WO2024028779A1 - Formulations et dispositifs de vaporisateur d'amanite tue-mouche - Google Patents

Formulations et dispositifs de vaporisateur d'amanite tue-mouche Download PDF

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Publication number
WO2024028779A1
WO2024028779A1 PCT/IB2023/057813 IB2023057813W WO2024028779A1 WO 2024028779 A1 WO2024028779 A1 WO 2024028779A1 IB 2023057813 W IB2023057813 W IB 2023057813W WO 2024028779 A1 WO2024028779 A1 WO 2024028779A1
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disorder
extract
formulation
muscaria
vaporizable formulation
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PCT/IB2023/057813
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English (en)
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Jeffrey Stevens
Brian TANCOWNY
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Psyched Wellness Ltd.
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Publication of WO2024028779A1 publication Critical patent/WO2024028779A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D261/12—Oxygen atoms
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
    • A24B15/10—Chemical features of tobacco products or tobacco substitutes
    • A24B15/16—Chemical features of tobacco products or tobacco substitutes of tobacco substitutes
    • A24B15/167—Chemical features of tobacco products or tobacco substitutes of tobacco substitutes in liquid or vaporisable form, e.g. liquid compositions for electronic cigarettes
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
    • A24B15/18—Treatment of tobacco products or tobacco substitutes
    • A24B15/28—Treatment of tobacco products or tobacco substitutes by chemical substances
    • A24B15/30—Treatment of tobacco products or tobacco substitutes by chemical substances by organic substances
    • A24B15/302—Treatment of tobacco products or tobacco substitutes by chemical substances by organic substances by natural substances obtained from animals or plants
    • A24B15/303—Plant extracts other than tobacco
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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
    • A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
    • 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
    • A61K9/10—Dispersions; Emulsions
    • 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
    • A61K9/148—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 compounds of unknown constitution, e.g. material from plants or animals
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24F—SMOKERS' REQUISITES; MATCH BOXES; SIMULATED SMOKING DEVICES
    • A24F40/00—Electrically operated smoking devices; Component parts thereof; Manufacture thereof; Maintenance or testing thereof; Charging means specially adapted therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/04—Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised
    • A61M11/041—Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised using heaters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/06—Inhaling appliances shaped like cigars, cigarettes or pipes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M21/00—Other devices or methods to cause a change in the state of consciousness; Devices for producing or ending sleep by mechanical, optical, or acoustical means, e.g. for hypnosis
    • A61M2021/0005—Other devices or methods to cause a change in the state of consciousness; Devices for producing or ending sleep by mechanical, optical, or acoustical means, e.g. for hypnosis by the use of a particular sense, or stimulus
    • A61M2021/0077—Other devices or methods to cause a change in the state of consciousness; Devices for producing or ending sleep by mechanical, optical, or acoustical means, e.g. for hypnosis by the use of a particular sense, or stimulus with application of chemical or pharmacological stimulus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M21/00—Other devices or methods to cause a change in the state of consciousness; Devices for producing or ending sleep by mechanical, optical, or acoustical means, e.g. for hypnosis
    • A61M21/02—Other devices or methods to cause a change in the state of consciousness; Devices for producing or ending sleep by mechanical, optical, or acoustical means, e.g. for hypnosis for inducing sleep or relaxation, e.g. by direct nerve stimulation, hypnosis, analgesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/04—Liquids
    • A61M2202/0468—Liquids non-physiological
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/33—Controlling, regulating or measuring
    • A61M2205/3324—PH measuring means
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/33—Controlling, regulating or measuring
    • A61M2205/3368—Temperature
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/82—Internal energy supply devices
    • A61M2205/8206—Internal energy supply devices battery-operated
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2207/00—Methods of manufacture, assembly or production
    • 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

Definitions

  • vaporizer formulations comprising fungal material from Amanita muscaria and/or extract thereof, as well as devices comprising the same. Also provided are methods of using the disclosed formulations and devices to modulate neurotransmission, improve mental and physical health and wellness, and treat medical conditions.
  • Mushrooms of the Amanita genus have long been a part of the human diet, and certain Amanita species are also known for their psychoactive properties.
  • Amanita muscaria also known as the fly agaric, is a mycorrhizal basidiomycete fungus native to temperate and boreal regions of the Northern Hemisphere. Ingestion of the Amanita muscaria by indigenous peoples of Siberia and Mexico is a centuries-old practice of cultural and religious significance. Amanita muscaria use for spiritual and recreational purposes continues in the present day.
  • a vaporizable formulation comprising: (a) an Amanita muscaria extract; (b) a base liquid; and (c) optionally, a flavorant; wherein the mass ratio of muscimokibotenic acid in the Amanita muscaria extract is greater than about 10:1.
  • the muscimokibotenic acid ratio is greater than about 100:1. In embodiments, the muscimokibotenic acid ratio is greater than about 1000:1. In embodiments, the muscimokibotenic acid ratio is between about 10:1 and 50:1. In embodiments, the muscimokibotenic acid ratio is between about 10:1 and 30:1. In embodiments, the muscimokibotenic acid ratio is about 12.5:1. In embodiments, the muscimokibotenic acid ratio is about 25:1.
  • the Amanita muscaria extract comprises less than about 550 pg/g of muscarine. In some embodiments, the Amanita muscaria extract comprises less than about 40 pg/g of stizolobinic acid.
  • the vaporizable formulation of claim 1 wherein the Amanita muscaria extract comprises less than about 40 pg/g or 20 pg/g of stizolobinic acid.
  • the Amanita muscaria extract comprises less than about 0.05 ppm, 0.04 ppm, or 0.03 ppm of arsenic. In embodiments, the Amanita muscaria extract comprises less than about 0.30 ppm, 0.25 ppm, 0.20 ppm, 0.15 ppm, 0.10 ppm, or 0.09 ppm of cadmium. In embodiments, the Amanita muscaria extract comprises less than about 0.15 ppm, 0.10 ppm, 0.05 ppm, or 0.02 ppm of mercury. In embodiments, the Amanita muscaria extract comprises less than about 0.09 ppm, 0.05 ppm, 0.04 ppm, 0.03 ppm, or 0.02 ppm of lead.
  • the vaporizable formulation is produced by: (a) suspending an Amanita muscaria extract in a solvent; (b) mixing the suspension; (c) isolating the supernatant from the suspension, thereby producing an extract solution; (d) evaporating the extract solution to provide a residue; and (e) dissolving the residue in a base liquid to produce the vaporizable formulation.
  • the Amanita muscaria extract is a ground powder extract.
  • the solvent is an organic solvent.
  • the solvent is a methanol.
  • the supernatant comprises centrifuging of the suspension.
  • evaporating the extract solution comprises heating the extract solution.
  • the vaporizable formulation is produced by: (a) performing an aqueous extraction of Amanita muscaria mushroom biomass in the presence of heat to produce the extract; (b) reducing the pH of the extract; (c) concentrating the extract; and (d) dissolving the extract in a base liquid to produce the vaporizable formulation.
  • the aqueous extraction is performed in water heated to between about 70 °C and 100 °C.
  • the aqueous extraction is performed in water heated to between about 80 °C.
  • the pH is reduced to between about 2.5 and about 3.0.
  • the base liquid comprises propylene glycol, vegetable glycerin, or a combination thereof.
  • the mass ratio of the Amanita muscaria extract to the base liquid is about 1 part extract to about 10 parts base liquid.
  • the vaporizer formulation comprises between about 40% v/v to 90% v/v of the base liquid.
  • the vaporizer formulation comprises between about 40% v/v and about 90% v/v of propylene glycol.
  • the vaporizer formulation comprises between about 40% v/v and about 90% v/v of vegetable glycerin.
  • the vaporizer formulation comprises between about 0.1% v/v and about 10% v/v of the flavorant.
  • the vaporizer formulation comprises between about 0.1% v/v and about 5% v/v of the flavorant.
  • the vaporizer formulation comprises between about 0.1 % v/v and about 1% v/v of the flavorant.
  • a method of producing the vaporizable formulation of any of the disclosed embodiments comprising: (a) suspending an Amanita muscaria extract in a solvent; (b) mixing the suspension; (c) isolating the supernatant from the suspension, thereby producing an extract solution; (d) evaporating the extract solution to provide a residue; and (e) dissolving the residue in a base liquid to produce the vaporizable formulation.
  • the Amanita muscaria extract is a ground powder extract.
  • the solvent is an organic solvent.
  • the solvent is a methanol.
  • isolating the supernatant comprises centrifuging of the suspension.
  • evaporating the extract solution comprises heating the extract solution.
  • the method further comprises dissolving a flavorant in the base liquid.
  • a method of producing the vaporizable formulation of any of the disclosed embodiments comprising: (a) performing an aqueous extraction of Amanita muscaria mushroom biomass in the presence of heat to produce the extract; (b) reducing the pH of the extract; (c) concentrating the extract; and (d) dissolving the extract in a base liquid to produce the vaporizable formulation.
  • the aqueous extraction is performed in water heated to between about 70 °C and 100 °C.
  • the aqueous extraction is performed in water heated to between about 80 °C.
  • the pH is reduced to between about 2.0 and about 4.0.
  • the pH is reduced to between about 2.5 and about 3.0.
  • the method further comprises dissolving a flavorant in the base liquid.
  • a method of modulating neurotransmission in a subject comprising administering to the subject the vaporizable formulation of any of the disclosed embodiments. Also provided is the vaporizable formulation of any of the disclosed embodiments, for use in modulating neurotransmission.
  • modulating neurotransmission comprises modulating one or more of gabaminergic, glutaminergic, and cholinergic neurotransmission.
  • a method of treating a medical condition in a subject in need of such treatment comprising administering to the subject the vaporizable formulation of any of the disclosed embodiments.
  • the medical condition is a disorder linked to dysregulation or inadequate functioning of gabaminergic, glutaminergic, or cholinergic neurotransmission.
  • the medical condition is a mental, behavioral, or neurodevelopmental disorder.
  • the mental, behavioral, or neurodevelopmental disorder is a neurodevelopmental disorder, schizophrenia or another primary psychotic disorder, catatonia, a mood disorder, an anxiety or fear-related disorders, an obsessive-compulsive or related disorder, a disorder specifically associated with stress, a dissociative disorder, a feeding or eating disorder, an elimination disorder, a disorder of bodily distress or bodily experience, a disorder due to substance use or addictive behavior, an impulse control disorder, a disruptive behavior or dissocial disorder, a personality disorder, a paraphilic disorder, a factitious disorder, a neurocognitive disorder, a mental or behavioral disorder associated with pregnancy, childbirth or the puerperium, a sleep-wake disorder, or a sexual dysfunction.
  • the medical condition is pain or a pain disorder, inflammation or an inflammatory disorder, an immune or autoimmune disorder, or a sleep disorder.
  • the pain disorder is any of arthritis, allodynia, atypical trigeminal neuralgia, trigeminal neuralgia, somatoform disorder, hypoesthesis, hypealgesia, neuralgia, heuritis, neurogenic pain, analgesia, anesthesia dolorosa, causlagia, sciatic nerve pain disorder, degenerative joint disorder, fibromyalgia, visceral disease, chronic pain disorders, migraine/headache pain, chronic fatigue syndrome, complex regional pain syndrome, neurodystrophy, plantar fasciitis, or pain associated with cancer.
  • the autoimmune disorder is any of acute disseminated encephalomyelitis (ADEM), Addison disease, allergy or hypersensitivity, amyotrophic lateral sclerosis, antiphospholipid antibody syndrome (APS), arthritis, autoimmune hemolysis anemia, autoimmune hepatitis, autoimmune inner ear disease, autoimmune pancreatitis, bullous pemphigoid, celiac disease, Chagas disease, chronic obstructive pulmonary disease (COPD), type 1 diabetes (T1 D), endometriosis, fibromyalgia, goodpasture's syndrome, Graves' disease, Guillain-Barre syndrome (GBS), Hashimoto's thyroiditis, suppurative spondylitis, idiopathic thrombocytopenic purpura, inflammatory bowel disease, interstitial cystitis, lupus, including discoid lupus erythematosus, drug-induced lupus lupus erythemat
  • the autoimmune disorder is a systemic autoimmune disorder, including systemic lupus erythematosus (SLE), Sjogren's syndrome, scleroderma, rheumatoid arthritis, and polymyositis.
  • the sleep disorder is any of an insomnia, a hypersomnia, a parasomnia, and a disorder of sleep-wake schedule
  • improving health and wellness comprises any of reducing stress, easing muscular tension, promoting restorative sleep, soothing the body, calming the mind, reducing physical distress, reducing anxiety, and inducing euphoria.
  • improving health and wellness comprises treating a medical condition.
  • a vaporizer device comprising: (a) a mouthpiece; (b) a heating element; (c) a power source; and (d) a chamber comprising the vaporizable formulation of any of the disclosed embodiments.
  • the heating element is capable of heating the vaporizable formulation to a set temperature.
  • the set temperature is sufficient to vaporize the vaporizable formulation.
  • the power source powers the heating element.
  • the heating element comprises a wick element.
  • the chamber comprises a first end configured to attach to the mouthpiece.
  • the chamber comprises a second end configured to attach to the heating element and the power source.
  • the chamber is refillable.
  • the chamber is removable.
  • the vaporizer device further comprises a means for controlling the device.
  • the means for controlling the device comprises switches, buttons, touch sensors, or a combination thereof.
  • the vaporizer device further comprises a means for displaying information.
  • the means for displaying information comprises a screen, a number of lights, or a combination thereof.
  • the vaporizer device further comprises a number of sensors configured to sense temperature, pH, volume, the means for controlling the device, or a combination thereof.
  • FIG. 1 is a flowchart of an exemplary process for producing a vaporizer formulation in accordance with a first embodiment described herein;
  • FIG. 2 is a flowchart of an exemplary process for producing a vaporizer formulation in accordance with an additional embodiment described herein.
  • vaporizer formulations comprising fungal material, including mushrooms, such as Amanita muscaria mushrooms, fungal extracts such as Amanita muscaria extracts, as well as compounds from such extracts, including muscimol and muscarine, chambers and devices comprising the same, and methods of their use for the general improvement of mental and physical health and wellness, and for treating diseases and disorders.
  • the terms “including,” “may include,” and “include,” as used herein mean, and are used interchangeably with, the phrase “including but not limited to.”
  • the word “exemplary” is used herein to mean “serving as an example, instance, or illustration.” Any aspect, embodiment, process, or implementation described as “exemplary” is thus not to be construed as necessarily preferred or advantageous over others.
  • “about” means a range extending to -+-/-10% of the specified value. Accordingly, in embodiments, the numerical parameters set forth in the written description and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment.
  • the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable, taking into consideration production variances and manufacturing tolerances and the like. Accordingly, the numerical values presented In embodiments of the invention may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
  • Amanita muscaria (equivalently, “A. muscaria”) will be understood to include the Amanita muscaria var. Muscaria (Euro-Asian fly agaric), Amanita muscaria var. flavivolvata (American fly agaric), Amanita muscaria var. guessowii (American fly agaric, yellow variant), and Amanita muscaria var.
  • inzengae (“Inzenga’s” fly agaric); also within the scope and spirit of the invention, and which thus shall be considered within the definition of Amanita muscaria or as equivalents thereof, are such other ibotenic acid and muscimol containing Amanita species that are not known to be deadly poisonous, as will be appreciated as within the general knowledge in the art.
  • Amanita muscaria is known to contain several psychoactive compounds as well as some other biologically active substances. Accordingly, chemists, pharmacologists, and ethnobotanists have deployed great efforts in attempts to resolve the chemical composition of these mushrooms and to explain the physiological effects attributed to them for over 100 years. Muscimol (5-(aminomethyl)-1,2-oxazol- 3(2H)-one) is one of the main psychoactive components of A. muscaria. Muscimol is known to be an agonist for GABA A receptors (Johnston, Eurochem Res. 2014;39(10):1942-7).
  • Muscimol When binding to a GABA A receptor, muscimol activates the receptor, causing anxiolytic, anticonvulsant, amnesic, sedative, hypnotic, euphoriant, and muscle relaxant properties. Muscimol also may have hallucinogenic effects.
  • Ibotenic acid ((S)-2-amino-2-(3-hydroxy- isoxazol-5-yl)), a conformationally-restricted analogue of the neurotransmitter glutamate that acts as a non-selective glutamate receptor agonist.
  • Ibotenic acid can also act as a neurotoxin under certain conditions; for example, in scientific research, cranially injected ibotenic acid has been employed as a “brain-lesioning agent.” Ibotenic acid can be converted to muscimol by a chemical process known as decarboxylation.
  • “Decarboxylation” refers to a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO 2 ), thereby replacing a carboxyl group (— COOH) with a hydrogen atom (H); e.g., as RCO 2 H — RH + CO 2 . ibotenic acid muscimol
  • Amanita muscaria contains more ibotenic acid than muscimol. At least some of the ibotenic acid in Amanita muscaria is converted by decarboxylation to muscimol in the acid environment of the stomach. Ibotenic acid therefore serves as a prodrug to muscimol.
  • Muscarine (2,5-anhydro-1 ,4,6-trideoxy-6-(trimethyl-ammonio)-D-ribo-hexitol) is another component of A. musca a, typically found in lower quantities than ibotenic acid and muscimol. Muscarine is a nonselective agonist of the muscarinic acetylcholine receptors (Broadley et al., Molecules, 2001 ;6(3): 142-193). Muscarine may be toxic in concentrations found in certain mushroom species, but not typically in the concentrations found in Amanita muscaha.
  • Extracts such as disclosed herein offer additional advantages: they can have improved shelf stability (especially when preservatives are incorporated into the extract), they can improve consumer or patient experience (e.g., by providing a more flavorful product), they can be purified and subjected to chemical analysis to ensure they are free of toxins and pollutants, and they can be more easily incorporated into other consumable products, such as inhalable or vaporizable formulations (e.g., for use in a vaporizer).
  • A. muscaha extracts useful in the practice of the invention include extracts produced according to disclosed methods, or those disclosed in Applicant’s prior applications published as WO2022/187974A1 and W02023/015395A1 , each of which is hereby incorporated by reference in its entirety, as if fully set forth herein.
  • the extract will be the one styled here and in the field by Applicant as AME-1® or herein “AME-1” (with characteristics as shown in Tables 1-7) obtained from certain exemplary methods disclosed herein.
  • FIG. 1 is a flowchart of an exemplary extraction and concentration procedure, Amanita muscaha mushrooms (below as shorthand and for convenience, “mushrooms”) are harvested or gathered, or are otherwise obtained as fresh mushrooms. Alternatively, mushrooms may be obtained dried. Optionally, the mushrooms are inspected to ensure that they are of suitable quality (100). Mushrooms may already have been inspected at this point, rendering further inspection unnecessary, or only for spot quality control.
  • Such inspection may identify debris, dirt, and other organic matter (which will be discarded), may be useful in confirming the correct species, and removing mistaken species, especially those that are toxic or poisonous; and/or may aid in determining general “quality,” meaning overall appearance, cleanliness, color, damage, apparent age, presence or absence of signs of worms or insects, etc.
  • the mushrooms may be frozen for a period of storage prior to further processing, upon which time the mushrooms may be thawed (140).
  • mushroom caps will have the highest concentration of target compounds, and thus in certain preferred embodiments, the caps are removed from the stipes prior to processing, and only the caps are used, therefore leading to greater overall yields of muscimol, and higher potency. In some embodiments, both caps and stipes are used. In some embodiments, only stipes are used.
  • the mushrooms utilized in a disclosed process are sufficiently dry, having a moisture content of from about 2% to about 3% moisture by weight. That said, in some embodiments, the mushrooms may have less than 2% or more than 3% moisture by weight. For example, dehydrated mushrooms may have a moisture content of from about 4% to about 7% by weight. If not sufficiently dry when harvested, the mushrooms may be dried (also termed “dehydrated”) (105) in a dehydrator or by application of heat in any conceivable method known to those of skill, including but not limited to conduction, convection, or radiation.
  • dryness will be considered sufficient when the mushrooms will be able to be ground into a powder. That said, drying the harvested mushrooms is merely an optional step.
  • embodiments wherein the mushrooms are not dried, or are of a moisture content outside the range disclosed above e.g., 1 %, 2%, 3%, 4%, 5%, 6%, 7%, or greater than 7%, wherein the range is inclusive and each number may be modified by the term “about”
  • the present disclosure are also encompassed by the present disclosure.
  • drying may be completed at a maximum temperature of 50 °C, including 49 °C, 48 °C, 47 °C, 46 °C, 45 °C, 44 °C, 43 °C, 42 °C, 41 °C, 40 °C, 39 °C, 38 °C, 37 °C, 36 °C, 35 °C, 34 °C, 33 °C, 32 °C, 31 °C, 30 °C, 29 °C, 28 °C, 27 °C, 26 °C, 25 °C, 24 °C, 23 °C, 22 °C, 21 °C, 20 °C, or less than 20 °C.
  • the mushrooms may be dried in a circulated air dehydration unit, a forced air food dryer, or any other such device capable of maintaining a substantially constant temperature set by a user, wherein heating is completed via conduction (direct heating), convection (heating via continuous currents of a gas or liquid), and/or radiation (heating via absorption of heat by a cooler body from a warmer body).
  • heating is completed via conduction (direct heating), convection (heating via continuous currents of a gas or liquid), and/or radiation (heating via absorption of heat by a cooler body from a warmer body).
  • drying may, in some embodiments, last from about 24 hours to about 48 hours, including 24 hours, 25 hours, 26 hours, 27 hours, 28 hours, 29 hours, 30 hours, 31 hours, 32 hours,
  • heating may be completed for less than 24 hours, such as 20 hours, 16 hours, 12 hours, 8 hours, or less than 8 hours; or greater than 48 hours, such as 56 hours, 60 hours, 65 hours, 72 hours, or 80 hours (inclusive).
  • the mushrooms may be sealed in plastic bags or airtight containers and stored in darkness until processing.
  • the temperature at which the mushrooms are stored should correspond with how soon processing may take place.
  • mushrooms are stored at between about -25 °C and about 3 °C.
  • storage at the warmer temperatures of the aforementioned range is only recommended if processing will imminently occur (such as within about 5 days) because prolonged storage at temperatures above 3 °C may result in a loss of potency and gradual destruction of the mushrooms by macroscopic and microscopic organisms.
  • the appropriate amount of drying may be determined by one of ordinary skill. Drying the harvested mushrooms is also an optional step, and should not be construed as limiting.
  • the mushrooms including dried mushrooms, are ground (e.g., to a powder) by a food processor, coffee grinder, blender, or similar device, including like devices of commercial or industrial scale (110). Mushrooms also may be chopped, pulverized, and/or otherwise rendered to smaller pieces or particles, by methods and devices known to those of skill. Although steps below may be described as using “ground mushrooms,” it will be appreciated that such mushrooms may be whole or in pieces or in particles of various sizes, all of which are within the scope of the methods, but will have properties that may differ according to ordinary skill, for example that smaller pieces or particles may require lower processing times, fewer steps such as fewer extraction steps, less total solvent, and/or provide an extract of greater potency.
  • mushrooms are subjected to quality assurance analyses prior to grinding.
  • a small batch of mushrooms or the ground powder thereof (together below for convenience simply “mushrooms”) is optionally analyzed to determine whether the muscimol, muscarine, and ibotenic acid are within safety and production specifications.
  • the batch may or may not be analyzed for heavy metal and pesticide content.
  • the analysis may be performed by any means known to those of skill capable of completing such an analysis, e.g., high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS).
  • An aqueous extraction may then be conducted.
  • water is obtained, the pH is determined, and is maintained at about 7, with adjustments made as necessary and as known in the art.
  • the water is boiled, and the mushrooms are placed in the boiled water and stirred.
  • the aqueous extraction is performed in water heated to between about 70 °C and 100 °C.
  • the temperature of the mixture of water and mushrooms is maintained at 95 °C to 100 °C.
  • the temperature of the mixture of water and mushrooms is maintained at about 80 °C.
  • the mixture is stirred for between about 5 minutes to about 180 minutes at between about 700 rpm and about 2500 rpm.
  • the mixture is stirred for between about 5 minutes to about 180 minutes, including 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55 minutes, 60 minutes, 65 minutes, 70 minutes, 75 minutes, 80 minutes, 85 minutes, 90 minutes, 95 minutes, 100 minutes, 105 minutes, 110 minutes, 115 minutes, 120 minutes, 125 minutes, 130 minutes, 135 minutes, 140 minutes, 145 minutes, 150 minutes, 155 minutes, 160 minutes, 165 minutes, 170 minutes, 175 minutes, 180 minutes, or greater than 180 minutes, wherein the range is inclusive and each value may be modified by the term “about;” at between 700 rpm and 2500 rpm, including about 750 rpm, 800 rpm, 850 rpm, 900 rpm, 950 rpm, 1000 rpm, 1050 rpm, 1100 rpm, 1150 rpm, 1200 rpm,
  • mixing may be performed by hand, for example by utilization of a stirring utensil, such as a whisk, a spoon, or a spatula; or using a stir plate, for example using an electronic hand mixer, using an electronic mixture having its own arm, or, in some embodiments, using an industrial vat capable of containing the mixture of the invention and possessing at least one agitation means (such as, but not limited to, paddles or arms).
  • a stirring utensil such as a whisk, a spoon, or a spatula
  • a stir plate for example using an electronic hand mixer, using an electronic mixture having its own arm, or, in some embodiments, using an industrial vat capable of containing the mixture of the invention and possessing at least one agitation means (such as, but not limited to, paddles or arms).
  • agitation may be completed for between about 5 minutes, to at least 180 minutes— the specific amount of time required reflecting the given embodiment being practiced. Meaning, in some embodiments, the duration of time required for agitation may be based on a standard amount of time known for that given embodiment, such as but not limited to an embodiment wherein the suggested agitation time is 60 minutes. In other embodiments, agitation may be an iterative process wherein agitation ceases when the mixture forms a substantially homogeneous slurry. In some embodiments, a substantially homogeneous slurry is characterized by substantially uniform dispersion of the mushroom particles within the water, which may be evidenced by the naked eye, and would be immediately apparent to one of skill. However, such uniform dispersion may additionally be determined electronically, using devices known to those of skill capable of determining sample variance.
  • the water is heated, in some embodiments, to between about 70 °C to about 100 °C. Such temperatures aid in extracting muscimol from the tissue of the mushroom.
  • the ratio of ground mushroom caps to water may be about 1 gram of mushroom:40 mL of water, such that 1 gram, 5 grams, 7 grams, 10 grams, 12 grams, 15 grams, 17 grams, 20 grams, 25 grams, 30 grams, 35 grams, 40 grams, 45 grams, 50 grams, 55 grams, 60 grams, 65 grams, 70 grams, 75 grams, 80 grams, 85 grams, 90 grams, 95 grams, or 100 grams of mushroom extract may be combined with 40 mL, 80 mL, 280 mL, 400 mL, 480 mL, 600 mL, 680 mL, 800 mL, 1000 mL, 1200 mL, 1400 mL, 1600 mL, 2000 mL, 2200 mL, 2400 mL, 2600 mL, 2800 mL, 3000
  • the ratio of water to mushroom may be from about 5 mL of water per 1 g of mushroom (i.e., a 5:1 watenmushroom ratio), up to about 20 mL of water per 1 g of mushroom (i.e., a 20:1 water: mushroom ratio).
  • the water:mushroom ratio is about 5:1 , 10:1, 11 :1 , 12:1, 13:1, 14:1, 15:1 , 16:1 , 17:1 , 18:1 , 19:1 or 20:1, or values in between these ratios.
  • the mushroom powder is added to water at about from 65 °C to about 150 °C.
  • the water temperature is about 65 °C, about 70 °C, about 75 °C, about 80 °C, about 85 °C, about 90 °C, about 95 °C, about 100 °C, about 105 °C, about 110 °C, about 115 °C, about 120 °C, about 125 °C, about 130 °C, about 135 °C, about 140 °C, about 145 °C, about 150 °C.
  • the boiled water is allowed to cool to about 75 °C before adding the ground mushrooms.
  • the water is heated to about 75 °C before adding the ground mushrooms. In some embodiments, the water is maintained at a temperature of 75 °C prior to adding the ground mushrooms. In embodiments, the water is maintained at a temperature of 80 °C prior to adding the ground mushrooms.
  • the mixture is then filtered to remove solids (120).
  • the filtrate may be collected in a flask.
  • this is an exemplary, non-limiting embodiment, and any such container sufficient to contain the filtrate may be used for collection.
  • pressure is applied during the filtration process (150), such as with use of a fruit press.
  • the mixture may be drawn through the filter(s) by vacuum filtration.
  • the filtrate is centrifuged to separate particulate matter and a supernatant (155).
  • centrifuging it may take place for between about 1 and about 25 minutes, including 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 6 minutes, 7 minutes, 8 minutes, 9 minutes, 10 minutes, 11 minutes, 12 minutes, 13 minutes, 14 minutes, 15 minutes, 16 minutes, 17 minutes, 18 minutes, 19 minutes, 20 minutes, 21 minutes, 22 minutes, 23 minutes, 24 minutes, 25 minutes, and values in between, wherein each value may be modified by the term “about;” at between about 2000 to about 6000 rpm, including about 2100 rpm, 2200 rpm, 2300 rpm, 2400 rpm, 2500 rpm, 2600 rpm, 2700 rpm, 2800 rpm, 2900 rpm, 3000 rpm, 3100 rpm, 3200 rpm, 3300 rpm, 3400 rpm, 3500 rpm, 3600 rpm,
  • centrifuging may take place for about 15 minutes at about 4000 rpm at room temperature. In some embodiments, if there is a resulting pellet of non-soluble and/or fibrous material, it is discarded. The supernatant is then collected.
  • the pH of the filtrate may be adjusted (125) to between about 5-6, or lower, by adding an acid to the flask.
  • the pH of the extract is reduced.
  • the pH of the extract is reduced to between about 2.0 and about 4.0.
  • the pH of the extract is reduced to between about 2.5 and about 3.0.
  • the acid is acetic acid, boric acid, carbonic acid, citric acid, hydrochloric acid (HCI), hydrofluoric acid (HF), nitric acid, oxalic acid, phosphoric acid, sulfuric acid, or any other compound known to those of skill capable of lowering the pH of the filtrate.
  • the acid may be HCI and the pH may be lowered to about 3.0, for example, by the addition of 1 M HCI, for example. In some embodiments, the pH may be lowered to about 2.5.
  • the increased acidic environment may cause ibotenic acid to convert into muscimol by decarboxylation. If the mushrooms are not sufficiently dried (to between about 2% to about 3% moisture content), a higher concentration of HCI or other acid may be needed to achieve the same degree of conversion of ibotenic acid to muscimol.
  • the acidified mushroom filtrate or extract is concentrated (130) to accelerate decarboxylation of ibotenic acid into muscimol.
  • the concentrating step comprises heating the acidified mushroom extract.
  • the duration of heat exposure is from about 0.5 hours to about 6 hours.
  • the extract is heated from about 75 °C to about 177 °C (200 °F-350 °F).
  • the acidified mushroom filtrate or extract is concentrated to accelerate decarboxylation of ibotenic acid into muscimol.
  • the concentrating step comprises heating the acidified mushroom extract.
  • the duration of heat exposure is from about 0.5 hours to about 6 hours, wherein the range is inclusive.
  • the duration of heat exposure is about 0.5 h, 1 h, 1 .5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, or 6 hours. In embodiments, the heat exposure exceeds 6 hours.
  • the extract is heated from about 75 °C to about 177 °C, including about 76 °C, 77 °C, 78 °C, 79 °C, 80 °C, 81 °C, 82 °C, 83 °C, 84 °C, 85 °C, 86 °C, 87 °C, 88 °C, 89 °C, 90 °C, 91 °C, 92 °C, 93 °C, 94 °C, 95 °C, 96 °C, 97 °C, 98 °C, 99 °C, 100 °C, 101 °C, 102 °C, 103 °C, 104 °C, 105 °C, 106 °C, 107 °C, 108 °C, 109 °C, 110 °C, 111 °C, 112 °C, 113 °C, 114 °C, 115 °C
  • the concentration step comprises application of pressure.
  • the applied pressure is between about 10 psi and about 25 psi, including at least about 10 psi, 11 psi, 12 psi, 13 psi, 14 psi, 15 psi, 16 psi, 17 psi, 18 psi, 19 psi, 20 psi, 21 psi, 22 psi, 23 psi, 24 psi, 25 psi, and values in between, as would be apparent to one of skill, wherein the values are modified by the term about.
  • the applied pressure is 15 psi.
  • the concentrating is performed with use of heat and pressure.
  • distillation assists the conversion of ibotenic acid to muscimol.
  • refluxing assists the conversion of ibotenic acid to muscimol.
  • a combination of distillation and refluxing assists the conversion of ibotenic acid to muscimol.
  • pressure cooking assists the conversion of ibotenic acid to muscimol.
  • a condenser may be used, a non-limiting example of which is a Pyrex Graham condenser.
  • a Graham condenser includes a coolant-jacketed spiral coil running the length of the condenser serving as the vapor-condensate path.
  • the Graham condenser may be attached to another flask, such as a round bottom flask, for example, for collection.
  • the Graham condenser may be placed in a downward position for distillation, so that the acidic mixture enters the condenser at the bottom.
  • the unused neck is stoppered with a plug.
  • steps are taken to avoid light exposure throughout the process, due to the potential for muscimol degradation.
  • aluminum foil may be wrapped around the round bottom flask and up the condenser part way to lower light intensity inside the round bottom flask during refluxing.
  • any such method of reducing light penetration is acceptable, including completing the process in a dark room, setting the flask itself in an enclosure, using an opaque flask that reflects light, etc.
  • such “high” heat is between about 110 °C, to about 130 °C, including 111 °C, 112 °C, 113 °C, 114 °C, 115 °C, 116 °C, 117 °C, 118 °C, 119 °C, 120 °C, 121 °C, 122 °C, 123 °C, 124 °C, 125 °C, 126 °C, 127 °C, 128 °C, 129 °C, 130 °C, and values in between, wherein each value may be modified by the term “about.” In one example, distillation is performed for about 0.5 hours to about 6 hours.
  • distillation is performed for about 5 to about 6 hours. In another example, it is performed for about 2 to about 3 hours. In another example, it is performed for about 3 hours. Distillation for 3 hours, for example, has been found to increase the muscimol content by a significant amount and to modulate the amount of muscimol relative to ibotenic acid, as demonstrated in Example 1.
  • Another exemplary extraction procedure comprises the steps of: (a) performing an aqueous extraction of A. muscaria mushroom biomass in the presence of heat to produce an extract; (b) filtering the extract; (c) reducing the pH of the extract; and (d) heating the extract.
  • the procedure further comprises the step of (e) increasing the pH of the extract.
  • performing the aqueous extraction comprises mixing water with ground mushrooms, which may be dried and otherwise prepared for extraction as described in embodiments herein.
  • the temperature of the mixture of water and ground mushrooms is maintained at a temperature of about 70 °C to about 100 °C, including about 70 °C, 75 °C, 80 °C, 85 °C, 90 °C, 95 °C, or 100 °C.
  • the mixture is stirred for between about 5 minutes to about 20 minutes, including 5 minutes, 10 minutes, 15 minutes, 20 minutes, or greater than 20 minutes; at between 700 rpm and 2500 rpm, including about 750 rpm, 800 rpm, 850 rpm, 900 rpm, 950 rpm, 1000 rpm, 1050 rpm, 1100 rpm, 1150 rpm, 1200 rpm, 1250 rpm, 1300 rpm, 1350 rpm, 1400 rpm, 1450 rpm, 1500 rpm, 1550 rpm, 1600 rpm, 1650 rpm, 1700 rpm, 1750 rpm, 1800 rpm, 1850 rpm, 1900 rpm, 1950 rpm, 2000 rpm, 2050 rpm, 2100 rpm, 2150 rpm, 2200 rpm, 2250 rpm, 2300 rpm, 2350 rpm, 2400 rpm, 2450 rpm,
  • the water: mushroom ratio is about 5:1 , 10:1, 11 :1 , 12:1, 13:1, 14:1, 15:1, 16:1 , 17:1, 18:1, 19:1 or 20:1, or values in between these ratios.
  • the extract is then filtered to remove solids, such as particles of ground mushroom. Any filter known to those of skill may be utilized, so long as the filter is capable of filtering out both large and small particles.
  • a plurality of filters may be used in a sequential arrangement, wherein the filter pore size decreases with each additional filter.
  • at least two, at least three, at least four, at least five, or more than five filters may be utilized in series. This is particularly useful if certain particles of a given size are desired in the extract, or to be individually isolated.
  • pressure is applied during the filtration process, such as with use of mechanical pressing, compressed gas, or any suitable means of applying pressure to the feed side of a filtration apparatus.
  • the extract may be drawn through the filter(s) by vacuum filtration.
  • the filtered extract i.e., the filtrate
  • the filtrate is centrifuged to separate particulate matter and a supernatant.
  • the pH of the extract is then reduced by the addition of a suitable acid.
  • the acidic environment causes ibotenic acid to convert into muscimol by a decarboxylation reaction, as discussed above.
  • the pH is reduced from the initial pH of the extract, which may be about 7 (the pH of distilled water) to a pH of about 1.0 to about 4.0.
  • the pH of the extract is reduced to about 1 .0, to about 1 .5, to about 2.0, to about 2.5, to about 3.0, to about 3.5, or to about 4.0, wherein the range is inclusive.
  • the pH of the extract is reduced to between about 2.0 and 3.0.
  • the pH of the extract is reduced to between about 2.5 and 3.0.
  • the acid is a mineral acid— for example, hydrochloric acid (HCI), hydrofluoric acid (HF), hydrobromic acid (HBr), hydroiodic acid (HI), nitric acid, phosphoric acid, sulfuric acid, boric acid, or carbonic acid.
  • the acid is an organic acid— for example, acetic acid, citric acid, or oxalic acid.
  • the acid can also be any other compound known to those of skill capable of lowering the pH of the extract.
  • the extract is then heated.
  • the extract is heated to a temperature of between about 95 °C and about 105 °C.
  • the extract is heated to a temperature of between about 95 °C, 96 °C, 97 °C, 98 °C, 99 °C, 100 °C, 101 °C, 102 °C, 103 °C, 104 °C, or 105 °C.
  • the extract is heated to reflux.
  • the duration of the heating is about 1 to 6 hours.
  • the duration of the heating may be about 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, or 6 hours, or times in between these values.
  • the pH of the extract is then increased by addition of a suitable base.
  • the pH is raised to a pH of about 4 to about 11.
  • the pH of the extract is raised to a pH of about 4, 4.5, 5, 6, 7, 8, 9, 10, 11, or pH levels in between these values.
  • the base is a hydroxide base (e.g., NaOH, KOH, Mg(OH) 2 , Ca(OH) 2 ).
  • the base is a carbonate base (e.g., Na 2 CO 3 , K 2 CO 3 , MgCO 3 , CaCO 3 ).
  • the base is a bicarbonate base (e.g., NaHCO 3 , KHCO 3 , NH 4 HCO 3 ).
  • the base is added in solid form (e.g., as pellets, granules, or powder).
  • the base is added as a solution, such as an aqueous solution (e.g., aqueous NaOH).
  • the base is 1 M aqueous NaOH.
  • the base can alternatively be any other compound known to those of skill capable of raising the pH of the extract.
  • Amanita muscaria mushrooms were obtained from Vashon Island, Washington. The mushrooms were harvested in the fall, dried to a moisture content of from about 2% to about 4% by weight, sealed in plastic 4-liter bags, and stored frozen in darkness at -15 °C until used. The mushrooms were allowed to thaw to room temperature, were then removed from the plastic bags, and were then inspected to ensure dryness so they can be easily ground to a powder. Dryness was determined by attempting to snap mushroom caps in half. Mushroom caps in the desired range of dryness snapped in half. This was determined one hour prior to beginning the extraction process.
  • Mushrooms that were not sufficiently dry were dehydrated in a forced air food dehydrator (internal dimensions, 30 cm x 30 cm x 30 cm) at 50 °C for 90 minutes. Drying continued until each mushroom was sufficiently dehydrated (about 2-3% moisture content by weight).
  • the dried mushrooms were mixed with distilled water.
  • the pH of the distilled water was first measured after calibration with a pH meter. The pH of the distilled water was about 7. Since distilled water was stored in a plastic container, the distilled water was boiled to remove any organic material that may have leached into the water from the plastic container. 1000 mL of the distilled water was placed in a 2000 mL Pyrex beaker and boiled at 100 °C for 10 minutes in a microwave oven.
  • a 23-gram piece of 10 cm x 10 cm x 5 cm glass wool was cut in a circular shape approximately the same diameter as the Buchner funnel. It was placed on top of the glass filter in the funnel. Four grams of cheese cloth measuring 25 cm x 30 cm was folded into four layers and placed on top of the glass wool. The cheese cloth captured larger particles while the glass wool captured smaller particles.
  • the filter setup was attached to a 1000 ml Erlenmeyer flask.
  • the filter layers were seated by pouring 100 ml of the distilled water that was earlier boiled, through the setup with vacuum turned on. Filtrate was removed from the flask after pouring water through the filters.
  • the pH of the filtrate was adjusted from the pH of about 7 (the pH of the distilled water) to a pH of about 3.0 by the addition of 1 M hydrochloric acid.
  • the filtrate was refluxed through a Pyrex Graham condenser having a coolant-jacketed spiral coil running the length of the condenser serving as the vapor-condensate path.
  • the length of the Graham condenser was 43 cm.
  • the length of the water jacket was 30 cm and it had 24/60 glass joints.
  • the Graham condenser was attached to a 2000 ml round bottom flask for collection.
  • the Graham condenser was in a downward position for distillation.
  • the unused neck was stoppered with a glass 24/40 plug.
  • a round bottom flask was secured to the condenser with burette/test tube clamps that were attached to a generic 60 cm high ring stand. Aluminum foil was wrapped around the round bottom flask and up the condenser part way to lower light intensity inside the round bottom flask during refluxing. The Erlenmeyer flask was attached to the inlet of the Graham condenser.
  • the condenser coil was cooled with cold water pumped in by a pump.
  • the setup Graham condenser was heated with a heating mantle/magnetic stirrer.
  • the distillation was performed in a fume hood. Distillation took place at 250°F (-121 °C) at 15 psi (-1.0 bar).
  • a 2.5 cm magnetic stir bar was placed in the pH distillate to be distilled before starting distillation. During distillation, the magnetic stirring was provided at from about 30 rpm to about 60 rpm, to prevent bumping.
  • the heating level was set on high until the distillation began and was then adjusted so that 1 drop per second was observed and collected.
  • HPLC-MS/MS was used to analyze mushrooms and extracts at various stages of the process.
  • the starting material for the extraction process had the following concentrations: muscimol (625 pg/g), muscarine (340 g/g), and ibotenic acid (2930 pg/g).
  • ICP-MS inductively coupled plasma mass spectrometry
  • a ground powder extract is provided.
  • the same mushrooms as in Example 1 were pressed through a filter to obtain filtered extract.
  • a total amount of 1 .5 kg of mushrooms were inspected and dehydrated, and then cut into pieces having dimensions of about 1 cm x 1 cm.
  • the pH of distilled water was confirmed to be about 7 by a calibrated pH meter and the water was boiled for 10 minutes.
  • the cut pieces of the mushrooms were placed in the boiled water.
  • the temperature of the water was maintained at 95 °C.
  • a fruit press was used to press the mushrooms through a filter to extract filtrate.
  • a 1 L beaker was added to the bottom of the fruit press to collect the filtrate.
  • Twenty-five grams of the heated mushroom pieces were added to a 125-micron filter bag having a volume of 40 liters.
  • the filter bag containing mushroom pieces was placed in the fruit press, and the pressure of the fruit press was increased in about 5-minute increments over the course of 1 hour to press the mushroom pieces through the filter bag. The process was repeated with a second bag containing 25 grams of heated mushroom pieces. 14-15 liters of filtrate were collected, having a moisture content of from about 50% to about 70%. Following filtration via the fruit press, the pH of the filtrate was reduced to a pH of about 3.0 by the addition of 1M hydrochloric acid.
  • the filtrate was placed in a Pyrex beaker, placed on a heating plate in a microwave oven, and heated at 100% power for 2 hours to reduce the volume to 10% of the original amount, as measured with the Pyrex beaker.
  • the filtrate on visual inspection was thick and colored black, and it was therefore determined that the filtrate needed to be further dried or cured.
  • the filtrate was heated again in the microwave oven at 80% power at one-minute intervals, with stirring in between, for a total of one hour, until the color of the filtrate turned from black to light brown, demonstrating the desired change in moisture content.
  • the resulting filtrate had a thick appearance on visual inspection and was similar in physical consistency to bread dough upon tactile inspection.
  • filtrate was cut into pieces having a length and width of from about 3 cm to about 4 cm. Each piece was ground into a fine powder using a coffee grinder. The ground power extract was placed into a sealed plastic bag, and stored in the dark at -15 °C.
  • vaporizer formulations (also referred to herein as vaporizable formulations) comprising fungal material (e.g., Amanita muscaria mushroom biomass) or an extract or compound thereof, a base liquid, and optionally a flavorant.
  • Vaporizer formulations may include such formulations as are referred to by such terms as are used and will be readily recognized in the art, including as non-limiting examples vape juice, e-liquid, e-juice, and the like, which may be used interchangeably herein, unless a specific type is indicated by context, and all of which will be understood to be within the scope and spirit of the disclosed invention.
  • vaporizable formulations comprising an Amanita muscaria extract.
  • a disclosed vaporizable formulation comprises an A. muscaria extract and a base liquid.
  • a disclosed vaporizable formulation comprises an A. muscaria extract; a base liquid; and, optionally, a flavorant.
  • Vaporizer formulations may be a liquid (including, e.g., an oil) and/or solid (including, e.g., a wax) solution.
  • the formulation comprises fungal material or an extract thereof in an amount of between 1% v/v, to 50% v/v of the formulation, wherein the range is inclusive. In embodiments, the formulation comprises one or more compounds thereof in an amount of between 0.01 w/v% to 20 w/v%.
  • the vaporizer formulation comprises fungal material, which may be Amanita muscaria mushrooms, such as dried and ground and/or pulverized A. muscaria mushrooms. That is, A. muscaria fungal material that has not been extracted, and, e.g., is used directly in the formulation.
  • the vaporizer formulation may include one or more of fungal material, an extract thereof, and a compound thereof, including one or more of each of a fungal material, an extract thereof, and a compound thereof, i.e., one or more fungal materials, and/or one or more extracts thereof, and/or one or more compounds thereof.
  • the fungal material(s), extract(s) thereof, and/or compound(s) thereof comprise the “fungal portion” of a vaporizer formulation.
  • the vaporizer formulation comprises a fungal extract.
  • the fungal extract is an Amanita muscaria extract.
  • the A. muscaria extract is an AME-1 extract.
  • the A. muscaria extract is obtained as a liquid distillate.
  • the Amanita muscaria extract is obtained as a ground powder.
  • the Amanita muscaria extract comprises no potentially toxic compounds in amounts that are significant for human health.
  • the A. muscaria extract comprises no stizolobinic acid and no more than 0.09 ppm of cadmium, 0.03 ppm of arsenic, 0.09 ppm of lead and 0.02 ppm of mercury.
  • the A. muscaria extract comprises less than about 40 pg/g of stizolobinic acid.
  • the A. muscaria extract comprises less than about 30 pg/g of stizolobinic acid.
  • the A. muscaria extract comprises less than about 20 pg/g of stizolobinic acid.
  • muscaria extract comprises less than about 10 pg/g of stizolobinic acid. In embodiments, the A. muscaria extract comprises less than about 5 pg/g of stizolobinic acid. In embodiments, the A. muscaria extract comprises less than about 2 pg/g of stizolobinic acid. In embodiments, the A. muscaria extract comprises less than about 1 pg/g of stizolobinic acid. In embodiments, the A. muscaria extract comprises less than about 0.5 pg/g of stizolobinic acid. In embodiments, the A. muscaria extract comprises less than about 0.1 pg/g of stizolobinic acid. In embodiments, the A.
  • muscaria extract comprises less than about 0.05 pg/g of stizolobinic acid. In embodiments, the A. muscaria extract comprises less than about 0.025 pg/g of stizolobinic acid. In embodiments, the A. muscaria extract does not contain an amount of stizolobinic acid that is detectable by
  • the Amanita muscaria extract comprises less than about 2.5 ppm of arsenic. In some embodiments, the Amanita muscaria extract comprises less than about 1 ppm of arsenic. In some embodiments, the Amanita muscaria extract comprises less than about 0.1 ppm of arsenic. In some embodiments, the Amanita muscaria extract comprises less than about 0.05 ppm of arsenic. In some embodiments, the Amanita muscaria extract comprises less than about 0.04 ppm of arsenic. In embodiments, the A. muscaria extract comprises less than about 0.03 ppm of arsenic. In embodiments, the A.
  • the A. muscaria extract comprises less than about 0.02 ppm of arsenic. In embodiments, the A. muscaria extract comprises less than about 0.018 ppm of arsenic. In embodiments, the A. muscaria extract comprises less than about 0.01 ppm of arsenic. In embodiments, the A. muscaria extract does not contain an amount of arsenic that is detectable by ICP-MS.
  • the Amanita muscaria extract comprises less than about 0.30 ppm of cadmium. In some embodiments, the Amanita muscaria extract comprises less than about 0.25 ppm of cadmium. In some embodiments, the Amanita muscaria extract comprises less than about 0.20 ppm of cadmium. In some embodiments, the Amanita muscaria extract comprises less than about 0.10 ppm of cadmium. In embodiments, the A. muscaria extract comprises less than about 0.090 ppm of cadmium. In embodiments, the A. muscaria extract comprises less than about 0.080 ppm of cadmium. In embodiments, the A.
  • muscaria extract comprises less than about 0.073 ppm of cadmium. In embodiments, the A. muscaria extract comprises less than about 0.070 ppm of cadmium. In embodiments, the A. muscaria extract does not contain an amount of cadmium that is detectable by ICP-MS.
  • the Amanita muscaria extract comprises less than about 0.15 ppm of mercury. In some embodiments, the Amanita muscaria extract comprises less than about 0.10 ppm of mercury. In some embodiments, the Amanita muscaria extract comprises less than about 0.05 ppm of mercury. In embodiments, the A. muscaria extract comprises less than about 0.04 ppm of mercury. In embodiments, the A. muscaria extract comprises less than about 0.03 ppm of mercury. In embodiments, the A. muscaria extract comprises less than about 0.02 ppm of mercury. In embodiments, the A. muscaria extract comprises less than about 0.015 ppm of mercury. In embodiments, the A. muscaria extract comprises less than about 0.01 ppm of mercury. In embodiments, the A. muscaria extract does not contain an amount of mercury that is detectable by ICP-MS.
  • the Amanita muscaria extract comprises less than about 2.5 ppm of lead. In some embodiments, the Amanita muscaria extract comprises less than about 1 ppm of lead. In some embodiments, the Amanita muscaria extract comprises less than about 2 ppm of lead. In some embodiments, the Amanita muscaria extract comprises less than about 1.6 ppm of lead. In some embodiments, the Amanita muscaria extract comprises less than about 1 ppm of lead. In some embodiments, the Amanita muscaria extract comprises less than about 0.1 ppm of lead. In some embodiments, the Amanita muscaria extract comprises less than about 0.10 ppm of lead.
  • the A. muscaria extract comprises less than about 0.09 ppm of lead. In embodiments, the A. muscaria extract comprises less than about 0.08 ppm of lead. In embodiments, the A. muscaria extract comprises less than about 0.07 ppm of lead. In embodiments, the A muscaria extract comprises less than about 0.06 ppm of lead. In embodiments, the A. muscaria extract comprises less than about 0.05 ppm of lead. In embodiments, the A. muscaria extract comprises less than about 0.04 ppm of lead. In embodiments, the A. muscaria extract comprises less than about 0.03 ppm of lead. In embodiments, the A. muscaria extract comprises less than about 0.02 ppm of lead.
  • the A. muscaria extract comprises less than about 0.015 ppm of lead. In embodiments, the A muscaria extract comprises less than about 0.011 ppm of lead. In embodiments, the A. muscaria extract comprises less than about 0.01 ppm of lead. In embodiments, the A. muscaria extract does not contain an amount of lead that is detectable by ICP-MS. In embodiments, the A. muscaria extract comprises less than or no more than the limits for respective pesticides in USP General Chapter 561, “Articles of Botanical Origin” (USP 561). In embodiments, the extract is also in compliance with EPA (40 C.F.R. ⁇ 180) and FDA action levels (21 C.F.R. ⁇ 109, 509). In embodiments, the extract is manufactured in compliance with GLP or GMP requirements.
  • HPLC-MS/MS may be used to determine the presence and concentration of other target compounds in the Amanita muscaria extract. In embodiments, HPLC-MS/MS is used to determine the concentration of muscimol, ibotenic acid, and muscarine.
  • the Amanita muscaria extract comprises muscimol and ibotenic acid in a ratio of at least 3:1, where the ratio is preferably a mass (i.e, weight) ratio. In embodiments, the ratio also may be a mole ratio. In embodiments, the muscimol to ibotenic acid ratio is from about 3:1 to about 150: 1 .
  • the muscimol to ibotenic acid ratio is about 10:1, 12.5:1 15:1 , 20:1 , 25:1, 30:1, 35:1, 40:1, 45:1, 50:1, 55:1, 60:1 , 65:1 , 70:1, 75:1 , 80:1, 85:1 , 90:1, 95:1, 100:1, 105:1 , 110:1, 115:1 , 120:1, 125:1 , 130:1, 135:1, 140:1, 145:1 , or 150:1, including ranges in between these values.
  • the muscimol to ibotenic acid ratio is between about 10:1 and about 50:1.
  • the muscimol to ibotenic acid ratio is between about 10:1 and about 40:1. In embodiments, the muscimol to ibotenic acid ratio is between about 10:1 and about 30:1. In embodiments, the muscimol to ibotenic acid ratio is between about 10:1 and about 20:1. In embodiments, the muscimol to ibotenic acid ratio is between about 10:1 and about 15:1. In embodiments, the muscimol to ibotenic acid ratio is between about 15:1 and about 50:1. In embodiments, the muscimol to ibotenic acid ratio is between about 15:1 and about 30:1.
  • the muscimol to ibotenic acid ratio is between about 20:1 and about 50:1 . In embodiments, the muscimol to ibotenic acid ratio is between about 20:1 and about 30:1. In embodiments, the Amanita muscaria extract comprises muscimol and ibotenic acid in a mass ratio of between about 20:1 and about 150:1. In embodiments, the A. muscaria extract comprises muscimol and ibotenic acid in a mass ratio of greater than about 100:1. In embodiments, the A muscaria extract comprises muscimol and ibotenic acid in a mass ratio of greater than about 1000:1. In embodiments, the A.
  • muscaria extract comprises muscimol and ibotenic acid in a mass ratio of about 12.5:1.
  • the A. muscaria extract comprises muscimol and ibotenic acid in a mass ratio of about 25:1.
  • the Amanita muscaria extract comprises between about 0.5% and about 5.0% w/w or w/v muscimol, between about 0.05% and about 0.5% w/w or w/v muscarine, and less than about 0.05% w/w or w/v ibotenic acid.
  • the Amanita muscaria extract comprises less than 18 mg/g of muscimol, less than 600 pg/g of muscarine, and less than 20 pg/g of ibotenic acid. In embodiments, the A. muscaria extract comprises less than about 550 pg/g of muscarine. In embodiments, the A. muscaria extract comprises less than about 500 pg/g of muscarine. In embodiments, the A. muscaria extract comprises less than about 250 pg/g of muscarine. In embodiments, the A. muscaria extract comprises less than about 200 pg/g of muscarine. In embodiments, the A.
  • muscaria extract comprises less than about 100 pg/g of muscarine. In embodiments, the A. muscaria extract comprises less than about 50 pg/g of muscarine. In embodiments, the A. muscaria extract comprises less than about 25 pg/g of muscarine. In embodiments, the A. muscaria extract comprises less than about 15 pg/g of muscarine.
  • the Amanita muscaria extract comprises at least 15,000 pg/g. In embodiments, as illustrated in Table 4, the A muscaria extract comprises between about 500 pg/g and 20,000 pg/g, wherein the range is inclusive.
  • the Amanita muscaria extract comprises less than 250 pg/g of ibotenic acid. In embodiments, as illustrated in Table 4, the Amanita muscaria extract comprises between about 240 pg/g and about 50 pg/g.
  • the potency of muscimol in the Amanita muscaria extract is at least about 0.25%, including about 0.25%, 0.5%, 0.75%, 1 %, 1.25%, 1.5%, 1.75%, 2.0%, and greater than 2%, as may be obtained through utilizing the methods of the invention as disclosed herein. In embodiments, potency is equivalent to concentration.
  • the Amanita muscaria extract comprises ibotenic acid having a potency of less than 0.025%.
  • potency can be determined by w/w %, e.g., by dividing the weight of a compound to be assessed with the total weight of an extract.
  • the potency of muscimol is determined by dividing the weight of muscimol (16922 pg, i.e., 0.016922 g) per equivalent weight of the extract (1 g) to obtain a potency of 0.016922/1 or 1.69 % muscimol, as also shown in Table 5.
  • the Amanita muscaria extract has a muscimol purity of at least 90%, including about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, and greater than 99%.
  • the purity of a compound can be determined by dividing the weight of the compound by the total weight of the compounds against which its purity is measured (i.e., as a w/w %).
  • the purity of muscimol is determined by dividing the weight of muscimol (16922 pg) by the total weight of the muscimol and the other compounds, i.e., muscarine (1468 pg), ibotenic acid (159 pg/g), and the heavy metals cadmium (0.14 pg), arsenic (2.5 pg), mercury (0.12 pg), and lead (1.6 pg), which in total equal 18553.36 pg, in other words, to divide 16922 pg by 18553.36 pg, which results in a purity of 91.21 % muscimol.
  • a purity of muscimol may be determined by dividing the weight of muscimol (16922 pg) by the total weight of the muscimol and the other compounds (i.e., muscarine and ibotenic acid), but not any heavy metals (e.g., cadmium, arsenic, mercury, or lead).
  • muscimol 16922 pg
  • the other compounds i.e., muscarine and ibotenic acid
  • heavy metals e.g., cadmium, arsenic, mercury, or lead
  • the Amanita muscaria extract which may optionally be further concentrated, is standardized.
  • the Amanita muscaria extract is standardized to a muscimol purity of 90% or greater.
  • the Amanita muscaria extract is standardized to a muscimol potency of between about 0.5% and about 5.0%.
  • a “standardized” extract refers to an extract comprising a specified quantity of a standardized ingredient, which may be a bioactive compound such as muscimol.
  • a bioactive compound such as muscimol.
  • an amount of the bioactive compound is standardized to a particular concentration (e.g., w/w or w/v % of the extract).
  • an Amanita muscaria extract will be standardized so as to contain by weight percent an amount of muscimol (i.e., mg muscimol per mg or mL of extract, depending on whether such extract is a dry powder or a liquid) of between 0.5% and 5.0% w/w or w/v muscimol, wherein the range is inclusive.
  • w/w or w/v muscimol may be used in various embodiments, for example in amounts of between 5.0% and 10.0% or greater than 10% muscimol and also including amounts lower than those explicitly listed above.
  • the Amanita muscaria extract will contain by weight percent an amount of muscarine (i.e., mg muscarine per mg extract) of at least 0.05% w/w or w/v muscarine.
  • Standardization may be accomplished by various methods, such as by measuring a concentration of compound in an extract to be standardized, determining the concentration of the compound to be standardized, determining an amount of excipient necessary to obtain a desired (standardized) concentration, and then adding the amount of excipient necessary to obtain the desired (standardized) concentration, resulting in a standardized extract.
  • An excipient will be as known by ordinary skill, and may be a dry or liquid excipient, to create a dry powder or liquid standardized extract.
  • the concentration of standardized compound in standardized extract may be measured after adding one or more portions of excipient or after the final standardized extract is prepared, to confirm the standardization method and for quality control.
  • the Amanita muscaria extract is further concentrated so that the bioactive compounds (including, and in particular muscimol) are increased in total concentration from an initial extract, such as an increase in w/w% (for a powder extract) or w/v% (for a liquid extract), in an amount such as by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100% (2X), at least 125%, at least 150%, at least 175%, at least 200% (3X), at least 250%, at least 300% (4X), at least 400% (5X), at least 500% (6X), at least 600% (7X), at least 700% (8X), at least 800% (9X), at least 900% (10X), and in amounts of 1 ,000% or more.
  • an initial extract such as an increase in w/w% (for a powder extract) or w/v%
  • the vaporizer formulation comprises a compound from fungal material, which may be Amanita muscaria mushrooms, such as either or both of muscimol and muscarine.
  • the one or more compounds includes ibotenic acid; however, it will be understood that In embodiments the concentration of ibotenic acid is relatively low (e.g., in relation to unextracted Amanita muscaria fungal material), trace, or zero.
  • the formulation comprises muscimol having a potency of at least 0.15% w/v.
  • the formulation comprises ibotenic acid having a potency of less than 0.0025% w/v.
  • the formulation is standardized to a muscimol potency of between about 0.01 % w/v and about 2% w/v.
  • the formulation comprises between about 0.1 mg/mL and about 200 mg/mL of muscimol, inclusive. In embodiments, the formulation comprises between about 1 mg/mL and about 20 mg/mL of muscimol, inclusive. In embodiments, the formulation comprises at least 15 mg/mL of muscimol.
  • the formulation comprises between about 0.1 mg/mL and about 200 mg/mL of muscarine, inclusive. In embodiments, the formulation comprises between about 1 mg/mL and about 20 mg/mL of muscarine, inclusive.
  • the formulation comprises less than about 2 mg/mL of ibotenic acid, inclusive. In embodiments, the formulation comprises less than about 0.2 mg/mL of ibotenic acid, inclusive. [131] In some embodiments, the formulation comprises less than 20 mg/mL of muscimol, less than 1 mg/mL of muscarine, and less than 0.02 mg/mL of ibotenic acid.
  • the compounds from Amanita muscaria are provided in A. muscaria fungal material (i.e., the vaporizer formulation comprises A. muscaria fungal material, which comprises one or more compounds from A. muscaria).
  • the compounds from Amanita muscaria are provided in an A. muscaria extract (i.e., the vaporizer formulation comprises an A. muscaria extract, which comprises one or more compounds from A. muscaria).
  • the compounds from Amanita muscaria are provided directly, e.g., as pure or substantially pure chemical compounds that are isolated or synthesized (i.e., the vaporizer formulation comprises one or more compounds from A. muscaria).
  • the compounds are obtained commercially, e.g., from Cayman Chemical Company, Ann Arbor, Michigan (e.g., Muscimol, Item No. 13667; Muscarine, Item No. 24269).
  • the formulation comprises between 40% v/v to 90% v/v of base liquid, wherein the range is inclusive.
  • the formulation comprises one or more compounds from fungi, such as Amanita muscaria, or from an extract thereof
  • the formulation may comprise up to about 99.99% v/v base liquid, e.g., where the compounds from A. muscaria material or extract are 0.01 w/v% of the formulation.
  • the base liquid comprises one or more of propylene glycol (PG) and vegetable glycerin (VG). In embodiments, the base liquid comprises between 1% v/v to 100% v/v of propylene glycol, wherein the range is inclusive. In embodiments, the base liquid comprises between 1% v/v to 100% v/v of vegetable glycerin, wherein the range is inclusive.
  • the base liquid may be a base liquid obtained in a specific proportion. Common proportions include 50:50 (PG/VG), 30:70 (PG/VG), and 20:80 (PG/VG). However, said proportions should not be construed as limiting, and the base liquid may comprise anywhere from 1 % to 100% PG, and/or anywhere from 1 % to 100% VG.
  • PEG polyethylene glycol
  • the base liquid may further comprise water, ethanol, or a mixture thereof.
  • the water may be tap water, mineral water, spring water, glacier water, distilled water, purified water, deionized water, and/or alkaline water.
  • the mixture of water and ethanol is between about 10% v/v to about 99% v/v ethanol, wherein the range is inclusive.
  • the mixture of water and ethanol is an alcoholic drink or spirit, including vodka.
  • the mass ratio of the Amanita muscaria extract to the base liquid is about 1 part extract to about 2 parts base liquid. In embodiments, the mass ratio of the A. muscaria extract to the base liquid is about 1 part extract to about 5 parts base liquid. In embodiments, the mass ratio of the A. muscaria extract to the base liquid is about 1 part extract to about 10 parts base liquid. In embodiments, the mass ratio of the A. muscaria extract to the base liquid is about 1 part extract to about 15 parts base liquid. In embodiments, the mass ratio of the A. muscaria extract to the base liquid is about 1 part extract to about 20 parts base liquid. In embodiments, the mass ratio of the A.
  • the mass ratio of the A. muscaria extract to the base liquid is about 1 part extract to about 25 parts base liquid. In embodiments, the mass ratio of the A. muscaria extract to the base liquid is about 1 part extract to about 30 parts base liquid. In embodiments, the mass ratio of the A. muscaria extract to the base liquid is about 1 part extract to about 40 parts base liquid. In embodiments, the mass ratio of the A. muscaria extract to the base liquid is about 1 part extract to about 50 parts base liquid.
  • disclosed vaporizable formulations comprise an additional excipient.
  • suitable excipients to be incorporated in disclosed formulations may include a flavoring agent (i.e., a flavorant), a colorant, a dye, a pigment, an antioxidant, a solvent, a humectant, a viscosity modifier, a solubilizer, a complexing agent, a preservative, a pH adjusting agent, an opacifier, a surfactant, a gelling agent, or a combination thereof.
  • a flavoring agent i.e., a flavorant
  • a colorant i.e., a dye, a pigment, an antioxidant, a solvent, a humectant, a viscosity modifier, a solubilizer, a complexing agent, a preservative, a pH adjusting agent, an opacifier, a surfactant, a gelling agent, or a combination thereof.
  • disclosed formulations may include a flavoring agent or a mixture of flavoring agents including natural or synthetic flavorants, such as flavoring oils, flavoring aldehydes, esters, alcohols, similar materials, and combinations thereof.
  • Flavorants may include vanillin, spearmint oil, cinnamon oil, oil of Wintergreen (methylsalicylate), peppermint oil, clove oil, anise oil, eucalyptus oil, citrus oils, fruit oils, essences, limonene, menthone, carvone, menthol, anethole, eucalyptol, anethole, eugenol, cassia, oxanone, a-irisone, propenyl guaiethol, thymol, linalool, benzaldehyde, cineole, cinnamaldehyde, cinnamaldehyde glycerol acetal (CGA), methone glycerol ace
  • CGA me
  • a vaporizer formulation comprises fungal material or an extract or compound thereof, a base liquid, and optionally a flavorant.
  • the formulation comprises between about 1% v/v and about 50% v/v of a flavorant, wherein the range is inclusive.
  • the formulation comprises between about 1% v/v and about 20% v/v of a flavorant.
  • the formulation comprises between about 1% v/v and about 10% v/v of a flavorant.
  • the formulation comprises between about 0.1 % v/v and about 20% v/v of a flavorant.
  • the formulation comprises between about 0.1 % v/v and about 10% v/v of a flavorant.
  • the formulation comprises between about 0.1 % v/v and about 5% v/v of a flavorant.
  • the formulation comprises between about 0.1 % v/v and about 1 % v/v of a flavorant.
  • a formulation comprises a flavoring agent, which may be a flavor.
  • a flavor may be any of a liquid flavor, a powder flavor, a powdered encapsulated flavor, a spray-dried flavor, an emulsion flavor, a plant, fruit, vegetable, or other extraction-based flavor, a seasoning, an organic flavor, a natural flavor, a non-GMP flavor, a clean label flavor, a concentrated flavor, a savory flavor, a sweet flavor, a masking flavor, and the like, including combinations thereof.
  • Flavors may be produced using methods known to those in the art, or obtained from flavor suppliers as known in the art.
  • Flavorants include flavor concentrates known to those of skill, for example, flavor concentrates that replicate different food and drink flavors.
  • exemplary flavors include peach, mango, pineapple, strawberry, kiwi, watermelon, lime, green apple, strawberry watermelon, apple, peach strawberry, mango peach guava, kiwi dragonberry, peach pear, blueberry, raspberry, lemon, Fiji melons, passionfruit orange guava, honeydew, banana, lychee, blueberry lemon, dragonfruit, apple, fruit cocktail, watermelon, key lime, cannoli, cookie butter, cinnamon funnel cake, sweet cinnamon banana, strawberry cheesecake, creme brulee, strawberry a la mode, lemon crumble cake, vanilla bean ice cream, glazed donut, coffee ice cream, birthday cannoli, banana cream pie, caramel brulee, a la mode, strawberry milkshake, lemon drop, pink lemonade, blackberry lemonade, caramel coffee, Caribbean punch, pina colada, java yogi, Caribbean rum, cherry
  • Colorants and/or dyes and/or pigments may be added to disclosed formulations in some embodiments.
  • Suitable colorants and/or dyes and/or pigments may include colors such as e.g., white, black, yellow, blue, green, pink, red, orange, violet, indigo, brown, and combinations thereof, pigments such as, e.g., Timica Extra Large Sparkles, titanium dioxide and chromium oxide greens, ultramarine blues and pinks and ferric oxides.
  • Colorants and/or dyes and/or pigments may be present, individually or in total (if more than one colorant and/or dye and/or pigment is included), in disclosed formulations in an amount ranging from about 0.01 wt% to about 5 wt% (calculated as the total weight of colorants and/or dyes and/or pigments in the formulation divided by the total weight of the formulation).
  • a disclosed formulation does not comprise a colorant.
  • a disclosed formulation does not comprise a dye.
  • a disclosed formulation does not comprise a pigment.
  • Antioxidants may be added to disclosed formulations in some embodiments. Suitable antioxidants may include, but not be limited to, natural antioxidants such as tocopherol and tocopherol acetate. Antioxidants may be present, individually or in total (if more than one antioxidant is included), in disclosed formulations in an amount ranging from about 0.1 wt% to about 5 wt% (calculated as the total weight of antioxidants in the formulation divided by the total weight of the formulation). In embodiments, a disclosed formulation does not comprise an antioxidant.
  • Solvents that may be included in disclosed formulations may include, without limitations, water, polyhydric alcohols (e.g., glycerin), 1,3-butylene glycol, propylene glycol, hexylene glycol, propane diol, ethylene glycol, diethylene glycol, dipropylene glycol, diglycerin, sorbitol, other sugars which are liquid at room temperature, water-soluble alkoxylated nonionic polymers such as polyethylene glycol, and combinations thereof.
  • polyhydric alcohols e.g., glycerin
  • 1,3-butylene glycol propylene glycol
  • hexylene glycol propane diol
  • ethylene glycol diethylene glycol
  • dipropylene glycol dipropylene glycol
  • diglycerin diglycerin
  • sorbitol other sugars which are liquid at room temperature
  • water-soluble alkoxylated nonionic polymers such as polyethylene glycol, and combinations thereof.
  • Solvents may be present, individually or in total (if more than one solvent is included), in the formulation in an amount ranging from about 0.1 wt% to about 95 wt% (calculated as the total weight of solvents in the formulation divided by the total weight of the formulation). In embodiments, a disclosed formulation does not comprise a solvent.
  • Humectant(s) such as low molecular weight polyethylene glycol (e.g., PEG6-PEG12), may be present, individually or in total (if more than one humectant is included), in the formulation in an amount of up to about 10 wt%, up to about 5 wt%, up to about 3 wt%, up to about 1 wt%, or up to about 0.1 wt% (calculated as the total weight of humectants in the formulation divided by the total weight of the formulation). In embodiments, a disclosed formulation does not comprise a humectant.
  • PEG6-PEG12 low molecular weight polyethylene glycol
  • Surfactants may be incorporated in disclosed formulations.
  • the surfactants that can be included in the formulation may be anionic, nonionic, or amphoteric compounds.
  • Suitable examples of anionic surfactants are one or more of higher alkyl sulfates such as potassium or sodium lauryl sulfate, higher fatty acid monoglyceride monosulfates, such as the salt of the monosulfated monoglyceride of hydrogenated coconut oil fatty acids, alkyl sulfonates such as sodium dodecyl benzene sulfonate, higher fatty sulfoacetates, higher fatty acid esters of 1 ,2 dihydroxypropane sulfonate.
  • water soluble nonionic surfactants are condensation products of ethylene oxide with various hydrogen-containing compounds that are reactive therewith and have long hydrophobic chains (e.g., aliphatic chains of about 12 of 20 carbon atoms), which condensation products contain hydrophilic polyoxyethylene moieties, such as condensation products of poly (ethylene oxide) with fatty acids, fatty alcohols, fatty amides and other fatty moieties, and with propylene oxide and polypropylene oxides, e.g., Pluronic materials such as Pluronic F127.
  • Exemplary suitable alkyl polyglycoside (APG) surfactant(s) that may be used in the formulation may comprise APG C8-C10, APG C10-C16, decyl glucoside, coco-glucoside, anionic APG carboxylate, sodium lauryl glucose carboxylate, lauryl glucoside, D-glucopyranose (oligomeric, CIO-16 glycosides, carboxymethyl ethers, sodium salts), C12-C16 fatty alcohol glycoside, and combinations thereof.
  • Exemplary APG surfactant(s) that may be used may have an industry designation of Plantaren® 2000 N UP/MB, Plantapon® LGC Sorb, Plantaren® 1200 N UP/MB, and Plantaren® 818 UP/MB.
  • Surfactants may be present, individually or in total (if more than one surfactant is included) in the formulation in an amount ranging from about 0.01 wt% to about 10 wt% (calculated as the total weight of surfactants in the formulation divided by the total weight of the formulation).
  • a disclosed formulation does not comprise a surfactant.
  • Exemplary gelling agent(s) that may be issued in disclosed formulations may comprise pectins, starches, and gelatin forms derived from animals or from plants (e.g., pork gelatin) or a different gelling agent that would be suitable for consumption by individuals who do not consume meat products (e.g., vegeterians, vegans).
  • the pectin in the formulation may include, e.g., high methoxyl pectin, low methoxyl pectin, or a combination thereof.
  • the pectin is amidated pectin.
  • the pectin is non-amidated pectin.
  • the pectin is a combination of amidated pectin and non-amidated pectin.
  • the gelatin in the formulation may include Type A gelatin, Type B gelatin, a hide or skin gelatin (e.g., calf skin, pig skin) and/or a bone gelatin (e.g., calf bone, pig bone) used alone or in combination.
  • Gelling agent(s) may be present, individually or in total (if more than one gelling agent is included) in the formulation in an amount ranging from about 0.1 wt% to about 20 wt% (calculated as the total weight of gelling agents in the formulation divided by the total weight of the formulation).
  • a disclosed formulation does not comprise a gelling agent.
  • disclosed formulations may comprise a preservative.
  • Preservatives can be used to inhibit microbial growth or increase stability of the formulation, thereby prolonging the shelf life of the formulation.
  • Suitable preservatives are known in the art and include EDTA, EGTA, benzalkonium chloride or benzoic acid or benzoates (e.g., sodium benzoate), vitamin A, vitamin C (ascorbic acid), citric acid, vitamin E, and tocopherol.
  • a disclosed formulation does not comprise a preservative.
  • a method of producing a vaporizable formulation comprising: (a) performing an aqueous extraction of Amanita muscaria mushroom biomass in the presence of heat to produce the extract (e.g., 115); (b) reducing the pH of the extract (e.g., 125); (c) concentrating the extract (e.g., 130); and (d) dissolving the extract in a base liquid to produce the vaporizable formulation (e.g., 135).
  • a method of producing a vaporizable formulation comprising: (a) suspending an Amanita muscaria extract (e.g., a solid A. muscaria extract) in a solvent (e.g., 200); (b) mixing the suspension (e.g., 210); (c) isolating the supernatant from the suspension, thereby producing an extract solution (e.g., 220); (d) evaporating the extract solution to provide a residue (e.g., 230); and (e) dissolving the residue in a base liquid to produce the vaporizable formulation (e.g., 240).
  • an Amanita muscaria extract e.g., a solid A. muscaria extract
  • a solvent e.g. 200
  • a solvent e.g. 200
  • mixing the suspension e.g., 210
  • isolating the supernatant from the suspension thereby producing an extract solution (e.g., 220);
  • the Amanita muscaria extract is a solid A. muscaria extract.
  • the A. muscaria extract is a ground powder extract (e.g., as described in Example 2).
  • the A. muscaria extract is AME-1 in solid form.
  • the Amanita muscaria extract is suspended in a solvent (200).
  • the solvent can be any solvent suitable for extraction.
  • the solvent is an aqueous solvent (e.g., water, or a mixture that consists primarily of water).
  • the solvent is an organic solvent (e.g., an alcohol, ester, ether).
  • the solvent is an alcohol (e.g., methanol, ethanol, propanol).
  • the solvent is methanol.
  • the A. muscaria extract is mixed with the solvent at a fixed ratio (e.g., a fixed ratio of the weight of the A. muscaria extract to the volume of solvent).
  • the ratio of A. muscaria extract to solvent is from about 1 :1 to about 1:100. In embodiments, the ratio of A. muscaria extract to solvent is from about 1 :1 to about 1 :50. In embodiments, the ratio of A. muscaria extract to solvent is from about 1 :1 to about 1:20. In embodiments, the ratio of A. muscaria extract to solvent is from about 1 :5 to about 1 :20. In embodiments, the ratio of A muscaria extract to solvent is from about 1 :5 to about 1 :15. In embodiments, the ratio of A muscaria extract to solvent is from about 1 :5 to about 1 :10.
  • the ratio of A muscaria extract to solvent is from about 1 :10 to about 1 :20. In embodiments, the ratio of A. muscaria extract to solvent is from about 1 :1 O to about 1 :15. In embodiments, the ratio of A. muscaria extract to solvent is about 1 :10.
  • the solvent is an alcohol, and the ratio of A. muscaria extract to the alcohol solvent is about 1 :10.
  • the solvent is methanol, and the ratio of A. muscaria extract to methanol is about 1 :10.
  • the mixture is then mixed (210) for between about 1 minute to about 20 minutes, including 1 minute, 2, minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, or greater than 20 minutes, including ranges in between these values. In embodiments, the mixture is mixed for about 15 minutes. In embodiments, wherein the mixture is stirred (e.g., using a magnetic stir plate), the stirring is performed at between 700 rpm and 2500 rpm, including about 750 rpm, 800 rpm, 850 rpm, 900 rpm,
  • the temperature of the mixture is approximately ambient temperature, or room temperature.
  • the mixture is heated (e.g., by using a hot plate, water/oil bath, sand bath, or any other suitable means known to one of skill) to facilitate the extraction.
  • the mixture is heated to a temperature of about 30 °C to about 100 °C, including about 30 °C, 40 °C, 50 °C, 60 °C, 70 °C, 80 °C, 90 °C, 95 °C, or 100 °C, and ranges in between these values.
  • the mixture is not heated.
  • the solvent e.g., methanol
  • the solid components of the supernatant containing, e.g., residual Amanita muscaria extract or portions thereof
  • the mixture is filtered to remove solids.
  • any filter known to those of skill may be utilized, so long as the filter is capable of filtering out both large and small particles.
  • a plurality of filters may be used in a sequential arrangement, wherein the filter pore size decreases with each additional filter.
  • the filter is a sock filter.
  • the sock filter has a pore size of about 50 microns to about 500 microns.
  • the sock filter has a pore size of about 50 microns, 75 microns, 100 microns, 150 microns, 200 microns, 250 microns, 300 microns, or 500 microns.
  • a plurality of filters may be used in a parallel arrangement, wherein the filter pore size is the same for each filter.
  • at least two, at least three, at least four, at least five, or more than five filters may be utilized in parallel.
  • pressure is applied during the filtration process, such as with use of mechanical pressing, compressed gas, or any suitable means of applying pressure to the feed side of a filtration apparatus.
  • the solvent (e.g., methanol) and the solids are separated by centrifugation.
  • the mixture is centrifuged for between about 1 minute to about 20 minutes, including 1 minute, 2, minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, or greater than 20 minutes, including ranges in between these values.
  • the mixture is centrifuged for 5 minutes.
  • the mixture is centrifuged at between about 5,000 rpm and 30,000 rpm, including about 5,000 rpm, about 10,000 rpm, about 15,000 rpm, about 20,000 rpm, about 25,000 rpm, and about 30,000 rpm, including ranges in between these values.
  • the mixture is centrifuged at about 15,000 rpm.
  • the mixture may be centrifuged at about 15,000 rpm for about 5 minutes.
  • isolation of the supernatant solution from the mixture of solvent and solids yields an extract (e.g., a solution comprising compounds derived from the Amanita muscaria extract).
  • the extract is concentrated. Exemplary methods of concentrating an extract include, e.g., evaporating a portion or an entirety of a solvent to create a volume of concentrated slurry at a desired concentration.
  • the extract is concentrated by evaporation of the solvent (230). The evaporation can be carried out by any suitable method known to one of skill, including, for example., evaporation under reduced pressure (e.g., rotary evaporation), distillation, or by directly heating the extract to boil off the solvent.
  • evaporation of the solvent produces a residue (e.g., a powder, or a resin) comprising compounds derived from the Amanita muscaria extract (240).
  • This residue may be redissolved in a solvent suitable for use in vaporizer formulations, as described in various embodiments herein for base liquids.
  • the residue may be dissolved in propylene glycol (PG), vegetable glycerin (VG), or a combination thereof.
  • the residue is mixed with the solvent at a fixed ratio (e.g., a fixed ratio of the weight of the residue to the volume of base liquid).
  • the ratio of residue to base liquid (e.g., PG, VG) is from about 1 :1 to about 1 :100. In embodiments, the ratio of residue to base liquid is from about 1 :1 to about 1 :50. In embodiments, the ratio of residue to base liquid is from about 1 :1 to about 1 :20. In embodiments, the ratio of residue to base liquid is from about 1 :5 to about 1 :20. In embodiments, the ratio of residue to base liquid is from about 1 :5 to about 1 :15. In embodiments, the ratio of residue to base liquid is from about 1 :5 to about 1 :10. In embodiments, the ratio of residue to base liquid is from about 1 :10 to about 1 :20.
  • the ratio of residue to base liquid is from about 1 :10 to about 1 :20.
  • the ratio of residue to base liquid is from about 1 :10 to about 1 :15. In embodiments, the ratio of residue to base liquid is about 1 :10.
  • the base liquid is PG, and the ratio of residue to PG is about 1 :10.
  • the vaporizable formulation produced according to methods described herein is then packed (i.e., packaged) and labeled for commercial sale (e.g., 160, 250).
  • a disclosed vaporizer formulation is packed and labeled in bulk form, for example in a bottle or vial that contains multiple doses, which may be used by individuals to fill a vaporizer device containing a refillable chamber.
  • a disclosed vaporizer formulation is filled into a glass vial.
  • a disclosed vaporizer formulation is filled into an amber glass vial.
  • a disclosed vaporizer formulation is filled into a glass bottle.
  • a disclosed vaporizer formulation is filled into an amber glass bottle.
  • the container into which a disclosed vaporizer formulation is filled comprises a dispensing device (e.g., a pump or a dropper).
  • a disclosed vaporizer formulation is packaged as in a unit dosage form.
  • a disclosed vaporizer formulation is packaged as a single-use or disposable chamber, such as those disclosed in embodiments herein.
  • a disclosed vaporizer formulation is packaged as a disposable or single use vaporizer device as described in embodiments herein.
  • the following formulations may be used in the devices and methods of the invention, wherein the Amanita muscaria extract is as described in embodiments herein.
  • the A. muscaria extract may be any extract described herein, including an extract produced according to Examples 1-2, and specifically may be an AME-1 extract as described and illustrated in Tables 1-5.
  • the following examples will be understood to be merely exemplary and not limiting of the A. muscaria extracts useful in the formulations of the present invention.
  • Any number of A. muscaria extracts can be prepared using the teachings herein in combination with the knowledge in the art, and will further understand that such extracts can be concentrated and/or standardized to create additional concentrated and/or standardized A. muscaria extracts useful in the practice of the invention, again in view of the teachings of this disclosure combined with the general knowledge of one of ordinary skill.
  • Solid Amanita Muscaria extract (in ground powder form) was suspended in methanol at a ratio of 1 part powder to 10 parts methanol (w/v). The suspension was mixed thoroughly for approximately 15 minutes to break apart solids. Then, the mixture was centrifuged at 15000 rpm for 5 minutes. The supernatant was removed and heated to evaporate the solvent, which yielded a gold-colored resin.
  • This resin may be used as an extract in disclosed vaporizable formulations, for example by redissolving the resin in a vaporizable formulation base liquid.
  • the resin obtained by the procedure described in this Example was dissolved in propylene glycol (as the base liquid) at a ratio of 1 part resin to 10 parts propylene glycol (w/v), with heating as necessary for full dissolution of the resin.
  • propylene glycol as the base liquid
  • w/v propylene glycol
  • Example 4 50:50 Base Liquid Formulation, 10% Amanita muscaria extract
  • Example 5 30:70 Base Liquid Formulation, 10% AME-1
  • Example 6 70:30 Base Liquid Formulation, 10% Amanita muscaria extract
  • Example 7 20:80 Base Liquid Formulation, 10% Amanita muscaria extract
  • Example 8 80:20 Base Liquid Formulation, 10% Amanita muscaria extract
  • Example 9 100% PG Base Liquid Formulation, 10% Amanita muscaria extract
  • Example 10 100% VG Base Liquid Formulation, 10% Amanita muscaria extract
  • Example 11 30:70 Base Liquid Formulation, 10% Amanita muscaria extract, 5% Flavorant
  • Example 12 70:30 Base Liquid Formulation, 10% Amanita muscaria extract, 5% Flavorant
  • Example 13 20:80 Base Liquid Formulation, 10% Amanita muscaria extract, 5% Flavorant
  • Example 14 80:20 Base Liquid Formulation, 10% Amanita muscaria extract, 5% Flavorant
  • Example 15 100% PG Base Liquid Formulation, 10% A. muscaria extract, 5% Flavorant
  • Example 16 100% VG Base Liquid Formulation, 10% A. muscaria extract, 5% Flavorant
  • the Amanita muscaria extract in the above formulation examples may be substituted for A. muscaria fungal material, or may be substituted by any of muscimol, ibotenic acid, and muscarine provided as compounds, in amounts (e.g., by % v/v, % w/v, mg/mL, etc.) determined based on the teachings herein, in combination with the general knowledge in the art.
  • any of muscimol, ibotenic acid, and muscarine may be present in the formulation in concentrations of between about 0.1 mg/mL and about 200 mg/mL, and in some embodiments between about 1 and about 20 mg/mL.
  • Such examples may also be modified to include base liquids comprising PEG in addition to, or instead of PG and VG, and further comprising water, ethanol, or a mixture thereof.
  • base liquids comprising PEG in addition to, or instead of PG and VG, and further comprising water, ethanol, or a mixture thereof.
  • one of skill may modify the formulation by subtracting the volume of water from the total volume of the base liquid used in the formulation and calculating the proportion based on the result.
  • the base liquid comprises 9 mL of the formulation and one wishes to utilize a 30:70 PG/VG base liquid comprising 5% water
  • one may subtract 5% of 9 mL (0.45 mL) from the total base liquid volume (9 mL) to yield the volume of the 30:70 PG/VG mixture (8.55 mL).
  • the same logic can be applied to base liquids containing ethanol and base liquids containing a mixture of ethanol and water, such as vodka.
  • One of skill may also combine the liquids to the desired proportion via the density of the liquids, which are, for example:
  • the Amanita muscaria extract which may or may not be AME-1, may be obtained as a ground powder, rather than a liquid extract.
  • the ground powder may be utilized in a heat-not-burn (HnB) composition, wherein the composition comprising the ground powder is heated to a sufficient degree to vaporize, but not combust.
  • HnB heat-not-burn
  • fungal material such as dried Amanita muscaria mushrooms, including dried, ground and/or pulverized Amanita muscaria mushrooms, may be used in a HnB device.
  • Examples 4-16 may be produced by combining the ingredients according to the specific proportions of each example. It will be appreciated that the formulation of each example may be produced in any desired volume, and the ingredients may be combined with tools known to those in the art. Thus, while the following preparation examples list specific final volumes, such volumes are merely illustrative and may be altered according to methods known to those of skill.
  • EXAMPLE 17 Preparing a 100 mL formulation comprising a 50:50 PG/VG base liquid that comprises 90% of the formulation, with 10% being AME-1
  • a 100 mL formulation comprising 90% 50:50 PG/VG base liquid and 10% AME-1 may be produced by utilizing, e.g., a 100 mL adjustable volume pipette to combine individually 45 mL PG, 45 mL VG, and 10 mL AME-1 extract. Such formulation may be added to a chamber such as those described herein.
  • This example may be modified by substituting AME-1 extract with fungal material such as Amanita muscaha mushrooms, another extract thereof, or muscimol and/or muscarine.
  • fungal material such as Amanita muscaha mushrooms, another extract thereof, or muscimol and/or muscarine.
  • muscimol and/or muscarine may be present in the formulation in concentrations of between about 0.1 mg/mL and about 200 mg/mL, and in embodiments between about 1 mg/mL and about 20 mg/mL.
  • muscimol and/or muscarine may each be present in an amount of between 10 mg and 20,000 mg, including between 100 mg and 2,000 mg.
  • EXAMPLE 18 Preparing a 1 L formulation comprising a 30:70 PG/VG base liquid that comprises 90% of the formulation, with 10% being AME-1
  • a 1 L formulation comprising a 90% 30:70 PG/VG base liquid and 10% AME-1 may be produced by individually combining 270 mL PG, 630 mL VG, and 100 mL of AME-1 extract in a container suitable for such volumes. The formulation may then be agitated to form a uniform mixture, which may be done by an operator, or via paddles, arms, or other agitation means within the container.
  • This example may be modified by substituting AME-1 extract with fungal material such as Amanita muscaha mushrooms, another extract thereof, or muscimol and/or muscarine.
  • fungal material such as Amanita muscaha mushrooms, another extract thereof, or muscimol and/or muscarine.
  • muscimol and/or muscarine may be present in the formulation in concentrations of between about 0.1 mg/mL and about 200 mg/mL, and in some embodiments between about 1 mg/mL and about 20 mg/mL.
  • muscimol and/or muscarine may each be present in an amount of between 0.1 g and 200 g, including between 1 g and 20 g.
  • EXAMPLE 19 Preparing a 1,000 L formulation comprising a 80:20 PG/VG base liquid that comprises 90% of the formulation, with 10% being AME-1
  • a 1,000 L formulation comprising 90% 80:20 PG/VG base liquid and 10% AME-1 may be produced by individually combining 720 L of PG, 180 L of VG, and 100 L of AME-1 extract in a container suitable for such volumes.
  • the formulation may then be agitated to form a uniform mixture, which may be done by an operator, or via paddles, arms, or other agitation means within the container, including by using a commercial or industrial mixer.
  • This example may be modified by substituting AME-1 extract with fungal material such as Amanita muscaha mushrooms, another extract thereof, or muscimol and/or muscarine.
  • fungal material such as Amanita muscaha mushrooms, another extract thereof, or muscimol and/or muscarine.
  • muscimol and/or muscarine may be present in the formulation in concentrations of between about 0.1 mg/mL and about 200 mg/mL, and in some embodiments between about 1 mg/mL and about 20 mg/mL.
  • muscimol and/or muscarine may each be present in an amount of between 100 g and 200,000 g, including 1 ,000 g and 20,000 g.
  • the vaporizer formulation further comprises an additional composition.
  • the additional composition comprises tobacco, an extract from tobacco, or nicotine.
  • the additional composition is cannabis, a cannabis concentrate, or a cannabis extract.
  • the cannabis extract is a cannabis oil, a cannabis distillate, or a cannabis isolate.
  • the cannabis extract is a full spectrum cannabis extract or a broad spectrum cannabis extract.
  • the cannabis extract is from cannabis plants high in THC.
  • the cannabis extract is from cannabis plants high in CBD.
  • the cannabis extract is from cannabis plants low in THC.
  • the cannabis extract is free from THC, or is substantially free from THC.
  • the cannabis extract is an extract from industrial hemp.
  • the additional composition comprises a cannabinoid.
  • cannabinoid includes all naturally occurring phytocannabinoids.
  • Naturally-occurring phytocannabinoids in Cannabis plants include THC and CBD among numerous others, including as non-limiting examples, cannabinol (CBN), cannabigerol (CBG), cannabinodiol (or cannabidinodiol) (CBDL, CBND), cannabichromene (CBC), cannabielsoin (CBE), cannabicyclol (CBL), cannabicitran (CBT), cannabivarin (CBV), cannabidivarin (CBDV), tetrahydrocannabivarin (THCV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), and cannabigerol monomethyl ether (CBGM).
  • CBD cannabinol
  • CBG cannabigerol
  • CBD cannabinodiol (or cannabidinodiol)
  • cannabinoid also includes cannabinoid acids.
  • Cannabinoid acids refers generally to a heterogenous group of naturally-occurring compounds found within the cannabis plant that are the carboxylic acid precursors of their corresponding “neutral” cannabinoid (see, e.g., Burstein, S. Bioorg. Med. Chem. 2014, 22(10), 2830-2843).
  • Non-limiting examples of cannabinoid acids include, among others, cannabichromenenic acid (CBCA), cannabichromevarinic acid (CBCVA), cannabidiolic acid (CBDA), cannabidiolic acid monomethyl ether (CBDMA), CBDPA (cannabidiphorolic acid), CBDVA (cannabidivarinic acid), CBFA (cannabifuranic acid), CBEA (cannabielsoinic acid), CBGA (cannabigerolic acid), CBGVA (cannabigerovarinic acid), CBLA (cannabicyclolic acid), CBNA (cannabinolic acid), CBNDA (cannabinodiolic acid), CBTA (cannabitriolic acid), THCA (tetrahydrocannabinolic acid, including A8 and A9 THCA), THCPA (tetrahydrocannabipgorolic acid), and THCVA (tetrahydrocanabivarinic acid).
  • Neuronabinoids refer to the decarboxylated form of a given cannabinoid acid; i.e., the cannabinoid where the additional carboxyl group is removed. Without being bound by theory, decarboxylation generally is a function of pressure, temperature, and time, and typically occurs when a given cannabinoid acid is exposed to heat.
  • each cannabinoid acid listed herein i.e., CBCA, CBCVA, CBDA, CBDMA, CBDPA, CBDVA, CBEA, CBFA, CBGA, CBGVA, CBLA, CBNA, CBNDA, CBTA, THCA, THCPA, and THCVA
  • isomers such as structural isomers and stereoisomers (including enantiomers), the -A and -B isomers for each cannabinoid acid, double bond isomers, and other such isomers known to those of skill.
  • THCA will, in some embodiments, be understood to include THCA-A and THCA-B.
  • cannabinoids included among cannabinoids are the cannabinoid carboxylic acids and their carboxylate salts (see, e.g., U.S. Pat. No. 9,376,367).
  • reference to a cannabis extract includes, in such embodiments, cannabinoid carboxylic acid-rich extracts and other extracts containing cannabinoid carboxylic acids, as well as the crystalline salts of cannabinoid carboxylic acids.
  • “Cannabinoids” will be as described above and as generally known to those in the art, for example as set forth and described by Radwan et al. Molecules 2021 :26(9);2774 (Radwan 2021), as an exemplary and non-limiting categorization, which is incorporated by reference as if fully set forth herein.
  • cannabinoids according to the categorization of Radwan 2021 include compounds with a characteristic C21 terpenophenolic backbone that are part of one of 11 cannabinoid sub-classes, namely: cannabichromene (CBC)-type, cannabidiol (CBD) type, cannabielsoin (CBE) type, cannabigerol (CBG) type, cannabicyclol (CBL) type, cannabinol (CBN) type, cannabinodiol (CBND) type, cannabitriol (CBT) type, (-)-A 8 -frans- tetrahydrocannabinol (A 8 -THC) type, (-)-A 9 -trans-tetrahydrocannabinol (A 9 -THC) type, and miscellaneous-type cannabinoids.
  • CBC cannabichromene
  • CBD cannabidiol
  • CBE cannabi
  • a disclosed formulation comprises any one or more of such cannabinoids.
  • the cannabinoid is any of a A 9 -THC-type cannabinoid, a A 8 -THC-type cannabinoid, a CBG-type cannabinoid, a CBD-type cannabinoid, a CBND-type cannabinoid, a CBE-type cannabinoid, a CBL-type cannabinoid, a CBN-type cannabinoid, a CBC-type cannabinoid, a CBT-type cannabinoid, and a miscellaneous-type cannabinoid.
  • a 9 -THC-type cannabinoids include A 9 -THC-C 5 , A 9 -THCAA-C 5 , A 9 -THCAB-C 5 , A 9 -THC-C 4 , A 9 -THCAA-C 4 , A 9 -THCV, A 9 -THCVAA, A 9 -THCO, A 9 -THCOAA, A 9 -THC-aldehyde, 0-fenchyl (-)-A9-trans-tetrahydrocannabinolate, a-fenchyl (-)-A9-trans- tetrahydrocannabinolate, epi-bornyl (-)-A9-trans-tetrahydrocannabinolate, bornyl (-)-A9-trans- tetrahydrocannabinolate, o-terpenyl (-)-A9-trans-tetrahydrocannabinolate, 4-terpenyl
  • a 8 -THC-type cannabinoids include A 8 -THC, A 8 -THCA, 10O-OH-A 8 -THC, 10p-OH-A 8 -THC, and 10a-a-hydroxy-10-oxo-A8-THC.
  • CBG-type cannabinoids include (E)CBG, (E)CBGA, (E)CBGG, (E)CBGAM, (E)CBGV, (E)CBGVA, (Z)CBGA, 5-acetyl-4-hydroxy-cannabigerol, ( ⁇ )-6,7-trans- epoxycannabigerolic acid, ( ⁇ )-6,7-c/s-epoxycannabigerolic acid, ( ⁇ )-6,7-c/s-epoxycannabigerol, ( ⁇ )-6,7-frans-epxoycannabigerol, camagerol, and sesquicannabigerol.
  • CBD-type cannabinoids include CBD-C 5 , CBDA-C 5 , CBDM-C 5 , CBD-C 4 , CBDV, CBDVA, CBD-C ⁇ CBDH, CBDP, and CBDD.
  • CBND-type cannabinoids include CBND-C 3 and CBND-C 5 .
  • CBE-type cannabinoids include CBE-C 5 , CBEAA-C 5 , CBEAB-C 5 , CBE-C 3 , and CBEAB-C 3 .
  • CBL-type cannabinoids include CBL, CBLA, and CBLV
  • CBC-type cannabinoids include CBC, CBCA, ⁇ CBCV, +CBCV, CBCVA, 4-acetoxy-CBC, ( ⁇ )-3”-hydroxy-A4”-cannabichromene, (-)-7-hydroxy-cannabichromene, and CBC-C 3 .
  • CBN-type cannabinoids include CBN-C 5 , CBNA-C 5 , CBN-C 4 , CBN-C 3 , CBN-C 2 , CBN-CL CBNM-C 5 , 8-OH-CBN, 8-OH-CBNA, 1’S-OH-CBN, and 4-terpenyl-cannabinolate.
  • CBT-type cannabinoids include (-)-trans-CBT-C 5 , (+)-trans-CBT-C 5 , ( ⁇ )-c/s-CBT-C 5 , ( ⁇ )-trans-CBT-C 3 , CBT-C 3 -homologue, (-)-trans-CBT- OEt-C 5 , (-)-trans-CBT-OEt-C 3 , 8,9-DI-OH-CBT-C 5 , and CBDA-C 5 , and 9-OH-CBT-C 5 ester.
  • miscellaneous-type cannabinoids include DCBF-C 5 , CBF-C 5 , OH-iso-HHCV-C 3 OTHC, cannabicitran, c/s-A 9 -THC, CBCON-C 5 , CBR, CBTT, CBCN-C 5 , CBCN-C 3 , c/s-iso-A 7 -THCV, frans-iso-A 7 -THCV, trans-iso-A 7 -THC, CBCNB, CBCNC, CBCND, (-)-(7R)-cannabicoumarononic acid,
  • the cannabinoid is THC. In embodiments, the THC is delta-9 THC. In embodiments, the THC is delta-8 THC. In embodiments, the cannabinoid is CBD. In embodiments, the cannabinoid is one or more of cannabinol (CBN), cannabichromene (CBC), cannabigerol (CBG), tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), tetrahydrocannabivarin (THCV), and cannabidivarin (CBDV).
  • CBD cannabinol
  • CBD cannabinoid is one or more of cannabinol (CBN), cannabichromene (CBC), cannabigerol (CBG), tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), tetrahydrocannabivarin (THCV), and cannabidivarin (CB
  • the vaporizer formulation further comprises an additional compound.
  • the additional compound is nicotine.
  • the additional compound is CBD.
  • the additional compound is THC.
  • the THC is delta-9 THC.
  • the THC is delta-8 THC.
  • the additional compound is a cannabinoid other than CBD and THC.
  • the cannabinoid is one or more of cannabinol (CBN), cannabichromene (CBC), cannabigerol (CBG), tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), tetrahydrocannabivarin (THCV), and cannabidivarin (CBDV), including combinations thereof.
  • CBN cannabinol
  • CBC cannabichromene
  • CBG cannabigerol
  • THCA tetrahydrocannabinolic acid
  • CBDA cannabidiolic acid
  • THCV cannabidivarin
  • CBDDV cannabidivarin
  • the additional compound is a terpene.
  • Terpenes are major components of the essential oils present in various plants, including Cannabis. Terpenes are a significant component of the distinctive aromas and flavors, and may themselves have psychoactive properties or contribute to the biological effects of formulations, including disclosed vaporizer formulations.
  • the terpene is one or more of pinene (e.g., alpha-pinene, beta-pinene), limonene, linalool, caryophyllene, caryophyllene oxide, myrcene, humulene, borneol, eucalyptol, terpineol, nerolidol, phytol, geraniol, bisabolol, bisabolene, camphene, beta-amyrin, thujone, citronellol, pulegone, cycloartenol, cymene, sabinene, carene, terpinene, fenchol, isopulegol, guaiol, phellandrene, eudesmol, ocimene, cardinene, elemene, gurjunene, farnesene, friedelin, carvacrol, eugenol, cam
  • the vaporizer formulation comprises a psychedelic as an additional compound.
  • psychedelic compounds that induce altered states of consciousness, characterized by perceptual and cognitive distortions, changes in mood, and often profound changes in thought and self-perception.
  • Psychedelics are typically used for their psychoactive effects, which can have therapeutic, spiritual, or recreational applications.
  • Psychedelics include naturally-occurring substances such as N,N-dimethyltryptamine (DMT), as well as synthetic compounds like 2-5-dimethoxy-4-bromophenethylamine (2C-B).
  • psychedelic may encompass the psychedelic compound itself (e.g., psilocin or DMT), any fungal or plant sources thereof (e.g., mushrooms of the Psilocybe genus, root bark of Mimosa hostilis), as well as fungal or plant extracts (e.g., aqueous extracts, alcoholic extracts), as will be understood depending on context.
  • a psychedelic may be obtained, isolated, and/or purified from a natural source, may be chemically synthesized, may be produced by biosynthesis, as well as combinations thereof (e.g., semisynthesis or partial chemical synthesis from a natural isolate).
  • the psychedelic is a tryptamine, phenethylamine, or lysergamide, such compounds being generally known in the art (Shulgin A, Shulgin A. PiHKAL: A Chemical Love Story. Berkeley, CA: Transform Press; 1991 ; Shulgin A, Shulgin A. TiHKAL: The Continuation. Berkeley, CA: Transform Press; 1997; Grob CS, Grigsby J. Handbook of Medical Hallucinogens. New York, NY: Guilford Press; 2021 ; Nichols DE. Psychedelics. Pharmacological Reviews. 2016;68(2):264-355; Glennon RA. Arylalkylamine Drugs of Abuse: An Overview of Drug Discrimination Studies. Pharmacology Biochemistry and Behavior. 1999;64:251-256; each of which is incorporated by reference as if fully set forth herein).
  • the psychedelic included in a disclosed vaporizer formulation is a tryptamine.
  • tryptamines are compounds having the general structure below, wherein R N1 , R N2 , R Q , R p , R 2 , R 4 , R 5 , R 6 , and R 7 are as defined herein and as generally understood in the art:
  • R N1 , R N2 , R a , R p , R 2 , R 4 , R 5 , R 5 , and R 7 are each independently hydrogen, deuterium, halogen (F, Cl, Br, or I), OH, phosphoryloxy, optionally substituted alkoxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted aryl, or optionally substituted heterocyclyl.
  • any two of R N1 , R N2 , R a , R p , R 2 , R 4 , R 5 , R 6 , and R 7 and the intervening atoms can be taken together to form an optionally substituted optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted aryl, or optionally substituted heterocyclyl.
  • the tryptamine is a quaternary salt, in which an additional R N3 is connected to the nitrogen to which R N1 and R N2 are bound; wherein R N3 is optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted aryl, or optionally substituted heterocyclyl.
  • a disclosed vaporizer formulation comprises DMT. In some embodiments, a disclosed vaporizer formulation comprises 5-methoxy-/V,A/-dimethyltryptamine (5-MeO-DMT).
  • the psychedelic included in a disclosed vaporizer formulation is a phenethylamine.
  • phenethylamines are compounds having the general structure below, wherein R N1 , R N2 , R a , R p , and each of R 2 -R 5 are as taught herein and as generally understood in the art:
  • R N1 , R N2 , R a , R p , and each of R 2-6 are independently hydrogen, deuterium, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted aryl, or optionally substituted heterocyclyl.
  • R 3 and R 4 are joined together to form an optionally substituted heterocyclyl, such as a dioxole (as with MDMA), a furan, a tetrahydrofuran, a thiophene, a pyrrole, a pyridine, a pyrrolidine, an ethylene oxide, an ethylenimine, a trimethylene oxide, a pyran, a piperidine, an imidazole, a thiazole, a dioxane, a morpholine, or a pyrimidine.
  • R 3 and R 4 are joined together to form an optionally substituted aryl, such as a phenyl.
  • the phenethylamine comprises a quaternary ammonium cation wherein each of R N1 , R N2 , and an additional R N3 are independently an alkyl group or an aryl group, and with all other substituents as above.
  • the phenethylamine is a quaternary salt, in which an additional R N3 is connected to the nitrogen to which R N1 and R N2 are bound; wherein R N3 is optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted aryl, or optionally substituted heterocyclyl.
  • a disclosed vaporizer formulation comprises 4-bromo-2,5-dimethoxyphenethylamine (2C-B), 4-benzyloxy-3,5-dimethoxy-amphetamine (3C-BZ), 4-chloro-2,5-dimethoxyphenethylamine (2C-C), 2,5-dimethoxy-4-methyl-phenethylamine (2C-D),
  • a disclosed vaporizer formulation comprises 2C-B. In embodiments, a disclosed vaporizer formulation comprises 2C-C.
  • a disclosed vaporizer formulation comprises 2C-D. In embodiments, a disclosed vaporizer formulation comprises 2C-E. In embodiments, a disclosed vaporizer formulation comprises 2C-I. In embodiments, a disclosed vaporizer formulation comprises 2C-T. In embodiments, a disclosed vaporizer formulation comprises a 2C-T analog (i.e., 2C-T-2, 2C-T-4, 2C-T-7, 2C-T-8, 2C-T-9, 2C-T-21, etc.).
  • the disclosed formulations may also be used with any vaporizer device, whether it be a vaporizer device that is mouth-to-lung or direct-to-lung, a device that uses single-use pods, a device that uses disposable pods, a device that uses refillable pods, a modified or “mod” pod device, including a closed pod system and an open pod system; a pen device that can be refilled with the formulations disclosed herein, including simple refillable pens, such as fixed voltage pens; a device having a vape cartridge or cart, e.g., standard 0.5 mL or 1.0 ml_ cartridges, variable voltage pens, and variable temperature pens; and modified pens (mods) that are custom-crafted by the user, including regulated mods (containing a circuit board) and unregulated mods (not containing a circuit board), tube mods, box mods, and mechanical mods (mechs); a disposable, single-use pen device; other “vape pens;” an e-cigarette device,
  • a vaporizer device comprising the disclosed formulations.
  • a vaporizer device comprises a mouthpiece, a heating element, a power source, and a chamber comprising a formulation disclosed herein.
  • the device comprises a mouthpiece.
  • the mouthpiece may be any mouthpiece made of any solid material with an airway passage by which the user may be supplied a vapor comprising the vaporizer formulations disclosed herein.
  • the solid material may be any of plastic, glass, metal, wood, or a combination thereof.
  • the mouthpiece may be removable.
  • the mouthpiece may be non-removable.
  • the mouthpiece may be connected to the device directly, or may be connected via an extending member, such as a hose.
  • the mouthpiece has an extension piece protruding from the mouthpiece; which may be constructed of any of glass, metal, wood, plastic, rubber, or a combination thereof.
  • the extension piece may be removable.
  • the mouthpiece is connected to a chamber capable of holding the formulations disclosed herein, such that when the mouthpiece is removed, the chamber is also removed.
  • the mouthpiece is contoured for a user’s mouth (including where the mouthpiece is specially designed for a specific user). In embodiments, the mouthpiece contains no such contouring.
  • the device comprises a heating element.
  • the heating element includes any such means of heating the formulations disclosed herein sufficient to vaporize at least a portion of the vaporizer formulations (the heating element may also be referred to as an atomizer).
  • Vape heating elements generally comprise a coil in contact with a power unit, and may or may not include a wicking material.
  • the wicking material may include any of cotton, wood, metal, ceramic, polymer, or other materials suitable for absorbing the vaporizable formulation.
  • the heating element may include any of metal, glass, ceramic, or quartz.
  • the heating element contains a coil of a given gauge (thickness), which will affect the resistance (measured in ohms), and the ramp-up time (the time it takes the coil to generate enough heat to supply the user with the formulation).
  • the coil gauge may be any of 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, and 50 gauge.
  • the resistance of the wire is between about 0.1 and 6 ohm, inclusive.
  • the heating element comprises a wicking material.
  • the wicking material is any of silica, cotton, including organic cotton; cellucotton, including cotton cellucotton and rayon cellucotton; EKOWOOLTM or other cellulose fiber, and stainless steel mesh. That said, the wicking material may be any flammable material known to those of skill capable of absorbing the disclosed formulations.
  • the heating element is connected to a power source.
  • the power source is a battery.
  • the battery is an internal battery within the device.
  • the battery is an external battery connected to the device.
  • the battery is a rechargeable battery.
  • the battery is a replaceable battery.
  • the battery is not rechargeable or replaceable (e.g., a single use device).
  • the vaporizer further comprises a means for controlling the device.
  • a user is able to cause the battery to apply a power and a voltage to the heating element by actuating a button, switch, knob, or any other such actuating input known to those of skill.
  • the user can control either or both of the power and the voltage applied to the heating element.
  • the user controls the power and/or voltage with one or more buttons on the exterior of the device.
  • the user controls the power and/or voltage with one or more touch sensitive elements, such as a screen.
  • the vaporizer further comprises means for displaying information.
  • the device includes a graphical user interface that illustrates to the user the power and/or voltage being applied to the heating element.
  • the graphical user interface allows touch input from the user to select a given power, voltage, and/or mode of operation.
  • the graphical user interface is a screen.
  • the graphical user interface is an LED array.
  • the device further comprises a number of censors configured to monitor and communicate information such as temperature, pH, volume, or a combination thereof.
  • the sensors communicate said information to the user through the screen and/or the LED array.
  • the heating element will heat the formulations disclosed herein to a degree sufficient to vaporize the formulations.
  • the heating element will heat the formulation to a degree sufficient to supply the user with the ingredients of the fungal extract without combusting the extract (e.g., in heat-not-burn devices).
  • a heat-not-burn (HnB) or like device is used to vaporize dried fungus, including dried A muscaria mushrooms, directly. Such dried mushrooms generally will be crushed, ground, and/or pulverized before use in the HnB device.
  • the device comprises a chamber comprising a formulation disclosed herein.
  • the device is obtained by a user with the formulation contained within the device.
  • the device is a single use device.
  • the device is a device wherein the individual may refill the chamber with a formulation or replace the chamber with a chamber filled with a formulation.
  • the chamber is a refillable chamber, including a refillable chamber in a pen, a mod device, including a mech, a regulated mod, an unregulated mod, a tube mod, and a box mod; a refillable cigalike, an e-pipe, or a mod pod device that utilizes refillable pods.
  • the chamber is a removable chamber, including a single use container, such as a single use pod or single use cartridge.
  • the chamber is a refillable chamber and a removable chamber, including a removable and refillable pod, such as those for a mod pod device; or in a removable and refillable cartridge.
  • a user may purchase the formulation separately from the device, e.g., as a liquid formulation (including any of the formulations disclosed herein) to be added to a chamber.
  • the formulation is contained within a removable chamber within the device.
  • the removable chamber may be a single use container, such as those described above.
  • the formulation is contained within a refillable chamber within the device.
  • the formulation is contained within a refillable chamber and a removable chamber, such as those described above.
  • the device is constructed of a solid material, including any of glass, metal, wood, plastic, rubber, paper, cardboard, or any other such solid material known to those of skill.
  • chambers for use with a vaporizer device comprising a disclosed formulation.
  • the chamber is refillable.
  • the chamber is removable.
  • the chamber is refillable and removable.
  • the removable chamber is a single use container.
  • the disclosed A. muscaria formulations are used in the manufacture of a medicament to modulate neurotransmission.
  • the disclosed A. muscaria formulations are administered, e.g., in a therapeutically effective amount, to a subject to modulate neurotransmission in said subject.
  • modulating neurotransmission promotes health and wellness.
  • modulating neurotransmission results in an improvement, such as clinical improvement, of a condition, such as a disease or a disorder.
  • Detecting a change in neurotransmitter levels in a subject can be achieved according to methods known to one of skill, for example, brain microdialysis ( chefser et al., Curr Protoc Neurosci. 2009; Chapter: Unit 7.1 ; Darvesh et al., Expert Opin Drug Discov. 2011; 6(2): 109-127) and brain imaging, for example, positron emission tomography (PET) and single photon emission computed tomography (SPECT) (see e.g., Wong & Gjedde, Encyclopedia of Neuroscience, 2009; 939-952 and Takano, Front Psychiatry., 2018; 9:228).
  • PET positron emission tomography
  • SPECT single photon emission computed tomography
  • the modulation or regulation of neurotransmission is that of gabaminergic or cholinergic neurotransmission.
  • the modulation or regulation of gabaminergic or cholinergic neurotransmission is without significant modulation or regulation of glutaminergic neurotransmission.
  • the modulation or regulation of neurotransmission is without significant modulation or regulation of glutaminergic neurotransmission because of a lack of, only trace amounts of, or a relatively low amount of, ibotenic acid.
  • the modulation or regulation of neurotransmission is without significant modulation or regulation of glutaminergic neurotransmission caused by ibotenic acid.
  • GABA A receptors are ion channels which can be activated by the neurotransmitter GABA, or by drugs (e.g., muscimol). When these channels open they are permeable to negatively charged chloride ions (Cl-).
  • GABA A receptors are extremely important for regulating nerve activity throughout the nervous system. When dysregulated, an individual often experiences anxiety. GABA A also regulates nerve activity and plays a role in pain stimulation. Most depressant and sedative drugs such as benzodiazepine tranquilizers, barbiturates, anesthetics, and alcohol are believed have a modulatory effect on the GABA A receptor by binding to allosteric sites on GABA A receptors where they enhance the actions of GABA in accumulating negatively charged chloride ions into the cell, inducing sedative or anesthetic effects.
  • depressant and sedative drugs such as benzodiazepine tranquilizers, barbiturates, anesthetics, and alcohol are believed have a modulatory effect on the GABA A receptor by binding to allosteric sites on GABA A receptors where they enhance the actions of GABA in accumulating negatively charged chloride ions into the cell, inducing sedative or anesthetic effects.
  • benzodiazepines results in the development of tolerance to some of the effects, reducing their clinical efficacy.
  • the disclosed A. muscaria formulations offer significant benefits versus other gabaminergic compounds like benzodiazepines and barbiturates.
  • administration of a disclosed A muscaria composition results in binding and activation of GABA A receptors.
  • Muscarine mimics the action of the neurotransmitter acetylcholine by agonizing muscarinic acetylcholine receptors, which modulates cholinergic neurotransmission.
  • muscarinic receptors There are five different types of muscarinic receptors: M1, M2, M3, M4 and M5.
  • M1 and M4 subtypes mediate muscarinic responses at peripheral autonomic tissues; M1 and M4 subtypes are more abundant in brain and autonomic ganglia.
  • M1 , M3, and M5 interact with Gq proteins to stimulate phosphoinositide hydrolysis and the release of intracellular calcium.
  • M2 and M4 by contrast, interact with Gi proteins to inhibit adenylyl cyclase, which results in a decrease of intracellular concentration of cyclic adenosine monophosphate (cAMP).
  • Muscarinic receptors also signal via other pathways, for instance via G beta-gamma complex modulation of potassium channels. This allows muscarine to modulate cellular excitability via the membrane potential.
  • use of a disclosed vaporizer formulation such as in a disclosed vaporizer device will result in modulation or regulation of gabaminergic and/or cholinergic neurotransmission.
  • the modulation or regulation of such neurotransmission via the disclosed methods will improve health and wellness, such as described below.
  • the modulation or regulation of such neurotransmission via the disclosed methods results in mild euphoria, such as described below.
  • the methods comprise heating the vaporizer formulations with the vaporizer devices to vaporize at least a portion of the vaporizer formulations.
  • the portion of the vaporizer formulations becomes a vapor that may include a mist or an aerosol that includes fine solid and/or liquid particles suspended in a gas or, in embodiments, the vapor may be substantially formed as a gas.
  • the vapor may also include a gaseous substance having small droplets of oil, water and/or other chemical compounds suspended therein.
  • a vapor includes liquid (e.g., water, oil, etc.) particles mixed with hot ambient air, which is cooled down so as to condense into a fine cloud of visible airborne droplets.
  • a user of a vaporizer device in which at least a portion of the vaporizer formulation is vaporized will inhale the vaporized portion, that is, at least some quantity of the vaporized portion, such as through the mouthpiece of the device.
  • a disclosed formulation including as delivered via a disclosed device, such as when inhaled by a user through the mouthpiece of the device, are useful for modulating or regulating neurotransmission.
  • the formulations when so inhaled, will modulate or regulate neurotransmission.
  • a vaporizer formulation or a vaporizer device disclosed herein to improve health and wellness.
  • Improvements to “health and wellness” will include such improvements to health and improvements to wellness as will be readily appreciate in the art, and include improvements to general feelings of well-being, such as increases in or increased time spent in a state of being comfortable, content, at peace, calm, unstressed, healthy, happy, joyful, uplifted, and other such positive states, feelings, and moods.
  • an improvement to health and happiness is a state, feeling, or mood of euphoria, including of mild euphoria.
  • the methods of using a vaporizer formulation or a vaporizer device result in an improvement to health and wellness.
  • improving health and wellness comprises eliciting or enhancing calmness in a subject.
  • the disclosed A. muscaria formulations are used to elicit or enhance calmness in a subject.
  • administering the disclosed A. muscaria formulations to a subject elicits or enhances calmness in said subject.
  • eliciting or enhancing calmness in a subject comprises a reduction in any of anxiety, worry, and hopelessness.
  • eliciting or enhancing calmness in a subject comprises promoting feelings of calm, tranquility, and a sense of peace.
  • Physiological responses to eliciting or enhancing calmness in a subject may include a reduction in blood pressure and heart rate, as well as other signs of calmness known to those in the art
  • improving health and wellness comprises reducing stress in a subject.
  • reducing stress comprises a reduction in any of anxiety, worry, and hopelessness.
  • reducing stress comprises promoting feelings of calm, tranquility, and a sense of peace.
  • Physiological responses to a reduction in stress may include a reduction in blood pressure and heart rate, as well as other signs of a reduction of stress known to those in the art.
  • the disclosed A. muscaria composition provides methods for improving a sense of calm and elicits feelings of comfortability, tranquility, and relaxation. Improvements in feeling a sense of calm may include a state of mind being free from agitation, excitement or disturbance. Additionally, improvements in a sense of calm may include improvements in emotional regulation and an increased sense of acceptance of self and of others (see Kraus et al., Social Indicators Research. 2008; 92, 169-181 Juneau et al., Peerj. 2020; 1-19). Measurements of such will be readily understood and appreciated according to ordinary skill.
  • EQUA-S the EQUA-S
  • BMIS Brief Mood Introspection Scale
  • improving health and wellness comprises promoting restorative sleep, including any of waking up feeling refreshed, increasing the amount of time spent in deep sleep, increasing the quantity of peaceful dreams, and reducing the amount of sleep necessary to feel refreshed, as well as other signs of a promotion of restorative sleep as will be known to those in the art.
  • improving health and wellness comprises preventing insomnia.
  • improving health and wellness comprises preventing insomnia.
  • improving health and wellness comprises reducing the severity of insomnia. The severity of insomnia may be determined, e.g., with use of The Insomnia Severity Index (ISI), a brief self-report instrument measuring the subject’s perception of both nocturnal and diurnal symptoms of insomnia.
  • ISI The Insomnia Severity Index
  • improving health and wellness comprises any of a soothing of the body, a calming of the mind, and a reduction in physical distress; including feeling relaxed, at peace, and content; and a decrease in aches, pains, numbness, and tingling.
  • improving health and wellness comprises includes any one or more of a reduction in feelings of nervousness, ‘jitters,” nervous tension, or anxiety; a reduction in feelings of malaise, unhappiness, existential angst, ennui, and general discontent; and an increase in feelings of wellbeing, wellness, relaxation, contentment, happiness, openness to experience, and life satisfaction.
  • the improvement to health and wellness is a reduction in stress, including any of a reduction in anxiety, worry, and hopelessness; a promotion of feelings of calm, tranquility, and a sense of peace; and a reduction in blood pressure and heart rate, as well as other signs of a reduction of stress as will be known to those in the art.
  • the improvement to health and wellness is an easing of muscular tension, including any of a reduction in soreness, tightness, aches, and pains; and an increase in flexibility and range of motion, as well as other signs of an easing of muscular tension as will be known to those in the art.
  • the improvement to health and wellness is a promotion of restorative sleep, including any of waking up feeling refreshed, increasing the amount of time spent in deep sleep, increasing the quantity of peaceful dreams, and reducing the amount of sleep necessary to feel refreshed, as well as other signs of a promotion of restorative sleep as will be known to those in the art.
  • the improvement to health and wellness is any of a soothing of the body, a calming of the mind, and a reduction in physical distress; including feeling relaxed, at peace, and content; and a decrease in aches, pains, numbness, and tingling.
  • the improvement to health and wellness is an improvement of a condition or disorder linked to dysregulation or inadequate functioning of neurotransmission.
  • the condition or disorder linked to dysregulation or inadequate functioning of neurotransmission is that of gabaminergic, glutaminergic, or cholinergic neurotransmission.
  • the improvement to health and wellness is an improvement in any of a pain disorder, an inflammatory disorder, and an immune or autoimmune disorder.
  • the improvement to health and wellness is an improvement in a sleep disorder.
  • the improvement to health and wellness is an improvement in a mental health disorder.
  • the mental health disorder is an anxiety disorder or a substance use disorder.
  • the improvement to health and wellness includes any one or more of: a reduction in feelings of nervousness, “jitters,” nervous tension, or anxiety; a reduction in feelings of malaise, unhappiness, existential angst, ennui, and general discontent; and an increase in feelings of wellbeing, wellness, relaxation, contentment, happiness, openness to experience, and life satisfaction.
  • a vaporizer formulation including with a disclosed vaporizer device to induce a sense of euphoria, such methods comprising heating the vaporizer formulation with the vaporizer device to vaporize at least a portion of the vaporizer formulation.
  • the methods of using a vaporizer formulation or a vaporizer device result in an inducement of a sense of euphoria.
  • the improvement to health and wellness is inducing a sense of euphoria.
  • a sense of euphoria includes a sense of pleasure characterized by strong feelings of happiness, excitement, and well-being. Those experiencing a sense of euphoria may describe it as being joyful and pleasurable, as well as feeling safe, secure, carefree, and supported (Cherry, What is a euphoric mood? 2022).
  • a sense of euphoria is a euphoric mood.
  • a sense of euphoria is a transient feeling of euphoria.
  • a sense of euphoria may include mild euphoria as well as greater relative feelings of euphoria.
  • a sense of euphoria may include other signs as will be known to those in the art.
  • the A. muscaria composition provides methods of improving mental health and/or functioning, such as cognitive functioning.
  • Improvements in mental health and functioning may include one or more of a reduction of neuroticism or psychological defensiveness, an increase in creativity or openness to experience, an increase in decision-making ability, an increase in feelings of wellness or satisfaction, or an increase in ability to fall or stay asleep.
  • improvements in mental health and functioning may include improvements in or a return to baseline in processing speed, learning and memory, autobiographical memory, shifting, and IQ. Measurements of such will be readily understood and appreciated according to ordinary skill. See, e.g., cognitive functioning aspects reviewed by Ahern & Semskova, Neuropsychology. 2017;31 (1 ):52-72.
  • Exemplary measures of improvements of mental health and/or functioning include the Global Assessment of Functioning (GAF) scale, the Sleep Quality Scale (SQS) and other measures of sleep quality (see, e.g., Fabbri et al., Int J Environ Res Public Health. 2021 ; 18(3): 1082, and the Social Functioning Scale (SFS) (see, e.g., Chan et al., Psychiatry Res. 2019;276:45-55).
  • GAF Global Assessment of Functioning
  • SQS Sleep Quality Scale
  • FSS Social Functioning Scale
  • the disclosed A. muscaria composition may be useful as a nootropic.
  • Nootropics or smart drugs are well-known compounds or supplements that enhance cognitive performance. They work by increasing the mental function such as memory, creativity, motivation, and attention (Suliman et al., Evidence-Based Compl. and Alt. Med. 2016;4391375: 1-12).
  • Nootropic properties are present within the makeup of the disclosed A. muscaria formulations and, due to its cellular and molecular mechanisms of action, which enable a structural and functional plasticity, or synaptic plasticity, responsible for synaptic remodeling or known as cellular learning. In turn, nootropics mediate and enhance cognitive performance.
  • a user of a vaporizer device in which at least a portion of the vaporizer formulation is vaporized will inhale the vaporized portion, that is, at least some quantity of the vaporized portion, such as through the mouthpiece of the device.
  • the disclosed A. muscaria composition is useful as an adjunct to meditation and/or meditative practice.
  • meditation refers to a variety of practices that focus on mind and body integration and are used to calm the mind and enhance overall well-being. While some forms of meditation involve maintaining mental focus on a particular sensation, other forms include the practice of mindfulness, which involves maintaining attention or awareness of the present moment without making judgements (see NCCIH NIH, “Meditation and Mindfulness: What You Need To Know’’ accessed 8/10/2022).
  • the benefits of meditation include stress reduction, decreased anxiety, decreased depression, reduction in pain (both physical and psychological), improved memory, and increased efficiency.
  • Physiological benefits include reduced blood pressure, heart rate, lactate, cortisol, and epinephrine, decreased metabolism and breathing pattern, oxygen utilization, and carbon dioxide elimination.
  • Neurological and physiological correlates of meditation have been researched extensively in the past, and can be measured using electroencephalogram (EEG)(Sharma H., AYU. 2015;36:233-7).
  • the A. muscaria composition is administered together with psychotherapy, such as psychosocial or behavioral therapy, including any of (or adapted from any of) cognitive behavioral therapy (e.g., as described in Arch. Gen. Psychiatry 1999; 56:493-502), interpersonal therapy (e.g., as described in Psychol Addict Behav 2009; 23(1): 168-174), contingency management based therapy (e.g., as described in Psychol Addict Behav 2009; 23(1): 168-174; in J. Consul. Clin. Psychol. 2005; 73(2): 354-59; or in Case Reports in Psychiatry, Vol. 2012, Article ID 731638), motivational interviewing based therapy (e.g., as described in J.
  • psychotherapy such as psychosocial or behavioral therapy, including any of (or adapted from any of) cognitive behavioral therapy (e.g., as described in Arch. Gen. Psychiatry 1999; 56:493-502), interpersonal therapy (e.g., as described in Psychol Addict Behav 2009; 23
  • psychotherapy is specifically “psychedelic-assisted psychotherapy.”
  • Psychedelic-assisted psychotherapy broadly, includes a range of related approaches that involve at least one session where the patient ingests a psychedelic and is monitored, supported, or otherwise engaged by one or more trained mental health professionals while under the effects of the psychedelic (see, e.g., Schenberg 2018).
  • Protocols have been developed for the standardization of procedures which emphasize a high degree of care (see, e.g., Johnson 2008), such as the therapeutic approach used by MAPS to treat patients with PTSD using MDMA (e.g., as described in Mithoefer 2017).
  • psychotherapy comprises any accepted modality of standard psychotherapy or counseling sessions, whether once a week, twice a week, or as needed; whether in person or virtual (e.g., over telemedicine or by means of a web program or mobile app); and whether with a human therapist or a virtual or Al “therapist.”
  • therapist refers to a person who treats a patient using the formulations and methods of the invention, whether that person is a psychiatrist, clinical psychologist, clinical therapist, registered therapist, psychotherapist, or other trained clinician, counselor, facilitator, or guide, although it will be understood that certain requirements will be appropriate to certain aspects of the drug-assisted therapy (e.g., prescribing, dispensing, or administering a drug, offering psychotherapeutic support).
  • a “person” may also include an Al.
  • a patient will participate in a treatment protocol or a method of the invention, or be administered a composition of the invention as part of such a method, if the patient meets certain specified inclusion criteria, does not meet certain specified exclusion criteria, does not meet any specified withdrawal criteria during the course of treatment, and otherwise satisfies the requirements of the embodiment of the invention as claimed.
  • disclosed A. muscaria formulations may be administered in conjunction with or as an adjunct to psychotherapy.
  • psychotherapy is neither necessitated nor desired, or no specific type of psychotherapy is necessitated or desired, however any of the disclosed methods can be used in combination with one or more psychotherapy sessions.
  • the flexibility to participate in specific therapies, as well as to choose between any such therapies (or to decide to forgo any specific therapy), while still receiving clinically significant therapeutic effects, is among the advantages of the invention.
  • a patient can participate in numerous other therapeutically beneficial activities, where such participation follows or is in conjunction with the administration of the composition, including breathing exercises, meditation and concentration practices, focusing on an object or mantra, listening to music, physical exercise, stretching or bodywork, journaling, grounding techniques, positive self-talk, or engaging with a pet or animal, and it should be understood that such participation can occur with or without the participation or guidance of a therapist.
  • disclosed formulations are used to treat a medical condition, such as a disease or disorder.
  • disclosed formulations are used in the manufacture of a medicament to treat a condition, such as a disease or disorder.
  • methods of administering disclosed formulations to a subject having a condition, such as a disease or disorder, thereby treating said condition are also provided.
  • treating and/or preventing a condition in a mammal comprising administering to the mammal a therapeutically effective amount of a disclosed formulation.
  • “treating” or “treatment” refers to treating a disease or disorder in a mammal, and preferably in a human, and includes causing a desired biological or pharmacological effect, such as: (a) preventing a disorder from occurring in a subject who may be predisposed to the disorder but has not yet been diagnosed with it; (b) inhibiting a disorder, i.e.
  • CNS disorders include diseases of the nervous system (e.g., movement disorders, neurodegenerative disorders) as well as mental, behavioral, and neurodevelopmental disorders, such as those characterized by the DSM-5, Merck Manual, ICD-11 , or other such diagnostic resources in the art.
  • diseases of the nervous system e.g., movement disorders, neurodegenerative disorders
  • mental, behavioral, and neurodevelopmental disorders such as those characterized by the DSM-5, Merck Manual, ICD-11 , or other such diagnostic resources in the art.
  • disclosed formulations are used to treat a mental, behavioral, or neurodevelopmental disorder.
  • disclosed formulations are administered, such as in a therapeutically effective amount, to a subject having a mental, behavioral, or neurodevelopmental disorder, thereby treating said mental, behavioral, or neurodevelopmental disorder.
  • the disclosed formulations when administered in a therapeutically effective amount, provide beneficial therapeutic effects for the treatment of a mental, behavioral, or neurodevelopmental disorder.
  • the ICD-11 which is incorporated by reference herein in its entirety, defines “mental, behavioral, or neurodevelopmental disorders” as syndromes characterized by clinically significant disturbance in an individual's cognition, emotional regulation, or behavior that reflects a dysfunction in the psychological, biological, or developmental processes that underlie mental and behavioral functioning.
  • Such disorders include, but are not limited to, neurodevelopmental disorders, schizophrenia or other primary psychotic disorders, catatonia, mood disorders, anxiety or fear-related disorders, obsessive-compulsive or related disorders, disorders specifically associated with stress, dissociative disorders, feeding (or eating) disorders, elimination disorders, disorders of bodily distress or bodily experience, disorders due to substance use or addictive behaviors, impulse control disorders, disruptive behavior or dissocial disorders, personality disorders (and related traits), paraphilic disorders, factitious disorders, neurocognitive disorders, mental or behavioral disorders associated with pregnancy, childbirth or the puerperium, sleep-wake disorders, sexual dysfunctions, and gender incongruence.
  • a mental, behavioral, or neurodevelopmental disorder where otherwise undefined, will be understood to refer to the disorder as defined in the ICD-11.
  • the term mental disorder (or “mental health disorder”) generally refers to a disease condition that involves negative changes in emotion, mood, thinking, and/or behavior.
  • mental health disorders are characterized by clinically significant disturbances in an individual's cognition, emotion, behavior, or a combination thereof, resulting in impaired functioning, distress, or increased risk of suffering.
  • mental disorder and “mental health disorder,” as well as terms that define specific diseases and disorders, generally shall refer to the criteria in the ICD-11, or a patient with a diagnosis based thereon, it will be appreciated that disclosed methods are equally applicable to patients having an equivalent underlying disorder, whether that disorder is diagnosed based on the criteria in ICD-11 , ICD-10, DSM-5, or DSM-IV (each of which is incorporated by reference herein in its entirety) whether the diagnosis is based on other clinically acceptable criteria, or whether the patient has not yet had a formal clinical diagnosis.
  • disclosed formulations are used to treat a mental health disorder.
  • disclosed formulations are administered, such as in a therapeutically effective amount, to a subject having a mental health disorder, thereby treating said mental health disorder.
  • the disclosed formulations when administered in a therapeutically effective amount, provide beneficial therapeutic effects for the treatment of a mental health disorder.
  • disclosed formulations are used to reduce the symptoms of a mental health disorder. The symptoms of the mental health disorder to be treated shall be able to be determined by one of skill in the art, by reference to the general understanding of the art regarding that disorder.
  • measures of therapeutic efficacy include reports by a subject or an observer.
  • measures of therapeutic efficacy include responses to a questionnaire.
  • measures of symptom improvement include the Generalized Anxiety Disorder Scale-7 (GAD-7), Montgomery-Asberg Depression Rating Scale (MADRS), Global Assessment of Functioning (GAF) Scale, Clinical Global Impression (CGI), Substance Abuse Questionnaire (SAQ), Mini International Neuropsychiatric Interview 5 (MINI 5), Columbia Suicide Severity Rating Scale (C-SSRS), Patient Health Questionnaire (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), Interpersonal Reactivity Index (IRI), Short Form (36) Health Survey (SF-36), Self-Compassion Scale (SCS), Trauma History Questionnaire (THQ), Beck Depression Index (BDI), and related subject- or observer-reported measures.
  • GID-7 Generalized Anxiety Disorder Scale-7
  • MADRS Montgomery-Asberg Depression Rating Scale
  • GAF Global Assessment of Functioning Scale
  • CGI Clinical Global Impression
  • a disclosed formulation is used to treat a neurodevelopmental disorder.
  • a “neurodevelopmental disorder” is a neurological and/or cognitive disorder that arises during the developmental period that involves significant difficulties in the acquisition and execution of specific neurological functions (e.g., intellectual, motor, language, or social functions).
  • the neurodevelopmental disorder is a disorder of intellectual development, a developmental speech or language disorder, autism spectrum disorder, a developmental learning disorder, a developmental motor coordination disorder, attention deficit hyperactivity disorder, or stereotypic movement disorder.
  • a disclosed formulation is used to treat schizophrenia or another primary psychotic disorder.
  • these disorders are characterized by significant impairments in reality and alterations in behavior manifest in positive symptoms like persistent delusions, persistent hallucinations, disorganized thinking and speech, grossly disorganized behavior, as well as experience of negative symptoms such as blunted or flat affect and avolition and psychomotor disturbances.
  • a disclosed formulation is used to treat schizophrenia, schizoaffective disorder, schizotypal disorder, acute and transient psychotic disorder, delusional disorder, or a substance-induced psychotic disorder.
  • a disclosed formulation is used to treat a mood disorder.
  • mood disorders are categorized according to the specific type(s) of mood episodes, and their pattern over time.
  • the primary types of mood episodes are depressive episodes, manic episodes, mixed episodes, and hypomanic episodes.
  • the mood disorder is a bipolar or related disorder (e.g., bipolar type I disorder, bipolar type II disorder, cyclothymic disorder), a depressive disorder, or a substance-induced mood disorder.
  • the mood disorder is a depressive disorder.
  • the depressive disorder is single-episode depressive disorder, major depressive episode disorder, persistent depressive disorder (formally known as dysthymia), disruptive mood dysregulation disorder, premenstrual dysphoric disorder, postpartum depression, substance/medication-induced depressive disorder, depressive disorder due to another medical condition, seasonal affective disorder, mixed depressive and anxiety disorder, or an unspecified depressive disorder.
  • depression is assessed through the Patient Health Questionnaire-9 (PHQ-9) screening tool, Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale, Beck Depression Inventory (BDI-II), Zung Self-Rating Depression Scales (SDS), Major Depression Inventory (MDI), Center for Epidemiologic Studies Depression Scale (CED-D), Rome Depression Inventory (RDI), Hamilton Rating Scale for Depression (HRSD), and Carroll Rating Scale (CRS).
  • PHQ-9 Patient Health Questionnaire-9
  • MADRS Montgomery-Asberg Depression Rating Scale
  • BDI-II Beck Depression Inventory
  • SDS Zung Self-Rating Depression Scales
  • MDI Major Depression Inventory
  • CED-D Center for Epidemiologic Studies Depression Scale
  • RDI Rome Depression Inventory
  • Hamilton Rating Scale for Depression HRSD
  • CRS Consumer Rating Scale
  • a disclosed formulation is used to treat an anxiety or fear-related disorder.
  • An “anxiety disorder” refers to a class of mental disorders that induce excessive or abnormal fear, dread, or worry.
  • the anxiety disorder is selected from the group consisting of generalized anxiety disorder, panic disorder, agoraphobia, specific phobia, social anxiety disorder, separation anxiety disorder, selective mutism, or a substance-induced anxiety disorder.
  • a disclosed formulation is used to treat an obsessive-compulsive or related disorder.
  • these disorders are characterized by repetitive thoughts and behaviors, such as cognitive phenomena (obsessions, intrusive thoughts and preoccupations).
  • the disorder is characterized by a compulsive need to accumulate possessions and distress related to discarding them (i.e., hoarding disorder).
  • the disorder is body-focused and can be characterized by recurrent and habitual actions (hair-pulling, skin-picking).
  • the disorder is obsessive-compulsive disorder, body dysmorphic disorder, olfactory reference disorder, hypochondriasis, hoarding disorder, a body-focused repetitive behavior disorder, or a substance-induced obsessive-compulsive disorder.
  • a disclosed formulation is used to treat a disorder associated with stress.
  • the disorder associated with stress has an identifiable stressor that is a causal factor, like exposure to a stressful or traumatic event, or a series of such events or adverse experiences. Stressors may be within the normal range of life experiences (e.g., divorce, socioeconomic problems), or from a threatening or traumatizing experience. In general, the nature and duration of the symptoms that arise in response to the stressor can distinguish the disorder from everyday stress.
  • a disclosed formulation is used to treat post-traumatic stress disorder, complex post-traumatic stress disorder, prolonged grief disorder, adjustment disorder, reactive attachment disorder, or disinhibited social engagement disorder.
  • a disclosed formulation is used to treat a feeding or eating disorder.
  • Feeding or eating disorders generally involve abnormal eating or feeding behaviors that are not explained by another health condition, and are not developmentally appropriate or culturally sanctioned. These disorders can involve preoccupation with food as well as body weight and shape concerns.
  • a disclosed formulation is used to treat anorexia nervosa (including anorexia with significantly low body weight, anorexia with dangerously low body weight, or anorexia in recovery with normal body weight), bulimia nervosa, binge eating disorder, avoidant-restrictive food intake disorder, pica, or rumination-regurgitation disorder.
  • a disclosed formulation is used to treat a disorder of bodily distress or bodily experience.
  • Disorders of bodily stress typically involve bodily symptoms that the subject finds distressing and to which the subject devotes excessive attention.
  • Bodily integrity dysphoria typically involves a disturbance in the person’s experience of the body manifested by persistent discomfort or intense feelings of body configuration.
  • a disclosed formulation is used to treat a bodily distress disorder (including mild, moderate, and severe bodily distress disorder) or body integrity dysphoria.
  • a disclosed formulation is used to treat a disorder due to substance use or addictive behaviors.
  • Individual self-administration of Amanita muscaria mushrooms is reportedly effective for treating various addictions, including substance addiction (e.g., nicotine addiction, alcohol addiction) as well as behavioral addictions (e.g., pornography addiction, other compulsive behaviors).
  • substance addiction e.g., nicotine addiction, alcohol addiction
  • behavioral addictions e.g., pornography addiction, other compulsive behaviors.
  • disorders due to substance use or addictive behaviors are mental and/or behavioral disorders that develop predominantly as a result of the use of psychoactive substances (including medications and illegal or illicit substances), or specific repetitive rewarding and reinforcing behaviors.
  • a disclosed formulation is used to treat disorders due to substance use (i.e., a substance use disorder, or SUD).
  • the substance use disorder is associated with alcohol, cannabis, synthetic cannabinoids, opioids, sedatives, hypnotics or anxiolytics, cocaine, stimulants (e.g., amphetamines, methamphetamines, methcathinone, synthetic cathinones, caffeine), hallucinogens, nicotine, volatile inhalants, MDMA or MDA, dissociative drugs like ketamine and phencyclidine, or another substance (including medications and non-psychoactive substances).
  • the substance use disorder is selected from alcohol use disorder, cannabis use disorder, caffeine use disorder, phencyclidine use disorder, inhalants use disorder, opioids use disorder, sedatives use disorder, hypnotics use disorder, anxiolytics use disorder, stimulants use disorder, and tobacco use disorder.
  • the substance use disorder is alcohol use disorder.
  • the substance use disorder is cannabis use disorder.
  • the substance use disorder is caffeine use disorder.
  • the substance use disorder is phencyclidine use disorder.
  • the substance use disorder is inhalant use disorder.
  • the substance use disorder is opioids use disorder.
  • the substance use disorder is sedatives use disorder.
  • the substance use disorder is hypnotics use disorder.
  • the substance use disorder is anxiolytics use disorder. In embodiments, the substance use disorder is stimulants use disorder. In embodiments, the substance use disorder is tobacco use disorder. In embodiments, the substance use disorder is alcohol use disorder, wherein said alcohol use disorder is selected from alcohol abuse, alcohol dependence, and alcoholism. In embodiments, the disorder is associated with another addictive behavior (e.g., gambling disorders, gaming disorder).
  • a substance use disorder can be screened using a Screening to Brief Intervention (S2BI), Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), Brief Screener for Alcohol, Tobacco, and other Drugs (BSTAD), Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS), the Opioid Risk Tool - OUD (ORT-OUD) Chart, Drug Abuse Screen Test (DAST-10), and Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS).
  • S2BI Screening to Brief Intervention
  • ASSIST Alcohol, Smoking, and Substance Involvement Screening Test
  • BTAD Brief Screener for Alcohol, Tobacco, and other Drugs
  • TAPS Tobacco, Alcohol, Prescription medication, and other Substance use
  • ORT-OUD Opioid Risk Tool - OUD Chart
  • DAST-10 Drug Abuse Screen Test
  • TAPS Tobacco, Alcohol, Prescription medication, and other Substance use
  • the behavioral addiction is gambling disorder. In embodiments, the behavioral addiction is gaming disorder. In embodiments, the behavioral addiction is sexual addiction. In embodiments, the behavioral addiction is compulsive buying disorder. In embodiments, the behavioral addiction is technology addiction. In embodiments, the behavioral addiction is pornography addiction.
  • the disclosed A muscaria formulations reduce compulsive behaviors.
  • Compulsive behaviors are described, e.g., in the ICD-11.
  • a disclosed formulation is used to treat an impulse control disorder.
  • impulse control disorders are characterized by the repeated failure to resist an impulse, drive, or urge to perform an act that is rewarding to the subject despite negative long-term consequences, such as harm to the subject or a significant impairment in important areas of the subject’s functioning.
  • impulse control behaviors include fire-setting, stealing, inappropriate sexual behavior, and explosive outbursts.
  • a disclosed formulation is used to treat pyromania, kleptomania, compulsive sexual behavior disorder, or intermittent explosive disorder.
  • a disclosed formulation is used to treat a personality disorder.
  • Personality disorders may be generally characterized by problems in perceiving one’s identity, self-worth, accuracy of self-view, and self-discretion that is manifest in patterns of cognition, emotional experience, emotional expression, and maladaptive behavior.
  • a disclosed formulation is used to treat a mild, moderate, or severe personality disorders.
  • a disclosed formulation is used to treat a prominent personality trait or patterns (e.g., negative affectivity, detachment, dissociality, disinhibition, anankastia, borderline pattern).
  • the personality disorder is antisocial personality disorder, avoidant personality disorder, borderline personality disorder, dependent personality disorder, histrionic personality disorder, masochistic or sadistic behavior, narcissistic personality disorder, obsessive-compulsive personality disorder, paranoid personality disorder, psychopathy, sociopathy, schizoid personality disorder, or schizotypal personality disorder.
  • a disclosed formulation is used to treat a paraphilic disorder.
  • Paraphilic disorders can be characterized by persistent and intense patterns of atypical sexual arousal, the focus of which involves others whose age or status renders them unwilling or unable to consent.
  • a disclosed formulation is used to treat exhibitionistic disorder, voyeuristic disorder, pedophilic disorder, coercive sexual sadism disorder, frotteuristic disorder, other paraphilic disorders involving non-consenting individuals, or paraphilic disorders involving solitary behavior or consenting individuals.
  • a disclosed formulation is used to treat a neurocognitive disorder.
  • Neurocognitive disorders may be characterized by primary clinical defects in cognitive functioning that are acquired (rather than developmental), and therefore the subject experiences a decline from a previously attained level of functioning.
  • a disclosed formulation is used to treat delirium.
  • the delirium is associated with another disease or disorder.
  • the delirium is associated with a psychoactive substance (including medications and illicit or illegal substances).
  • a disclosed formulation is used to treat mild neurocognitive disorder.
  • a disclosed formulation is used to treat an amnestic disorder.
  • the amnestic disorder is associated with another disease or disorder.
  • the delirium is associated with a psychoactive substance (including medications and illicit or illegal substances).
  • a disclosed formulation is used to treat dementia.
  • the dementia is associated with Alzheimer’s disease, Parkinson’s disease, cerebrovascular disease, Lewy body disease, a psychoactive substance (including medications and illicit or illegal substances).
  • a disclosed formulation is used to treat a behavioral or psychological disturbance associated with dementia.
  • dementia is assessed using a Functional Activities Questionnaire (FAQ), Ascertain Dementia 8 (AD8), Mini-Cog, Mini-Mental State Exam (MMSE), the Montreal Cognitive Assessment (MoCA), and the Neuropsychiatric Inventory Questionnaire (NPI-Q).
  • FAQ Functional Activities Questionnaire
  • AD8 Ascertain Dementia 8
  • MMSE Mini-Cog
  • MMSE Mini-Cog
  • MSE Mini-Mental State Exam
  • MoCA Montreal Cognitive Assessment
  • NPI-Q Neuropsychiatric Inventory Questionnaire
  • a disclosed formulation or composition is administered together with psychotherapy, such as psychosocial or behavioral therapy, including any of (or adapted from any of) cognitive behavioral therapy (CBT) (e.g., as described in Arch. Gen. Psychiatry 1999; 56:493-502), interpersonal therapy (e.g., as described in Psychol Addict Behav 2009; 23(1): 168-174), contingency management based therapy (e.g., as described in Psychol Addict Behav 2009; 23(1): 168-174; in J. Consul. Clin. Psychol. 2005; 73(2): 354-59; or in Case Reports in Psychiatry, Vol.
  • CBT cognitive behavioral therapy
  • disclosed formulations may be administered in conjunction with or as an adjunct to psychotherapy.
  • psychotherapy is neither necessitated nor desired, or no specific type of psychotherapy is necessitated or desired, however any of the disclosed methods can be used in combination with one or more psychotherapy sessions.
  • the flexibility to participate in specific therapies, as well as to choose between any such therapies (or to decide to forgo any specific therapy), while still receiving clinically significant therapeutic effects, is among the advantages of the invention.
  • a patient can participate in numerous other therapeutically beneficial activities, where such participation follows or is in conjunction with the administration of the composition, including breathing exercises, meditation and concentration practices, focusing on an object or mantra, listening to music, physical exercise, stretching or bodywork, journaling, grounding techniques, positive self-talk, or engaging with a pet or animal, and it should be understood that such participation can occur with or without the participation or guidance of a therapist.
  • breathing exercises, meditation and concentration practices focusing on an object or mantra, listening to music, physical exercise, stretching or bodywork, journaling, grounding techniques, positive self-talk, or engaging with a pet or animal, and it should be understood that such participation can occur with or without the participation or guidance of a therapist.
  • the GABAergic system is implicated in neurodegeneration; for example, imbalance between glutamate and GABA has been shown to decrease synaptic strength and hence lead to neurodegeneration, which may in turn contribute to the progression of neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis (Sood et al. JNR. 2021 ;99(12):3148-3189).
  • the disclosed A. muscaria formulations are used to treat a CNS disorder or neurodegenerative condition.
  • the disclosed A. muscaria formulations are used in the manufacture of a medicament to treat a CNS disorder or neurodegenerative condition.
  • muscaria formulations e.g., in a therapeutically effective amount, are administered to a subject having a CNS disorder or neurodegenerative condition to treat said CNS disorder or neurodegenerative condition.
  • a disclosed A. muscaria composition prevents or treats, such as alleviates, a CNS disorder or neurodegenerative condition mediated by viral infection.
  • Neurodegeneration may be assessed, e.g., by measuring markers of neuronal loss, such as cerebrospinal fluid markers, e.g., visinin-like protein 1 (VILIP-1), tau, and p-tau181 (Tarawneh et al., Neurol. 2015; 72(6): 656-665).
  • VILIP-1 visinin-like protein 1
  • tau tau
  • Methods for assessing cognitive decline e.g., comprehensive neuropsychological testing, are known to one of skill in the art. Exemplary cognitive evaluations include Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). See, e.g., Toh et al., Transl Neurodegener. 2014;3:15.
  • Cognitive decline and the progression of disease state may also be assessed using a condition-specific measure, e.g., the Unified Huntington’s Disease Rating Scale (UHDRS).
  • UHDRS Unified Huntington’s Disease
  • Neurodegenerative conditions such as diseases or disorders include, e.g., dementia, Alzheimer's disease, Huntington’s disease, multiple sclerosis, and Parkinson’s disease.
  • a feature of neurodegenerative conditions is neuronal cell death, which, among other aspects, has been implicated in the promotion of inflammation. See, e.g., Chan et al., Annu Rev Immunol. 2015; 33: 79-106 and Chi et al., Int J Mol Sci. 2018;19(10):3082.
  • Neurodegenerative diseases can be classified according to primary clinical features, e.g., dementia, parkinsonism, or motor neuron disease, anatomic distribution of neurodegeneration, e.g., frontotemporal degenerations, extrapyramidal disorders, or spinocerebellar degenerations, or principal molecular abnormality (Dugger & Dickson, Cold Spring Harb Perspect Biol. 2017;9(7):a028035. iii. Pain and Pain Disorders
  • disclosed formulations are used to treat a pain disorder.
  • disclosed formulations are administered, such as in a therapeutically effective amount, to a subject having a pain disorder, thereby treating said pain disorder.
  • the disclosed formulations when administered in a therapeutically effective amount, provide beneficial therapeutic effects for the treatment of a pain disorder.
  • a “pain disorder” refers to a class of medical conditions characterized by the experience of persistent or recurrent physical or psychological pain, either localized or widespread, that significantly impairs an individual's daily functioning and quality of life. These disorders may involve various etiologies, including but not limited to nociceptive, neuropathic, psychogenic, idiopathic or radicular origins.
  • a compound is used to treat neuropathic pain.
  • a compound is used to treat psychogenic pain.
  • a compound is used to treat idiopathic pain.
  • a compound is used to treat radicular pain.
  • Pain disorders may manifest as acute or chronic pain, and they can affect different parts of the body, such as musculoskeletal, neurological, gastrointestinal, or visceral systems. Pain can be expressed as including but not limited to, post-herpetic pain, trigeminal pain, occipital pain, or pudendal pain.
  • a disclosed formulation is used to treat pain associated with cancer or chemotherapy.
  • a disclosed formulation is used to treat arthritis, back pain, central pain, chronic fatigue syndrome, cluster headaches, migraine headaches, complex regional pain syndrome, compression mononeuropathy, diabetic neuropathy, fibromyalgia, focal neuropathy, herniated disc pain, or sciatica.
  • pain is assessed using the Pain, Consumment, and General Activity Scale (PEG), the Numeric Rating Scale (NRS), the Visual Analog Scale (VAS), Behavioral Pain Scale (BPS), and the Faces Pain Scale-Revised (FPS-R).
  • PEG Pain, Consumment, and General Activity Scale
  • NRS Numeric Rating Scale
  • VAS Visual Analog Scale
  • BPS Behavioral Pain Scale
  • FPS-R Pain Scale-Revised
  • the disclosed A muscaria formulations are used to treat inflammation or an inflammatory disorder.
  • the disclosed A. muscaria formulations are used in the manufacture of a medicament to treat an inflammatory disorder.
  • the disclosed A. muscaria formulations e.g., in a therapeutically effective amount, are administered to a subject having an inflammatory disorder to treat said pain disorder and/or said inflammatory disorder.
  • an inflammatory disorder is a disorder that causes acute inflammation, or that exhibits chronic inflammation as a symptom, including any of pressure ulcers, including acne vulgaris; oxalic acid/heartburn, age-related macular degeneration (AMD), allergies, allergic rhinitis, Alzheimer's disease, amyotrophic lateral sclerosis, Anemia, appendicitis, arteritis, arthritis, including osteoarthritis, rheumatoid arthritis, juvenile idiopathic arthritis, spondyloarthropathy such as ankylosing spondylitis, reactive arthritis (Reiter syndrome), psoriatic arthritis, enteroarthritis associated with inflammatory bowel disease, Whipple and Behcet's disease, septic arthritis, gout (also known as gouty arthritis, crystalline synovitis, metabolic arthritis), pseudogout (calcium pyrophosphate deposition disease), and Still's disease.
  • ASD age-related macular degeneration
  • Arthritis can affect a single joint (monoarthritis), two to four joints (oligoarthritis), or five or more joints (polyarthritis); asthma, atherosclerosis, autoimmune disorder, balanitis, blepharitis, bronchiolitis, bronchitis, bullous pemphigoid, burns, bursitis, cancer, incluiding NF-KB-induced inflammatory cancer; cardiovascular disease, including hypertension, endocarditis, myocarditis, heart valve dysfunction, congestive heart failure, myocardial infarction, diabetic heart abnormalities, vascular inflammation, including arteritis, phlebitis, and vasculitis; arterial occlusive disease, including arteriosclerosis and stenosis; inflammatory cardiac hypertrophy, peripheral arterial disease, aneurysm, embolism, incision, pseudoaneurysm, vascular malformation, vascular nevus, thrombosis, thrombophlebitis, varicose veins,
  • chronic inflammation includes tissue inflammation, e.g., skin inflammation, muscle inflammation, tendon inflammation, ligament inflammation, bone inflammation, cartilage inflammation, lung inflammation, heart inflammation, liver inflammation, pancreatic inflammation, kidney inflammation, bladder inflammation, gastric inflammation intestinal inflammation, neuroinflammation, and brain inflammation.
  • tissue inflammation e.g., skin inflammation, muscle inflammation, tendon inflammation, ligament inflammation, bone inflammation, cartilage inflammation, lung inflammation, heart inflammation, liver inflammation, pancreatic inflammation, kidney inflammation, bladder inflammation, gastric inflammation intestinal inflammation, neuroinflammation, and brain inflammation.
  • the disclosed A. muscaria formulations are used to reduce inflammation.
  • the disclosed A. muscaria formulations are used in the manufacture of a medicament to reduce inflammation.
  • the disclosed A. muscaria formulations e.g., in a therapeutically effective amount, are administered to a subject to reduce inflammation.
  • a reduction in inflammation may be measured according to various methods available to one of skill.
  • Inflammatory biomarkers may be detected from biological specimens, for example, a subject’s blood, such as plasma or serum, or saliva.
  • inflammation may be detected by measuring high-sensitivity C-reactive protein (CRP) and white blood cell count from a blood test.
  • CRP may also be detected in a saliva sample.
  • Salivary CRP is not synthesized locally in the mouth and may reflect more systemic levels of inflammation compared to other inflammatory biomarkers, such as cytokines (Szabo & Slavish, Psychoneuroendocrinology. 202; 124: 105069).
  • clinical pathology data e.g., hematology data on erythrocyte parameters, platelet count, total number of leukocytes, and leukocyte differentials and morphology, coagulation data on clotting times and fibrinogen, and clinical chemistry data on total protein, albumin and globulin, liver enzymes, renal parameters, electrolytes, and bilirubin can provide an initial indication of the presence and potentially the location of inflammation, in the absence of specific data on immune tissues. See, e.g., Germolec et al., Methods Mol Biol. 2018;1803:57-79 and Luo et al., Clin Lab. 2019 1;65(3). v. Sleep Disorders
  • the disclosed A muscaria formulations are used to treat a sleep disorder.
  • the disclosed A muscaria formulations are used in the manufacture of a medicament to treat a sleep disorder.
  • the disclosed A. muscaria formulations e.g., in a therapeutically effective amount, are administered to a subject having a sleep disorder to treat said sleep disorder.
  • the sleep disorder may or may not be comorbid with one or more mental health disorders.
  • DSCAD Diagnostic Classification of Sleep and Arousal Disorders
  • sleep disorders broadly into nine categories: (1) psychophysiological insomnia; (2) sleep disorders associated with mental disorders; (3) sleep disorders associated with a regular use of drugs and alcohol; (4) insomnias associated with sleep-induced breathing disorders; (5) sleep disorders associated with nocturnal myoclonus and restless legs syndrome (RLS); (6) sleep disorders by other disorders, drugs, and environmental conditions; (7) childhood onset insomnias; (8) other types of insomnia; and (9) sleep abnormalities with no symptoms of insomnia.
  • RLS nocturnal myoclonus and restless legs syndrome
  • sleep disorders by other disorders, drugs, and environmental conditions (7) childhood onset insomnias; (8) other types of insomnia; and (9) sleep abnormalities with no symptoms of insomnia.
  • Each of these categories is based on the state of disorder.
  • the International Classification of Sleep Disorders classifies sleep disorders broadly into four categories: (1) dyssomnias comprising disorders that are primarily disorders of sleep per se [for example, intrinsic sleep disorders such as narcolepsy, extrinsic sleep disorders, and circadian rhythm sleep disorders]; (2) parasomnias comprising disorders of abnormal behaviors that occur during sleep (also known as abnormal behavior during sleep) [arousal disorders, sleep-wake transition disorders, parasomnias usually associated with REM sleep, and other parasomnias]; (3) sleep disorders associated with medical/psychiatric disorders [sleep disorders associated with mental disorders, sleep disorders associated with neurologic disorders, and sleep disorders associated with other medical disorders]; and (4) proposed sleep disorders , for example, short sleeper, long sleeper, subwakefulness syndrome, and the like. To this date, this classification includes about 90 categories of sleep disorders. Currently, further classifications have been made continuously based on etiology.
  • sleep disorders are classified into (1) nonorganic sleep disorders (F51 : for example, nonorganic insomnia, nonorganic hypersomnia, sleep walking, sleep terrors, nonorganic disorder of the sleep-wake schedule, nightmares, and the like); (2) sleep disorders [G47: for example, sleep apnoea, disorders of initiating and maintaining sleep (insomnias), disorders of excessive somnolence (hypersomnia), cataplexy, narcolepsy, cataplexy attacks, disorders of the sleep-wake schedule (such as irregular sleep pattern, sleep rhythm disorder, and delayed sleep phase syndrome), and the like]; (3) other respiratory conditions originating in the perinatal period (P28: for example, primary sleep apnoea of newborn, and the like); and (4) personal history of risk-factors, not elsewhere classified (Z91 : e.g., personal history of unhealthy sleep-
  • sleep disorders are classified into the following symptoms: (1) insomnia (disorders falling asleep, difficulty staying asleep, or a disturbance in sleep patterns that causes inadequate sleep, and the like; for example, sleep-onset insomnia (difficulty falling asleep), early morning awakening, sleep-wake reversals, rebound insomnia, and the like); (2) hypersomnia (defined as a pathological increase of at least 25% in total sleeping time; for example, narcolepsy, sudden episode of sleep, and the like); (3) sleep apnoea syndromes, parasomnias (based on patients' chief complaints); and the like.
  • insomnia disorders falling asleep, difficulty staying asleep, or a disturbance in sleep patterns that causes inadequate sleep, and the like
  • hypersomnia defined as a pathological increase of at least 25% in total sleeping time; for example, narcolepsy, sudden episode of sleep, and the like
  • sleep apnoea syndromes parasomnias (based on patients' chief complaints); and the like.
  • sleep disorders are often broadly classified into (1) insomnias, (2) hypersomnia, (3) parasomnias, and (4) disorders of sleep-wake schedule (corresponding to the circadian rhythm sleep disorders of ICSD), made symptomatically based on patients’ chief complaints, separately from the international classifications described above.
  • the sleep disorder is any of an insomnia, a hypersomnia, a parasomnia, and a disorder of sleep-wake schedule.
  • the disclosed A. muscaria formulations are used to treat sleep disorders such as, but not limited to, insomnia disorders, sleep-related breathing disorders, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, sleep-related movement disorders, parasomnias, non-24-hour sleep wake disorder, excessive daytime sleepiness, shift work disorder, and others.
  • sleep disorders such as, but not limited to, insomnia disorders, sleep-related breathing disorders, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, sleep-related movement disorders, parasomnias, non-24-hour sleep wake disorder, excessive daytime sleepiness, shift work disorder, and others.
  • the sleep disorder is insomnia.
  • the disclosed A. muscaria formulations are used to treat insomnia.
  • the disclosed A. muscaria formulations are used in the manufacture of a medicament to treat insomnia.
  • insomnia is defined as a persistent difficulty with sleep initiation, duration, consolidation, or quality, by the ICSD-3 manual.
  • Chronic insomnia is characterized by persistent insomnia that occurs at least three times per week for at least three months, while the same symptoms for less than three months is termed short-term insomnia.
  • insomnia Regardless of whether an individual is diagnosed with chronic, or short-term insomnia, most instances of the disorder present as either sleep-onset insomnia, or sleep maintenance insomnia, wherein the former is characterized by a difficulty falling asleep, while those suffering with the latter experience trouble staying asleep. Criteria for diagnosing insomnia include (1) a report of sleep initiation or maintenance problems, (2) adequate opportunity and circumstances to sleep, and (3) daytime consequences (Sateia, Chest. 2014;146(5):1387-1394).
  • insomnia There are multiple factors that may cause, or exasperate symptoms of insomnia; however, stress and anxiety are each significant contributing factors.
  • a disclosed formulation is used to treat a sleep-wake disorder.
  • sleep-wake disorders are associated with difficulty initiating or maintaining sleep (e.g., insomnia), excessive sleepiness (e.g., hypersomnolence disorders), respiratory disturbance during sleep (e.g., sleep-related breathing disorders (SRBDs), such as obstructive sleep apnea (OSA), central sleep apnea (CSA), sleep-related hypoventilation disorders, sleep-related hypoxemia disorder, snoring, catathrenia, Cheyne-Stokes breathing, and sleep-disordered breathing), disorders of the sleep-wake schedule (e.g., circadian rhythm sleep-wake disorders), abnormal movements during sleep, or problematic behavioral or psychological events that occur while falling asleep, during sleep, or upon arousal from sleep (e.g., parasomnia disorders).
  • a disclosed formulation is used to treat an insomnia disorder, a hypersomnolence disorder, a
  • the disclosed A. muscaria formulations are used to treat a circadian rhythm sleep-wake disorder.
  • the disclosed A. muscaria formulations are used in the manufacture of a medicament to treat a circadian rhythm sleep-wake disorder. Delayed sleep-wake phase disorder, advanced sleep-wake phase disorder, irregular sleep-wake rhythm disorder, non-24-h sleep-wake rhythm disorder, shift work disorder, and jet lag disorder are all classified as circadian rhythm sleep-wake disorders.
  • Such disorders are diagnosed with the following criteria: (1) a chronic or recurrent pattern of sleep-wake rhythm disruption primarily caused by an alteration in the endogenous circadian timing system or misalignment between the endogenous circadian rhythm and the sleep-wake schedule desired or required, (2) a sleep-wake disturbance (ie, insomnia or excessive sleepiness, and (3) associated distress or impairment (Sateia, Chest. 2014; 146(5): 1387-1394)
  • Non-24-Hour Sleep Wake disorder refers to a condition wherein an individual’s natural circadian rhythm is shorter or (more commonly) longer than 24 hours (Pacheco, Sleep Foundation, “Non-24-Hour Sleep Wake Disorder,” 2022). This causes such individuals to struggle with fluctuations in appetite, mood, and alertness that— hile following their body’s internal clock— is generally at odds with rising and setting of the sun. When heavily desynchronized, individuals with N24SWD exhibit a natural preference for sleeping during the day, and experience difficulty sleeping at night. [303] In some embodiments, the disclosed A. muscaria formulations are used to treat shiftwork disorder.
  • the disclosed A muscaria formulations are used in the manufacture of a medicament to treat shift work disorder.
  • Shift work disorder is generally caused by an activity (e.g., an obligatory obligation like work, as the name suggests) that forces an individual to stay awake when they would ordinarily be asleep. This causes individuals to lose, on average, between 1-4 hours of sleep each day, leading to lethargy, mood swings, low testosterone, and negatively impacting the ability to function while attempting to accomplish day-to-day tasks (Pacheco, Sleep Foundation, “Diagnosing Shift work Disorder,” 2022).
  • the disclosed A. muscaria formulations are used to treat excessive daytime sleepiness.
  • the disclosed A muscaria formulations are used in the manufacture of a medicament to treat excessive daytime sleepiness.
  • excessive daytime sleepiness is characterized by abnormal levels of drowsiness during the day, and a desire to sleep (Pacheco, American Sleep Association, “Excessive Daytime Sleepiness: Causes, Test and Treatments,” 2022).
  • Excessive daytime sleepiness may be caused by a combination of complex factors, but is generally due to a chronic lack of sleep, or fragmented, poor-quality sleep.
  • Poor sleep quality is known to contribute to a wide range of diseases, including mental health conditions, neurological disorders, neurodegenerative diseases, and cardiovascular diseases.
  • diseases including mental health conditions, neurological disorders, neurodegenerative diseases, and cardiovascular diseases.
  • disclosed formulations are useful in the treatment of such conditions (which are described in further detail in various embodiments herein) through a mechanism in which improving sleep quality in an individual, whether ot not said individual has been diagnosed with a sleep disorder, treats a concomitant medical condition that is associated with poor sleep quality.
  • improving sleep quality in an individual through the use of disclosed vaporizer formulations is useful in the treatment of asthma, diabetes, heart attack, stroke, or cancer.
  • the GABAergic system is implicated in immune cell functions, inflammatory conditions and diseases in peripheral tissues, and hence GABA agonists may be promising drugs for a variety of immune-mediated medical conditions (Barragan et al. Acta. Physiol. 2015;213(4):819-827).
  • the disclosed A. muscaria formulations are used to treat an immune disorder.
  • the disclosed A muscaria formulations are used in the manufacture of a medicament to treat an immune disorder.
  • the disclosed A muscaria formulations e.g., in a therapeutically effective amount, are administered to a subject having an immune disorder to treat said immune disorder.
  • Autoimmune diseases can be divided into systemic and organ-specific autoimmune disorders according to the main clinical and pathological characteristics of each disease.
  • immune disorders include disorders characterized by deregulation of Toll-like receptor signaling and/or type I interferon-mediated immunity.
  • the immune disorder is any of acne vulgaris, acute respiratory distress syndrome, Addison's disease, adrenocortical insufficiency, adrenogenital syndrome, allergic conjunctivitis, allergic rhinitis, allergic intraocular inflammatory diseases, ANCA-associated small-vessel vasculitis, angioedema, ankylosing spondylitis, aphthous stomatitis, arthritis, asthma, atherosclerosis, atopic dermatitis, Behcet's disease, Bell's palsy, berylliosis, bronchial asthma, bullous herpetiformis dermatitis, bullous pemphigoid, carditis, celiac disease, cerebral ischaemia, chronic obstructive pulmonary disease, cirrhosis, Cogan's syndrome,
  • the immune disorder is an autoimmune disorder.
  • an autoimmune disorder is any of acute disseminated encephalomyelitis (ADEM), Addison disease, allergy or hypersensitivity, amyotrophic lateral sclerosis, antiphospholipid antibody syndrome (APS), arthritis, autoimmune disease, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune inner ear disease, autoimmune pancreatitis, bullous pemphigoid, celiac disease, Chagas disease, chronic obstructive pulmonary disease (COPD), type 1 diabetes (T1 D), endometriosis, fibromyalgia, goodpasture's syndrome, Graves' disease, Guillain-Barre syndrome (GBS), Hashimoto's thyroiditis, suppurative spondylitis, idiopathic thrombocytopenic purpura, inflammatory bowel disease, interstitial cystitis, lupus, including discoid lupus ery
  • the disclosed A. muscaria formulations are used to treat a sexual disorder, such as a disorder characterized by sexual dysfunction.
  • the disclosed A. muscaria formulations are used in the manufacture of a medicament to treat a sexual disorder, such as a disorder characterized by sexual dysfunction.
  • muscaria formulations e.g., in a therapeutically effective amount, are administered to a subject having a sexual disorder to treat said sexual disorder.
  • sexual dysfunctions can be defined as syndromes wherein a subject may have difficulty experiencing personally satisfying, non-coercive sexual activities.
  • a disclosed formulation is used to treat hypoactive sexual desire dysfunction, sexual arousal dysfunction, orgasmic dysfunction, ejaculatory dysfunction, or sexual dysfunction associated with pelvic organ prolapse.
  • the sexual disorder is delayed ejaculation and erectile disorder.
  • the sexual disorder is female orgasmic disorder.
  • the sexual disorder is female sexual interest or arousal disorder.
  • the sexual disorder is genito-pelvic pain/penetration disorder.
  • the sexual disorder is female hypoactive sexual desire disorder.
  • the sexual disorder is male hypoactive sexual desire disorder.
  • the sexual disorder is premature ejaculation.
  • the sexual disorder is substance/medication-induced sexual dysfunction.
  • sexual function is assessed by evaluating, for example determining improvements in, one or more of sexual desire, sexual aversion, sexual enjoyment, sexual drive, genital response, such as vaginal dryness/impotence and male erectile disorder, orgasm disorders, such as orgasmic dysfunction and premature ejaculation, disorders of sexual pain, such as dyspareunia and vaginismus, and other forms of dysfunction.
  • genital response such as vaginal dryness/impotence and male erectile disorder
  • orgasm disorders such as orgasmic dysfunction and premature ejaculation
  • disorders of sexual pain such as dyspareunia and vaginismus, and other forms of dysfunction.
  • the autoimmune disorder is a systemic autoimmune disorder, such as systemic lupus erythematosus (SLE), Sjogren's syndrome, scleroderma, rheumatoid arthritis, and polymyositis.
  • the autoimmune disorder is a local autoimmune disorder, including those of the endocrine system, including type 1 diabetes, Hashimoto's thyroiditis, and Addison’s disease; the cutaneous, including pemphigus vulgaris; the blood, including autoimmune hemolytic anemia; and the nervous system, including multiple sclerosis.
  • Example 20 Administration of a disclosed vaporizable formulation to enhance calmness
  • An individual is administered or self-administers in a single day a suitable amount of a disclosed vaporizable formulation comprising an Amanita muscaria extract.
  • the formulation is administered by inhalation, for example using a vaporizer device as disclosed herein or otherwise known in the art.
  • Example 21 Administration of disclosed vaporizable formulation to reduce muscle tension
  • An individual is administered or self-administers in a single day a suitable amount of a disclosed vaporizable formulation comprising an Amanita muscaria extract.
  • the formulation is administered by inhalation, for example using a vaporizer device as disclosed herein or otherwise known in the art.
  • the individual experiences reduced muscle tension compared to the level of muscle tension experienced prior to administration of the formulation, as measured by, e.g., an assessment completed by the individual prior to, and after such application.
  • an individual may rate their muscle tension on a scale of 0-10 prior to, and after administering the formulation, wherein “0” represents an absence of muscle tension, and “10” represents severe muscle tension that restricts movement.
  • administration of the formulation will result in a reduced muscle tension rating.
  • an individual may measure their range of motion prior to, and after administering the formulation. In such an example, the individual will experience increased range of motion after administering the formulation.
  • Example 22 Administration of a disclosed vaporizable formulation to reduce insomnia
  • An individual is administered or self-administers in a single day a suitable amount of a disclosed vaporizable formulation comprising an Amanita muscaria extract.
  • the formulation is administered by inhalation, for example using a vaporizer device as disclosed herein or otherwise known in the art.
  • the individual will experience the ability to, for example, fall asleep faster, stay asleep longer once asleep, and awake feeling more restful. This may be measured by, for example, a sleep assessment completed without ingesting, and after ingesting the beverage powder or ready to drink beverage.
  • Example assessments include, for example, the insomnia severity index. In such an example, the Insomnia Severity Index Insomnia severity index - ons.org) will decrease in score after ingesting the A. muscaria formulation.
  • Example 23 Administration of a disclosed vaporizable formulation to treat a medical condition
  • An individual is administered or self-administers in a single day a suitable amount of a disclosed vaporizable formulation comprising an Amanita muscaria extract.
  • the formulation is administered by inhalation, for example using a vaporizer device as disclosed herein or otherwise known in the art.
  • the medical condition is a mental, behavioral, or neurodevelopmental disorder.
  • the mental, behavioral, or neurodevelopmental disorder is a disorder as disclosed herein.

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Abstract

L'invention concerne des formulations de vaporisateur comprenant un matériau fongique provenant d'amanite tue-mouche et/ou un extrait de celle-ci, ainsi que des dispositifs les comprenant. L'invention concerne également des procédés d'utilisation des formulations et des dispositifs divulgués pour moduler la transmission synaptique, améliorer la santé mentale et physique et le bien-être, et traiter des affections médicales.
PCT/IB2023/057813 2022-08-01 2023-08-01 Formulations et dispositifs de vaporisateur d'amanite tue-mouche WO2024028779A1 (fr)

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Citations (4)

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WO2021003467A1 (fr) * 2019-07-04 2021-01-07 Sw Holdings, Inc. Compositions de dosage et procédés d'utilisation de composés psychédéliques
CA3200255A1 (fr) * 2020-12-16 2022-06-23 Andrew R. Chadeayne Composes d'amanite tue-mouche
WO2022187974A1 (fr) * 2021-03-12 2022-09-15 Psyched Wellness Ltd. Procédés d'extraction de muscimol à partir d'amanita muscaria

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US20140000408A1 (en) * 2012-06-27 2014-01-02 Denso Corporation Accelerator apparatus for vehicle
WO2021003467A1 (fr) * 2019-07-04 2021-01-07 Sw Holdings, Inc. Compositions de dosage et procédés d'utilisation de composés psychédéliques
CA3200255A1 (fr) * 2020-12-16 2022-06-23 Andrew R. Chadeayne Composes d'amanite tue-mouche
WO2022187974A1 (fr) * 2021-03-12 2022-09-15 Psyched Wellness Ltd. Procédés d'extraction de muscimol à partir d'amanita muscaria

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KONDEVA-BURDINA MAGDALENA; VOYNOVA MARIA; SHKONDROV ALEKSANDAR; ALUANI DENITSA; TZANKOVA VIRGINIA; KRASTEVA ILINA: "Effects of Amanita muscaria extract on different in vitro neurotoxicity models at sub-cellular and cellular levels", FOOD AND CHEMICAL TOXICOLOGY, PERGAMON, GB, vol. 132, 17 July 2019 (2019-07-17), GB , XP085785681, ISSN: 0278-6915, DOI: 10.1016/j.fct.2019.110687 *
STEPHANIE PRICE: "Preliminary data demonstrate neuroprotective properties of amanita extract", 25 March 2022 (2022-03-25), XP093137357, Retrieved from the Internet <URL:https://psychedelichealth.co.uk/2022/03/25/data-neuroprotective-properties-amanita-extract/> [retrieved on 20240304] *
TSUNODA KOUJUN, INOUE NORIKO, AOYAGI YASUO, SUGAHARA TATSUYUKI: "Simultaneous Analysis of Ibotenic Acid and Muscimol in Toxic Mushroom, Amanita muscaria, and Analytical Survey on Edible Mushrooms", SHOKUHIN EISEIGAKU ZASSHI = JOURNAL OF THE FOOD HYGIENIC SOCIETY OF JAPAN, NIHON SHOKUHIN EISEI GAKKAI, JP, vol. 34, no. 1, 1 January 1993 (1993-01-01), JP , pages 12 - 17_1, XP093137354, ISSN: 0015-6426, DOI: 10.3358/shokueishi.34.12 *
VOYNOVA MARIA, SHKONDROV ALEKSANDAR, KONDEVA-BURDINA MAGDALENA, KRASTEVA ILINA: "Toxicological and pharmacological profile of Amanita muscaria (L.) Lam. – a new rising opportunity for biomedicine", FARMATSIA, INFORMATION CENTER, SOFIA, BULGARIA, vol. 67, no. 4, Bulgaria , pages 317 - 323, XP093137351, ISSN: 0428-0296, DOI: 10.3897/pharmacia.67.e56112 *

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