moment in which the participant and therapist sit together in the room, all preparations having been made, and the playlist started.
  • the therapist may lead a breathing exercise of the participant's choice, if the participant is open to engaging in one, and ask the participant to reflect on the values they choose in the preparation session, or any other value or intention that is important to them.
  • a member of the research team will administer the nasal spray to the participant.
  • Trust and safety are not only communicated verbally, but also this may be nonverbally through how a therapist holds themselves in the presence of the participant. If a therapist is overly anxious, or fearful, this may be felt by the participant. It is important that the therapist is centred throughout the dosing session, particularly at times when a participant is expressing intense affect, unusual somatic expressions, or is asking for support.
  • Expectations can be defined as mental representations and beliefs of how something in the future will be. Sometimes expectations can be explicitly identified, and sometimes they are sub perceptual, taken for granted. Both kinds of expectations may be important to treatment.
  • the therapist should ask about explicit expectations and encourage the participant to acknowledge and set these aside such that they do not engage in comparing their experience to expectations. The therapist is also listening for sub perceptual expectations that may come into awareness through the therapy. Intentions are ways of relating to a behaviour or experience. In the 5-MeO- DMT treatment, it can be important for the therapist to elicit and understand the participant's intentions as these can vary greatly and may be taken for granted.
  • Therapists are to engage participants in a process of identifying and setting their intentions such that these are explicit and can be referenced later in integration. The purpose of the intention is for it to be identified and then let go of, with the knowledge that it can be part of the 5MED. Recurrence of acute effects
  • Therapeutic touch is touch that is intended to connect with, sooth, or otherwise communicate with the participant for therapeutic aims. It is always fully consensual, non-sexual, and the participant is encouraged to decline or cease therapeutic touch at any time.
  • Touch for safety reasons can include supporting a participant who is having trouble walking by offering an arm to hold, or blocking a patient back from leaving the room while under acute drug effects. This touch is agreed to in advance, is always non-sexual, and limited to specific safety concerns. Therapists should discuss both of these and establish boundaries with participants ahead of session.
  • Breathing practices include: Balancing Breath, Diaphragmatic Breath and Counted Breath.
  • the therapeutic protocol may use a customised Personal Values Card Sort to assist with the therapeutic focus on shift in sense of self. This is done by asking about how people relate to their chosen values before the session, and how they relate to them afterward, drawing attention to shifts, changes, and using these as a guide for the kind of changes the participant may desire to make. It is used as a way to elicit conversation about the participant's sense of self, beliefs about self, and changes in those senses/beliefs throughout the therapy. Therapists may engage participants in the card sort exercise in the third preparation session such that it occurs 1-2 days before the dosing session.
  • the session may be conducted by the therapist with an assistant therapist such that a second person is available to assist in case of any adverse event or physical complication in the participants safety.
  • the assistant who will be present for the session should be introduced in Prep Session 3 and included in a conversation such that they get to know the participant.
  • the therapist is present with the participant during the session — including pre-experience and post-experience times. This is the only session that must be conducted in-person.
  • the site and therapist should schedule about 3 hours for the session, including pre-experience and post-experience time. This does not include the time allotted to engage in baseline measures and enrolment confirmation prior to the session.
  • Local regulatory approvals will determine the minimum length of time a participant must be under observation following 5-MeO- DMT administration.
  • the Therapist, Assistant Therapist, and participant together in the room review all aspects of the room and safety procedures.
  • the therapist should introduce the participant to the team member administering the 5-MeO-DMT, to create a sense of familiarity.
  • Therapist introduces any Assistant Therapist and reviews safety features of the room and the equipment present.
  • Participant has time to ask any questions. The therapist will ask about any responses to the situation and how the participant is feeling about their session. The participant should not be rushed into the dosing by the therapists. The therapist will ask the participant to engage in a period of relaxation prior to dosing.
  • Participants will be asked to lie down, close their eyes, listen to the music, and, if willing, engage in at least one of the breathing exercises with the therapist's guidance.
  • the therapist will initiate the Session Opening. This practice helps contain and emphasise the specialness of the experience.
  • Therapists will contact the member of the research team to come to the room and administer the 5-MeO-DMT.
  • the team member should be aware not to disrupt the peaceful atmosphere of the room.
  • the participant should be in a seated position when insufflating the 5-MeO- DMT, as the effects may be felt quickly, the participant should be transitioned to a prone position and remain prone for the duration of the effect of the 5-MeO-DMT.
  • Experience (Around 60 Minutes)
  • This may be in the form of slow intentional inhaling and exhaling, or any other activity that helps the therapist ground and self-regulate. This is both for the therapist's benefit, as well as the participants', because a participant in a heightened non-ordinary state may be particularly attune to or pick up on their therapist's anxiety. It is optimal for the therapist to follow the participant's lead when choosing to verbally engage as the 5-MeO-DMT experience appears to be subsiding. Therapists may be eager to ask the participant about their experience, but it is preferable to wait until the participant is ready to share on their own. A participant may wish to remain in a period of silence, even after the apparent acute 5-MeO-DMT effect is gone. It is appropriate for therapists to greet participants with a friendly smile and welcoming nonverbal behaviour, and allow participants to take the lead on sharing when they feel ready.
  • BPL-003 was administered as a dry powder from a single-use FDA-approved intranasal delivery device.
  • the acute subjective experience in TRD patients was comparable to the findings of the Phase I clinical trial described in Example 10. Both groups of subjects were able to reach a score of equal to or greater than 3 out of 5 (as measured by the MEQ-30), which has previously been shown to correlate with short-term and longterm clinical symptom improvement.
  • PPP Per Protocol Population
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of reducing pessimistic thoughts in a patient in need thereof.
  • the patient is a depressed patient.
  • the patient is a treatment resistant depressed patient.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of reducing pessimistic thoughts in a treatment resistant major depressive disorder patient.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of reducing apparent sadness in a patient in need thereof.
  • the patient is a depressed patient.
  • the patient is a treatment resistant depressed patient.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of reducing an inability to feel in a treatment resistant major depressive disorder patient.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of improving sleep quality in a patient in need thereof.
  • the patient is a depressed patient.
  • the patient is a treatment resistant depressed patient.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of improving sleep quality in a treatment resistant major depressive disorder patient.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of reducing sadness in a patient in need thereof.
  • the patient is a depressed patient.
  • the patient is a treatment resistant depressed patient.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of reducing sadness in a treatment resistant major depressive disorder patient.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of reducing lassitude in a patient in need thereof.
  • the patient is a depressed patient.
  • the patient is a treatment resistant depressed patient.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of reducing lassitude in a treatment resistant major depressive disorder patient.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of reducing inner tension in a patient in need thereof.
  • the patient is a depressed patient.
  • the patient is a treatment resistant depressed patient.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of reducing inner tension in a treatment resistant major depressive disorder patient.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of reducing suicidal thoughts in in a patient in need thereof.
  • the patient is a depressed patient.
  • the patient is a treatment resistant depressed patient.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of reducing suicidal thoughts in a treatment resistant major depressive disorder patient.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of improving appetite in in a patient in need thereof.
  • the patient is a depressed patient.
  • the patient is a treatment resistant depressed patient.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of improving appetite in a treatment resistant major depressive disorder patient.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of treatment of depression/major depressive disorder.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of treatment of depression/major depressive disorder.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of treatment of treatment resistant depression/major depressive disorder.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of treatment of treatment resistant depression/major depressive disorder.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of treatment of treatment resistant depression/major depressive disorder in a patient in need thereof, wherein the treatment resistant depression/major depressive disorder has failed to be treated with one or more of the following: citalopram, sertraline, mirtazapine, escitalopram, venlafaxine, fluoxetine, paroxetine, amitriptyline and/or quetiapine.
  • the treatment resistant depression/major depressive disorder has failed to be treated with one or more of the following: citalopram, sertraline, mirtazapine, escitalopram, venlafaxine, fluoxetine, paroxetine, amitriptyline and/or quetiapine, in the current episode.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of treatment of depression/major depressive disorder, or treatment resistant depression/major depressive disorder, wherein the method is a rapid method of treatment which produces sustained results from a single dose.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of treatment of depression/major depressive disorder, or treatment resistant depression/major depressive disorder, wherein the method is a rapid method of treatment which produces sustained results from a single dose, wherein the pharmaceutical composition is as described herein and wherein the method is a as described herein.
  • a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, in a method of treatment of depression/major depressive disorder, or treatment resistant depression/major depressive disorder, wherein the method is a rapid method of treatment which produces sustained results from a single dose, wherein the depression/major depressive disorder or treatment resistant depression/major depressive disorder, is treated within 1 day of the single dose and wherein the response is sustained for 12 weeks or more.
  • the disease/condition to be treated has previously failed to be treated with one or more treatments.
  • the disease/condition has previously failed to be treated with one or more antidepressants, such as citalopram and/or sertraline.
  • the disease/condition has previously failed to be treated with one or more treatments, in the current episode of the disease/condition.
  • the disease/condition has previously failed to be treated with two or more treatments, in the current episode of the disease/condition.
  • the disease/condition has previously failed to be treated with three or more treatments, in the current episode of the disease/condition.
  • the disease/condition has previously failed to be treated with four or more treatments, in the current episode of the disease/condition.
  • the disease/condition has previously failed to be treated with five or more treatments, in the current episode of the disease/condition.
  • the one or more treatments were administered at an adequate dose for an adequate length of time.
  • the disease/condition has previously failed to be treated with one or more antidepressants, such as citalopram and/or sertraline.
  • the disease/condition has previously failed to be treated with one or more treatments, in the current episode of the disease/condition.
  • the disease/condition has previously failed to be treated with two or more treatments, in the current episode of the disease/condition.
  • the disease/condition has previously failed to be treated with three or more treatments, in the current episode of the disease/condition.
  • the disease/condition has previously failed to be treated with four or more treatments, in the current episode of the disease/condition. In an embodiment, the disease/condition has previously failed to be treated with five or more treatments, in the current episode of the disease/condition. In an embodiment, the one or more treatments were administered at an adequate dose for an adequate length of time.
  • the method of treatment comprises the administration of a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, not more often than once every 1, 2 or 3 months.
  • the method of treatment comprises the administration of a pharmaceutical composition comprising 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, once every three months.
  • a discharge questionnaire may be utilised by a professional.
  • this professional is a licensed medical professional.
  • a discharge questionnaire may include one or more of the following statements, which must be agreed with in order for a patient/subject to be assessed as ready for discharge: The patient/subject is fully responsive, aware of their surroundings, and reacts adequately; The acute psychedelic effects of the drug have completely subsided; The patient/subject is fully orientated (e.g. name, location, time); Blood pressure and pulse rate have returned to normal or only slightly elevated levels.
  • the breathing frequency and body temperature are normal;
  • the patient/subject has a stable gate and normal muscle coordination and can walk safely; Potential side effects are mild to moderate in intensity and do not need to be medically monitored;
  • the patient/subject has no acute suicidal ideations or suicidal intentions; Possible distress or feelings of being overwhelmed have sufficiently subsided to a degree that the patient/subject themselves feel safe to be discharged; In the opinion of the assessor, the patient/subject is safe to be discharged.
  • a dry powder intranasal pharmaceutical composition comprising 10 mg of 5-MeO-DMT benzoate, and one or more pharmaceutically acceptable carriers or excipients, for use in a rapid method of treatment of treatment resistant depression/major depressive disorder in a patient/subject in need thereof, the method comprising a single intranasal administration of the composition to a single nostril of the patient/subject and wherein a clinically significant reduction in MADRS score is obtained within 1 day of said administration and wherein the clinical significant reduction is sustained for at least 12 weeks.
  • a dry powder intranasal pharmaceutical composition comprising 10 mg of 5-MeO-DMT benzoate, and one or more pharmaceutically acceptable carriers or excipients, for use in a rapid method of treatment of treatment resistant depression/major depressive disorder in a patient/subject in need thereof, the method comprising a single intranasal administration of the composition to a single nostril of the subject, wherein a clinically significant reduction in MADRS score is obtained within 1 day of said administration, wherein the clinical significant reduction is sustained for at least 12 weeks and wherein said patient/subject is ready for discharge within 90 minutes post-administration.
  • a dry powder intranasal pharmaceutical composition comprising 5-MeO- DMT benzoate, and one or more pharmaceutically acceptable carriers or excipients, for use in a rapid method of treatment of treatment resistant depression/major depressive disorder in a patient/subject in need thereof, the method comprising a single intranasal administration of the composition to a single nostril of the subject, wherein a clinically significant reduction in MADRS score is obtained within 1 day of said administration, wherein the clinical significant reduction is sustained for at least 12 weeks and wherein said patient/subject is ready for discharge within 90 minutes post-administration.
  • a pharmaceutical composition comprising 5-MeO-DMT benzoate, and one or more pharmaceutically acceptable carriers or excipients, for use in a rapid method of treatment of treatment resistant depression/major depressive disorder in a patient/subject in need thereof, the method comprising a single intranasal administration of the composition to a single nostril of the subject, wherein a clinically significant reduction in MADRS score is obtained within 1 day of said administration, wherein the clinical significant reduction is sustained for at least 12 weeks and wherein said patient/subject is ready for discharge within 90 minutes post-administration.
  • a dry powder intranasal pharmaceutical composition comprising 8 mg, 10 mg, 12 mg or 14 mg of 5-MeO-DMT, or a pharmaceutically acceptable salt, prodrug, hydrate, ester, co-crystal or deuterated form thereof, and one or more pharmaceutically acceptable carriers or excipients, for use in a rapid method of treatment of treatment resistant depression/major depressive disorder in a patient/subject in need thereof, the method comprising a single intranasal administration of the composition to a single nostril of the subject, wherein a clinically significant reduction in MADRS score is obtained within 1 day of said administration, wherein the clinical significant reduction is sustained for at least 12 weeks and wherein said patient/subject is ready for discharge within 90 minutes post-administration.
  • a dry powder intranasal pharmaceutical composition comprising 8 mg, 10 mg, 12 mg or 14 mg of 5-MeO-DMT benzoate, and one or more pharmaceutically acceptable carriers or excipients, for use in a rapid method of treatment of treatment resistant depression/major depressive disorder in a patient/subject in need thereof, the method comprising a single intranasal administration of the composition to a single nostril of the subject, wherein a clinically significant reduction in MADRS score is obtained within 1 day of said administration, wherein the clinical significant reduction is sustained for at least 12 weeks and wherein said patient/subject is ready for discharge within 90 minutes post-administration.
  • the psychotherapy is provided prior to administration of the composition.
  • psychotherapy is provided during administration of the composition.
  • psychotherapy is provided after administration of the composition.
  • psychotherapy is provided prior to, during and after administration of the composition.
  • the psychological support is provided prior to administration of the composition.
  • the psychological support is provided during administration of the composition.
  • the psychological support is provided after administration of the composition.
  • the psychological support is provided prior to, during and after administration of the composition.
  • the method comprises the concurrent use of SSRIs.
  • a rational modification of such endpoint e.g. changing the MADRS recall period to 2 hours and carrying forward the sleep item recorded at baseline before drug administration may be applied.
  • Non-REM sleep may be divided into four stages (l-IV). These non-REM stages correspond to an increasing depth of sleep.
  • Non-REM and REM sleep alternate during each of the four to five cycles of normal human sleep each night.
  • non-REM sleep is deeper and occupies a disproportionately large amount of time, particularly within the first cycle of sleep.
  • non- REM sleep becomes shallow and more of each cycle is allocated to REM sleep.
  • sleep disturbance is frequently associated with mental disorders, such as depression.
  • treatment of depression does not necessarily lead to an improvement of the concomitant sleep disturbances.
  • antidepressants While most antidepressants have been proven to influence the sleep architecture, some classes of antidepressants improve sleep, but others may cause sleep impairment. Sleep may be assessed by measuring parameters such as sleep duration, sleep architecture, sleep latency, and the frequency and duration of awakenings throughout the night. The quantitative metrics may be measured using objective methods, including polysomnography, actigraphy, and the determination of sleep latency, or by way of self reported measures (questionnaires).
  • Polysomnography is a technique requiring that a patient/subject is monitored overnight at a specialised clinic. A variety of functions are measured throughout the night, including eye movements, brain and muscle activity, respiratory effort and airflow, blood oxygen levels, body positioning and movements, snoring, and heart rate. Another quantitative measurement is actigraphy. An actimetry sensor is worn to measure motor activity, which is recorded continually and used to assess sleep-wake cycles. This technique allows the patient/subject to continue normal routines while the required data are being recorded in a natural sleep environment.
  • Sleep latency may be measured by the multiple sleep latency test (MSLT). This test provides an objective measure to determine how long it takes a person to fall asleep across a multiplicity of test naps. An average sleep latency of approximately 10 minutes is considered to be normal; less than eight minutes is indicative of sleep disturbance (excessive daytime sleepiness). Accompanying analysis of brain activity may assist in the further diagnosis of the sleep disturbance.
  • MSLT multiple sleep latency test
  • Sleep-rating questionnaires capture ratings of components of sleep quality, such as perceptions of sleep depth, rousing difficulties, and restfulness after sleep, in addition to other factors that could affect sleep quality, such as comorbid conditions and medication use.
  • the evaluation of the qualitative aspects of sleep experience is important, as sleep complaints may often persist despite normal values for quantitative measures of sleep.
  • Questionnaires not only facilitate a quick and accurate assessment of a complex clinical problem, but they are potentially also helpful for tracking a patient's progress.
  • indexes include examples of questionnaires to assess sleep in general and questionnaires to assess in particular insomnia, hypersomnia, circadian rhythm disorders and parasomnia, respectively.
  • the invention is, however, not limited to the use of a particular index or questionnaire.
  • recall periods recall windows
  • the recall period may be modified so that the scores obtained reflect a period after treatment.
  • Questionnaires specifically discussed herein to assess effects of a treatment on sleep in patients/subjects suffering from specific conditions rely on a recall period that does not start earlier than the time point when complete mystical experiences have subsided after the last administration. To meet this criterion, the normally applied recall period is modified if necessary.
  • the Sleep quality in general may be assessed, for instance, with the Sleep-50 questionnaire.
  • the SLEEP-50 questionnaire consists of 50 items designed to screen for a variety of sleep disorders in the general population.
  • the scale consists of nine subscales, reflecting some of the most common disorders and complaints related to sleep and the factors required for diagnosis such as sleep apnoea, insomnia, narcolepsy, restless legs/periodic leg movement disorder, circadian rhythm sleep disorder, sleepwalking, nightmares, factors influencing sleep, and the impact of sleep complaints on daily functioning.
  • respondents are provided with a scale ranging from 1 ("not at all") to 4 ("very much") and are asked to indicate the extent to which the statement has matched their experience over the previous month or another appropriate recall window.
  • a sleep disorder For diagnosing a sleep disorder not only the specific subscale (e.g., insomnia) must exceed a certain cut-off point, but respondents must also meet a cut-off of at least 3 or 4 ("rather much” or "very much", respectively) on the subscale evaluating the impact of sleep complaints on daily functioning. Treatment success may be indicated (i) by a decrease of the score, preferably (ii) by a decrease to below the cut-off value.
  • a common questionnaire assessing sleep disturbance is the Pittsburgh Sleep Quality Index.
  • Other instruments are the insomnia severity index, the Espie sleep disturbance questionnaire and the patient/subject Reported Outcomes Measurement Information System (PROMIS®) Sleep Disturbance.
  • the Pittsburgh Sleep Quality Index assesses overall sleep quality and disturbances.
  • the PSQI is a selfrated questionnaire comprising 19 questions. Respondents are asked to indicate how frequently they have experienced certain sleep difficulties over the past month or another appropriate recall window.
  • the 19 selfrated questions assess a wide variety of factors relating to sleep quality, including estimates of sleep duration and latency and of the frequency and severity of specific sleep-related problems. These 19 items are grouped into seven component scores: (1) patient/subjective sleep quality; (2) sleep latency; (3) sleep duration; (4) habitual sleep efficiency; (5) sleep disturbances; (6) use of sleeping medication; (7) daytime dysfunction. Each component is assigned a score of 0 to 3. Higher scores indicate more acute sleep disturbances.
  • treatment success may be indicated (i) by a decrease of the score, preferably (ii) by a decrease to 5 or below.
  • the insomnia severity index is a short questionnaire relating to patient/subjective sleep quality, severity of symptoms, patient/subjective satisfaction with sleep, the degree to which insomnia interferes with daily functioning, how noticeable the respondent feels his or her insomnia is compared to others, and the overall level of distress created by the sleep problem.
  • a total score of 0-7 indicates "no clinically significant insomnia," 8-14 means “subthreshold insomnia," 15-21 is “clinical insomnia (moderate severity),” and 22-28 means “clinical insomnia (severe)".
  • the recall window is two weeks. Another appropriate recall window may also be used.
  • Treatment success may be indicated (i) by a decrease of the score, for instance, by >7 points, in particular >8 point; preferably (ii) by a decrease to below the cut-off value for clinically significant insomnia.
  • the Espie sleep disturbance questionnaire evaluates patient/subjective experiences of insomnia. With ratings on restlessness/agitation, mental overactivity, consequences of insomnia, and lack of sleep readiness, the SDQ is concerned specifically with beliefs about the sources of sleep issues. Respondents use a five-point scale to indicate how often certain statements about insomnia are representative of their experience. 1 means “never true,” while 5 means “very often true.” Higher scores are indicative of more dysfunctional beliefs about the causes and correlates of insomnia.
  • the Patient- Reported Outcomes Information System (PROMIS)® Sleep Disturbance instrument is a universal measure to evaluate sleep disturbances.
  • the instrument is available as a long form and 4 different short forms (e.g., 4-, 6-, and 8- items) and assesses selfreported perceptions of sleep quality, sleep depth, and any perceived difficulties related to getting and staying asleep over a 7-day period.
  • Each item on the measure is rated on a 5-point scale.
  • the raw scores on the items are summed to obtain a total raw score. Total raw scores are then converted into a standardised T-score using conversion tables.
  • Treatment success may be indicated by a decrease of the T-score.
  • Hypersomnia or hypersomnolence may be assessed by the Epworth Sleepiness Scale, the Stanford Sleepiness Scale, or the Idiopathic Hypersomnia Severity scale.
  • the Epworth Sleepiness Scale (ESS) evaluates overall daytime sleepiness.
  • the questionnaire asks respondents to rate how likely they are to fall asleep in eight different situations representing a moment of relative inactivity, such as a nap in the afternoon or sitting in a car stopped in traffic. Using a scale of 0-3 (with 0 meaning "would never doze” and 3 meaning "high chance of dozing"), respondents rate their likelihood of falling asleep. Scoring ranges from 0-24; the higher the score, the higher the severity of daytime sleepiness.
  • a cut-off score of 10 identifies daytime sleepiness at a potentially clinical level. Treatment success may be indicated (i) by a decrease of the score, preferably (ii) by a decrease to 10 or below.
  • PADSS Paris Arousal Disorders Severity Scale
  • a common questionnaire that assesses sleep-related breathing disorders is the Berlin Questionnaire. An appropriate recall period may also be chosen. Treatment success may be indicated by a decrease of the score.
  • a common questionnaire that assesses sleep-related movement disorders is the International Restless Legs Syndrome Study Group Rating Scale.
  • the 10-item questionnaire asks respondents to use Likert-type ratings to indicate how acutely the disorder has affected them over the course of the past week. Questions may be divided into one of two categories: disorder symptoms (nature, intensity, and frequency) and their impact (sleep issues, disturbances in daily functioning, and resultant changes in mood.
  • Each of the ten questions requires respondents to rate their experiences with RLS on a scale from 0 to 4, with 4 representing the most severe and frequent symptoms and 0 representing the least. Total scores may range from 0 to 40.
  • the instrument may be suitable for a variety of research and clinical purposes, including screening and assessment of treatment outcomes. Treatment response may be assessed by a decrease of the score.
  • Bipolar disorder has various aspects and is characterised by various symptoms.
  • the predominant psychopathology is depression, and the presentation of a patient/subject experiencing a depressive phase may initially result in the diagnosis of that patient/subject as having major depressive disorder (MDD).
  • MDD major depressive disorder
  • BD possesses multiple characteristics that define it as distinct from the latter even during the depressive phase.
  • Characteristic symptoms further include suicidal ideation. Still further, characteristic symptoms include mixed symptoms (psychotic symptoms; irritability; lability; increased motor drive; increased speech; agitation).
  • BDRS Bipolar Depression Rating Scale
  • the Bipolar Depression Rating Scale is designed to measure the severity of depressive symptoms in bipolar depression.
  • the BDRS is validated for clinical use by trained raters. Based on a clinical interview, the BDRS items rate the severity of depressive and/or mixed symptoms expressed by patients/subjects currently and during the past few days. If there is a discordance between symptoms currently and the last few days, the rating should reflect current symptoms.
  • the scale contains 20 questions and the maximum score possible is 60. Higher scores indicate greater severity.
  • the questions address depressed mood; sleep disturbance; appetite disturbance; reduced social engagement; reduced energy and activity; reduced motivation; impaired concentration and memory; anxiety; anhedonia; affective flattening; feelings of worthlessness; feelings of helplessness and hopelessness; suicidal ideation; feelings of guilt; psychotic symptoms; irritability; lability; increased motor drive; increased speech; agitation.
  • Each of these aspects is assessed and assigned a score of 0, 1, 2 or 3.
  • Depressed mood is scored as 0 if there is no self-reported and/or observed depression as evidenced by gloom, sadness, pessimism, hopelessness, and helplessness; 1 (mild) in case of brief or transient periods of depression, or mildly depressed mood; 2 (moderate) in case a depressed mood is clearly but not consistently present and other emotions are expressed, or depression is of moderate intensity; 3 (severe) in case of pervasive or continuous depressed mood of marked intensity.
  • Sleep disturbance is assessed based on the change in total amount of sleep over a 24- hour cycle, rated independent of the effect of external factors. It may either take the form of insomnia (reduction in total sleep time) or the form of hypersomnia (increase in total sleep time, inclusive of daytime sleep).
  • the rating for insomnia involves scores of 0 (no reduction in total sleep time); 1 (mild; reduction up to 2 hours); 2 (moderate; 2 - 4 hours); 3 (severe; more than 4 hours).
  • the alternative rating for hypersomnia involves scores of 0 (no increase in total sleep time, inclusive of daytime sleep); 1 (mild; less than 2 hours, or normal amount but nonrestorative); 2 (moderate; 2 - 4 hours); 3 (severe; greater than 4 hours).
  • Appetite disturbance is assessed based on the change in appetite and food consumption, rated independent of the effect of external factors. It may either take the form of loss of appetite or the form of increase in appetite.
  • the rating for loss of appetite involves scores of 0 (no change in appetite and food consumption); 1 (mild; no change in food intake, but has to push self to eat or reports that food has lost taste); 2 (moderate; some decrease in food intake); 3 (marked decrease in food intake, hardly eating).
  • the alternative rating for increase in appetite involves scores of 0 (no change in appetite and food consumption); 1 (mild; no change in food intake, but increased hunger); 2 (moderate; some increase in food intake, e.g., comfort eating); 3 (marked increase in food intake or cravings).
  • Reduced social engagement is scored as 0 if there are no patient/subjective reports of reduced social and interpersonal engagement or interactions; 1 (mild) in case of slight reduction in social engagement with no impairment in social or interpersonal function; 2 (moderate) in case of clear reduction in social engagement with some functional sequelae, e.g., avoiding some social engagements or conversations; and 3 (severe) in case of marked reduction in social interaction or avoidance of almost all forms of social contact, e.g., refusing to answer the phone or see friends or family.
  • Reduced energy and activity is scored as 0 if there is no reduced energy, drive or goal directed behaviour; 1 (mild) in case of ability to engage in usual activities but with increased effort; 2 (moderate) in case of significant reduction in energy leading to reduction of some role-specific activities; and 3 (severe) in case of leaden paralysis or cessation of almost all role specific activities, (e.g., spending excessive time in bed, avoiding answering the phone, poor personal hygiene).
  • Impaired concentration and memory are scored as 0 if there are no patient/subjective reports of reduced attention, concentration, or memory, and consequent functional impairment; 1 (mild) in case of slight impairment of attention, concentration, or memory with no functional impairment; 2 (moderate) in case of significant impairment of attention, concentration, or forgetfulness with some functional impairment; 3 (severe) in case of marked impairment of concentration or memory with substantial functional impairment, e.g., unable to read or watch TV).

Landscapes

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

Abstract

L'invention concerne des compositions pharmaceutiques comprenant de la 5-méthoxy-N,N-diméthyltryptamine (5-MeO-DMT) et un ou plusieurs supports ou excipients pharmaceutiquement acceptables, ainsi que leurs utilisations en tant que médicament.
PCT/GB2024/052500 2023-09-28 2024-09-27 Compositions pharmaceutiques comprenant de la 5-méthoxy-n,n-diméthyltryptamine (5-meo-dmt) Pending WO2025068714A1 (fr)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
GBGB2314911.5A GB202314911D0 (en) 2023-09-28 2023-09-28 Dosing of 5-MeO-DMT
GB2314911.5 2023-09-28
GB2403419.1 2024-03-08
GBGB2403419.1A GB202403419D0 (en) 2024-03-08 2024-03-08 Dosing of 5-MeO-DMT
GBGB2403721.0A GB202403721D0 (en) 2024-03-14 2024-03-14 Dosing of 5-meo-dmt
GB2403721.0 2024-03-14
GBGB2405965.1A GB202405965D0 (en) 2024-04-29 2024-04-29 Dosing of 5-meO-DMT
GB2405965.1 2024-04-29

Publications (1)

Publication Number Publication Date
WO2025068714A1 true WO2025068714A1 (fr) 2025-04-03

Family

ID=93061712

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2024/052500 Pending WO2025068714A1 (fr) 2023-09-28 2024-09-27 Compositions pharmaceutiques comprenant de la 5-méthoxy-n,n-diméthyltryptamine (5-meo-dmt)

Country Status (1)

Country Link
WO (1) WO2025068714A1 (fr)

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160296957A1 (en) 2013-07-05 2016-10-13 Aptar France Sas Fluid or powdery product dispensing device
WO2021005308A2 (fr) 2019-07-10 2021-01-14 Aptar France Sas Dispositif de distribution nasale de poudre
GB2596884A (en) * 2020-06-12 2022-01-12 Beckley Psytech Ltd Pharmaceutical composition
US20220071958A1 (en) * 2019-02-22 2022-03-10 GH Research Ireland Limited 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) for treating depression
WO2022123128A1 (fr) 2020-12-09 2022-06-16 Aptar France Sas Dispositif de distribution de doses de poudre
WO2022171969A1 (fr) 2021-02-15 2022-08-18 Aptar France Sas Tête de distribution pour dispositif de distribution nasale d'un produit fluide ou pulvérulent
WO2022208014A1 (fr) 2021-03-29 2022-10-06 Aptar France Sas Dispositif de distribution nasale de poudre
US11518742B2 (en) * 2020-06-12 2022-12-06 Beckley Psytech Limited Composition comprising a benzoate salt of 5-methoxy-N,N-dimethyltryptamine
US20230094051A1 (en) * 2021-09-30 2023-03-30 Biomind Labs UK Limited Dimethyltriptamine-based nasal spray for the personalised treatment of neurological and psychiatric disorders
US11773063B1 (en) * 2022-08-19 2023-10-03 Beckley Psytech Limited Pharmaceutically acceptable salts and compositions thereof
WO2024105379A1 (fr) * 2022-11-14 2024-05-23 Beckley Psytech Limited Formulations de 5-meo-dmt

Patent Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160296957A1 (en) 2013-07-05 2016-10-13 Aptar France Sas Fluid or powdery product dispensing device
US20220071958A1 (en) * 2019-02-22 2022-03-10 GH Research Ireland Limited 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) for treating depression
WO2021005308A2 (fr) 2019-07-10 2021-01-14 Aptar France Sas Dispositif de distribution nasale de poudre
US20220362491A1 (en) 2019-07-10 2022-11-17 Aptar France Sas Nasal powder delivery device
GB2596884A (en) * 2020-06-12 2022-01-12 Beckley Psytech Ltd Pharmaceutical composition
US11518742B2 (en) * 2020-06-12 2022-12-06 Beckley Psytech Limited Composition comprising a benzoate salt of 5-methoxy-N,N-dimethyltryptamine
WO2022123128A1 (fr) 2020-12-09 2022-06-16 Aptar France Sas Dispositif de distribution de doses de poudre
WO2022171969A1 (fr) 2021-02-15 2022-08-18 Aptar France Sas Tête de distribution pour dispositif de distribution nasale d'un produit fluide ou pulvérulent
WO2022208014A1 (fr) 2021-03-29 2022-10-06 Aptar France Sas Dispositif de distribution nasale de poudre
US20230094051A1 (en) * 2021-09-30 2023-03-30 Biomind Labs UK Limited Dimethyltriptamine-based nasal spray for the personalised treatment of neurological and psychiatric disorders
US11773063B1 (en) * 2022-08-19 2023-10-03 Beckley Psytech Limited Pharmaceutically acceptable salts and compositions thereof
WO2024105379A1 (fr) * 2022-11-14 2024-05-23 Beckley Psytech Limited Formulations de 5-meo-dmt

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
BUSNER, J.TAGRUM, S. D.: "The Clinical Global Impressions Scale: Applying a Research Tool in Clinical Practice", PSYCHIATRY, 2007, pages 29 - 37
MONTGOMERY, S. A.ASBERG, M.: "A new depression scale designed to be sensitive to change", THE BRITISH JOURNAL OF PSYCHIATRY, vol. 134, 1979, pages 382, XP093153449, DOI: 10.1192/bjp.134.4.382
RECKWEG JOHANNES ET AL: "A Phase 1, Dose-Ranging Study to Assess Safety and Psychoactive Effects of a Vaporized 5-Methoxy-N, N-Dimethyltryptamine Formulation (GH001) in Healthy Volunteers", FRONTIERS IN PHARMACOLOGY, vol. 12, 25 November 2021 (2021-11-25), CH, XP055932663, ISSN: 1663-9812, DOI: 10.3389/fphar.2021.760671 *
RECKWEG JOHANNES T. ET AL: "A phase 1/2 trial to assess safety and efficacy of a vaporized 5-methoxy-N,N-dimethyltryptamine formulation (GH001) in patients with treatment-resistant depression", FRONTIERS IN PSYCHIATRY, vol. 14, 20 June 2023 (2023-06-20), Frontiers in psychiatrySwitzerland2020, XP093182606, ISSN: 1664-0640, Retrieved from the Internet <URL:https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1133414/full> DOI: 10.3389/fpsyt.2023.1133414 *
RUCKER JAMES ET AL: "105. Intranasal 5-MeO-DMT: Safety, PK and Effect on Altered States of Consciousness in Healthy Volunteers", BIOLOGICAL PSYCHIATRY, ELSEVIER, AMSTERDAM, NL, vol. 93, no. 9, 10 April 2023 (2023-04-10), XP087295084, ISSN: 0006-3223, [retrieved on 20230410], DOI: 10.1016/J.BIOPSYCH.2023.02.345 *
RUCKER JAMES JONATHAN ET AL: "Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy- N,N -dimethyltryptamine benzoate) in healthy participants", JOURNAL OF PSYCHOPHARMACOLOGY., vol. 38, no. 8, 1 August 2024 (2024-08-01), GB, pages 712 - 723, XP093229586, ISSN: 0269-8811, Retrieved from the Internet <URL:https://journals.sagepub.com/doi/pdf/10.1177/02698811241246857> DOI: 10.1177/02698811241246857 *
UTHAUG MALIN V. ET AL: "A comparison of reactivation experiences following vaporization and intramuscular injection (IM) of synthetic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting", JOURNAL OF PSYCHEDELIC STUDIES, vol. 4, no. 2, 1 June 2020 (2020-06-01), pages 104 - 113, XP093055117, DOI: 10.1556/2054.2020.00123 *

Similar Documents

Publication Publication Date Title
US11680044B2 (en) Pharmaceutical composition comprising 5-methoxy-n,n-dimethyltryptamine
AU2022413759A1 (en) Benzoate salt of 5-methoxy-n,n-dimethyltryptamine
WO2023186835A1 (fr) Traitement de troubles mentaux
AU2023246681A1 (en) Treatment of postnatal depression
WO2024160389A1 (fr) 5-méthoxy-n,n-diméthyltryptamine destinée à être utilisée dans le traitement de troubles mentaux chez des mères allaitantes
WO2024160391A1 (fr) Traitement de troubles mentaux
WO2025068714A1 (fr) Compositions pharmaceutiques comprenant de la 5-méthoxy-n,n-diméthyltryptamine (5-meo-dmt)
WO2024224115A1 (fr) Compositions pharmaceutiques de 5-méthoxy-n,n-diméthyltryptamine (5-meo-dmt)
US20250241894A1 (en) Treatment of mental disorders
CN120641095A (zh) 精神障碍的治疗
CN118973568A (zh) 精神障碍的治疗

Legal Events

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

Ref document number: 24787545

Country of ref document: EP

Kind code of ref document: A1