CA3103707C - Standardized psychoactive alkaloid extract composition - Google Patents

Abstract

A psychoactive alkaloid composition having, by weight, 0.1-99.9% of a psychoactive alkaloid extract, and 0.1-99.9% excipient. The psychoactive extract may have 0.1-99% psychoactive alkaloid concentration depending on the purification steps. The excipients include a carrier, a flow agent and/or a preservative. The composition is standardized to a desired, specific amount of psychoactive alkaloid, which may be accurately defined, and is repeatable from batch to batch. The composition can be in a free-flowing powder form, and thus easy to handle during a packaging or tabulation process. The composition may also include other excipients.

Description

Standardized Psychoactive Alkaloid Extract Composition TECHNICAL FIELD
[0001] This application relates to a composition. Particularly, this application relates to psychoactive alkaloid compositions comprising a natural extract.
BACKGROUND

[0002] 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 following information constitutes prior art against the present invention.

[0003] A psychoactive substance is a chemical substance that changes brain function and results in alterations in perception, mood, consciousness, cognition, or behavior.
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, or as entheogens for ritual, spiritual, or shamanic purposes. Some categories of psychoactive compounds have also shown therapeutic value and are prescribed by physicians and other healthcare practitioners.

[0004] 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 Date Recue/Date Received 2020-12-18 immense interest from researchers as therapeutic agents for treating various conditions like alcoholism, opioid addiction, pain to name a few.

[0005] However, naturally occurring psychoactive alkaloid comprising species have inconsistent and often low contents of active psychoactive alkaloid (e.g. 0.1-1% dry wt).
Considering fresh weight, this would mean a further 20X reduction in content due to the large moisture content of, for example, fresh mushrooms. The content of psychoactive alkaloid in natural sources depends on various factors such as the type of source, harvesting season, and type of extraction process, to name a few. Thus, the lack of compositions having a specific desired psychoactive alkaloid content with no or minimal variability between different batches is a major issue.

[0006] Maintaining physical and chemical stability is another challenge with psychoactive alkaloid compositions. Usually a psychoactive alkaloid extract is in the form of a sticky tar, which would difficult to handle and formulate into standardized compositions with specified amounts of ingredients. Extracts are not usually amenable to processing due to poor flowability. Extracts themselves are often not amenable to drying because many of the components that are pulled out of a plant or fungus with a lower alcohol solvent are not "dry" at room temperature (reduced sugars, oils and waxes for example). These same compounds even in low concentration can cause the product to be hygroscopic and become clumpy, which makes encapsulation impossible, and makes tabulation difficult because the powder will not "flow" in the equipment.

[0007] Thus, exposure to moisture causes psychoactive alkaloid extracts to absorb moisture to form clumps and become susceptible to microbial growth. Further, the alkaloids in these extracts can degrade, usually because of oxidation.
SUMMARY OF INVENTION

[0008] The primary aim of the invention is to standardize the amount of psychoactive alkaloid present in the composition. Depending on the embodiment, and the specific types of excipient added, a secondary, optional aspect of the invention is the provision of a psychoactive alkaloid extract in the form of a dry, flowable and shelf-stable powder. The Date Recue/Date Received 2020-12-18 powder may be used as a dietary supplement or medicine and can be added to various edible products, tablets, or capsules, or it may be used for medical research, including the study of the treatment of mental illnesses.

[0009] By increasing the active alkaloid concentration through extraction and then titrating back to a lower, standardized alkaloid concentration, the product achieves consistency in bioactive content from lot to lot. By the addition of specific types of excipient, flowability and stability may also be improved in the composition, as compared to the extract.

[0010] A useful formulation needs to contain a minimum amount of the active ingredient and also be of an acceptable total size. For example, a psilocybin dose might be 25 mg. If this is required in a single capsule and the powder has a concentration of the active ingredient of only 1%, then 2500 mg of powder would be needed. This would be too much for a single capsule. However, if the extract can be concentrated to approx. 15%, then there is room to add an excipient to get it down to say, a repeatable 10%, which now means that only 250 mg of powder is needed in the capsule, which is an acceptable size.

[0011] While the concentration of psychoactive alkaloid in the composition may, in some embodiments, be lower than that found in some of the source raw material (mushrooms or seeds for example), it is a known concentration, which can be stable from batch to batch, eliminating the variability found in the natural sources. This allows for control and standardization of the dose, even if it is lower than some of the raw materials themselves.

[0012] Disclosed herein is a psychoactive alkaloid composition consisting essentially of, by weight: 0.1-99.9% of a psychoactive alkaloid extract; a preservative up to 10%, a flow agent up to 2%, or both the preservative up to 10% and the flow agent up to 2%; and 0-94% of a carrier.

[0013] This summary does not necessarily describe all features of the invention.

Date Recue/Date Received 2020-12-18 BRIEF DESCRIPTION OF DRAWINGS

[0014] The following drawings illustrate embodiments of the invention, which should not be construed as restricting the scope of the invention in any way.

[0015] FIG. 1 illustrates steps of a process for obtaining a standardized psychoactive alkaloid composition, according to an embodiment of the present invention.

[0016] FIG. 2 illustrates a process for extracting psychoactive alkaloid from Psilocybe cubensis, according to an embodiment of the present invention.

[0017] FIG. 3 illustrates detailed steps of a process for purifying psychoactive alkaloid from Psilocybe cubensis, according to an embodiment of the present invention.

[0018] FIG. 4 is a schematic diagram of the apparatus used for obtaining a psychoactive alkaloid composition, according to an embodiment of the present invention.
DESCRIPTION
A. Glossary

[0019] 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.

[0020] As will be understood by one skilled in the art, for any and all purposes, such as in terms of providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, etc.
As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, etc. As will also be understood by one skilled in the art, Date Recue/Date Received 2020-12-18 all language such as "up to," and the like include the number recited, and any tolerance explicitly or implicitly associated with it, and refer to ranges which can be subsequently broken down into subranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member.

[0021] 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-Me0-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 source of the psychoactive alkaloid can also be another extract or a solution comprising a psychoactive alkaloid.

[0022] The term "psychoactive alkaloid extract" or "extract" refers to a psychoactive alkaloid extract that is obtained after a psychoactive alkaloid source has been extracted 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.

[0023] 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.

[0024] The "impurities" herein are commonly undesired, but not necessarily harmful, substances encountered while extracting psychoactive alkaloids from a natural source.
Date Recue/Date Received 2020-12-18 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.

[0025] 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.

[0026] 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.

[0027] The term "adsorbed psychoactive alkaloid" refers to one or more alkaloids that are adsorbed onto an adsorbent material such as a resin.

[0028] The term "psychoactive alkaloid composition" or "composition" or "standardized composition" or "standardized purified composition" is used herein to describe a composition including a psychoactive alkaloid extract or a purified psychoactive alkaloid extract, which has been standardized by the addition of excipients according to a presently described process. The standardized psychoactive alkaloid composition includes the psychoactive alkaloid in a specific amount.

[0029] The term "standardization" when used herein refers to a process for obtaining a standardized psychoactive alkaloid composition, i.e. a composition with a defined concentration by weight of psychoactive alkaloid.

[0030] 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.

[0031] The term "% wt" is used to describe the weight percentage of one component in a mixture of components.

[0032] The term "resin" used herein is intended to refer to a solid or highly viscous substance of plant or synthetic origin that is typically convertible into polymers. Resins are Date Recue/Date Received 2020-12-18 usually mixtures of organic compounds. Resins 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.

[0033] As used herein, the term "ion exchange resin" refers to an insoluble organic polymer containing charged groups that attract 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 attract and hold anions present in a surrounding solution and are sometimes referred to as "anionic ion-exchange resins". Similarly, ion exchange resins to be used herein contain anionic groups that attract and hold cations present in a surrounding solution and are sometimes referred to as "cationic ion-exchange resins".

[0034] The term "macroporous resin" used herein refers to a member of a class of very small, highly cross-linked polymer particles. Macroporous resins are generally used for the absorption of organic constituents due to their hydrophobic properties and thus 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.

[0035] 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.

Date Recue/Date Received 2020-12-18

[0036] 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.

[0037] 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 starch, maltodextrin, tapioca maltodextrin or rice maltodextrin, alpha and beta cyclodextrin, microcrystalline cellulose (MCC), gum arabic, xanthum gum, guar gum, or cellulose gum.

[0038] 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.

[0039] 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.

[0040] 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 Date Recue/Date Received 2020-12-18 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.

[0041]
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.
B. Composition

[0042] In some embodiments, the present invention relates to a composition having, by weight, 2-99.7% of a psychoactive alkaloid extract, and 0.3-98%, i.e. the remainder, being one or more excipients.

[0043] While a broad range of psychoactive extract is possible, if it is above 90% (e.g. as much as 99.9%) it is likely not to be dryable and/or flowable. Nevertheless, such a composition, when standardized, may still have its uses, due to the reliability and repeatability of the psychoactive alkaloid content. Below about 2%, the composition may be considered to provide too low a dose of psychoactive alkaloid. However, compositions with less than 2% (e.g. down to 0.1%) may be possible if micro-dosing is desired.

[0044] In some embodiments, the psychoactive alkaloid extract has a psychoactive alkaloid concentration ranging from 0.1% to 99% by weight of the extract.
Typically 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 Date Recue/Date Received 2020-12-18 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.

[0045] In other embodiments, the psychoactive alkaloid extract includes naturally occurring substances selected from fats, sugars, carbohydrates, and proteins, or any combination selected therefrom. The aforesaid naturally occurring substances do not lead to any side effects or adverse effects when ingested as a part of the composition.

[0046] The naturally occurring substances are present in the psychoactive alkaloid extract in a concentration ranging from 1 - 99.9% by dry weight. The concentration range of the naturally occurring substances in the psychoactive alkaloid extract will vary due to various factors for example, but not limited to, the source of the psychoactive alkaloid extract, the extraction technique used, the efficiency of the extraction process, and the amount of the psychoactive alkaloid in the extract.

[0047] In some embodiments, the psychoactive alkaloid extract includes the psychoactive alkaloid and the naturally occurring substances.

[0048] The psychoactive alkaloid extract of the composition low in (e.g. <20%) or almost free of undesired impurities allows a smaller amount of the composition to achieve a desired therapeutic effect than if the extract were less concentrated, with more impurities.

[0049]
The excipients described herein refer to excipients to aid in the manufacturing and/or administration of the compositions described herein. Non-limiting examples of such excipients are known in the art and 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, 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.

[0050] In some embodiments, the excipient is a carrier, a flowability agent, a preservative or any combination selected therefrom. The amount of excipient in the composition will vary depending on the desired amount of the psychoactive alkaloid Date Recue/Date Received 2020-12-18 extract in the composition, and on the concentration of psychoactive alkaloids in the extract. It will also depend on the degree of flowability required and the stability required.

[0051] In some embodiments, the excipients include a flowability agent, in an amount up to 2% by weight of the composition. Above 2%, little extra benefit is gained. In other embodiments, the excipients include a flowability agent in a concentration equal to or less than 2% by weight of the composition. In some embodiments, the flowability agent is silicon dioxide. In other embodiments, the flowability agent is magnesium stearate, stearic acid or talc, or is selected from any other known, suitable flowability agent.
A combination of any of these flowability agents may be used. It is also envisaged that other flowability agents can be used. The impurities present in the extract tend to have a negative effect on the flowability, and flow agents are added to counter these effects. While there are known methods of measuring flowability, this is not always necessary as the product's lack of adequate flowability is often very evident when one handles the product.

[0052] In some embodiments, the excipients include a carrier, in an amount up to 94%
by weight of the composition. In some embodiments, the excipients include a carrier ranging from 10-94% by weight of the composition.

[0053] In some embodiments, the carrier is maltodextrin, or in other embodiments it is microcrystalline cellulose, coconut flour or corn starch, or any other known, suitable carrier. A combination of any of these carriers may be used. It is also envisaged that other carriers can be used.

[0054] The preservative is selected from ascorbic acid, citric acid, lactose, vitamin A, vitamin E, retinyl palmitate, selenium, sodium citrate, sodium ascorbate, calcium ascorbate, sodium benzoate, and potassium benzoate. A combination of any of these preservatives may be used. It is also envisaged that other preservatives can be used.

[0055] In some embodiments, the excipients include a preservative, up to 10%
by weight of the composition. In some embodiments, preservatives are not added to the composition. There may be cases where a preservative is not required, or not wanted in the final product, and so the concentration of preservative will be 0%. At a certain point (>10% in this example), the preservative will not give any further benefit, and so the upper limit of preservative is 10%.

Date Recue/Date Received 2020-12-18

[0056]
The composition of the present invention is 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.

[0057] 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.

[0058] The main consideration is that, depending on the source material's concentration and the efficiency of the extraction, the concentration of the extract needs to be blended down to the required value of standardization. This dictates the amount of excipient for each batch, which may be different. Therefore, the amount of excipient that can be added can be anywhere between say 0.100% to 99.9%, depending on the source concentration before blending. The other excipient components may be held relatively constant between batches, or within a much narrower range (i.e. 0-2% flowability agent, 0-10%
preservative, 0-0.5% antioxidant, 0-0.5% bioavailability agent).
C. Basic Standardization Process

[0059] In one embodiment, referring to FIG. 1, a basic process for obtaining the composition is shown. The process includes the step 10 of extracting a psychoactive alkaloid from a psychoactive alkaloid source to obtain a psychoactive alkaloid extract. The extract from the psychoactive alkaloid source may be a fluid, as either a liquid or a slurry, or is made into a fluid by the addition of a solvent. In one embodiment, the extraction step is followed by completely or partially concentrating the obtained psychoactive alkaloid Date Recue/Date Received 2020-12-18 extract (or solution) by evaporation of the solvent from the extract. In other embodiments, partially or completely evaporating the solvent may be considered to be part of the extraction step 10. If the solvent from the extract has been completely evaporated, then water, more solvent or another solvent is added back.

[0060] In step 12, the extract obtained is filtered, followed by concentration to obtain a concentrated psychoactive alkaloid extract. Filtration is performed by any suitable known technique.

[0061] In step 14, the concentrated psychoactive alkaloid extract is then standardized by adding one or more excipients to the extract, followed by drying to obtain the standardized psychoactive alkaloid composition. The concentration of alkaloids in the extract is measured and the proportion of dry weight in the extract is calculated. Based on this concentration and dry weight content, the amount of excipient to be added is chosen to result in a powered composition with a specific amount of psychoactive alkaloid when the concentrated extract is dried.

[0062] The drying can be achieved by any technique known in the art for drying moist compositions including, for example, spray drying or freeze drying.
D. Extraction

[0063] In some embodiments, referring to FIG. 2, a process for extracting the psychoactive alkaloid is shown. The psychoactive alkaloid source is dried in step 16 by techniques known in the art, such as using a forced air oven.

[0064] In step 18, the dried psychoactive alkaloid source or dried biomass is mixed with a solvent and/or left to soak. The solvent in which the extract is carried or dissolved may be a primary aliphatic alcohol, a ketone, water, and any combination selected therefrom.
In some embodiments, the primary aliphatic alcohol is a C1-4 alcohol. In some embodiments, the primary aliphatic alcohol is 5% ethanol. In some embodiments, the primary aliphatic alcohol is ethanol. In some embodiments, the ketone is a C3-4 ketone. In yet other embodiments, the water is selected from deionized, distilled, reverse osmosis, or otherwise purified water, which is substantially without free ions. In other embodiments, Date Recue/Date Received 2020-12-18 the water is not purified. In an exemplary embodiment, the solvent is a hydro-ethanol mixture with 3 parts of ethanol to 1 part of water, by weight.

[0065] In step 20, the mixture of the solvent and the dried psychoactive alkaloid source is filtered to obtain a filtrate and a filtrate residue. Some or all of the solvent is evaporated from the filtrate residue to obtain the psychoactive alkaloid extract.
Standardization of the obtained psychoactive alkaloid extract is carried out according to the standardization step 14 described above.

[0066] Optionally, the filtrate residue obtained in step 20 is extracted with the solvent again. The filtrate residue is extracted by repeating the steps 18 and 20.
This results in another filtrate. The first filtrate and the second filtrate are mixed together after their respective filtration steps to result in a bulk filtrate. The solvent from this bulk filtrate is partially evaporated to obtain the psychoactive alkaloid extract in a slurry form for the standardization step 14.

[0067] In one embodiment, the extraction is carried out at a temperature ranging from 5-95 C. The useful temperature range spans most of the liquid state of the solvent used, and upper and lower limits are determined by physical practicalities and limits of the available apparatus. Still, the temperature of the solvent may be outside of this range in other embodiments.

[0068] In other embodiments, the extraction is carried out at a temperature of 70 C.
Temperature, and pressure if applied, are generally selected so that the solvent does not boil if elevated temperatures are used. In one embodiment, the extraction is carried out for a time duration ranging from 10 minutes to 12 hours. In yet another embodiment, the extraction is carried out for a time duration of 4 hours.
E. Purification Process

[0069] In some embodiments, referring to FIG. 3, a process for purifying the psychoactive alkaloid extract obtained in step 12 (FIG. 1) or step 20 (FIG. 2) is shown.

[0070] The process includes adding, in step 22, an acid or a base to the psychoactive alkaloid extract previously obtained, to result in a specific pH psychoactive alkaloid solution.

Date Recue/Date Received 2020-12-18

[0071] 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.

[0072] 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 selected therefrom. In one embodiment, the base is solely sodium hydroxide, for example. Other bases may be used in other embodiments.

[0073] In some embodiments, the specific pH psychoactive alkaloid solution has a pH
ranging from 2.5-4.5, or from 9-10. In other embodiments, the specific pH
psychoactive alkaloid solution has a pH of 3, 4, or 9.5. The selection of the pH is chosen in a manner to allow for the efficient adsorption of the psychoactive alkaloids onto the resin(s).

[0074] The process optionally includes partially evaporating the solvent from the specific pH psychoactive alkaloid solution.
Date Recue/Date Received 2020-12-18

[0075] The process optionally includes filtering, centrifuging, or clarifying the psychoactive alkaloid solution or specific pH psychoactive alkaloid solution, as the case may be, and utilizing the obtained filtrate for the next step 24 of adsorption. Clarifying may be performed, for example, by adding an agglomeration agent.

[0076] In step 24, the process involves adsorbing the psychoactive alkaloid(s) in the specific pH psychoactive alkaloid solution onto a resin to obtain an adsorbed psychoactive alkaloid.

[0077] In step 26, the process involves washing the resin to remove adsorbed impurities from the resin. While not all the impurities are adsorbed onto the resin, some of them may be. The washing step, substantially, does not remove the adsorbed psychoactive alkaloids. The washing solvent may be 100% ethanol, 100% reverse osmosis water, or any other washing solvent used in ion-exchange resin chromatography, provided that the washing removes impurities or by-products that are adsorbed on the resin.
Impurities or by-products may include, for example, sugars, carbohydrates, chitin, chitosan, fats, minerals, waxes, or proteins. There may be one, two or more washing steps depending on the embodiment, and the same or different washing solvents may be used for each wash.

[0078] In other embodiments, the solvent(s) for washing may include a primary aliphatic alcohol, a ketone, water, and any combination selected therefrom. In some embodiments, the primary aliphatic alcohol is a C1-4 alcohol. In some embodiments, the primary aliphatic alcohol is 5% ethanol. In some embodiments, the primary aliphatic alcohol is ethanol. In some embodiments, the ketone is a C3-4 ketone. In yet other embodiments, the water is selected from deionized, distilled, reverse osmosis, or otherwise purified water that is substantially without free ions.

[0079] After the washing, the process involves eluting, in step 28, the adsorbed psychoactive alkaloid from the resin using a solvent to obtain a purified psychoactive alkaloid extract. The solvent may be an organic solvent, an acid, a base, or water, a combination of an organic solvent and a base, or a combination of an organic solvent and an acid, a combination of an organic solvent and water, a combination of water and a base, or combination of water and an acid. The solvent from the purified psychoactive Date Recue/Date Received 2020-12-18 alkaloid extract is partially evaporated to obtain the purified psychoactive alkaloid extract in a slurry form for the standardization step 14.

[0080] In some embodiments, the solvent used in the elution step 28 may be a alcohol, a C3-4 ketone, water, and any combination selected therefrom. In one embodiment, the primary aliphatic alcohol is 5% ethanol. In yet another embodiment, the water is deionized, distilled, reverse osmosis, or otherwise purified water, which is substantially without free ions. In one embodiment, the solvent used in the elution step 14 is a combination of an organic solvent and an acid. In general, any acidic environment will displace some of the ions from the resin, but the rate and optimization of the desorption will be affected by the acid concentration. In one embodiment, the solvent used is a combination of an organic solvent and a base. In general, any basic environment will displace some of the ions from the resin, but the rate and optimization of the desorption will be affected by the concentration of the base.

[0081] All the above solvents and combinations thereof are suitable for the elution step because all of the psychoactive alkaloids of interest are soluble therein and, depending on the choice of resin, they are all capable of pulling the alkaloids of interest off a resin.
There are many different resins available, and it is a straightforward matter to select a suitable resin and elution solvent pair.

[0082] In one embodiment, the elution step is carried out at a temperature in the range of 4-75 C. These temperatures are limited by the boiling point of the solvent used, as well as the specifications of allowable food-grade resins, as determined by the manufacturers of the resins and governmental food and drug administrations. In another embodiment, the elution step is carried out at room temperature for convenience, i.e. at 21-25 C.

[0083] In other embodiments, the process for obtaining the purified psychoactive alkaloid extract further includes repeating the steps 22 to 28 with the purified psychoactive alkaloid extract obtained in step 28 to obtain a further or twice purified psychoactive alkaloid extract. For the repeated steps in these embodiments, the resin may be the same or a different resin, and the solvent may be the same or a different solvent. While the purified psychoactive alkaloid extract may have a low psychoactive alkaloid content, this may be increased by evaporation of some or all of the solvent.

Date Recue/Date Received 2020-12-18 F. Variations

[0084] The psychoactive alkaloid source may be a fungus, a mycelium, an animal, a spore, a plant, a bacterium, 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-Me0-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, or any combination selected therefrom. It is possible that other psychoactive alkaloids, not yet discovered, may also be extracted using the methods disclosed herein.

[0085] 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.

[0086] In some embodiments, the resin is an adsorbent resin of the macroporous type, such as a cation or anion ion-exchange resin, a non-ionic resin, or any combination selected therefrom. Representative pharmaceutical, nutraceutical or food-grade grade resins for use in accordance with the present invention are known to those skilled in the art. For example, pharmaceutical grade non-ionic macroporous resins are commercially available, e.g. Amberlite XAD4. In one embodiment, the resin is a cationic ion-exchange resin or an anionic-exchange resin. The cationic ion-exchange resin may be selected from commercially available cationic ion-exchange resins known in the art, including but not limited to Amberlite MAC-3 H. The cationic ion-exchange resin may be in an H+
form or an Na+ form. The anionic ion-exchange resin may be selected from commercially available anion exchange resins known in the art, including but not limited to Amberchrom 50WX8. The anionic ion-exchange resin may be in an OH- form or a Cl-form. The resins used may be of any particle size. In some embodiments, the resins may be gel type resins, with any size of gel bead.

Date Recue/Date Received 2020-12-18

[0087] The concentration of psychoactive alkaloid in the purified psychoactive alkaloid extract may be different in other embodiments, depending on the amount of solvent used for the elution and the potency of the raw materials. In one embodiment, the purified psychoactive alkaloid extract is concentrated by evaporating the solvent to form a purified psychoactive slurry that has at least of 5% by weight or more of a psychoactive alkaloid.
In another embodiment, the purified psychoactive alkaloid slurry has 5-68% by weight of a psychoactive alkaloid. In yet other embodiments, the purified psychoactive alkaloid slurry has a concentration of psychoactive alkaloid outside these ranges, and, when dried, can be as low as 0.1% or as high as 99.9% dry wt/wt%.

[0088] In some embodiments, a bioavailability enhancing agent such as citric acid, beta cyclodextrin, or alpha cyclodextrin can be added (up to 0.5% by weight) as an excipient.
In other embodiments, an antioxidant agent such as ascorbic acid may be added (up to 0.5% by weight) as an excipient.
G. Examples

[0089] 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.

[0090] 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 baeocystin, norbaeocystin, norpsilocin, aeruginascin, bufotenin, bufotenidine, 5-Me0-DMT (5-methoxy-N,N-dimethyltryptamine), N,N-dimethyltryptamine (DMT), ergine (LSA), ergonovine, ergometrine, muscimol, ibotenic Date Recue/Date Received 2020-12-18 acid, lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine, and/or chanoclavine, to result in compositions with similar efficacy and efficiency as well. 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: Preparation of a non-purified psychoactive alkaloid extract

[0091] Fresh Psilocybe cubensis, 2.5 kilograms, was dried in a forced air oven at 25 C
for 5-10 hours, to result in 140 grams of dried biomass. The dried biomass was pulverized to a size of 200 mesh with a hammer mill. The dried powdered biomass was then placed into an agitated, heat-controlled vessel with 5 kilograms of solvent. The solvent was a hydro-ethanol mixture of 3 parts ethanol to 1 part water by weight. The extraction was controlled to a constant 70 C, and the time of extraction was 4 hours.

[0092] The extraction slurry was filtered while hot, and the filter residue was placed back into the extraction vessel, and extracted with an additional 5 kilograms of 3:1 ethanol:water mixture by weight. The temperature of extraction was again 70 C
and the time was 4 hours. The extraction slurry was filtered while hot and the filtrate from the first and second extraction were mixed together to obtain a bulk filtrate.

[0093] The bulk filtrate was immediately placed into a rotary evaporator and the solvent was concentrated in the rotary evaporator to obtain 186.6 g of the psychoactive alkaloid extract in form of a concentrated aqueous slurry at 30% solids, containing 700 mg of total alkaloids, which would be a concentration of 1.25% dry wt/wt%, if the slurry were to be dried.
Example 2: Preparation of a purified psychoactive alkaloid extract

[0094] Fresh Psilocybe cubensis, 2.5 kilograms, was dried in a forced air oven at 25 C
for 5-10 hours, resulting in 140 grams of dried biomass. The dried biomass was then pulverized to a size of 200 mesh with a hammer mill. The dried powdered biomass was Date Recue/Date Received 2020-12-18 placed into an agitated, heat-controlled vessel with 5 kilograms of solvent.
The solvent used was a hydro-ethanol mixture of 3 parts ethanol to 1 part water by weight.
The extraction was controlled to a constant 70 C, and the time of extraction was 4 hours.

[0095] The extraction slurry was filtered while hot, and the filter residue was placed back into the extraction vessel, and extracted with an additional 5 kilograms of 3:1 ethanol:water mixture by weight. The temperature of extraction was again 70 C
and the time was 4 hours. The extraction slurry was filtered while hot and the filtrate from the first and second extraction were mixed together to obtain a bulk filtrate. The bulk filtrate was left to cool, in case any precipitate had formed, the insoluble material was filtered out and discarded.

[0096] The bulk filtrate's pH was then adjusted to 9.5 (+/- 0.5) with 1 M
NaOH to form a specific pH psychoactive alkaloid solution. This solution was then mixed with 150g of Amberchrom 50WX8 Strong Anion Exchange resin in its hydrogen form. The solution was agitated for 4 hours and then filtered. The filtrate was discarded. The resin was rinsed with 2.0 L of 100% Et0H and then 2.0 L of H20. Finally, the psilocybin fraction was eluted with 2.0 L of 2% NaCI / 80% Et0H for 4 hours.

[0097] The eluted fraction was brought to a pH of 4.0 with 2 M HCI to result in another specific pH psychoactive alkaloid solution. This solution was then centrifuged at 3000g to remove any solid precipitates. The solvent from the solution was then evaporated in a rotary evaporator to result in a volume of solvent evaporated was 400 mL.

[0098] This solution was again centrifuged for 15 minutes at 3000g to remove any solid precipitate. The supernatant was loaded onto a column of Amberlite XAD4 macroporous resin (45.53 g of dry resin) at a flow rate of 2 bed volumes per hour. All 400 mL of the extract was loaded onto the column and washed with 5 bed volumes of reverse osmosis water. The washing step was followed by elution with 5 bed volumes with 5% ethanol (by weight). A final washing was carried out with 100% ethanol.
Each of these fractions was collected separately. The 5% ethanol fraction was collected and concentrated in a rotary evaporator to obtain 1.143 g of 30% liquid slurry containing 175 mg of total alkaloids, a concentration of 54% dry wt/wt%.

Date Recue/Date Received 2020-12-18 Example 3.1: Preparation of a psychoactive alkaloid composition with a non-purified psychoactive alkaloid extract

[0099] The psychoactive alkaloid extract obtained in example 1 was mixed with 2.8 g of silicon dioxide (flow agent), 0.140 g of ascorbic acid (preservative), and 81.06 g of tapioca maltodextrin (carrier). The final formulated slurry was then subjected to spray-drying and 140 g of the standardized powdered composition was produced with the desired specific amount of psychoactive alkaloid. The total psilocybin/psilocin concentration by dry weight was 0.5% in this composition. The exact weight percentages of the components in the composition are depicted TABLE 1.
Example 3.2: Preparation of a psychoactive alkaloid composition with a purified psychoactive alkaloid extract

[0100] The purified psychoactive alkaloid extract obtained in example 2 was mixed with 5.85 mg of ascorbic acid (preservative) and 822 mg of rice maltodextrin (carrier). The final formulated slurry was then subjected to lyophilization and 1.171 g of the standardized powdered composition was produced. The total psilocybin/psilocin concentration by dry weight was 15.01% in the composition. The exact weight percentages of the components in the composition are depicted TABLE 1.
Example 3.3

[0101] A purified psychoactive alkaloid solution resulting from resin treatment after extraction from 140 g of dried Psilocybe cubensis was concentrated in a rotary evaporator to form 3.90 g of concentrated aqueous slurry at 30% solids, containing 195.1 mg of total psychoactive alkaloids. The slurry, with a psychoactive alkaloid concentration of 5.00% by weight, was mixed with 0.03 g of SiO2, 0.02 g of ascorbic acid and 2.55 g of maltodextrin.
This standardized slurry was then subjected to spray-drying, and a final powdered alkaloid extract with a 5.00% total psilocybin, psilocin, baeocystin and norbaeocystin concentration by dry weight was obtained.

Date Recue/Date Received 2020-12-18 Example 3.4

[0102] An extract from 140 g dried Psilocybe cubensis mushrooms using a 75%

ethanol solvent resulted in a concentrated slurry, for which the alkaloid content was 2.16 g and the total solid content was 46.4 g. To the slurry, 4.7 g of ascorbic acid, 1.9 g of SiO2 and 47 g of maltodextrin were added. After spray drying, this resulted in 100 g of powdered psychedelic mushroom extract with a total alkaloid concentration of 1.00% by weight.
Example 3.5

[0103] Psychoactive compounds were extracted from 140 g of dried Psilocybe cubensis using 100% reverse osmosis water as the solvent. Water was evaporated to result in a concentrated slurry, for which the alkaloid content was 1.82 g and the total solid content was 68.18 g. In this example, 6.3 g of ascorbic acid, 2.5 g of SiO2 and 63 g of maltodextrin are added to the concentrated slurry, which was then dried. This resulted in 140 g of powdered psilocybin mushroom extract with a total alkaloid concentration of 0.50% by weight.
Example 3.6

[0104] An extraction of psychoactive compounds from 140 g dried Psilocybe cyanescens mushrooms was performed using 100% methanol as the solvent. The extraction slurry was filtered to remove residue with undissolved Psilocybe cyanescens from the filtrate. All the methanol was evaporated from the filtrate, then 1.25 liters of reverse osmosis water at room temperature was added to the remaining solid to form a slurry, for which the alkaloid content was 2.87 g and total solid content was 47.14 g. Next, 1.84 g of SiO2 and 46 g of maltodextrin were added to the slurry, which was then dried.
This resulted in 95 g of powdered psychedelic mushroom extract with a total alkaloid concentration of 1.50% by weight.

Date Recue/Date Received 2020-12-18 Example 3.7

[0105] An extract obtained according to example 2 was used as the starting point.
Compared to example 3.2, greater amounts of preservative (351 mg), flow agent (351 mg) and carrier (16.515 g) were added to the composition. This resulted in a standardization of the amount psychoactive alkaloid in the composition to 1.00% instead of 15.01%.
Example 3.8

[0106] A purified psychoactive alkaloid solution resulting from resin treatment after extraction from 140g of dried Psilocybe cubensis was concentrated in a rotary evaporator to form 3.90 g of concentrated aqueous slurry at 30% solids, containing 195.1 mg of total psychoactive alkaloids. Compared to example 3.3, greater amounts of preservative (0.49 g), flow agent (0.39 g) and carrier (18.43 g) were added to the composition. This resulted in a standardization of the amount psychoactive alkaloid in the composition to 1.00% instead of 5.00%.
Example 3.9

[0107] A purified psychoactive alkaloid solution was obtained after multiple cation exchange resin treatments following extraction from 140g of dried Psilocybe cubensis.
Silicon dioxide, maltodextrin and ascorbic acid were added to form a composition standardized to 60.00%.
Example 3.10

[0108] This is as example 3.9, except that the only excipient that was added was preservative (ascorbic acid). This resulted in a standardization of the psychoactive alkaloid content of the composition to 75.00%.

[0109] The exemplary compositions obtained are depicted in TABLE 1.
Compositions of examples 3.1 and 3.4-6 are compositions with a psychoactive alkaloid extract that has not been purified. Compositions of examples 3.2, 3.3 and 3.7-10 are compositions with a purified psychoactive alkaloid extract.

Date Recue/Date Received 2020-12-18 Alkaloid Alkaloid Amount in Extract Preservative Flow Agent Carrier Total Amount in Standardized Mass Mass Mass Mass Mass Extract Composition Ex. (dry %) (dry %) (dry %) (dry %) (dry %) (wt/wt%) (wt/wt%) 3.1 40.0 0.1 2.0 57.9 100.0 1.25 0.50 3.2 29.3 0.5 0.0 70.2 100.0 51.23 15.01 3.3 31.0 0.5 0.8 67.6 100.0 16.12 5.00 3.4 46.4 4.7 1.9 47.0 100.0 2.16 1.00 3.5 48.7 4.5 1.8 45.0 100.0 1.03 0.50 3.6 49.6 0.0 1.9 48.4 100.0 3.02 1.50 3.7 2.0 2.0 2.0 94.0 100.0 51.23 1.00 3.8 6.2 2.5 2.0 89.3 100.0 16.12 1.00 3.9 79.6 5.0 1.0 14.4 100.0 75.22 60.00 3.10 99.7 0.3 0.0 0.0 100.0 75.22 75.00 In the columns, the extract mass (dry %), preservative mass (dry %), flow agent mass (dry %), and carrier mass (dry %) are the dry weight percentages of the psychoactive alkaloid extract, preservative, flow agent and carrier in the standardized composition respectively. The total mass (dry %) is the total dry weight percentage of the standardized composition. The alkaloid amount in the extract (wt/wt%) is the dry weight percentage of the psychoactive alkaloid in the extract, as if the extract were in its dried state. Note that it is possible for the extract to remain in the slurry state as the excipients are added. The alkaloid amount in the standardized composition (wt/wt%) is the dry weight percentage of the psychoactive alkaloid in the final composition. It can be seen that a wide variability in extract concentration from different batches can be standardized to the same concentration in the composition, e.g. by looking at examples 3.4, 3.7 and 3.8.
Date Recue/Date Received 2020-12-18 F. Apparatus

[0110] Referring to FIG. 4, 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 dried biomass. The dried biomass was placed into a grinder 106 for grinding.

[0111] The dried powdered biomass was placed into a heat-controlled vessel 110 and solvent (S) was added to the heat-controlled vessel. The vessel 110 was surrounded by an insulating wall 108. Alternately, an insulating jacket can be 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 up to 100 MPa (15,000 psig).

[0112] 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 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.

[0113] After the two filtration stages, the filtrates were mixed in container 140 to obtain a bulk filtrate. In other embodiments, if there is only a single filtration step, this mixing step is not required.

[0114] The bulk filtrate was placed in a rotary evaporator 142 and part of the solvent was evaporated from the bulk filtrate. The resultant extract was transferred to a container 144, where the pH of the extract was adjusted, followed by centrifugation 146 to remove the solid precipitates. The resultant supernatant was loaded onto a column 150 of resin.
An initial wash was given to the column with a solvent to remove impurities from the resin, and fraction 154 was collected. A second wash was given to the column with another solvent to elute the psychoactive alkaloids from the column and result in fraction 156. A
final wash was given to the column with another solvent to wash any impurities from the Date Recue/Date Received 2020-12-18 column, to prepare the column for use again, and the fraction 158 was obtained. The elution fraction 156 with the psychoactive alkaloids was then concentrated in a rotary evaporator 160 to result in the purified psychoactive alkaloid extract.

[0115] In a container 164 the purified psychoactive alkaloid extract and desired excipients were added together and thoroughly mixed to result in a final standardized slurry having a specific amount of alkaloids. The final standardized slurry was then subjected to spray-drying 168 to obtain a final powdered composition 170 with a total psilocybin/psilocin concentration defined as a percentage to two decimal places or two significant figures by dry weight.

[0116] In other embodiments, parts of the apparatus may be reused or duplicated. For example, if desired, the elution fraction 156 may be reloaded into the container 144 for pH
adjustment and the steps from thereon can be repeated to allow for further purification of the obtained purified psychoactive alkaloid extract.

[0117] In one embodiment, the psychoactive alkaloid extract was obtained after evaporating the solvent from the bulk filtrate. The psychoactive alkaloid extract was transferred to a container 164 and desired excipients were added together, and thoroughly mixed to result in a final standardized slurry having a specific amount of alkaloids. The final standardized slurry was then subjected to spray-drying 168 to obtain a final powdered composition 170 with a total psilocybin/psilocin concentration defined as a percentage to two decimal places or two significant figures by dry weight.
H. Conclusion

[0118] Chemical and physical stability may be determined using rigorous stability testing protocols. This would be a necessary study for the product to be considered made using a good manufacturing process. The initial specifications and ongoing specifications of the extract should be determined during a testing regime over time, temperature, relative humidity etc. to determine the physical and chemical stability.
Studies are on-going, but a 5 year shelf life with a minimum of 2 years is targeted in terms of physical and chemical stability.

Date Recue/Date Received 2020-12-18

[0119] 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.

[0120] 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.

[0121] 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 flowcharts 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.

Date Recue/Date Received 2020-12-18

Claims (30)

PSU003-CANP

1. A powdered psychoactive alkaloid composition consisting essentially of, by weight:
0.1-90% of a psychoactive alkaloid extract from plant material, fungal material or both plant material and fungal material, wherein the psychoactive alkaloid extract comprises psychoactive alkaloid in a concentration of 0.1% to 99%
by weight of the psychoactive alkaloid extract, the psychoactive alkaloid being any selection from the group consisting of psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin, aeruginascin, bufotenin, bufotenidine, 5-MeO-DMT
(5-methoxy-N, N-d imethyltryptam ine), N,N-d imethyltryptamine (DMT), ergine (LSA), ergonovine, ergometrine, muscimol, ibotenic acid, lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine and chanoclavine, wherein the psychoactive alkaloid extract comprises naturally occurring substances selected from the group consisting of fats, sugars, carbohydrates, chitin, chitosan, minerals, waxes and proteins;
a preservative from over 0% up to 10%, a flow agent from over 0% up to 2%, or both the preservative from over 0% up to 10% and the flow agent from over 0% up to 2%; and 10-94% of a carrier;
wherein a concentration of the psychoactive alkaloid in the composition is over 0% and below exactly 10.5%.

2. The composition of claim 1, comprising 2-90% of the psychoactive alkaloid extract.

3. The composition of claim 1, wherein the preservative is selected from the group consisting of ascorbic acid, citric acid, lactose, vitamin A, vitamin E, retinyl palmitate, selenium, sodium citrate, sodium ascorbate, calcium ascorbate, sodium benzoate and potassium benzoate.

Date recue/Date received 2023-04-28

4. The composition of claim 1, wherein the flow agent is selected from the group consisting of silicon dioxide, stearic acid, magnesium stearate and talc.

5. The composition of claim 1 wherein the concentration of the psychoactive alkaloid in the composition is defined as a percentage with a precision of two decimal places.

6. The composition of claim 1, wherein the concentration of the psychoactive alkaloid in the psychoactive alkaloid extract is from 0.1% to 10% by weight.

7. The composition of claim 1, wherein the psychoactive alkaloid extract is a purified psychoactive alkaloid extract, and the concentration of the psychoactive alkaloid in the psychoactive alkaloid extract is from 10% to 99% by weight.

8. The composition of claim 1, comprising 0.1-79.6% of the psychoactive alkaloid extract.

9. The composition of claim 1, wherein the concentration of the psychoactive alkaloid in the psychoactive alkaloid extract is 0.1-75.22% by weight.

10. The composition of claim 1, wherein the naturally occurring substances are present in the psychoactive alkaloid extract in a concentration ranging from 1% -99.9% by weight.

11. The composition of claim 1, wherein the psychoactive alkaloid extract is from fungi.

12. The composition of claim 11, wherein the psychoactive alkaloid extract is from Psilocybe cyanescens, Psilocybe cubensis, Amanita muscaria, or any selection therefrom.
Date recue/Date received 2023-04-28

13. The composition of claim 1, wherein the psychoactive alkaloid extract is from psychoactive plants.

14. The composition of claim 13, wherein the psychoactive alkaloid extract is from Anadenanthera colubrina.

15. The composition of claim 13, wherein the psychoactive alkaloid extract is from Anadenanthera peregrina.

16. The composition of claim 1, wherein the carrier is selected from the group consisting of starch, maltodextrin, tapioca maltodextrin, rice maltodextrin, alpha cyclodextrin, beta cyclodextrin, microcrystalline cellulose, gum arabic, xanthum gum, guar gum and cellulose gum.

17. The composition of claim 1, wherein a total amount of the preservative, the flow agent and the carrier is selected so that the concentration of the psychoactive alkaloid in the composition is a desired specific amount defined to two significant figures.

18. The composition of claim 1, wherein a total amount of the preservative, the flow agent and the carrier is selected so that the concentration of the psychoactive alkaloid in the composition is a desired specific amount defined to three significant figures.

19. The composition of claim 1, wherein a total amount of the preservative, the flow agent and the carrier is selected so that the concentration of the psychoactive alkaloid in the composition is a desired specific amount defined to four significant figures.

Date recue/Date received 2023-04-28

20. The composition of claim 1, wherein the concentration of the psychoactive alkaloid in the composition is over 0.50% and below exactly 10.5%.

21. A powdered psychoactive alkaloid composition consisting essentially of, by weight:
0.1-90% of a psychoactive alkaloid extract from plant material, fungal material or both plant material and fungal material, wherein the psychoactive alkaloid extract comprises psychoactive alkaloid in a concentration of 0.1% to 99%
by weight of the psychoactive alkaloid extract, the psychoactive alkaloid being any selection from the group consisting of psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin, aeruginascin, bufotenin, bufotenidine, 5-MeO-DMT
(5-methoxy-N, N-dimethyltryptam ine), N, N-d imethyltryptam ine (DMT), ergine (LSA), ergonovine, ergometrine, muscimol, ibotenic acid, lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine and chanoclavine, wherein the psychoactive alkaloid extract comprises naturally occurring substances selected from the group consisting of fats, sugars, carbohydrates, chitin, chitosan, minerals, waxes and proteins;
a preservative from over 0% up to 10%, a flow agent from over 0% up to 2%, or both the preservative from over 0% up to 10% and the flow agent from over 0% up to 2%;
an antioxidant from over 0% up to 0.5%; and 10-94% of a carrier;
wherein a concentration of the psychoactive alkaloid in the composition is over 0% and below exactly 10.5%.

22. The composition of claim 21, wherein a total amount of the preservative, the flow agent, the antioxidant and the carrier is selected so that the concentration of the psychoactive alkaloid in the composition is a desired specific amount defined to two significant figures.

Date recue/Date received 2023-04-28

23. The composition of claim 21, wherein a total amount of the preservative, the flow agent, the antioxidant and the carrier is selected so that the concentration of the psychoactive alkaloid in the composition is a desired specific amount defined to three significant figures.

24. The composition of claim 21, wherein a total amount of the preservative, the flow agent, the antioxidant and the carrier is selected so that the concentration of the psychoactive alkaloid in the composition is a desired specific amount defined to four significant figures.

25. The composition of claim 21, wherein the concentration of the psychoactive alkaloid in the composition is over 0.50% and below exactly 10.5%.

26. A powdered psychoactive alkaloid composition consisting essentially of, by weight:
0.1-90% of a psychoactive alkaloid extract from plant material, fungal material or both plant material and fungal material, wherein the psychoactive alkaloid extract comprises psychoactive alkaloid in a concentration of 0.1% to 99%
by weight of the psychoactive alkaloid extract, the psychoactive alkaloid being any selection from the group consisting of psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin, aeruginascin, bufotenin, bufotenidine, 5-MeO-DMT
(5-methoxy-N, N-dimethyltryptamine), N, N-d imethyltryptam ine (DMT), ergine (LSA), ergonovine, ergometrine, muscimol, ibotenic acid, lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine and chanoclavine, wherein the psychoactive alkaloid extract comprises naturally occurring substances selected from the group consisting of fats, sugars, carbohydrates, chitin, chitosan, minerals, waxes and proteins;
a preservative from over 0% up to 10%, a flow agent from over 0% up to 2%, or both the preservative from over 0% up to 10% and the flow agent from over 0% up to 2%;
a bioavailability agent from over 0% up to 0.5%; and Date recue/Date received 2023-04-28 10-94% of a carrier;
wherein a concentration of the psychoactive alkaloid in the composition is over 0% and below exactly 10.5%.

27. The composition of claim 26, wherein a total amount of the preservative, the flow agent, the bioavailability agent and the carrier is selected so that the concentration of the psychoactive alkaloid in the composition is a desired specific amount defined to two significant figures.

28. The composition of claim 26, wherein a total amount of the preservative, the flow agent, the bioavailability agent and the carrier is selected so that the concentration of the psychoactive alkaloid in the composition is a desired specific amount defined to three significant figures.

29. The composition of claim 26, wherein a total amount of the preservative, the flow agent, the bioavailability agent and the carrier is selected so that the concentration of the psychoactive alkaloid in the composition is a desired specific amount defined to four significant figures.

30. The composition of claim 26, wherein the concentration of the psychoactive alkaloid in the composition is over 0.50% and below exactly 10.5%.

Date recue/Date received 2023-04-28