WO2025052309A1

WO2025052309A1 - A process for obtaining a purified psychoactive alkaloid

Info

Publication number: WO2025052309A1
Application number: PCT/IB2024/058679
Authority: WO
Inventors: Daniel Stark; Jessica Cid TORTA; Timothy William RICHMOND
Original assignee: Psyence UK Group Ltd
Current assignee: Psyence UK Group Ltd
Priority date: 2023-09-08
Filing date: 2024-09-06
Publication date: 2025-03-13
Anticipated expiration: 2026-03-08
Also published as: GB202313750D0

Abstract

The invention provides a process for obtaining a purified psychoactive alkaloid, the process comprising providing and extract of a psychoactive alkaloid from a psychoactive alkaloid source; contacting the psychoactive alkaloid extract with a first adsorbent material to obtain an adsorbed psychoactive alkaloid; eluting the adsorbed psychoactive alkaloid using a first solvent to obtain a purified psychoactive alkaloid solution; contacting the purified psychoactive alkaloid solution with a second adsorbent material to obtain an adsorbed psychoactive alkaloid; eluting the adsorbed psychoactive alkaloid using a second solvent to obtain a second purified psychoactive alkaloid solution and removing water from the second purified psychoactive alkaloid solution by the addition of another liquid that forms an azeotrope with the water to form a purified psychoactive alkaloid.

Description

A PROCESS FOR OBTAINING A PURIFIED PSYCHOACTIVE ALKALOID TECHNICAL FIELD This application relates to a process of obtaining a purified psychoactive alkaloid. More specifically, the present invention relates to purification processes for obtaining psychoactive alkaloids, compositions comprising such alkaloids and use of the alkaloids in the manufacture of medicaments for the treatment of diseases. BACKGROUND Varieties of mushrooms containing psychoactive alkaloids have played important roles in most societies. The active ingredients in mushrooms have been found to have medicinal properties including relief of symptoms of various diseases and conditions. The concentration of active ingredients for these applications may vary not only from species to species, but also from mushroom to mushroom inside a given species, subspecies, or variety. The same holds true even for different parts of the same mushroom or mycelium. Purification methods currently described in the art are inefficient such that a large portion of the target compounds are lost during the purification process or not extracted from the source material at all. It is currently infeasible and expensive to extract and purify psilocybin from mushrooms and certainly to Good Manufacturing Process (GMP) standards. Accordingly, there is a need of processes to produce high purity preparations of the target compounds for medical use. SUMMARY OF INVENTION In a first embodiment of the present invention there is provided a process for obtaining a purified psychoactive alkaloid, the process comprising: a) providing and extract of a psychoactive alkaloid from a psychoactive alkaloid source; b) contacting the psychoactive alkaloid extract with a first adsorbent material to obtain an adsorbed psychoactive alkaloid; c) eluting the adsorbed psychoactive alkaloid using a first solvent to obtain a purified psychoactive alkaloid solution, d) contacting the purified psychoactive alkaloid solution with a second adsorbent material to obtain an adsorbed psychoactive alkaloid; e) eluting the adsorbed psychoactive alkaloid using a second solvent to obtain a second purified psychoactive alkaloid solution, f) removing water from the second purified psychoactive alkaloid solution by the addition of another liquid that forms an azeotrope with the water to form a purified psychoactive alkaloid. The first adsorbent material may comprise silica based material. The first adsorbent material preferably comprises particles of silicon dioxide. The first adsorbent material may additionally comprise a linear alkylsilane phase bonded to a surface of the silicon dioxide particles. The linear alkylsilane phase is preferably octyldecylsilane and may contain 18 carbons bonded to a surface of the silicon dioxide particles. The first adsorbent material may be “normal phase”. "Normal Phase" chromatography is used to separate compounds on the basis of their polarity, the least polar eluting first. The first adsorbent material may be “reverse phase” wherein the sample components are retained in the system the more hydrophobic they are. The second adsorbent material may be cellulose based. In particular, the second adsorbent material may comprise cellulose microspheres or powder. The second adsorbent material may have 10 to 100 micron particle size, for example Sigma Aldric (RTM) 22183. The first and second adsorbent materials may be the same or different. In one embodiment the second absorbent material is reverse phase silica column such that the process includes purification by normal phase silica chromatography followed by a pass through a reverse phase silica column. The first and second solvents may be water, an organic solvent or a combination thereof, under basic, acidic or neutral pH. The liquid that forms an azeotrope with the water may be an alcohol including isopropyl alcohol. The purified psychoactive alkaloid from step f) is preferably recrystallised. A second embodiment of the present invention provides a composition comprising the purified psychoactive alkaloid obtained by a process according to the invention. The invention extends to the composition for use in a method for the treatment of addiction, post-traumatic stress disorder, anxiety, depression, cluster headaches, and other illnesses. A third embodiment of the present invention provides the use of a purified psychoactive alkaloid obtained by a process according to the invention in the manufacture of a medicament for use in a method for the treatment of addiction, post-traumatic stress disorder, anxiety, depression, cluster headaches, and other illnesses. It will be appreciated that the psychoactive alkaloid is preferably psilocybin and/or, psilocin but may extend to baeocystin, norbaeocystin, norpsilocin, aeruginascin, bufotenin, bufotenidine, 5-MeO-DMT (5-methoxy-N.Ndimethyltryptamine), N,N-dimethyltryptamine (DMT), 4- hydroxytryptamine, N,N,N-trimethyl-4-hydroxytryptamine ergine (LSA), ergonovine, ergometrine, muscimol, ibotenic acid, lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine, and/or chanoclavine, or any combination selected therefrom. DETAILED DESCRIPTION In some embodiments, the psychoactive alkaloid extract is from fungi. In some embodiments, the psychoactive alkaloid extract is from Psilocybe cyanescens, Psilocybe cubensis, Amanita muscaria, or any selection therefrom. In some embodiments, the psychoactive alkaloid extract is from psychoactive plants. In some embodiments, the psychoactive alkaloid extract is from Anadenanthera colubrina. In some embodiments, the psychoactive alkaloid extract is from Anadenanthera peregrina. In some embodiments, the psychoactive alkaloid extract is from psychoactive animals. In some embodiments, the psychoactive alkaloid extract is from Incilius alvarius. In some embodiments, the psychoactive alkaloid extract is from psychoactive yeasts. A method for generating a psychoactive alkaloid extract from a psychoactive organism, the method comprising: providing a biomass of the psychoactive organism; contacting the biomass with 10 to 100 milliliters (mL) of solvent per gram (g) of the biomass; and evaporating the solvent from the biomass to yield the psychoactive alkaloid extract. In some embodiments, the solvent is selected from 100% methanol, an alcohol:water mixture wherein the alcohol comprises 60% to 99% of the alcohol:water mixture, an alcohol:acid mixture wherein the alcohol comprises 60% to 99% of the alcohol:acid mixture, and acidified water. The invention provides a process for obtaining a purified psychoactive alkaloid , the process comprising: extracting a psychoactive alkaloid from a psychoactive alkaloid source to obtain a psychoactive alkaloid extract; contacting the psychoactive alkaloid extract with an adsorbent material to obtain an adsorbed psychoactive alkaloid; and eluting the adsorbed psychoactive alkaloid using a solvent to obtain a purified psychoactive alkaloid solution, wherein the solvent is water, an organic solvent or a combination thereof, under basic, acidic or neutral pH. In some embodiments, the process comprises prior to the treating step, adding an acid or a base to the psychoactive alkaloid extract. In some embodiments, after adding the acid or base, the psychoactive alkaloid extract has a pH ranging from 2.5-4.5 or from 9-10 respectively. In some embodiments, the acid is selected from the group consisting of 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, 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 therefrom. In some embodiments, the base is selected from the group consisting of 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, and any combination therefrom. In some embodiments, the adsorbent material is a gel resin, a macroporous resin, or a combination thereof. In some embodiments, the macroporous resin is a non-ionic macroporous resin, an ion-exchange macroporous resin, or a combination thereof. In some embodiments, the psychoactive alkaloid source comprises psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin, aeruginascin, bufotenin, bufotenidine, 5-MeO-DMT (5-methoxy-N.N-dimethyltryptamine), N,N-dimethyltryptamine (DMT), ergine (LSA), ergonovine, ergometrine, muscimol, ibotenic acid, lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine, chanoclavine, or any combination therefrom. In some embodiments, the organic solvent is selected from a group consisting of C1-4 primary aliphatic alcohols, C3-4 ketones, and any combination therefrom. In some embodiments, the process comprises further purifying the obtained purified psychoactive alkaloid solution by repeating, with the obtained purified psychoactive alkaloid solution, the treating step with a different adsorbent material and the eluting step with another solvent. In some embodiments, the process comprises evaporating a portion of solvent from the purified psychoactive alkaloid solution to obtain a purified psychoactive alkaloid slurry. In some embodiments, the purified psychoactive alkaloid slurry comprises 5% by weight or more of a psychoactive alkaloid. The purification process of the present invention may be, depending on the embodiment, a relatively simple and robust psychoactive alkaloid purification process, which is suitable for the production of food-grade, nutraceutical-grade, or pharmaceutical-grade psychoactive alkaloids, especially of psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin, aeruginascin, bufotenin, bufotenidine, 5-MeO-DMT (5-methoxy-N.N-dimethyltryptamine), N,N-dimethyltryptamine (DMT), ergine (LSA), ergonovine, ergometrine, muscimol, ibotenic acid, lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine, and/or chanoclavine. The purifies psychoactive alkaloids of the present invention can be used in, for example, medical research on the use of psychedelic substances as treatments for addiction, post- traumatic stress disorder, depression, cluster headaches, and other illnesses. They may also be used in traditional entheogenic practices or consumed recreationally where such activity is permitted by law. Disclosed herein is a psychoactive alkaloid composition comprising of, by weight: 0.1-99.9% of a pychoactive alkaloid extract; one or more preservatives, carriers and the like. This summary does not necessarily describe all features of the invention, and different embodiments thereof may provide at least one but not necessarily all of the benefits described herein. GLOSSARY To facilitate the understanding of this invention, a number of terms are defined below. Terms used herein have meanings as commonly understood by a person of ordinary skill in the areas relevant to the present invention, unless otherwise defined. 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 its usage does not delimit the invention, except as outlined in the claims. The term “azeotropic” refers to a constant heating point mixture which is a mixture of two or more components in fluidic states whose proportions cannot be altered or changed by simple distillation. This happens because when an azeotrope is boiled, the vapour has the same proportions of constituents as the unboiled mixture. Psilocybin fungi or psilocybin mushrooms—these are a group of fungi that contain at least one psychoactive alkaloid, and generally contain psilocybin and psilocin. They may also contain other psychoactive alkaloids such as baeocystin, norbaeocystin, ibotenic acid and norpsilocin. The genera of these mushrooms include Copelandia, Gymnopilus, Inocybe, Panaeolus, Pholiotina, Pluteus, Amanita, and Psilocybe. Psilocybe mushrooms—these form a genus of gilled mushrooms in the family Hymenogastraceae. Most species contain the psychedelic alkaloids psilocybin, psilocin, and baeocystin. Psilocybin—this is a psychedelic prodrug produced by numerous species of mushrooms, collectively known as psilocybin mushrooms. Psilocybin is converted by the body to psilocin, which has mind-altering effects such as euphoria and hallucinations, but can also lead to nausea and panic attacks. The term “psychoactive alkaloid extract” or “extract” refers to a psychoactive alkaloid extract that is obtained after a psychoactive alkaloid source has been extracted, possibly according to a process described herein. The extract may be a fluid, as either a liquid or a slurry, or is made into a fluid by the addition of a solvent. The term “extract” may also be used for the dried form of the fluid extract. 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. The term “psychoactive alkaloid” as used herein refers to alkaloids that upon ingestion are capable of changing brain function, resulting in alterations in perception, mood, consciousness, cognition, or behavior, for example. Psychoactive alkaloids are abundant in nature and can be obtained from sources such as a fungus, an animal, a mycelium, a spore, a plant, a bacterium, or a yeast. Examples of psychoactive alkaloids include, but are not limited to, psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin, aeruginascin, bufotenin, bufotenidine, 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), N,N-dimethyltryptamine (DMT), ergine (LSA), ergonovine, ergometrine, ibotenic acid, muscimol, lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine, and/or chanoclavine. The source of the psychoactive alkaloid can also be an extract or a solution comprising a psychoactive alkaloid. 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. The term “psychoactive alkaloid source” used herein refers to a fungus, a mycelium, a spore, a plant, a bacterium, a Protista, 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. The term “phosphorylatable psychoactive alkaloid” refers to psychoactive alkaloids that have phosphorylated derivatives and includes psychoactive alkaloids in both their phosphorylated and dephosphorylated forms. 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. 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. The term “purified psychoactive alkaloid extract” refers to a purified extract that is obtained after a psychoactive alkaloid extract is treated with one or more resins for purification as described herein, or by other means of purifying the concentration of the psychoactive alkaloid concentration. This purified psychoactive alkaloid extract is substantially free of impurities, or contains fewer impurities compared to a similar psychoactive alkaloid extract that has not undergone any purification. The purified psychoactive alkaloid extract is a fluid, either a liquid or a slurry, or is made into a fluid by the addition of a solvent. The term “purified psychoactive alkaloid solution” refers to a solution of one or more desired psychoactive alkaloids, where the solution is free of impurities or contains fewer impurities compared to a similar psychoactive alkaloid solution that has not undergone any purification. The purified solution is obtained after a psychoactive alkaloid extracted from its source has been purified by the purification process of the present invention. The impurities that are commonly encountered while extracting psychoactive alkaloids from a natural source include sugars, carbohydrates, chitin, chitosan, fats, minerals, waxes, and/or proteins. The impurities being removed from the psychoactive alkaloid extract will vary depending on the source of the psychoactive alkaloid. The “impurities” herein are commonly undesired, but not necessarily harmful, substances encountered while extracting psychoactive alkaloids from psychoactive organisms. Impurities may include sugars, carbohydrates, chitin, chitosan, fats, minerals, waxes, and/or proteins. The impurities being removed from a psychoactive alkaloid extract will vary depending on the source of the psychoactive alkaloid. Their removal increases the concentration of the desired psychoactive alkaloids remaining in the extract. The term “resin” as used herein is intended to refer to a solid or highly-viscous substance of plant, mineral, or synthetic origin that has been typically converted into a polymer. Resins are usually mixtures of organic compounds. They are typically used in chromatographic techniques as a stationary phase to purify and separate compounds depending on their polarity. Resins can be physically or chemically modified to provide specificity to bind or repel particular molecules within sometimes very complex mixtures. A resin is an example of an adsorbent material. As used herein, the term “ion exchange resin” refers to an insoluble organic polymer containing charged groups that tract and hold oppositely charged ions present in a surrounding solution in exchange for counterions previously held. Suitable ion exchange resins to be used herein contain cationic groups that tract and hold anions present in a surrounding solution and are sometimes referred to as “anion ion-exchange resins”. Similarly, other ion exchange resins to be used herein contain anionic groups that tract and hold cations present in a surrounding solution and are sometimes referred to as “cation ion-exchange resins”. The term “macroporous resin” as used herein refers to a nonionic, cation, or anion resin with very small, highly cross-linked polymer particles with tiny channels. Macroporous resins are generally used for the adsorption of organic constituents due to their hydrophobic properties and are thus used to separate and purify compounds. The adsorption capacity of macroporous resins not only correlates with the physical and chemical properties of the adsorbent, but also with the size and chemical features of the adsorbed substance. The term “adsorbed psychoactive alkaloid” refers to one or more alkaloids that are adsorbed onto an adsorbent material such as a resin. The term “other adsorbent material” as used herein refers to materials which can be used in place of the resin(s) to adsorb the psychoactive alkaloids. Examples of such materials include, but are not limited to, zeolites, clays, bentonite, minerals, alumina, diatomaceous earth, activated carbon, charred biomass, and others. The term “purification process” may be used herein to refer to the process described herein, i.e. a process for obtaining purified psychoactive alkaloids or a purified psychoactive alkaloid solution. As used herein, the term “specific amount” when referring to a psychoactive alkaloid content means a desired percentage, accurate to one or two decimal places or one or two significant figures, of the psychoactive alkaloid content 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. The term “excipient” means any component added to an active ingredient to make a composition. An excipient is inert in relation to the active ingredient, in that it essentially does not act in the same way as the active ingredient. An excipient may be completely inert, or it may have some other property that protects the integrity of the active ingredient or assists its uptake into the human body. There are multiple types of excipient, each having a different purpose, and a given excipient may fulfill more than one purpose. Examples of types of excipient include flowability agents, flavorants, colorants, palatants, antioxidants, bioavailability-increasing agents, viscosity modifying agents, tonicity agents, drug carriers, sustained-release agents, comfort-enhancing agents, emulsifiers, solubilizing aids, lubricants, binding agents and stabilizing agents. Specific excipients include pectin, rice husks, rice, xanthum gum, gum arabic, beta cyclodextrin, alpha cyclodextrin, microcrystalline cellulose, sorbitol, dextrose, guar gum, acacia gum, cellulose gum, talc, magnesium stearate. 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. The term “carrier” means an excipient that aids in delivery of the active ingredient or provides bulk to the composition. The amount of carrier included in a composition can vary widely in order to control the concentration of the active ingredient in the composition. An example of a carrier is mannitol, starch, maltodextrin, tapioca maltodextrin or rice maltodextrin, alpha and beta cyclodextrin, microcrystalline cellulose (MCC), gum arabic, xanthum gum, guar gum, or cellulose gum. In some embodiments, the starch is potato starch, corn starch, tapioca starch, arrowroot starch, wheat starch, rice starch, sweet potato starch, sago starch, rung bean starch, and any combination of thereof. In some embodiments, mannitol is a cryoprotectant (allowing for efficient freeze-drying) and bulking agent. The term “flow agent”, “flowability agent” or “anti-caking agent” or “anti-adherent” means an excipient that prevents or reduces the formation of lumps in a powdered composition. An example of a flow agent is silicon dioxide, stearic acid, magnesium stearate, or talc. The term “preservative” means an excipient that is added to the composition to prevent microbial growth or microbial degradation of the composition. Examples of preservative are ascorbic acid, citric acid, lactose, vitamin A, vitamin E, retinyl palmitate, selenium, sodium citrate, sodium ascorbate, calcium ascorbate, sodium benzoate, and potassium benzoate. The term “purified water” includes deionized water, distilled water, reverse osmosis water, or otherwise purified water which is substantially without free ions. The term “substantially” as used herein refers to a majority of, or mostly, as in at least about 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, 99.99%, or at least about 99.999% or more. 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. The term “specific pH psychoactive alkaloid solution” used herein refers to a solution that is obtained after addition of a suitable acid or a base to a psychoactive alkaloid extract to achieve a solution with a desired pH level. The term “% wt” is used to describe the weight percentage of one component in a mixture of components. The term “a trace” herein refers more than, but close to about 0%. The term “about” herein refers to ±10%, ±20%, ±30%, ±40%, or ±50%, or to the nearest significant figure. 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. 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. In some embodiments, as the ranges become narrower and more central compared to the greatest range, the properties of the embodiments generally become more balanced, such properties being solubility, viscosity, flowability, stability, taste, potency, immediate potency, delayed potency, cost of production, efficiency of production, production time, compatibility of the psychoactive alkaloid composition, psychoactive efficacy of the psychoactive alkaloid extract, psychoactive efficacy of the psychoactive alkaloid composition, and so on. As the ranges become narrower towards one extreme or other of the widest range, a particular property of the composition or process becomes more pronounced relative to the other properties. The specific range is to be chosen depending on how the properties are to be traded-off against each other. 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. 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 process. Source of Psychoactive Alkaloid Extract In one embodiment, the psychoactive alkaloid source is a psychoactive organism. In one embodiment, the psychoactive organism is a fungus. In one embodiment, the fungus is a mushroom from the genus Conocybe, Copelandia, Galerina, Gymnopilus, Inocybe, 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. The psychoactive organism may be a fungus, a mycelium, an animal, a spore, a plant, a bacterium, a protista, or a yeast. The psychoactive alkaloid source in some embodiments may be a prior extract of one or more psychoactive alkaloids, where the prior extract is to undergo a further extraction process. The psychoactive alkaloid may include, but is not limited to, psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin, aeruginascin, bufotenin, bufotenidine, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), N,N-dimethyltryptamine (DMT), ergine (LSA), ergonovine, ergometrine, muscimol, ibotenic acid, lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine, and/or chanoclavine, or any combination selected therefrom. It is possible that other psychoactive alkaloids, not yet discovered, may also be extracted using the methods disclosed herein. In some embodiments, the psychoactive alkaloid is a combination of psilocybin and psilocin. In another embodiment, the psychoactive alkaloid is psilocybin. In yet another embodiment, the psychoactive alkaloid is psilocin. Although the examples of the present invention have been formulated specifically using Psilocybe cubensis and Anadenanthera peregrina as sources to obtain a psychoactive alkaloid extract, the extract including psilocybin and psilocin in the first case and bufotenin, bufotenidine, and 5-MeO-DMT in the second, other sources are also possible. A person skilled in the art would appreciate that Psilocybe cubensis and Anadenanthera peregrina can be readily substituted by other sources of psychoactive alkaloids to obtain a variety of purified psychoactive alkaloids having similar properties, such alkaloids being, besides those mentioned above, baeocystin, norbaeocystin, norpsilocin, aeruginascin, N,N- dimethyltryptamine (DMT), ergine (LSA), ibotenic acid, ergonovine, ergometrine, muscimol, lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine, and/or chanoclavine, to name a few, and to result in compositions with similar efficacy and efficiency as well. For example, the venom of the toad Incilius alvarius, the Anandenanthera colubrina tree or the Amanita muscaria mushroom may be used as other sources of psychoactive alkaloids. Note that the lists of sources and psychoactive alkaloids are included to provide examples and are non-exhaustive lists. Psychoactive Ingredient In some embodiments, the present disclosure comprises a composition having, by weight, 2- 99.7% of a psychoactive alkaloid and 0.3-98%, i.e., the remainder, being one or more excipients. In some embodiments, the psychoactive ingredient is present in the composition at, by weight, about 50% to about 99.7%. In some embodiments, the psychoactive ingredient is present in the composition at, by weight, about 50% to about 60%, about 50% to about 70%, about 50% to about 80%, about 50% to about 90%, about 50% to about 92%, about 50% to about 94%, about 50% to about 96%, about 50% to about 98%, about 50% to about 99%, about 50% to about 99.7%, about 60% to about 70%, about 60% to about 80%, about 60% to about 90%, about 60% to about 92%, about 60% to about 94%, about 60% to about 96%, about 60% to about 98%, about 60% to about 99%, about 60% to about 99.7%, about 70% to about 80%, about 70% to about 90%, about 70% to about 92%, about 70% to about 94%, about 70% to about 96%, about 70% to about 98%, about 70% to about 99%, about 70% to about 99.7%, about 80% to about 90%, about 80% to about 92%, about 80% to about 94%, about 80% to about 96%, about 80% to about 98%, about 80% to about 99%, about 80% to about 99.7%, about 90% to about 92%, about 90% to about 94%, about 90% to about 96%, about 90% to about 98%, about 90% to about 99%, about 90% to about 99.7%, about 92% to about 94%, about 92% to about 96%, about 92% to about 98%, about 92% to about 99%, about 92% to about 99.7%, about 94% to about 96%, about 94% to about 98%, about 94% to about 99%, about 94% to about 99.7%, about 96% to about 98%, about 96% to about 99%, about 96% to about 99.7%, about 98% to about 99%, about 98% to about 99.7%, or about 99% to about 99.7%. In some embodiments, the psychoactive ingredient is present in the composition at, by weight, about 50%, about 60%, about 70%, about 80%, about 90%, about 92%, about 94%, about 96%, about 98%, about 99%, or about 99.7%. In some embodiments, the psychoactive ingredient is present in the composition at, by weight, at least about 50%, about 60%, about 70%, about 80%, about 90%, about 92%, about 94%, about 96%, about 98, or about 99%. In some embodiments, the psychoactive ingredient is present in the composition at, by weight, at most about 60%, about 70%, about 80%, about 90%, about 92%, about 94%, about 96%, about 98%, about 99%, or about 99.7%. In some embodiments, the psychoactive alkaloid extract has a psychoactive alkaloid concentration ranging from 0.1% to 99% by weight of the extract. It may be in the range of 1- 10% dry wt/wt % for the non-purified extract concentration. However, as the composition may be made with purified extract, the psychoactive concentration could be as high as 99%. In some embodiments, the psychoactive alkaloid extract has a psychoactive alkaloid concentration ranging from 1.03% to 75.22% by weight of the dry extract. In some embodiments, the psychoactive alkaloid extract has a psychoactive alkaloid concentration ranging from 1.03% to 3.02% by weight of the extract. In other embodiments, the psychoactive alkaloid extract is a purified psychoactive alkaloid extract. In some embodiments, the purified psychoactive alkaloid extract has a psychoactive alkaloid concentration ranging from 10% to 99% by weight of the extract. In other embodiments, the purified psychoactive alkaloid extract has a psychoactive alkaloid concentration ranging from 16.12% to 75.22% by weight of the extract. In some embodiments, the psychoactive ingredient is present in the composition at, by weight, about 5% to about 76%. In some embodiments, the psychoactive ingredient is present in the composition at, by weight, about 5% to about 10%, about 5% to about 20%, about 5% to about 30%, about 5% to about 40%, about 5% to about 50%, about 5% to about 60%, about 5% to about 70%, about 5% to about 75%, about 5% to about 76%, about 10% to about 20%, about 10% to about 30%, about 10% to about 40%, about 10% to about 50%, about 10% to about 60%, about 10% to about 70%, about 10% to about 75%, about 10% to about 76%, about 20% to about 30%, about 20% to about 40%, about 20% to about 50%, about 20% to about 60%, about 20% to about 70%, about 20% to about 75%, about 20% to about 76%, about 30% to about 40%, about 30% to about 50%, about 30% to about 60%, about 30% to about 70%, about 30% to about 75%, about 30% to about 76%, about 40% to about 50%, about 40% to about 60%, about 40% to about 70%, about 40% to about 75%, about 40% to about 76%, about 50% to about 60%, about 50% to about 70%, about 50% to about 75%, about 50% to about 76%, about 60% to about 70%, about 60% to about 75%, about 60% to about 76%, about 70% to about 75%, about 70% to about 76%, or about 75% to about 76%. In some embodiments, the psychoactive ingredient is present in the composition at, by weight, about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 75%, or about 76%. In some embodiments, the psychoactive ingredient is present in the composition at, by weight, at least about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, or about 75%. In some embodiments, the psychoactive ingredient is present in the composition at, by weight, at most about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 75%, or about 76%. The composition of the present invention has the psychoactive alkaloid present in a specific amount. In some embodiments, the specific amount of psychoactive alkaloid is accurate to one significant figure. In another embodiment, the specific amount psychoactive alkaloid is accurate to two, three or four significant figures. The presence of the psychoactive alkaloid in a specific amount in the composition allows for the same desired specific amount of the psychoactive alkaloid to be present in various batches of the psychoactive alkaloid composition. The composition of the present invention may be in a powder form. The components of the composition are also in powder form. The composition of the present invention may be in the form of a free-flowing powder depending on the embodiment. Such compositions are thus easy to handle during manufacturing and packaging processes. Further, the dry, free-flowing powder form allows the composition to be free from clumps and not be as susceptible to microbial growth as a composition with clumping due to moisture absorption. 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. Stability of a powder form product is superior to that of a slurry. In cGMP (Current Good Manufacturing Practice) API (Active Pharmaceutical Ingredient) manufacturing, it is disadvantageous to produce a slurry as there are quality and operational challenges. Release testing a drug substance that is a two phase mixture is not common and would be difficult to analyze. It is advantageous for an API to be isolated as solid so that it can be filtered, dried, accurately analyzed and stored suitably. It is known for alcohol solvents to be used for azeotropic removing water. However, conventional wisdom would dictate not using this approach if the active compound (psilocybin in this case) is unstable to the operation of distillation (heating for prolonged times – this can take several hours at large production scale). 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. In general, unless otherwise indicated, singular elements may be in the plural and vice versa with no loss of generality. Temperatures that have been given to the nearest degree include all temperatures within a range of ±0.5° C. of the given value. Likewise, numbers and percentages are specified to the nearest significant digit. Values of pH are specified to ±0.5. While exemplary pH ranges are given in some examples, other pH ranges are possible. The process may be scaled up using larger quantities and modified apparatus. The purification process in other embodiments may use varying applied pressures and temperatures, which vary during the steps. EXAMPLES 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 the claims. The process may be scaled up using larger quantities and modified apparatus. 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 including psilocybin and 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 other psychoactive alkaloids having similar properties, such as psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin, aeruginascin, bufotenin, bufotenidine, 4-hydroxytryptamine, 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), N,N- dimethyltryptamine (DMT), N,N,N-trimethyl-4-hydroxytryptamine, ergine (LSA), ergonovine, ergometrine, muscimol, ibotenic acid, lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine, chanoclavine, or any combination therefrom, to result in compositions with similar efficacy and efficiency as well. For example, mushrooms from the genus Conocybe, Copelandia, Galerina, Gymnopilus, Inocybe, Panaeolus, Pholiotina, Pluteus, Psilocybe, or any combination therefrom may be used. For example, Psilocybe cyanescens and Amanita muscaria fungi may be used. For example, the venom of the toad Incilius alvarius, the Anadenanthera colubrina tree or the Anadenanthera peregrina tree may be used as other sources of psychoactive alkaloids. Note that the lists of sources and psychoactive alkaloids are included to provide examples and are non-exhaustive lists. EXAMPLE 1 - XAD4 resin approach based on US Patent No.11,331,357B2 • 50 g input, ~200 mg pf psilocybin. • Precipitation with MeCN to remove impurities and obtain powder material. • Dissolved in 320 mL of water and adjusted to pH 4 (isoelectronic point of psilocybin). • XAD4 resin procedure: o Extract solution loaded onto the resin (100 g wet) at 2 bed volumes o per hour (~160 mL, 1 h). o Washed with water (480 mL, 3 bed volumes, 1h 30min). o Elution with 5% ethanol in water (800 mL, 5 bed volumes, 3 hours). o Washed with ethanol (800 mL, 5 bed volumes, 3 hours). • Solvent from 5% ethanol fraction removed under vacuum at NMT 40°C (using IPA azeotrope) to yield 0.4 g of an oily residue. • Oily residue recrystallised in MeOH/MeCN. • 190 mg of white solid collected (90% purity, 61% w/w). US Patent No.11,331,357B2 notes: • Slurry appears to be the final output. • Quote %w/w of solids and supernatant and %w/w of psychoactive components (psilocybin + psilocin + norbaeocystin+ baeocystin) in solids. • Reported 45-68% dry wt/wt% of total alkaloids. • Suggests that they are also isolating a mix of components, not a high psilocybin purity or assay product. • After the analysis the obtained solid (0.13g) was attempted to recrystallise in water saturated n-butanol (25ml) . • Most of the solids were not dissolved in water saturated butanol which indicated really low solubility of the psilocybin in water saturated n-butanol. • The solids in contact with the n-butanol became oily and a proper slurry was not formed . • Difficult to scale-up and not practical. • The resulting batch was filtered. • Solids not dissolved in n-butanol were dried and sampled as SP379/17I(0.07g). • Liquors were evaporated to give a white solid sampled as SP379/17J(0.02g). E_xperiment SP379/17 (Part A) SP379/17 Input 50.0g, 0.4% w/w, 200gA 50.0g, 0.4% w/w, 200gA Output Purity (% area) 79.9 89.9 Output Assay (% w/w) 5.2 61 Active Output (g) 0.411 0.19 Yield (%) - 95 EXAMPLE 2 - Silica Gel / Cellulose Chromatography Approach • Based on J. Nat. Prod.1981, 44, 362365. • Process reported in paper: o Extract residue from mushrooms into MeOH. o Prep TLC (not suitable for scale up could use silica gel chromatography). o Swapped from MeOH to n-BuOH /water (quantities not reported). o Chromatographed on cellulose powder column (ratio of active psilocybin to stationary phase unknown). ▪ 5 mL fractions with psilocybin obtained in fractions 32-42. ▪ Reported that product obtained as colourless needles (crystallise in fraction tubes? Concentrated to dryness?). o Further n-BuOH /water recrystallisation. o INPUT: 16 g of mushrooms, OUTPUT: 4 mg of psilocybin. o Structural elucidation and characterisation confirmed but no purity or assay data (as is typical with academic research papers). • Silica gel chromatography based on J. Nat. Prod.1981, 44, 362-365. • 150.9 g input, concentrated by ~50%. • Silica gel column procedure: o Concentrated methanolic extract loaded onto column. o Column eluted with methanol (120 mL, 4 column volumes, SP379/18A). ▪ Orange oil, 29.60 g, 1.0% w/w. o Column eluted with 5% aq. Ammonium hydroxide/methanol (9:91, 240 mL). ▪ Black band collected in fractions 4-16, confirmed to be UV active component at Rf 0.38 (TLC). ▪ Concentrated to dryness to give a brown oil, 3.90 g, 21.5% w/w, 90.8%area (SP379/18B). ▪ SP/379/18 dried further by azeotropic distillation with IPA to give brown residue (1.86 g, ~ 45%w/w assay). o Cellulose column preparation: o Cellulose significantly swelled, difficult to pack – potentially difficult to scale up. o Solvent quite viscous, slower packing. o Solvent changed to 5% v/v water in methanol due to SP379/17. o Some cracks at the end of the packing. ▪ Cellulose column procedure: o Residue dissolved in 5% v/v water in methanol (30 ml) and loaded onto the column. o (Figure 3). o Column eluted with 5% v/v water in methanol (~750ml). o Fractions 8-29 combined and concentrated to dryness to give an amber solution. ▪ IPA(50 ml) charged to the solution. o Precipitation of psilocybin forming a white slurry. ▪ Slurry filtered and wash with IPA(10 ml). o White solid (0.53 g) sampled as SP379/19A. ▪ 91%assay, 99.6%area(to be re-run due to baseline). o Liquors sampled as SP379/19B. ▪ The solid (0.49 g) was recrystallised in water (13 ml) at 60-65°C and then cooled to 3- 7°C over 2 hours. ▪ Slurry was stirred for 30 min at 3-7°C, filtered and washed with pre-cooled water (1.5 ml). o White solid (0.43 g, 88%recovery) sampled as SP379/19C. o Liquors sampled as SP379/19D. Experiment SP379/18 + SP379/19 SP379/20 100.05g, 0.6% w/w, 0.600 Input 150.94g, 0.4 w/w, 0.603 gA gA Output Purity (% area) 99.8 99.8 Output Assay (% w/w) 97.0 97.6 Active Output (g) 0.391 0.266 Yield (%) 65 44 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 practised 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. All parameters, dimensions, materials, quantities and configurations described herein are examples only and may be changed depending on the specific embodiment. Numbers and percentages are given to the nearest significant figure. For example, 10% includes the range between exactly 9.5% and exactly 10.5%. 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.

Claims

CLAIMS 1. A process for obtaining a purified psychoactive alkaloid, the process comprising: a) providing and extract of a psychoactive alkaloid from a psychoactive alkaloid source; b) contacting the psychoactive alkaloid extract with a first adsorbent material to obtain an adsorbed psychoactive alkaloid; c) eluting the adsorbed psychoactive alkaloid using a first solvent to obtain a purified psychoactive alkaloid solution; d) contacting the purified psychoactive alkaloid solution with a second adsorbent material to obtain an adsorbed psychoactive alkaloid; e) eluting the adsorbed psychoactive alkaloid using a second solvent to obtain a second purified psychoactive alkaloid solution; f) removing water from the second purified psychoactive alkaloid solution by the addition of another liquid that forms an azeotrope with the water to form a purified psychoactive alkaloid.

2. A process as claimed in claim 1 wherein the first adsorbent material comprises silica based material.

3. A process as claimed in claim 2 wherein the first adsorbent material comprises particles of silicon dioxide.

4. A process as claimed in claim 3 wherein the first adsorbent material additionally comprises a linear alkylsilane phase bonded to a surface of the silicon dioxide particles.

5. A process as claimed in claim 4 wherein the linear alkylsilane phase is octyldecylsilane and contains 18 carbons bonded to a surface of the silicon dioxide particles.

6. A process as claimed in any preceding claim wherein the second adsorbent material is cellulose based.

7. A process as claimed in claim 6 wherein the second adsorbent material comprises cellulose microspheres or powder.

8. A process as claimed in claim 1 wherein the first and second adsorbent materials are the same or different.

9. A process as claimed in any preceding claim wherein the first and second solvents are water, an organic solvent or a combination thereof, under basic, acidic or neutral pH.

10. A process as claimed in any preceding claim wherein the liquid that forms an azeotrope with the water is an alcohol including isopropyl alcohol.

11. A process as claimed in any preceding claim wherein the purified psychoactive alkaloid from step f) is recrystallised.

12. A composition comprising a purified psychoactive alkaloid obtained by a process as claimed in any one of claims 1-11.

13. A composition as claimed in claim 12 for use in a method for the treatment of addiction, post-traumatic stress disorder, anxiety, depression, cluster headaches, and other illnesses.

14. Use of a purified psychoactive alkaloid obtained by a process as claimed in any one of claims 1-11 in the manufacture of a medicament for use in a method for the treatment of addiction, post-traumatic stress disorder, anxiety, depression, cluster headaches, and other illnesses.

5. A process or composition as claimed in any preceding claim wherein the psychoactive alkaloid is psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin, aeruginascin, bufotenin, bufotenidine, 5-MeO-DMT (5-methoxy-N.Ndimethyltryptamine), N,N- dimethyltryptamine (DMT), 4-hydroxytryptamine, N,N,N-trimethyl-4- hydroxytryptamine ergine (LSA), ergonovine, ergometrine, muscimol, ibotenic acid, lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine, and/or chanoclavine, or any combination selected therefrom.