CA3101765A1 - Psychoactive alkaloid extraction and composition with controlled dephosphorylation - Google Patents

Psychoactive alkaloid extraction and composition with controlled dephosphorylation Download PDF

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Publication number
CA3101765A1
CA3101765A1 CA3101765A CA3101765A CA3101765A1 CA 3101765 A1 CA3101765 A1 CA 3101765A1 CA 3101765 A CA3101765 A CA 3101765A CA 3101765 A CA3101765 A CA 3101765A CA 3101765 A1 CA3101765 A1 CA 3101765A1
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Prior art keywords
psychoactive
alkaloid
psychoactive alkaloid
dephosphorylated
phosphorylated
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CA3101765A
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French (fr)
Inventor
Ryan Moss
Benjamin Lightburn
Lisa Ranken
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Psilo Scientific Ltd
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Psilo Scientific Ltd
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Priority to CA3101765A priority Critical patent/CA3101765A1/en
Priority to CA3169140A priority patent/CA3169140A1/en
Priority to IL299453A priority patent/IL299453A/en
Priority to MX2022016533A priority patent/MX2022016533A/en
Priority to IL299449A priority patent/IL299449A/en
Priority to IL299451A priority patent/IL299451A/en
Priority to IL299448A priority patent/IL299448A/en
Priority to IL297791A priority patent/IL297791A/en
Priority to IL299450A priority patent/IL299450A/en
Priority to CA3137016A priority patent/CA3137016C/en
Priority to IL298561A priority patent/IL298561A/en
Priority to IL299452A priority patent/IL299452A/en
Priority to PCT/CA2021/050813 priority patent/WO2021253116A1/en
Priority to EP21825817.6A priority patent/EP4161546A1/en
Priority to AU2021290454A priority patent/AU2021290454B2/en
Priority to IL305632A priority patent/IL305632A/en
Priority to BR112022025780A priority patent/BR112022025780A2/en
Priority to CA3173030A priority patent/CA3173030A1/en
Priority to US17/348,697 priority patent/US11331357B2/en
Priority to US17/483,601 priority patent/US11298388B2/en
Priority to US17/587,731 priority patent/US11510952B2/en
Priority to US17/697,798 priority patent/US11571450B2/en
Priority to US17/702,701 priority patent/US11642385B2/en
Publication of CA3101765A1 publication Critical patent/CA3101765A1/en
Priority to AU2022291416A priority patent/AU2022291416B2/en
Priority to AU2022291413A priority patent/AU2022291413B2/en
Priority to AU2022291414A priority patent/AU2022291414B2/en
Priority to AU2022291411A priority patent/AU2022291411B2/en
Priority to AU2022291410A priority patent/AU2022291410B2/en
Priority to AU2023285751A priority patent/AU2023285751A1/en
Pending legal-status Critical Current

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    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
    • C07D209/16—Tryptamines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine

Abstract

A process for obtaining a psychoactive alkaloid extract with a desired amount of a phosphorylated psychoactive alkaloid and a desired amount of a dephosphorylated psychoactive alkaloid. Extraction is carried out with a strong acid or strong base to either promote or inhibit dephosphorylation. The extract in the slurry form is standardized with added excipient so that when it is dried the powdered composition has a specified total psychoactive alkaloid concentration, with a known ratio of phosphorylated to dephosphorylated psychoactive alkaloids. Compositions have a desired amount of a phosphorylated psychoactive alkaloid and a desired amount of a dephosphorylated psychoactive alkaloid. Phosphorylated compositions and dephosphorylated compositions are mixed to provide compositions with any specific ratio of phosphorylated to dephosphorylated psychoactive alkaloid.

Description

PSYCHOACTIVE ALKALOID EXTRACTION AND COMPOSITION WITH CONTROLLED
DEPHOSPHORYLATION
TECHNICAL FIELD
[0001] This application relates to a process of obtaining psychoactive alkaloid extracts. More specifically, the present invention relates to controlling dephosphorylation during extraction. Further, the present invention relates to psychoactive alkaloid compositions with controlled dephosphorylation.
BACKGROUND
[0002] A psychoactive substance is a chemical substance that changes brain function and results in alterations in perception, mood, consciousness, cognition, or behavior. The psychoactivity of these substances may include sedative, stimulant, euphoric, deliriant, and hallucinogenic effects. These substances have been used recreationally, to purposefully improve performance or alter one's consciousness, as entheogens for ritual, spiritual, or shamanic purposes. Some categories of psychoactive compounds have also shown therapeutic values and are prescribed by physicians and other healthcare practitioners.
[0003] The active constituents of the majority of psychoactive plants, fungi, animals, or yeasts fall within a class of basic, naturally occurring, nitrogen-containing, organic compounds called alkaloids (e.g. nicotine, morphine, cocaine, mescaline, caffeine, ephedrine, psilocin). Alkaloids have a wide range of pharmacological activities including antimalarial, antiasthma, anticancer, cholinomimetic, vasodilatory, antiarrhythmic, analgesic, antibacterial, and antihyperglycemic activities. Many alkaloids have found use in traditional or modern medicine, or as starting points for drug discovery.
Recently, psychotropic and stimulant activities of psychoactive alkaloids have been gaining interest from researchers as therapeutic agents for treating various conditions such as alcoholism, opioid addiction and pain to name a few.
[0004] Psychoactive alkaloids present in natural sources can be broadly divided into two categories, which are phosphorylated psychoactive alkaloids and dephosphorylated Date Recue/Date Received 2020-12-04 psychoactive alkaloids, although other non-phosphorylatable psychoactive alkaloids may also be present.
[0005] Phosphorylated psychoactive alkaloids are phosphoric acid esters of dephosphorylated psychoactive alkaloids. For example psilocybin is a phosphoric acid ester of psilocin, at the 4th position. Phosphorylated psychoactive alkaloids are biosynthesized in natural sources. Dephosphorylated psychoactive alkaloids are the bioactive forms that are converted from phosphorylated alkaloids, through phosphatase action or chemical hydrolysis, and released when the natural source is damaged, harvested, or eaten. Because of this phenomenon, phosphorylated psychoactive alkaloids are often either partially or entirely converted to dephosphorylated psychoactive alkaloids during the alkaloid extraction process, which involves harvesting as a necessary prior step.
[0006] Although the dephosphorylated psychoactive alkaloids are the bioactive form of their counterpart phosphorylated psychoactive alkaloids, dephosphorylated psychoactive alkaloids are easily degraded into non-bioactive compounds in the presence of light, heat, and oxygen. For example, oxidation of psilocin, the dephosphorylated counterpart to psilocybin, a phosphorylated alkaloid produced by biological synthesis in mushrooms, begins rapidly when exposed to air, especially in solution, and heat increases the oxidation rate. From our own data, the oxidation of psilocin in a moist and/or high light environment begins immediately, leading to about 10% decay within 30 minutes, 25%
after 5 hours, and 40-60% at 20 hours when shielded from light. Due to this instability of the dephosphorylated psychoactive alkaloids, the bioactivity of the psychoactive alkaloid extracts may also be unstable over time.
[0007] Extracts or compositions with an active ingredient made from natural sources generally have increased consumer acceptance and lower cost of production compared to synthetic compositions. There may be potential benefits of multiple natural compounds working synergistically, colloquially known as the "entourage" or "halo"
effect. However, the availability of psychoactive alkaloid compositions with a desired specific psychoactive alkaloid content is a major challenge faced by researchers. The variability in the content of the psychoactive alkaloids extracted from their natural sources is a hurdle in trying to Date Recue/Date Received 2020-12-04 avoid variability in the psychoactive alkaloid concentration in extracted compositions. It is even more challenging to produce consistent formulations when the concentration of active ingredients being extracted is typically very low in the natural source. Maintaining physical and chemical stability is also an issue with these compositions.
Extracts or compositions containing psychoactive alkaloids are often not amenable to drying, processing (due to poor flowability), or packaging methods such as tabulation or encapsulation.
[0008] This background information is provided to reveal information believed by the applicant to be of possible relevance to the present invention. No admission is necessarily intended, nor should be construed, that any of the preceding information constitutes prior art against the present invention.
SUMMARY OF INVENTION
[0009] The inventors have realized that there are occasions where it would be beneficial to control, either by halting or promoting, the conversion of phosphorylated alkaloids such as psilocybin during extraction and any subsequent purification process.
For example, there may be occasions where extracts with phosphorylated psychoactive alkaloids as the only or majority of the total psychoactive alkaloid in the extract are required. Likewise, there may be occasions where extracts with dephosphorylated psychoactive alkaloids as the only or majority of the total psychoactive alkaloid in the extract are required.
[0010] For example, the alkaloid in the psychoactive extract may be entirely psilocin, resulting from promotion of the conversion, or all or mostly psilocybin, from the halting or inhibition of the conversion. There will likely, but not necessarily, be some psilocin present in the process where the conversion is halted, as the harvesting of the mushrooms can often cause unavoidable conversion into psilocin.
[0011] Controlling the promotion or inhibition of dephosphorylation of the aforementioned alkaloids to result in a psychoactive alkaloid extract with a specific desired content of both phosphorylated and dephosphorylated psychoactive alkaloid has Date Recue/Date Received 2020-12-04 not been seen in the industry or academia to date. Likewise, compositions resulting from such control have not yet been seen.
[0012] Thus, there is a need in the art of a process for controlling the dephosphorylation of the aforementioned alkaloids to result in a psychoactive alkaloid extract with specific desired amounts of phosphorylated and dephosphorylated psychoactive alkaloid. Also required in the art is a psychoactive alkaloid composition having an accurate psychoactive alkaloid content, with specific desired amounts of phosphorylated and dephosphorylated psychoactive alkaloid.
[0013] Disclosed herein is a process for obtaining a psychoactive alkaloid extract with a desired amount of a phosphorylated psychoactive alkaloid and a desired amount of a dephosphorylated psychoactive alkaloid, the process comprising: drying and pulverizing a psychoactive alkaloid source to obtain a dried powdered biomass; extracting a psychoactive alkaloid from the dried powdered biomass with an acidified solvent or a basified solvent to obtain a psychoactive alkaloid liquid with a specific pH, wherein the specific pH is lower than 3.5 or greater than 10.5; adjusting the pH of the psychoactive alkaloid liquid to a pH ranging from 3.5-4.5; and evaporating the solvent from the psychoactive alkaloid liquid to obtain the psychoactive alkaloid extract with the desired amount of the phosphorylated psychoactive alkaloid and the desired amount of the dephosphorylated psychoactive alkaloid; wherein: the desired amount of the phosphorylated psychoactive alkaloid is 0-100% by weight of a total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract; and the desired amount of the dephosphorylated psychoactive alkaloid is the remainder of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract.
[0014] Also disclosed is a process for obtaining a psychoactive alkaloid composition with a specific ratio of a phosphorylated psychoactive alkaloid to a dephosphorylated psychoactive alkaloid, the process comprising: extracting a psychoactive alkaloid from a dried powdered biomass with a basified solvent to obtain a psychoactive alkaloid liquid with a pH greater than 10.5, wherein a majority of a total phosphorylatable psychoactive alkaloid content is the phosphorylated alkaloid and a remainder thereof is the dephosphorylated alkaloid; adjusting the pH of the psychoactive alkaloid liquid to a pH

Date Recue/Date Received 2020-12-04 ranging from 3.5-4.5; extracting another psychoactive alkaloid from another dried powdered biomass with an acidified solvent to obtain another psychoactive alkaloid liquid with a pH lower than 3.5, wherein all of a total phosphorylatable psychoactive alkaloid is the dephosphorylated alkaloid; adjusting the pH of the other psychoactive alkaloid liquid to a pH ranging from 3.5-4.5; evaporating a portion of the basified solvent from the psychoactive alkaloid liquid and a portion of the acidified solvent from the other psychoactive alkaloid liquid to obtain a psychoactive alkaloid extract slurry and another psychoactive alkaloid extract slurry respectively; mixing measured portions of the psychoactive alkaloid extract slurry and the other psychoactive alkaloid extract slurry to obtain a bulk psychoactive alkaloid extract slurry comprising the phosphorylated psychoactive alkaloid and the dephosphorylated psychoactive alkaloid in the specific ratio;
standardizing the bulk psychoactive alkaloid extract slurry by adding thereto a measured quantity of one or more excipients to obtain a standardized bulk slurry; and drying the standardized bulk psychoactive alkaloid slurry to obtain the psychoactive alkaloid composition, wherein the phosphorylated psychoactive alkaloid and the dephosphorylated psychoactive alkaloid are in the specific ratio; wherein the specific ratio of phosphorylated psychoactive alkaloid to dephosphorylated psychoactive alkaloid ranges from 1:1000 to 1000:1.
[0015] Further disclosed is a psychoactive alkaloid composition comprising:
a psychoactive alkaloid extract comprising a desired amount of a phosphorylated psychoactive alkaloid and a desired amount of a dephosphorylated psychoactive alkaloid, wherein: the desired amount of the phosphorylated psychoactive alkaloid is 0-100% by weight of a total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract, and the desired amount of the dephosphorylated psychoactive alkaloid is the remainder of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract; and one or more excipients.
[0016] Still further disclosed is a psychoactive alkaloid composition with a specific ratio of a phosphorylated psychoactive alkaloid and a dephosphorylated psychoactive alkaloid, the composition comprising: a psychoactive alkaloid extract having a total phosphorylatable psychoactive alkaloid content of 100% of a phosphorylated Date Recue/Date Received 2020-12-04 psychoactive alkaloid; another psychoactive alkaloid extract having a total phosphorylatable psychoactive alkaloid content of 100% of a dephosphorylated psychoactive alkaloid; and one or more excipients; wherein the psychoactive alkaloid extract and the other psychoactive alkaloid extract are present in a proportion such that the specific ratio of phosphorylated psychoactive alkaloid to phosphorylated psychoactive alkaloid ranges from 1:1000 to 1000:1.
[0017] This summary does not necessarily describe all features of the invention.
BRIEF DESCRIPTION OF DRAWINGS
[0018] The following drawings illustrate embodiments of the invention, which should not be construed as restricting the scope of the invention in any way.
[0019] FIG. 1 illustrates the key steps of a process for obtaining a psychoactive alkaloid extract with dephosphorylation control, according to an embodiment of the present invention.
[0020] FIG. 2 illustrates in detailed steps of a process for obtaining a psychoactive alkaloid extract with dephosphorylation control, according to an embodiment of the present invention.
[0021] FIG. 3 illustrates a process for standardizing a psychoactive alkaloid extract to obtain a standardized psychoactive alkaloid extract.
[0022] FIG. 4 illustrates a process for obtaining a psychoactive alkaloid composition with a specific ratio of a phosphorylated psychoactive alkaloid to a dephosphorylated psychoactive alkaloid, according to an embodiment of the present invention.
[0023] FIG. 5 illustrates detailed steps of a process for obtaining a psychoactive alkaloid composition with a specific ratio of a phosphorylated psychoactive alkaloid to a dephosphorylated psychoactive alkaloid, according to another embodiment of the present invention.
[0024] FIG. 6 illustrates a schematic diagram of the apparatus used for obtaining a psychoactive alkaloid extract and standardizing the same to result in a standardized psychoactive alkaloid extract, according to an embodiment of the present invention.

Date Recue/Date Received 2020-12-04 DESCRIPTION
A. GLOSSARY
[0025] To facilitate the understanding of this invention, a number of terms are defined below. Terms defined herein have meanings as commonly understood by a person of ordinary skill in the areas relevant to the present invention. Terms such as "a", "an" and "the" are not intended to refer to only a singular entity but include the general class of which a specific example may be used for illustration. The terminology herein is used to describe specific embodiments of the invention, but their usage does not delimit the invention, except as outlined in the claims.
[0026] The term "psychoactive alkaloid" used herein refers to alkaloids that upon introduction to the human body are capable of changing brain function, for example resulting in alterations in perception, mood, consciousness, cognition, or behavior. The psychoactive alkaloid to which the present invention applies is either a phosphorylated psychoactive alkaloid or a dephosphorylated psychoactive alkaloid, and there may be multiple different compounds in each.
[0027] The term "psychoactive alkaloid source" used herein refers to a fungus, a mycelium, a spore, a plant, a bacterium, an animal or a yeast, which has in it a phosphorylated psychoactive alkaloid, a dephosphorylated psychoactive alkaloid, or a combination or both. The source of the psychoactive alkaloid can also be another extract or a solution with a phosphorylated psychoactive alkaloid, a dephosphorylated psychoactive alkaloid, or a combination of both.
[0028] The term "phosphorylatable psychoactive alkaloid" refers to psychoactive alkaloids that have phosphorylated derivatives, and includes psychoactive alkaloids in both their phosphorylated and dephosphorylated forms.
[0029] The term "psychoactive alkaloid composition" used herein can also be referred to as "composition" and describes a mixture of psychoactive alkaloid and one or more excipients. The composition can be of pharmaceutical, nutraceutical, or veterinarian grade.

Date Recue/Date Received 2020-12-04
[0030] The term "psychoactive alkaloid liquid" used herein refers to psychoactive alkaloid obtained in liquid form after a dried powdered biomass of a psychoactive alkaloid source has been extracted using an acidified solvent or a basified solvent.
The liquid form can be a solution or a slurry.
[0031] The term "psychoactive alkaloid extract" used herein refers to a psychoactive alkaloid extract obtained by an extraction process of the present invention.
The extract can be in a solid, solid-powdered, semi-solid or a slurry form.
[0032] As used herein, the term "specific amount" when referring to a total psychoactive alkaloid content means a desired percentage, accurate to one or two decimal places or one or two significant figures, of total psychoactive alkaloid in a psychoactive alkaloid composition. The specific amount is defined as a percentage by weight and can be selected by a person of skill in the art according to preference.
[0033] The term "specific pH" herein refers to a desired pH value of a solvent or a psychoactive alkaloid liquid obtained by adding an acidified solvent or a basified solvent.
[0034] The term "specific ratio" herein refers to a weight ratio between a phosphorylated psychoactive alkaloid and a dephosphorylated psychoactive alkaloid present in a psychoactive alkaloid composition. The ratio can be altered by a person of skill in the art according to preference.
[0035] The term "desired amount" herein refers to an amount of a phosphorylated psychoactive alkaloid or a dephosphorylated psychoactive alkaloid in a total phosphorylatable psychoactive alkaloid content, in the psychoactive alkaloid liquid, extract or composition. The amount of each of these alkaloids is controlled by the process for making the psychoactive alkaloid extract or psychoactive alkaloid composition.
The amount can be altered by a person of skill in the art according to preference.
The amount is usually a percentage ratio by weight that may be accurate up to two significant figures.
[0036] As used herein, the expression "standardizing" the psychoactive alkaloid slurry or bulk psychoactive alkaloid extract slurry refers to adding an excipient to an extract to obtain a slurry with a specific, total concentration of alkaloid, by weight.
The slurry may then be dried to form a powdered composition with a pre-calculated percentage Date Recue/Date Received 2020-12-04 concentration by weight of psychoactive alkaloid. The total amount of alkaloid content can be specified to an accuracy of up to three significant figures.
[0037]
The phrase "one or more excipients" is used herein to refer that one excipient or more than one excipient can be used in any combination. The number of excipients to be used will be at the discretion of a person skilled in the art, and they may be of different types.
[0038]
The term "therapeutic effects" is intended to qualify the amount of active ingredients required in the treatment of a disease or disorder or on the effecting of a clinical endpoint. Reference to "treatment" of a patient is intended to include prophylaxis.
Treatment may also be preemptive in nature, i.e., it may include prevention of disease.
Prevention of a disease may involve complete protection from disease, for example as in the case of prevention of infection with a pathogen or may involve prevention of disease progression. For example, prevention of a disease may not mean complete foreclosure of any effect related to the diseases at any level, but instead may mean prevention of the symptoms of a disease to a clinically significant or detectable level.
Prevention of diseases may also mean prevention of progression of a disease to a later stage of the disease.
B. BASIC PROCESS
[0039] In one embodiment, referring to FIG. 1, a basic process for obtaining a psychoactive alkaloid extract with a desired amount of a phosphorylated psychoactive alkaloid and a desired amount of a dephosphorylated psychoactive alkaloid is shown. The phosphorylated alkaloid may be psilocybin, baeocystin, norbaeocystin, aeruginascin, or any combination selected therefrom. The dephosphorylated alkaloid may be psilocin, norpsilocin, 4-hydroxytryptamine, N ,N ,N-trimethy1-4-hydroxytryptamine, or any combination selected therefrom. The control aspect of the present invention relates to psychoactive alkaloids that have phosphorylated forms, and not to other psychoactive alkaloids that may be present in a psychoactive alkaloid source. Depending on the strain or harvest, there may be no or substantially no phosphorylatable psychoactive alkaloids in Date Recue/Date Received 2020-12-04 the psychoactive alkaloid source, or they may represent as much 80-90% of the total alkaloid content.
[0040] The process includes step 10 of obtaining powdered biomass from a psychoactive alkaloid source. The powdered biomass is obtained by drying and pulverizing a psychoactive alkaloid source. The drying is carried out via vacuum desiccation, freeze drying, timed forced air drying, or other suitable drying method known to a person of skill in the art, to obtain a dried biomass. The pulverization is carried out by milling, grinding, or other method to reduce the particle size of the dried biomass. In one embodiment, the drying is carried out in a forced air oven completely shielded from all light at 20-30 C for a time period of 5-10 hours. However, there is room for optimization of the drying step, using different temperatures (e.g. 10 ¨ 50 C) and different durations.
[0041] In one embodiment, the drying is carried out in a manner to not promote the conversion of phosphorylated psychoactive alkaloid. Taking care not to bruise while harvesting the psychoactive alkaloid source, harvesting at the right time of the fruiting body life cycle, potentially freeze drying the fruiting body, low heat desiccation, and gentle air drying are all ways that reduce the conversion of phosphorylated psychoactive alkaloid to dephosphorylated psychoactive alkaloid. It may be feasible to harvest the fungi in a basic or methanol environment, or soak the whole mycelium in methanol and cutting the fruits while soaked. Once dried, there is negligible conversion, so that subsequent pulverization has little effect on it, unless moisture is added back. The prevention of conversion of phosphorylated psychoactive alkaloid to dephosphorylated psychoactive alkaloid during harvesting allows for the preparation of psychoactive alkaloid extracts, by the present process, having a total phosphorylatable psychoactive alkaloid content that is up to 100% by weight of phosphorylated psychoactive alkaloid.
[0042] In one embodiment, the psychoactive alkaloid source is a mushroom from the genus Conocybe, Copelandia, Galerina, Gymnopilus, lnocybe, Panaeolus, Pholiotina, Pluteus or Psilocybe, or any combination of mushrooms selected therefrom. In one embodiment, gills, caps, stems, or the whole of the fungi is used as the alkaloid source.
[0043] Step 12 involves extracting a psychoactive alkaloid from the dried powdered biomass with an acidified solvent or a basified solvent to obtain a psychoactive alkaloid Date Recue/Date Received 2020-12-04 liquid with a specific pH, wherein the specific pH is lower than 3.5 or greater than 10.5.
Between pH3.5 and pH10.5, the conditions are such that psilocybin is readily converted to psilocin, and psilocin is converted to the quinoid dimer, which is completely inactive.
[0044]
When used, the acid may be acetic acid, adipic acid, ascorbic acid, phosphoric acid, ammonium aluminum sulphate, ammonium citrate dibasic, ammonium citrate monobasic, calcium citrate, calcium fumarate, calcium gluconate, calcium phosphate dibasic, calcium phosphate monobasic, hydrochloric acid, sulphuric acid monobasic, calcium phosphate tribasic, citric acid, fumaric acid, gluconic acid, magnesium fumarate, malic acid, phosphoric acid, potassium acid tartrate, potassium citrate, potassium fumarate, sodium citrate, sodium fumarate, sodium gluconate, sodium lactate, sodium potassium hexametaphosphate, sodium potassium tartrate, sodium potassium tripolyphosphate, sodium pyrophosphate tetrabasic, sodium tripolyphosphate, tartaric acid, and any combination of one or more of these. In some embodiments, the acid is either only hydrochloric acid or only phosphoric acid, for example. It is also envisaged that other acids may be used, for example non-food-grade acids that may be used by pharmaceuticals.
[0045] When used, the base may be ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, calcium acetate, calcium carbonate, calcium chloride, calcium hydroxide, calcium lactate, calcium oxide, calcium phosphate dibasic, calcium phosphate monobasic, magnesium carbonate, potassium aluminum sulphate, potassium bicarbonate, potassium carbonate, potassium hydroxide, potassium lactate, potassium phosphate dibasic, potassium pyrophosphate tetrabasic, potassium phosphate tribasic, potassium tripolyphosphate, sodium acetate, sodium acid pyrophosphate, sodium aluminum phosphate, sodium aluminum sulphate, sodium bicarbonate, sodium bisulphate, sodium carbonate, sodium hexametaphosphate, sodium hydroxide, sodium lactate, sodium phosphate dibasic, sodium phosphate monobasic, sodium phosphate tribasic or any combination therefrom. In one embodiment, the base is solely sodium hydroxide, for example. Other bases may be used in other embodiments, for example non-food-grade bases that may be used by pharmaceuticals.

Date Recue/Date Received 2020-12-04
[0046] After adding the acidified solvent or the basified solvent, the psychoactive alkaloid liquid has a pH ranging from 0.5-3.5 or from 10.5-13.5 respectively. In an exemplary embodiment, the pH of the psychoactive alkaloid liquid obtained after addition of the basified solvent is 13. In another exemplary embodiment, the pH of the psychoactive alkaloid liquid obtained after addition of the acidified solvent is 2.
[0047] The pH is adjusted in the extraction step 12 to halt or promote conversion of phosphorylated psychoactive alkaloid to dephosphorylated psychoactive alkaloid, thus allowing the preparation of the psychoactive alkaloid liquid with the desired amount of a phosphorylated psychoactive alkaloid and a desired amount of a dephosphorylated psychoactive alkaloid. A specific pH lower than 3.5 promotes the conversion of the phosphorylated psychoactive alkaloid to the dephosphorylated psychoactive alkaloid. A
specific pH greater than 10.5 halts the conversion of the phosphorylated psychoactive alkaloid to the dephosphorylated psychoactive alkaloid.
[0048] In step 14 of the process, the pH of the obtained psychoactive alkaloid liquid is adjusted to a pH ranging from 3.5-4.5. The pH is adjusted by adding a base or an acid.
The pH is adjusted to a value in this range as the psychoactive alkaloid liquid exhibits a good anti-microbial stability in this pH range. Also, there is no dephosphorylation at this pH after the alkaloids are removed from the biomass, which points to enzymatic hydrolysis being responsible for conversion in the source of the psychoactive alkaloids. In exemplary embodiments, the base is sodium hydroxide and the acid is citric acid. Any other appropriate acid or base can be used to adjust the pH, which a person of skill in the art may determine. The selection of the acid or the base will depend upon the nature of the pH of the psychoactive alkaloid liquid prior to adjusting it to the range of 3.5-4.5, according to which a person of skill in the art can make the appropriate acid or base selection.
[0049] Step 16 of the process involves evaporating the solvent from the psychoactive alkaloid solution to obtain the psychoactive alkaloid extract with the desired amount of the phosphorylated psychoactive alkaloid and the desired amount of the dephosphorylated psychoactive alkaloid. The solvent is completely or partially evaporated to result in the psychoactive alkaloid extract (slurry or powder) with the desired amount of the Date Recue/Date Received 2020-12-04 phosphorylated psychoactive alkaloid and the desired amount of the dephosphorylated psychoactive alkaloid. The evaporation is carried out by methods such as air drying, rotary evaporation, or other methods known in the art to suitably evaporate solvent from psychoactive alkaloid liquid. At this point in time, away from the biomass, psilocybin and/or psilocin are fairly heat resistant, more so under vacuum, and so rotary evaporation, for example, is a suitable process. The desired amount of the phosphorylated psychoactive alkaloid is 0-100% of a phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract. The desired amount of the dephosphorylated psychoactive alkaloid is the remainder of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract.
[0050] In some embodiments, when during the extraction step the psychoactive alkaloid liquid has a pH greater than 10.5, the desired amount of the phosphorylated psychoactive alkaloid is 50-90% by weight (crude extraction) of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract, without going to onerous lengths in selecting the raw material. The desired amount of the dephosphorylated psychoactive alkaloid is the remainder of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract.
[0051] In another embodiment, when using a psychoactive alkaloid source that has not undergone conversion (i.e. no significant conversion) of any phosphorylated alkaloid to dephosphorylated alkaloid, and when during the extraction step the psychoactive alkaloid liquid has a pH greater than 10.5, the desired amount of the phosphorylated psychoactive alkaloid is 100% by weight of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract. The desired amount of the dephosphorylated psychoactive alkaloid is 0% by weight of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract.
[0052] In yet another embodiment, when during the extraction step the psychoactive alkaloid liquid has a pH lower than 3.5, the desired amount of the phosphorylated psychoactive alkaloid is 0% by weight of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract. The desired amount of the dephosphorylated psychoactive alkaloid is 100% by weight of the total phosphorylatable psychoactive Date Recue/Date Received 2020-12-04 alkaloid content in the psychoactive alkaloid extract. Even with neutral hydroethanol extraction, a large portion of psilocybin may be converted to psilocin.
However, the low pH
environment (<3.5) protects the psilocin from oxidation.
C. EXTRACTION
[0053] In some embodiments, referring to FIG. 2, additional, optional steps in the extraction step 12 are shown. Step 20 is performed by adding the acidified solvent or the basified solvent to the powered biomass. The obtained psychoactive liquid has a specific pH, the specific pH being lower than 3.5 or greater than 10.5. After the addition of the acidified solvent or the basified solvent, the powered biomass and the solvent are mixed, followed by step 22 of filtration to result in the extracted filtrate of step 24 (i.e.
psychoactive alkaloid liquid). To this obtained filtrate, the acid or the base of step 14 is added to adjust the pH to within the range of 3.5-4.5.
[0054] In some embodiments, the extraction step comprises further extracting the psychoactive alkaloid by repeating the extraction step. Filtrate residue from step 22 is collected and to this filtrate residue, the same or a different acidified solvent, or the same or a different basified solvent is added. The resulting mixture is mixed followed by filtration to obtain another filtrate. This filtrate and the previous filtrate are mixed together to result in a bulk filtrate. To this bulk filtrate the acid or the base is added to adjust the pH to 3.5-4.5 according to step 14.
[0055] In some embodiments, further extraction of the filtrate obtained after extraction with the acidified or the basified solvent is repeated until a required amount of the phosphorylated psychoactive alkaloid and/or the dephosphorylated psychoactive alkaloid is extracted. The number of extraction cycles to be repeated will depend on various variable factors such as the source of the psychoactive alkaloid and the solubility of the psychoactive alkaloid in the acidified or the basified solvent.
[0056] In some embodiments, the extraction is performed at a temperature ranging from 5-95 C. In other embodiments, the extraction is performed at a temperature ranging from 50-75 C.

Date Recue/Date Received 2020-12-04
[0057] In some embodiments, the extraction is performed for a time period ranging from 10-720 minutes. For most cases, a time below 10 min would result in a mostly incomplete yield, and above 720 min the extraction may be incomplete but would be continuing at a negligible rate. In another embodiment, and more usually, the extraction is performed for a time period ranging from 30-240 minutes.
[0058] In some embodiments, the extraction is performed at a pressure ranging from 7 to 20,000 psi. In yet another embodiment, the extraction is performed at a pressure ranging from 10 to 20 psi.
[0059] In some embodiments, the extraction is performed with a solvent to solid ratio in the range 1L:1kg to 50L:1kg, wherein the solid is the dried powdered biomass.
In one embodiment, the extraction is performed with a solvent to solid ratio of 20L:1kg.
[0060] The solvent in the evaporation step can be completely or partially evaporated, to result in a powdered solid or a slurry. Evaporation may be paused, for standardization, and continued after.
D. STANDARDIZATION
[0061] Referring to FIG. 3, the present invention also relates to a process for obtaining a psychoactive alkaloid composition with a psychoactive alkaloid extract and one or more excipients.
[0062] At step 28 the evaporation step 16 (FIG. 1) is paused when a portion of the solvent has been evaporated from the psychoactive alkaloid liquid to obtain a psychoactive alkaloid slurry. The evaporation of a portion of the solvent, before collection of the psychoactive alkaloid slurry for standardization, is done to obtain a quantity of a psychoactive alkaloid slurry that is easy to handle in the subsequent steps of the standardization process. The quantity of the portion of the solvent to be evaporated before pausing the evaporation is not so much as to make it too viscous to handle well. The quantity of the portion of the solvent to be evaporated will depend on various factors, for example, but not limited to, the contents of the psychoactive alkaloid liquid and the quantity of the psychoactive alkaloid liquid present at the beginning of the evaporation step.
Date Recue/Date Received 2020-12-04
[0063] Step 30 includes standardizing the obtained psychoactive alkaloid slurry by adding thereto a measured quantity of one or more excipients to obtain a standardized slurry with a specific amount of psychoactive alkaloid content. The specified amount of the total psychoactive alkaloid content in the psychoactive alkaloid composition is achieved by first determining the proportion, by weight, of solids in the psychoactive alkaloid slurry.
The weight proportion of the psychoactive alkaloids in the slurry is also determined. Then a measured amount of one or more excipients is added to a measured amount of the psychoactive alkaloid slurry. Thus, after evaporation of the remaining solvent, the resultant composition is a standardized composition with a specified total psychoactive alkaloid content.
[0064] Step 32 includes continuing the evaporating step 16 (FIG. 1) by drying the standardized slurry to obtain a psychoactive alkaloid composition with the psychoactive alkaloid extract and the one or more excipients.
[0065] The evaporation in the standardization process is carried out by methods such as air drying, rotary evaporation, or other methods known in the art to suitably evaporate solvent from psychoactive alkaloid slurry.
[0066] The psychoactive alkaloid composition obtained has a specific total psychoactive alkaloid content in the composition due to the standardizing step. The specified amount of the total psychoactive alkaloid content may be accurate to one or two decimal places, or one or two significant figures depending on how accurately the measurements are made during the standardization process.
[0067] Thus, the psychoactive alkaloid composition obtained has a specific amount of a total psychoactive alkaloid content, which is made up of a desired amount of phosphorylated psychoactive alkaloid and a desired amount of dephosphorylated psychoactive alkaloid, and possibly other psychoactive alkaloids that are not phosphorylatable.
[0068] In one embodiment, the specific amount of the total psychoactive alkaloid content in the psychoactive alkaloid composition ranges from 0.1-99% by weight of the composition, the higher concentrations being obtained when purifying steps are included.
Purifying may involve treating the extract with a resinous material prior to the Date Recue/Date Received 2020-12-04 standardization step, to remove impurities such as sugars and proteins. In another embodiment, the specific amount of the total psychoactive alkaloid content in the psychoactive alkaloid composition ranges from 0.1-10% by weight of the composition, which may be achieved without purifying steps. In an exemplary embodiment, the specific amount of the total psychoactive alkaloid content in the psychoactive alkaloid composition is 0.53% by weight of the composition. In yet another exemplary embodiment, the specific amount of the total psychoactive alkaloid content in the psychoactive alkaloid composition is 0.501% by weight of the composition.
[0069]
In some embodiments, the desired amount of the phosphorylated psychoactive alkaloid is 0-100% by weight of a total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract, and the desired amount of the dephosphorylated psychoactive alkaloid is the remainder of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract. In one embodiment, the desired amount of the phosphorylated psychoactive alkaloid is 10-90% by weight of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract, and the desired amount of the dephosphorylated psychoactive alkaloid is the remainder of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract.
In another embodiment, the desired amount of the phosphorylated psychoactive alkaloid is 0% by weight of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract, and the desired amount of the dephosphorylated psychoactive alkaloid is 100% by weight of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract. In yet another embodiment, the desired amount of the phosphorylated psychoactive alkaloid is 100% by weight of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract, and the desired amount of the dephosphorylated psychoactive alkaloid is 0% by weight of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract.
E. MIXTURE
[0070] Referring to FIG. 4, in one embodiment, the present invention also relates to a process for preparing a psychoactive alkaloid composition by mixing a phosphorylated Date Recue/Date Received 2020-12-04 psychoactive alkaloid composition and a dephosphorylated psychoactive alkaloid composition in a specific ratio. In step 34, the psychoactive alkaloid composition obtained after step 32 (FIG. 3) is taken. The psychoactive alkaloid composition in step 32 has the desired amount of the dephosphorylated psychoactive alkaloid of 100% by weight of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract.
The aforesaid is achieved by extracting the psychoactive alkaloid from the dried powdered biomass with an acidified solvent having a specific pH lower than 3.5.
[0071] In step 36, another psychoactive alkaloid composition is obtained according to the process described above. This other psychoactive alkaloid composition has a desired amount of phosphorylated psychoactive alkaloid of 100% by weight of the total phosphorylatable psychoactive alkaloid content. The aforesaid is achieved by extracting the psychoactive alkaloid from the dried powdered biomass with a basified solvent having a pH greater than 10.5, where the biomass is not dephosphorylated or not significantly dephosphorylated.
[0072] In step 38, both psychoactive alkaloid compositions are mixed in a measured ratio to obtain a psychoactive alkaloid composition. This composition includes the dephosphorylated psychoactive alkaloid of the first psychoactive alkaloid composition and the phosphorylated psychoactive alkaloid of the second psychoactive alkaloid composition in a specific ratio. In some embodiments, the specific ratio of phosphorylated psychoactive alkaloid to dephosphorylated psychoactive alkaloid is in the range from 1000:1 to 1:1000. If the total phosphorylatable psychoactive alkaloid concentrations are the same in both starting compositions, then the final ratio of phosphorylated to dephosphorylated alkaloids is the same as the ratio in which the starting compositions are mixed. However, in other embodiments, the mixing ratio may need to be modified to take into account the different starting concentrations of the phosphorylated and dephosphorylated alkaloids in their respective compositions. In yet other embodiments, one of the starting compositions may include both phosphorylated and dephosphorylated alkaloids, and the mixing ratio of the two compositions may be adjusted to take this into account.

Date Recue/Date Received 2020-12-04 F. ALTERNATE PROCESS
[0073] FIG. 5, in another embodiment, describes a process for preparing a psychoactive alkaloid composition having a phosphorylated psychoactive alkaloid from one psychoactive alkaloid extraction and a dephosphorylated psychoactive alkaloid from another psychoactive alkaloid extraction in a specific ratio.
[0074] A dried powdered biomass is obtained in step 40. Step 42 includes extracting a psychoactive alkaloid with a basified solvent to obtain a psychoactive alkaloid liquid with a pH greater than 10.5. A majority, or all, of a total phosphorylatable psychoactive alkaloid content is phosphorylated alkaloid and a remainder thereof is dephosphorylated alkaloid.
[0075] In step 44 the pH of the resulting psychoactive alkaloid liquid is adjusted to a pH
ranging from 3.5-4.5. The pH is adjusted by adding an acid.
[0076] Another dried powdered biomass is obtained in step 50. Step 52 includes extracting a psychoactive alkaloid with an acidified solvent to obtain another psychoactive alkaloid liquid with a pH lower than 3.5. All of the psychoactive alkaloid present is dephosphorylated.
[0077] Step 54 involves adjusting the pH of the second psychoactive alkaloid liquid to a pH ranging from 3.5-4.5. The pH is adjusted by adding a base.
[0078]
In steps 46 and 56, a portion of the basified solvent from the first psychoactive alkaloid liquid, and a portion of the acidified solvent from the second psychoactive alkaloid liquid are evaporated to obtain first and second psychoactive alkaloid slurries 48, 58 respectively.
[0079] In step 60, measured portions of the psychoactive alkaloid slurries are mixed to obtain a bulk psychoactive alkaloid slurry. The bulk psychoactive alkaloid slurry includes the phosphorylated psychoactive alkaloid and the dephosphorylated psychoactive alkaloid in the specific ratio. The measured portions, by weight, of each of the psychoactive alkaloid slurries are chosen in such a manner as to achieve the specific ratio of the phosphorylated psychoactive alkaloid and the dephosphorylated psychoactive alkaloid, taking into account the percentage by weight of these psychoactive alkaloids in each of the initial slurries. In one exemplary embodiment, mixing 100 g of a 1.0%
phosphorylated Date Recue/Date Received 2020-12-04 psychoactive alkaloid slurry, with 50 g of a 0.5% dephosphorylated psychoactive alkaloid slurry results in the specific ratio of 4:1 of phosphorylated to dephosphorylated alkaloid.
[0080] In step 62, the obtained bulk psychoactive alkaloid slurry is standardized by adding thereto a measured quantity of one or more excipients to obtain a standardized bulk slurry with a specific total amount of psychoactive alkaloid.
[0081] Step 64 includes drying the standardized bulk psychoactive alkaloid slurry by evaporation to obtain the psychoactive alkaloid composition. The obtained psychoactive alkaloid composition has a specific total amount of psychoactive alkaloid content, and the phosphorylated psychoactive alkaloid and dephosphorylated psychoactive alkaloid are in the specific ratio. In some embodiments of the psychoactive alkaloid composition, the specific ratio of phosphorylated psychoactive alkaloid to dephosphorylated psychoactive alkaloid ranges from 1:1000 to 1000:1.
G. PSYCHOACTIVE ALKALOID COMPOSITION
[0082] In one embodiment, the present invention also relates to a psychoactive alkaloid composition. The psychoactive alkaloid composition includes a specific amount of a total phosphorylatable psychoactive alkaloid content, made up of a desired amount of a phosphorylated psychoactive alkaloid and a desired amount of a dephosphorylated psychoactive alkaloid, and one or more excipients.
[0083] In one embodiment, the specific amount of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid composition ranges from 0.1-99% by weight of the composition. In another embodiment, the specific amount of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid composition ranges from 0.1-10% by weight of the composition. In an exemplary embodiment, the specific amount of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid composition is 0.533% by weight of the composition. In yet another exemplary embodiment, the specific amount of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid composition is 0.501% by weight of the composition.
Date Recue/Date Received 2020-12-04
[0084] In one embodiment, the desired amount of the phosphorylated psychoactive alkaloid is 0-100% by weight of a total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract, and the desired amount of the dephosphorylated psychoactive alkaloid is the remainder of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract. In one embodiment, the desired amount of the phosphorylated psychoactive alkaloid is 10-90% by weight of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract, and the desired amount of the dephosphorylated psychoactive alkaloid is the remainder of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract.
In another embodiment, the desired amount of the phosphorylated psychoactive alkaloid is 0% by weight of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract, and the desired amount of the dephosphorylated psychoactive alkaloid is 100% by weight of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract. In yet another embodiment, the desired amount of the phosphorylated psychoactive alkaloid is 100% by weight of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract, and the desired amount of the dephosphorylated psychoactive alkaloid is 0% by weight of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract.
[0085] In some embodiments, a maximum desired amount of the phosphorylated alkaloid is limited by an amount of the dephosphorylated alkaloid in the psychoactive alkaloid source.
[0086] In an exemplary embodiment, the desired amount of the phosphorylated psychoactive alkaloid is 0.503% by weight of the psychoactive alkaloid composition; and the desired amount of the dephosphorylated psychoactive alkaloid is by 0.03%
weight of the psychoactive alkaloid composition. In yet another exemplary embodiment, the desired amount of the phosphorylated psychoactive alkaloid is 0.00% by weight of the psychoactive alkaloid composition, and the desired amount of the dephosphorylated psychoactive alkaloid is by 0.501% weight of the psychoactive alkaloid composition.

Date Recue/Date Received 2020-12-04
[0087] In one embodiment, the desired amount of the phosphorylated psychoactive alkaloid is 100% by weight of the total psychoactive alkaloid content in the psychoactive alkaloid extract.
[0088] In one embodiment, the desired amount of the dephosphorylated psychoactive alkaloid is 100% by weight of the total psychoactive alkaloid content in the psychoactive alkaloid extract.
[0089] The dephosphorylated psychoactive alkaloids are quicker in becoming bioavailable than their phosphorylated psychoactive alkaloids counterparts.
Thus, the psychoactive compositions comprising dephosphorylated psychoactive alkaloids 100% by weight in the total phosphorylatable psychoactive alkaloid content may exhibit therapeutic effects faster than psychoactive alkaloid compositions comprising phosphorylated psychoactive alkaloids as the majority alkaloids in the total phosphorylatable psychoactive alkaloid content.
[0090] In one embodiment, the psychoactive alkaloid composition is obtained by the process for obtaining a psychoactive alkaloid extract with a desired amount of a phosphorylated psychoactive alkaloid and a desired amount of a dephosphorylated psychoactive alkaloid of the present invention.
[0091] In one embodiment, the present invention also relates to a psychoactive alkaloid composition with a specific ratio of a phosphorylated psychoactive alkaloid and a dephosphorylated psychoactive alkaloid. The composition includes a psychoactive alkaloid extract having a total phosphorylatable psychoactive alkaloid content of 100% by weight of a phosphorylated psychoactive alkaloid, another psychoactive alkaloid extract having a total phosphorylatable psychoactive alkaloid content of 100% by weight of a dephosphorylated psychoactive alkaloid, and one or more excipients.
[0092] In one embodiment, one psychoactive alkaloid extract and another psychoactive alkaloid extract are present in a proportion such that the specific ratio of phosphorylated to dephosphorylated psychoactive alkaloid ranges from 1:1000; 1000:1. In exemplary embodiments, a phosphorylated psychoactive alkaloid extract and a dephosphorylated psychoactive alkaloid extract are present in a proportion such that the specific ratio of phosphorylated to dephosphorylated psychoactive alkaloid is 1:1, 1:3 and 3:1.

Date Recue/Date Received 2020-12-04
[0093] In other embodiments, the psychoactive alkaloid composition is defined by a specific total amount of psychoactive alkaloid content, which has a known ratio of phosphorylated and dephosphorylated alkaloids.
[0094] In some embodiments, the psychoactive alkaloid composition with a specific ratio of a phosphorylated psychoactive alkaloid and a dephosphorylated psychoactive alkaloid is made by the process for obtaining a psychoactive alkaloid composition with a specific ratio of a phosphorylated psychoactive alkaloid to a dephosphorylated psychoactive alkaloid of the present invention.
[0095] The psychoactive alkaloid composition of the present invention is in powder form.
This free-flowing powder form allows the composition to be easily handled. The components of the composition are also in powder form.
[0096] The psychoactive alkaloid composition of the present invention can be used, for example, in medical research on the use of psychedelic substances in treatments for mental illnesses.
H. VARIATIONS
[0097]
In some embodiments, the phosphorylated alkaloid is psilocybin, baeocystin, norbaeocystin, aeruginascin, or any combination therefrom; and the dephosphorylated alkaloid is psilocin, norpsilocin, 4-hydroxytryptamine, N,N,N-trimethy1-4-hydroxytryptamine, or any combination therefrom. In other embodiments, the phosphorylated alkaloid is psilocybin and the dephosphorylated alkaloid is psilocin.
[0098] In some embodiments, the acidified solvent is a mixture of an acid and a C1-C4 primary aliphatic alcohol, a C3-C4 ketone, water, or any combination selected therefrom.
The acid may be citric acid, ascorbic acid, formic acid, acetic acid, hydrochloric acid, phosphoric acid, sulphuric acid, or any combination selected therefrom. In other embodiments, the basified solvent is a mixture of a base and a C1-C4 primary aliphatic alcohol, a C3-C4 ketone, water, or any combination selected therefrom. The base may be sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium bicarbonate, calcium carbonate, or any combination selected therefrom.

Date Recue/Date Received 2020-12-04
[0099] The excipients described herein refer to excipients which aid in the manufacturing and/or administration of the compositions described herein. Non-limiting examples of such excipients are well known in the art and include flavorants, colorants, palatants, antioxidants, viscosity modifying agents, tonicity agents, drug carriers, sustained-release agents, comfort-enhancing agents, emulsifiers, solubilizing aids, lubricants, binding agents, stabilizing agents and other agents to aid in the manufacturing and/or administration of the compositions. The excipients used in the present invention are acceptable for use in pharmaceutical or nutraceutical applications or as food ingredients. The amount of excipients will vary depending on the concentration of psychoactive alkaloids in the psychoactive alkaloid extract to result in a flowable psychoactive alkaloid composition, which will be obvious to a person of skill in the art.
[0100] In some embodiments, the excipients are selected from silicon dioxide, ascorbic acid, maltodextrin from corn, potato or tapioca for example, gum arabic, microcrystalline cellulose, sodium benzoate, sodium phosphate, sodium citrate, rice hulls, and rice. A combination of any of these excipients may be used.
[0101] Any source that contains phosphorylated psychoactive alkaloids may be used as the psychoactive alkaloid source.
[0102] Other water may be used in place of reverse osmosis water, which was selected for its purity.
[0103] The temperature of extraction may be lowered to reduce conversion, and the duration may be in the range of 30-240 minutes.
I. EXAMPLES
[0104] In order to further illustrate the present invention, the following specific examples are given with the understanding that these examples are intended only to be illustrations without serving as a limitation on the scope of the present invention. All parameters, dimensions, materials, quantities and configurations described herein are examples only and may be changed depending on the specific embodiment.
Accordingly, the scope of the invention is to be construed in accordance with the substance defined by Date Recue/Date Received 2020-12-04 the appended claims. The process may be scaled up using larger quantities and modified apparatus.
[0105]
Although the examples of the present invention have been formulated specifically using psilocybe cubensis as a source to obtain a psychoactive alkaloid extract, the extract comprising phosphorylated psychoactive alkaloid (i.e. psilocybi)n and dephosphorylated psychoactive alkaloid (i.e. psilocin), other sources are possible. A
person skilled in the art would appreciate that the psilocybe cubensis can be readily substituted by other sources of psychoactive alkaloids to obtain a variety of psychoactive alkaloids having similar properties, such psilocybin, baeocystin, norbaeocystin, aeruginascin, psilocin, norpsilocin, 4-hydroxytryptamine, N,N,N-trimethy1-4-hydroxytryptamine, or any combination therefrom, to name a few, to result in compositions with similar efficacy and efficiency as well. For example, mushrooms from the genus Conocybe, Copelandia, Galerina, Gymnopilus, lnocybe, Panaeolus, Pholiotina, Pluteus, Psilocybe, or any combination therefrom may be used.
Example 1.1 Process with prevention of dephosphorylation
[0106]
2.5 kilograms of psilocybe cubensis were dried in a forced air oven at 25 C
for hours to result in 140 grams of dried biomass. The dried biomass was then pulverized to a size of 200 mesh with a mill.
[0107]
A basified solvent, i.e. a pH-adjusted, hydro-ethanol mixture, was prepared.

g of sodium hydroxide pellets were placed into a 5 L vessel with 1.25 L of RO
(reverse osmosis) water followed by addition of 3.75 L of ethanol. The contents were mixed until completely dissolved. A basified solvent with 75% Et0H v/v% and a pH of 13 was obtained.
[0108]
The dried powdered biomass was placed into an agitated, heat-controlled vessel with 5 L of the basified solvent and mixed for extraction of psychoactive alkaloid.
The extraction was controlled to a constant 75 C, and the time of extraction was 1 hour.
The extraction slurry was then filtered. Filtration resulted in a filtrate, i.e. the psychoactive alkaloid liquid, and a filter residue. The filter residue was placed back into the extraction vessel and extracted with an additional 5 L of the basified solvent. The temperature of Date Recue/Date Received 2020-12-04 extraction was again 75 C and the time was again 1 hour. The resulting extraction slurry was then filtered. The filtrates from the first and second extractions were mixed to form 10 L of mixed filtrate. The pH of the mixed filtrate was then reduced with 3 M
citric acid until a pH of 4.5 was achieved. Immediately after adjusting the pH, the mixed filtrate was placed into a rotary evaporator at 50 C and 250 torr, and the solvent was partially or completely evaporated to obtain a psychoactive alkaloid extract in a slurry or powdered form respectively. Final stages of evaporation were performed using a freeze dryer.
When dried to a powder, the desired amount of the phosphorylated psychoactive alkaloid obtained was 0.80% by weight (measured by HPLC analysis) in the psychoactive alkaloid extract. The desired amount of the dephosphorylated psychoactive alkaloid obtained was 0.05% by weight in the psychoactive alkaloid extract.
Example 1.2 Process for heavily phosphorylated psychoactive alkaloid composition
[0109] The evaporation of the solvent from the mixed filtrate from example 1.1 was paused when the final volume of the filtrate was reduced to 2.5 L. The resulting slurry contained 236.9 mg/L psilocybin and 15.12 mg/L psilocin. The obtained psychoactive alkaloid slurry was standardized by the addition of 38.64 g of maltodextrin, 1.12 g of ascorbic acid and 2.24 g of silicon dioxide. The standardization was followed by drying by freeze drying to yield 112 g of the psychoactive alkaloid composition in free-flowing powder form. The composition had a psilocybin content of 0.503% dry wt/wt% and a psilocin content of 0.003% dry wt/wt%. Further, the composition had a total phosphorylatable psychoactive alkaloid content of 0.506% dry wt/wt%.
Example 2.1 Process with promotion of dephosphorylation
[0110] 2.5 kilograms of psilocybe cubensis were dried in a forced air oven at 25 C for hours to result in 140 grams of dried biomass. The dried biomass was then pulverized to a size of 200 mesh with a hammer mill.
[0111] An acidified solvent, i.e. a pH-adjusted, hydro-ethanol mixture, was prepared.
144 g of anhydrous citric acid was placed into a 5 L vessel with 1.25 L of RO
water Date Recue/Date Received 2020-12-04 followed by the addition of 3.75 L of ethanol. The contents were mixed until completely dissolved. An acidified solvent with a pH of 2 was obtained.
[0112] The dried powdered biomass was placed into an agitated, heat-controlled vessel with 5 L of the acidified solvent and mixed for the extraction of psychoactive alkaloid. The extraction was controlled to a constant 75 C, and the duration of extraction was 1 hour. The extraction slurry was then filtered. Filtration resulted in a filtrate, i.e. the psychoactive alkaloid liquid, and a filter residue. The filter residue was placed back into the extraction vessel and extracted with an additional 5 L of the acidified solvent. The temperature of extraction was again 75 C and the time was 1 hour. The extraction slurry was filtered. The filtrates from the first and second extraction were mixed to form 10 L of mixed filtrate. The pH of the mixed filtrate was then increased with 5 M
sodium hydroxide until a pH of 4.5 was achieved. Immediately after adjusting the pH, the mixed filtrate was placed into a roto-evaporator at 50 C and 250 torr, and the solvent was partially or completely evaporated to obtain a psychoactive alkaloid extract. Final stages of evaporation were performed using a freeze dryer. When dried to a powder, the desired amount of the phosphorylated psychoactive alkaloid obtained was 0.00% by weight in the psychoactive alkaloid extract. The desired amount of the dephosphorylated psychoactive alkaloid obtained was 0.86% by weight in the psychoactive alkaloid extract.
Example 2.2 Process for preparation of a psychoactive alkaloid composition
[0113] The evaporation of the solvent from the mixed filtrate from example 2.1 was paused until the final volume of the filtrate was reduced to 2.5 L. The obtained psychoactive alkaloid slurry had a 241.85 mg/L of psilocin and a 0 mg/L of psilocybin. The slurry was standardized by the addition of 47.07 g of maltodextrin, 1.21 g of ascorbic acid and 2.41 g of silicon dioxide. The standardization was followed by freeze drying to yield 120.7 g of the psychoactive alkaloid composition in free-flowing powder form.
The composition had a psilocybin content of 0.00% dry wt/wt% and a psilocin content of 0.501% dry wt/wt%. Further, the composition had a total phosphorylatable psychoactive alkaloid content of 0.501% dry wt/wt%.

Date Recue/Date Received 2020-12-04 Example 2.3 Process for preparation of a psychoactive alkaloid composition containing a mixture of phosphorylated and dephosphorylated alkaloids
[0114] In an alternate method, the slurry from 1.1 and from 2.1 can be combined to form 5 L of slurry containing 118.45 mg/L of psilocybin and 128.49 mg/L of psilocin. The slurry was standardized by the addition of 85.70 g of maltodextrin, 2.33 g of ascorbic acid and 4.65 g of silicon dioxide. The standardization was followed by lyophilization to yield 232.70 g of the psychoactive alkaloid composition in the free-flowing powder form. The composition had a psilocybin content of 0.255% dry wt/wt% and a psilocin content of 0.276% dry wt/wt%. Further, the composition had a total phosphorylatable psychoactive alkaloid content of 0.502% dry wt/wt%.
J. APPARATUS
[0115] Referring to FIG. 6, an example of the apparatus is shown schematically. Raw psilocybe cubensis mushrooms were added to a hopper 100 and were released in batches into container 102. The raw fungal material was then dried in a forced air oven 104 to result in the dried biomass. The dried biomass was placed into a grinder 106 for grinding to result in dried powdered biomass.
[0116] The dried powdered biomass was placed into a heat-controlled vessel 110 and acidified/basified solvent (S) was added to the vessel to obtain a specific pH
(lower than 3.5 or greater than 10.5). The vessel 110 was surrounded by an insulating wall 108.
Alternately, an insulating jacket may have been wrapped around the vessel. The insulating wall 108 or jacket helps to maintain the contents 112 under a constant temperature (T) between 5 ¨ 95 C. The pressure (P) inside the extraction vessel 110 may be regulated from 7 to 20,000 psi. The extraction was performed with a solvent to solid (dried powdered biomass) proportion in the range of 1L:1kg to 50L:1kg.
[0117] After the extraction, the bottom of the extraction vessel 110 was opened at outlet 114 and the extraction slurry was collected in a container 120. The extraction slurry was then fed into a filter 122 and a first filtrate was collected in container 124. The first filtrate residue 130 was then fed back (R) into the agitated, heat-controlled vessel 110 and Date Recue/Date Received 2020-12-04 more solvent (S) was added for a second extraction. After the second extraction, the extraction slurry was collected in the container 120 and was then fed into a filter 132. After filtration, the obtained second filtrate was collected in container 136.
[0118] After the two filtration stages, the filtrates were mixed in container 140 to obtain a mixed filtrate i.e. the psychoactive alkaloid liquid. In other embodiments, if there is only a single filtration step, this mixing step is not required. By adding an acid or a base, the pH of the psychoactive alkaloid liquid was brought to a pH ranging from 3.5-4.5.
[0119] The pH-adjusted, mixed filtrate was then placed in a rotary evaporator 142 and part of the solvent was evaporated from the mixed filtrate to form the psychoactive alkaloid extract, which was here a slurry.
[0120] For obtaining the psychoactive alkaloid composition, the evaporation in the rotary evaporator 142 was stopped after a desired portion of solvent was evaporated. The resultant slurry was transferred to a container 144 where a measured quantity of one or more excipients was added to obtain a standardized slurry. The obtained standardized slurry was dried in a freeze dryer 146 to obtain the psychoactive alkaloid composition.
[0121] In other embodiments, parts of the apparatus may be reused or duplicated. For example, if desired, for further extraction the filtrate residue may be reloaded into the extraction vessel 110 and the obtained filtrate can be added to mixed filtrate container of 140 and the steps from thereon can be repeated to obtain the psychoactive alkaloid extract.
K. CONCLUSION
[0122] Throughout the description, specific details have been set forth in order to provide a more thorough understanding of the invention. However, the invention may be practiced without these particulars. In other instances, well known elements have not been shown or described in detail and repetitions of steps and features have been omitted to avoid unnecessarily obscuring the invention. Accordingly, the specification and drawings are to be regarded in an illustrative, rather than a restrictive, sense.
[0123] All parameters, dimensions, materials, quantities and configurations described herein are examples only and may be changed depending on the specific embodiment.

Date Recue/Date Received 2020-12-04 Numbers are given to the nearest significant figure, or to 10%, whichever is the greater.
Accordingly, the scope of the invention is to be construed in accordance with the substance defined by the claims. The process may be scaled up using larger quantities and a modified apparatus.
[0124] It will be clear to one having skill in the art that further variations to the specific details disclosed herein can be made, resulting in other embodiments that are within the scope of the invention disclosed. Steps in the flowchart may be performed in a different order, other steps may be added, or one or more may be removed without altering the main outcome of the processes.
Date Recue/Date Received 2020-12-04

Claims (21)

PSU004-CANP
1. A process for obtaining a dephosphorylated psychoactive alkaloid extract, the process comprising:
drying and pulverizing a psychoactive alkaloid source to obtain a dried powdered biomass;
extracting psychoactive alkaloid from the dried powdered biomass with an acidified solvent with a pH lower than 3.5 to obtain a psychoactive alkaloid liquid;
adjusting the pH of the psychoactive alkaloid liquid to a pH ranging from 3.5-4.5;
and evaporating the acidified solvent from the psychoactive alkaloid liquid to obtain the dephosphorylated psychoactive alkaloid extract.
2. The process of claim 1, wherein the dephosphorylated psychoactive alkaloid extract comprises psilocin, norpsilocin, 4-hydroxytryptamine, N,N,N-trimethyl-4-hydroxytryptamine, or any combination therefrom.
3. The process of claim 1, wherein the psychoactive alkaloid source comprises psilocybin, baeocystin, norbaeocystin, aeruginascin, psilocin, norpsilocin, 4-hydroxytryptamine, N,N,N-trimethyl-4-hydroxytryptamine, or any combination therefrom.
4. The process of claim 1, wherein the extracting step comprises:
mixing the dried powdered biomass with the acidified solvent to obtain a slurry; and filtrating the slurry to obtain a filtrate residue and the psychoactive alkaloid liquid.
5. The process of claim 4, wherein the extracting step comprises further extracting the psychoactive alkaloid by repeating, with the obtained filtrate residue, the extracting step with the same or a different acidified solvent.
6. The process of claim 4, wherein after the mixing step the slurry has a pH
ranging from 0.5-3.5.

Date recue/date received 2021-10-28
7. The process of claim 1, wherein the acidified solvent is a mixture of an acid; and a C1-C4 primary aliphatic alcohol, a C3-C4 ketone, water, or any combination selected therefrom.
8. The process of claim 1, wherein the extraction is performed:
at a temperature in a range of 5-95 C; and for a time period in a range of 10-720 minutes.
9. The process of claim 1, wherein the extraction is performed at a pressure in a range of 7 to 20,000 psi (50 kPa ¨ 138 MPa).
10. The process of claim 1, wherein the extraction is performed with a solvent to solid proportion of 1L:lkg to 50L:lkg, wherein the solid is the dried powdered biomass.
11. The process of claim 1, comprising:
pausing the evaporating step when a portion of the solvent has been evaporated from the psychoactive alkaloid liquid to obtain a psychoactive alkaloid slurry;
standardizing the psychoactive alkaloid slurry by adding thereto a measured quantity of one or more excipients to obtain a standardized slurry; and continuing the evaporating step by drying the standardized slurry to obtain a psychoactive alkaloid composition comprising the dephosphorylated psychoactive alkaloid extract and the one or more excipients;
wherein a dephosphorylated psychoactive alkaloid content in the psychoactive alkaloid composition is specified as a result of the standardizing step.
12. The process of claim 1 comprising:
adding a measured quantity of excipient to a psychoactive alkaloid slurry that is formed part way through the evaporating step, to result in the dephosphorylated Date recue/date received 2021-10-28 psychoactive alkaloid extract being a component of a standardized dephosphorylated psychoactive alkaloid composition;
drying and pulverizing a second psychoactive alkaloid source to obtain a second dried powdered biomass;
extracting second psychoactive alkaloid from the second dried powdered biomass with a basified solvent with a pH higher than 10.5 to obtain a second psychoactive alkaloid liquid;
adjusting the pH of the second psychoactive alkaloid liquid to a pH ranging from 3.5-4.5;
partially evaporating the basified solvent from the second psychoactive alkaloid liquid to obtain a second psychoactive alkaloid slurry;
adding a measured quantity of a second excipient to the second psychoactive alkaloid slurry;
evaporating the basified solvent from the second psychoactive alkaloid slurry to obtain a standardized phosphorylated psychoactive alkaloid composition, wherein a phosphorylated psychoactive alkaloid content in the standardized phosphorylated psychoactive alkaloid composition is specified as a result of adding the second excipient;
mixing at least some of the standardized dephosphorylated psychoactive alkaloid composition and at least some of the standardized phosphorylated psychoactive composition in a measured ratio to obtain a psychoactive alkaloid composition comprising dephosphorylated psychoactive alkaloid and phosphorylated psychoactive alkaloid in a specific ratio;
wherein the specific ratio is in a range of 1:1000 to 1000:1.
13. A process for obtaining a psychoactive alkaloid composition with a specific ratio of phosphorylated psychoactive alkaloid to dephosphorylated psychoactive alkaloid, the process comprising:
extracting a psychoactive alkaloid from a dried powdered biomass with a basified solvent with a pH greater than 10.5 to obtain a psychoactive alkaloid liquid, wherein a majority of a total phosphorylatable psychoactive alkaloid content in the psychoactive Date recue/date received 2021-10-28 alkaloid liquid is phosphorylated alkaloid and a remainder thereof is dephosphorylated alkaloid;
adjusting the pH of the psychoactive alkaloid liquid to a pH in a range of 3.5-4.5;
extracting another psychoactive alkaloid from another dried powdered biomass with an acidified solvent with a pH lower than 3.5 to obtain another psychoactive alkaloid liquid, wherein all of a total phosphorylatable psychoactive alkaloid content in the other psychoactive alkaloid liquid is dephosphorylated alkaloid;
adjusting the pH of the other psychoactive alkaloid liquid to a pH ranging from 3.5-4.5;
evaporating a portion of the basified solvent from the psychoactive alkaloid liquid and a portion of the acidified solvent from the other psychoactive alkaloid liquid to obtain a psychoactive alkaloid extract slurry and another psychoactive alkaloid extract slurry respectively;
mixing measured portions of the psychoactive alkaloid extract slurry and the other psychoactive alkaloid extract slurry to obtain a bulk psychoactive alkaloid extract slurry comprising phosphorylated psychoactive alkaloid and dephosphorylated psychoactive alkaloid in the specific ratio;
standardizing the bulk psychoactive alkaloid extract slurry by adding thereto a measured quantity of one or more excipients to obtain a standardized bulk slurry; and drying the standardized bulk slurry to obtain the psychoactive alkaloid composition with phosphorylated psychoactive alkaloid and dephosphorylated psychoactive alkaloid in the specific ratio;
wherein the specific ratio is in a range of 1:1000 to 1000:1.
14. A psychoactive alkaloid composition comprising:
a psychoactive alkaloid extract comprising a desired amount of phosphorylated psychoactive alkaloid and a desired amount of dephosphorylated psychoactive alkaloid, wherein:

Date recue/date received 2021-10-28 the desired amount of phosphorylated psychoactive alkaloid is 0-100% by weight of a total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract, and the desired amount of dephosphorylated psychoactive alkaloid is the remainder of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract; and one or more excipients.
15. The composition of claim 14, wherein the composition is in powder form.
16. The composition of claim 14, wherein:
the desired amount of phosphorylated psychoactive alkaloid is 0% by weight of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract, and the desired amount of dephosphorylated psychoactive alkaloid is 100% by weight of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract.
17. The composition of claim 14, wherein:
the desired amount of phosphorylated psychoactive alkaloid is 100% by weight of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract, and the desired amount of dephosphorylated psychoactive alkaloid is 0% by weight of the total phosphorylatable psychoactive alkaloid content in the psychoactive alkaloid extract.
18. The composition of claim 14, wherein:
the phosphorylated alkaloid is psilocybin, baeocystin, norbaeocystin, aeruginascin, or any combination selected therefrom; and Date recue/date received 2021-10-28 the dephosphorylated alkaloid is psilocin, norpsilocin, 4-hydroxytryptamine, N,N,N-trimethyl-4-hydroxytryptamine, or any combination selected therefrom.
19. The composition of claim 14, wherein a ratio of the desired amount of phosphorylated psychoactive alkaloid to the desired amount of dephosphorylated psychoactive alkaloid is in a range of 1:1000 to 1000:1.
20. A psychoactive alkaloid composition with a specific ratio of phosphorylated psychoactive alkaloid to dephosphorylated psychoactive alkaloid, the composition comprising:
a psychoactive alkaloid extract having a total phosphorylatable psychoactive alkaloid content that is100% phosphorylated psychoactive alkaloid;
another psychoactive alkaloid extract having a total phosphorylatable psychoactive alkaloid content that is 100% dephosphorylated psychoactive alkaloid; and one or more excipients;
wherein the psychoactive alkaloid extract and the other psychoactive alkaloid extract are present in a proportion such that the specific ratio of phosphorylated psychoactive alkaloid to dephosphorylated psychoactive alkaloid is in a range of 1:1000 to 1000:1.
21. A psychoactive alkaloid composition with a specific ratio of phosphorylated psychoactive alkaloid to dephosphorylated psychoactive alkaloid, the composition comprising:
a psychoactive alkaloid extract having a total phosphorylatable psychoactive alkaloid content that is a maximum of phosphorylated psychoactive alkaloid content limited by an amount of dephosphorylated psychoactive alkaloid in a psychoactive alkaloid source from which the psychoactive alkaloid extract is obtained;
another psychoactive alkaloid extract having a total phosphorylatable psychoactive alkaloid content that is 100% dephosphorylated psychoactive alkaloid; and one or more excipients;

Date recue/date received 2021-10-28 wherein the psychoactive alkaloid extract and the other psychoactive alkaloid extract are present in a proportion such that the specific ratio of phosphorylated psychoactive alkaloid to dephosphorylated psychoactive alkaloid is in a range of 1:1000 to 1000:1.

Date recue/date received 2021-10-28
CA3101765A 2019-06-17 2020-12-04 Psychoactive alkaloid extraction and composition with controlled dephosphorylation Pending CA3101765A1 (en)

Priority Applications (29)

Application Number Priority Date Filing Date Title
CA3101765A CA3101765A1 (en) 2020-12-04 2020-12-04 Psychoactive alkaloid extraction and composition with controlled dephosphorylation
IL305632A IL305632A (en) 2020-06-17 2021-06-14 Extraction of Psychoactive compounds from Psychedelic Fungus
BR112022025780A BR112022025780A2 (en) 2020-06-17 2021-06-14 METHOD FOR GENERATING A PSYCHOACTIVE ALKALOID EXTRACT, METHOD FOR GENERATING A PSYCHOACTIVE PHOSPHORYLATED ALKALOID EXTRACT, AND METHOD FOR GENERATING A DEPHOSPHORYLATED PSYCHOACTIVE ALKALOID EXTRACT
IL299453A IL299453A (en) 2020-06-17 2021-06-14 Psychoactive alkaloid extraction and composition with inhibited dephosphorylation
IL299449A IL299449A (en) 2020-06-17 2021-06-14 Standardized Psychoactive Alkaloid Extract Composition
IL299451A IL299451A (en) 2020-06-17 2021-06-14 Predominantly phosphorylated psychoactive alkaloid extraction using alkali
IL299448A IL299448A (en) 2020-06-17 2021-06-14 Process for Obtaining a Purified Psychoactive Alkaloid Solution
IL297791A IL297791A (en) 2020-06-17 2021-06-14 Compositions comprising psychoactive compounds from psychoactive organisms
IL299450A IL299450A (en) 2020-06-17 2021-06-14 Dephosphorylation-controlled extraction of phosphorylatable psychoactive alkaloids
CA3137016A CA3137016C (en) 2019-06-17 2021-06-14 Psychoactive alkaloid extraction and composition with inhibited dephosphorylation
IL298561A IL298561A (en) 2020-06-17 2021-06-14 Methanol-based extraction of psychoactive compounds from fungus
IL299452A IL299452A (en) 2020-06-17 2021-06-14 Psychoactive alkaloid extraction and composition with controlled dephosphorylation
PCT/CA2021/050813 WO2021253116A1 (en) 2020-06-17 2021-06-14 Compositions comprising psychoactive compounds from psychoactive organisms
EP21825817.6A EP4161546A1 (en) 2020-06-17 2021-06-14 Compositions comprising psychoactive compounds from psychoactive organisms
AU2021290454A AU2021290454B2 (en) 2020-06-17 2021-06-14 Process for Obtaining a Purified Psychoactive Alkaloid Solution
CA3169140A CA3169140A1 (en) 2019-06-17 2021-06-14 Dephosphorylation-controlled extraction of phosphorylatable psychoactive alkaloids
MX2022016533A MX2022016533A (en) 2020-06-17 2021-06-14 Compositions comprising psychoactive compounds from psychoactive organisms.
CA3173030A CA3173030A1 (en) 2019-06-17 2021-06-14 Predominantly phosphorylated psychoactive alkaloid extraction using alkali
US17/348,697 US11331357B2 (en) 2020-06-17 2021-06-15 Methods and compositions comprising psychoactive compounds from psychoactive organisms
US17/483,601 US11298388B2 (en) 2020-06-17 2021-09-23 Psychoactive alkaloid extraction and composition with controlled dephosphorylation
US17/587,731 US11510952B2 (en) 2020-06-17 2022-01-28 Ethanol extraction of psychoactive compounds from psilocybin fungus
US17/697,798 US11571450B2 (en) 2020-06-17 2022-03-17 Aqueous extraction of psychoactive compounds from psilocybin fungus
US17/702,701 US11642385B2 (en) 2020-06-17 2022-03-23 Basic extraction of psychoactive compounds from psychoactive organisms
AU2022291416A AU2022291416B2 (en) 2020-06-17 2022-12-19 Dephosphorylation-controlled extraction of phosphorylatable psychoactive alkaloids
AU2022291410A AU2022291410B2 (en) 2020-06-17 2022-12-19 Standardized psychoactive alkaloid extract composition
AU2022291411A AU2022291411B2 (en) 2020-06-17 2022-12-19 Psychoactive alkaloid extraction and composition with inhibited dephosphorylation
AU2022291414A AU2022291414B2 (en) 2020-06-17 2022-12-19 Psychoactive alkaloid extraction and composition with controlled dephosphorylation
AU2022291413A AU2022291413B2 (en) 2020-06-17 2022-12-19 Predominantly phosphorylated psychoactive alkaloid extraction using alkali
AU2023285751A AU2023285751A1 (en) 2020-06-17 2023-12-19 Powdered Composition Containing a Mushroom Extract Comprising a Psychoactive Alkaloid

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