Methods and compositions for enhancing health

Abstract

To provide compositions, methods, and kits.SOLUTION: Compositions, methods, and kits described herein may be formulated as nutritional supplements or dietary supplements. A composition described herein may provide nutrients or compounds that may otherwise not be consumed in sufficient quantities in a normal diet, and may contribute to physical wellbeing and emotional wellbeing of a subject. In one aspect, the present disclosure provides a unit dose comprising: a mixture of carboxylated cannabinoids and decarboxylated cannabinoids; and one or more terpenoids, a wt / wt ratio of decarboxylated cannabinoids to carboxylated cannabinoids being greater than 0.5, and the unit dose being substantially free of terpenoid degradation compounds.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] cross reference This application claims priority to U.S. Provisional Patent Application No. 62 / 479,091, filed March 30, 2017, U.S. Provisional Patent Application No. 62 / 506,475, filed May 15, 2017, and U.S. Provisional Patent Application No. 62 / 632,965, filed February 20, 2018, each of which is incorporated by reference in its entirety. [Background technology]

[0002] background Terpenoids are compounds that, when taken as nutritional or dietary supplements, can have a beneficial effect on a subject. Terpenoids can be beneficial to the health, physical well-being, and / or emotional well-being of a subject.

[0003] Terpenoids can also be used to treat or reduce symptoms of several classes of diseases, such as anti-inflammatory disorders, psychiatric disorders, and sleep disorders. When producing compositions containing terpenoids, terpenoid degradation compounds may be formed as by-products. Terpenoid degradation compounds may have little benefit, no effect, or may have deleterious effects on the subject. Summary of the Invention [Means for solving the problem]

[0004] Abstract In one aspect, the disclosure provides a unit dose comprising (i) a mixture of carboxylated and decarboxylated cannabinoids, and (ii) one or more terpenoids, wherein the wt / wt ratio of decarboxylated cannabinoids to carboxylated cannabinoids is greater than 0.5, and is substantially free of terpenoid degradation compounds. In some embodiments, the unit dose comprises at least 5 mg of decarboxylated cannabinoids. In some embodiments, the decarboxylated cannabinoids are Δ 9 Contains tetrahydrocannabinol.

[0005] In some embodiments, the one or more terpenoids are selected from the group consisting of myrcene, limonene, linalool, trans-ocimene, beta-pinene, alpha-pinene, beta-caryophyllene, delta-3-carene, trans-gamma-bisabolene, trans In some embodiments, the one or more terpenoid degrading compounds are selected from the group consisting of geraniol, geranyl isobutyrate, p-cymenene, p-cymene, p-mentha-1,5,8-triene, carvone, 3-methyl-6-(1-methylethylidene)-2-cyclohexen-1-one, 3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-one, eucarvone, thymol, p-mentha-1(7),8-dien-2-ol, perillyl alcohol, camphene, beta-myrcene, alpha-phellandrene, alkenyl alcohol ... Selected from the group consisting of p-terpinene, gamma-terpinene, terpinolene, 4-hydroxy-2-methyl-2-cyclohexenone, p-cymenene, o-cymene, 3-caren-2-one, 3-caren-5-one, 3-carene oxide, 3-carene-2,5-dione, trans-2-hydroxy-3-caren-5-one, thymol, carvacrol, 1,4-cineole, eucalyptol, 3-(1-methylethyl)-6-oxo-2-heptenal, and 3,7-dimethyl 6-oxo-2-octenal. In some embodiments, the unit dose further comprises a trace amount of an acid. In some embodiments, the unit dose further comprises a pharma- ceutically acceptable excipient.

[0006] In some embodiments, the pharma- ceutically acceptable excipient is selected from the group consisting of binders, fillers, plasticizers, lubricants, antifoaming agents, buffers, polymers, antioxidants, preservatives, chelating agents, flavorants, colorants, odorants, suspending agents, and combinations thereof. In some embodiments, the unit dose is formulated for oral, topical, inhalation, intravenous, or intramuscular administration. In some embodiments, the unit dose is in solid form. In some embodiments, the unit dose is in liquid form. In some embodiments, the unit dose is a tablet, chewable tablet, capsule, caplet, pill, granule, emulsion, gel, spray, multiple beads in a capsule, powder, suspension, liquid, semi-liquid, semi-solid, solution, syrup, or slurry. In some embodiments, the unit dose retains at least 80% of the cannabinoids after 6 months in a sealed container at a temperature of about 25° C. and a relative humidity level of about 50%. In some embodiments, the unit dose is packaged in a container selected from the group consisting of a tube, a jar, a box, a vial, a bag, a tray, a drum, a bottle, a syringe, and a can. In some embodiments, the kit includes a unit dose disclosed herein and instructions for supplementing a subject in need thereof with a mixture of carboxylated and decarboxylated cannabinoids and one or more terpenoids.

[0007] In one aspect, the present disclosure provides a method for producing a Δ 9 1. A kit for preparing tetrahydrocannabinol, comprising: (i) converting at least 50% tetrahydrocannabinol acid into Δ 9A kit is provided that includes an acid present in an amount effective to convert to tetrahydrocannabinol, (ii) a reaction vessel configured to hold a reaction mixture including the acid and tetrahydrocannabinolic acid, and (iii) instructions for carrying out the conversion utilizing the acid. In some embodiments, the kit further includes tetrahydrocannabinolic acid. In some embodiments, the acid is a weak acid. In some embodiments, the acid has a pKa of about 3 to about 7.

[0008] In some embodiments, the acid is selected from the group consisting of lactic acid, citric acid, malic acid, acetic acid, benzoic acid, ascorbic acid, tartaric acid, and oxalic acid.

[0009] In one aspect, the disclosure provides a method of supplementing a subject in need thereof with one or more cannabinoids and one or more terpenoids, comprising administering to the subject a unit dose comprising a mixture of carboxylated and decarboxylated cannabinoids and one or more terpenoids, the unit dose having a wt / wt ratio of decarboxylated cannabinoids to carboxylated cannabinoids greater than 0.5 and substantially free of terpenoid degrading compounds. In some embodiments, the subject suffers from a symptom selected from the group consisting of pain, stress, nausea, vomiting, insomnia, anxiety, and loss of appetite. In some embodiments, the unit dose is administered orally, topically, by inhalation, intravenously, or intramuscularly. In some embodiments, the unit dose is administered at least once a day. In some embodiments, the method further comprises monitoring the health or condition of the subject following administration of the unit dose to the subject.

[0010] In one aspect, the disclosure provides a method of supplementing a subject in need thereof with one or more cannabinoids and one or more terpenoids, comprising administering to the subject a unit dose as disclosed herein. In some embodiments, the subject suffers from a symptom selected from the group consisting of pain, stress, nausea, vomiting, insomnia, anxiety, and loss of appetite. In some embodiments, the unit dose is administered orally, topically, by inhalation, intravenously, or intramuscularly. In some embodiments, the unit dose is administered at least once a day. The unit dose may be administered intravenously to the subject before, during, or after a surgical procedure (e.g., within 1, 10, 20, or 30 minutes after surgery).

[0011] In one aspect, the disclosure provides a method of producing decarboxylated cannabinoids, the method comprising: (i) contacting a cannabis plant or part thereof with an acid under conditions effective to convert carboxylated cannabinoids present in the cannabis plant to decarboxylated cannabinoids to form a reaction mixture; and (ii) separating the cannabis plant or part thereof from the decarboxylated cannabinoids, thereby producing decarboxylated cannabinoids. In some embodiments, the decarboxylated cannabinoids are Δ 9 In some embodiments, the reaction mixture of (ii) has a wt / wt ratio of decarboxylated cannabinoids to carboxylated cannabinoids greater than 0.1. In some embodiments, the conditions are at a temperature of less than 300° C. In some embodiments, no external heat is applied during conversion of the carboxylated cannabinoids to decarboxylated cannabinoids. In some embodiments, the acid is a weak acid. In some embodiments, the contacting comprises blending, mixing, stirring, or a combination thereof. In some embodiments, the separation is selected from the group consisting of filtration, extraction, centrifugation, solubilization, concentration, washing, electrolysis, adsorption, purification, chromatography, fractionation, crystallization, and a combination thereof.

[0012] In another aspect, the disclosure provides a mixture comprising (i) a carboxylated cannabinoid and a decarboxylated cannabinoid, (ii) one or more terpenoids, and (iii) an acid, wherein the wt / wt ratio of the decarboxylated cannabinoid to the carboxylated cannabinoid is greater than 0.1, and the acid is present in an amount effective to convert at least a portion of the carboxylated cannabinoid to a decarboxylated cannabinoid. In some embodiments, the carboxylated cannabinoid comprises tetrahydrocannabinolic acid. In some embodiments, the mixture comprises at least 0.05 mol of the decarboxylated cannabinoid. In some embodiments, the decarboxylated cannabinoid comprises Δ 9 In some embodiments, Δ 9 The wt / wt ratio of tetrahydrocannabinol to tetrahydrocannabinolic acid is greater than about 0.1. In some embodiments, the mixture is substantially free of terpenoid degrading compounds. In some embodiments, the acid is an organic acid.

[0013] In one aspect, the disclosure provides a reaction vessel comprising a mixture disclosed herein and configured to achieve production of at least 10 g of decarboxylated cannabinoids.

[0014] In one aspect, the disclosure provides a method of producing a decarboxylated cannabinoid formulation comprising providing a reaction vessel containing a mixture, the mixture comprising carboxylated and decarboxylated cannabinoids, one or more terpenoids, and an acid, the mixture comprising a wt / wt ratio of the decarboxylated cannabinoids to the carboxylated cannabinoids being greater than 0.1, the acid being present in an amount effective to convert at least a portion of the carboxylated cannabinoids to decarboxylated cannabinoids, and mixing the mixture to obtain a decarboxylated cannabinoid formulation. In some embodiments, the decarboxylated cannabinoid formulation comprises at least 5 mg of decarboxylated cannabinoids. In some embodiments, the decarboxylated cannabinoid formulation comprises at least Δ9 In some embodiments, the one or more terpenoids are selected from the group consisting of myrcene, limonene, linalool, trans-ocimene, beta-pinene, alpha-pinene, beta-caryophyllene, delta-3-carene, trans-gamma-bisabolene, trans-alpha-farnesene, beta-fenchol, alpha-humulene, and guajole. In some embodiments, the acid is a weak acid. In some embodiments, the acid has a pKa of about 3 to about 7. In some embodiments, the acid is selected from the group consisting of lactic acid, citric acid, malic acid, acetic acid, benzoic acid, ascorbic acid, tartaric acid, and oxalic acid.

[0015] In one aspect, the disclosure provides a unit dose comprising a mixture of carboxylated and decarboxylated cannabinoids and one or more terpenoids, the unit dose comprising a wt / wt ratio of decarboxylated cannabinoids to carboxylated cannabinoids greater than 0.5, substantially free of terpenoid degrading compounds, and substantially free of acid. In some embodiments, the acid is a weak acid. In some embodiments, the acid has a pKa of about 3 to about 7. In some embodiments, the acid is selected from the group consisting of lactic acid, citric acid, malic acid, acetic acid, benzoic acid, ascorbic acid, tartaric acid, and oxalic acid.

[0016] Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in the art from the following detailed description, which shows and describes merely illustrative embodiments of the present disclosure. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modification in various obvious respects, all without departing from the present disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.

[0017] Incorporation by Reference All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

[0018] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (also referred to herein as "figures"). [Brief description of the drawings]

[0019] [Figure 1] FIG. 1 illustrates a computer control system that is programmed or otherwise configured to implement the methods provided herein. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] Detailed Description While various embodiments of the present invention have been shown and described herein, it will be understood by those skilled in the art that such embodiments are provided by way of example only. Numerous variations, modifications, and substitutions may occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be used.

[0021] The term "about" as used herein generally refers to an acceptable error range for a particular value as determined by one of ordinary skill in the art, and may depend in part on how the value is measured or determined. For example, "about" may mean within 1 or more than 1 standard deviation. Alternatively, "about" may mean within 20%, 10%, 5%, or 1% of a given value. Alternatively, particularly with respect to biological systems or processes, the term may mean within an order of magnitude, within 5-fold, and within 2-fold of a value.

[0022] The term "subject" as used herein generally refers to an animal. The subject may have or be suspected of having a disease or ailment. The subject may be a mammal. Non-limiting examples of mammals include humans and animals such as mice, monkeys, dogs and cats, including transgenic and non-transgenic mice. The methods described herein may be useful in both human therapeutics, pre-symptomatic and veterinary applications. The subject may be a mammal. The subject may be a human. Other Mammals include, but are not limited to, apes, chimpanzees, orangutans, monkeys; domestic animals (pets) such as dogs, cats, guinea pigs, hamsters, mice, rats, rabbits, ferrets, etc.; farm animals such as dairy cows, buffalo, bison, horses, donkeys, pigs, sheep, goats, etc.; or exotic animals typically found in zoos, for example, bears, lions, tigers, leopards, elephants, hippos, rhinos, giraffes, antelopes, sloths, gazelles, zebras, wildebeests, prairie dogs, koalas, kangaroos, pandas, giant pandas, hyenas, seals, sea lions, elephant seals.

[0023] The term "administering" as used herein generally refers to providing a composition to a subject by a route of administration, including, but not limited to, intravenous, intraarterial, oral, parenteral, buccal, topical, transdermal, rectal, intramuscular, subcutaneous, intraosseous, transmucosal, or intraperitoneal. The composition may also be administered by a suppository, such as a vaginal or rectal suppository. The oral route of administration may also be used. The unit dose may also be administered by inhalation.

[0024] The term "effective amount" or "therapeutically effective amount" as used herein generally refers to an amount of a compound described herein that is sufficient to affect a contemplated, predetermined, or prescribed application, including but not limited to the treatment of a disease or condition. The therapeutically effective amount may vary depending on the application (e.g., in vitro or in vivo), or the subject and condition to be treated, such as the subject's weight and age, the severity of the condition, and the mode of administration. The term may also be applied to a dose that induces a specific response in target cells, such as slowing down proliferation or downregulating the activity of a target protein. The exact dose may vary depending on the particular compound selected, the dosing regimen followed, whether it is administered in combination with other compounds, the timing of administration, the tissue to which it is administered, and the physical delivery system by which it is delivered.

[0025] As used herein, the term "isolated" generally refers to the preparation of a substance that is devoid of at least some of the other components that may be present when that substance or a similar substance occurs in nature or is initially obtained. Thus, for example, an isolated substance can be prepared by enrichment from a raw mixture using purification techniques. Enrichment can be measured on an absolute basis, such as weight per volume of solution, or can be measured relative to a potentially interfering second substance present in the raw mixture. Incremental enrichment can be used. A substance can also be provided in an isolated state by an artificial assembly process, such as chemical synthesis.

[0026] As used herein, the term "substantially free" generally refers to a composition that contains less than about 25%, less than about 15%, less than about 10%, less than about 5%, less than about 1%, less than about 0.5%, less than 0.1%, or even less of a specified component (e.g., by weight). Such compositions may not contain detectable amounts of such specified components. For example, a composition that is substantially free of weak acids (e.g., acids with a pKa of at most about 10) may contain less than about 1% of the weak acid. Percentages may be determined as a percentage of the total composition or as a percentage of a subset of the composition. For example, a composition that is substantially free of weak acids may contain less than 1% of the weak acid as a percentage of the total composition or as a percentage of the acid in the composition. Percentages may be mass, molar, or volume percentages. The presence or concentration of such components may be determined spectroscopically, such as by chromatography or nuclear magnetic resonance.

[0027] As used herein, the term "synergistic" generally refers to an effect in which the effect or effects of a combination of compositions is greater than the effect or effects of each component alone, or may be greater than the sum of the effect or effects of each component alone. A synergistic effect is an effect that is greater than the effect on a subject of only one of the components, or the additive effect of each of the components when administered individually. It may be about 10%, 20%, 30%, 50%, 75%, 100%, 110%, 120%, 150%, 200%, 250%, 350%, or 500% or greater. The effect may be any of the measurable effects described herein.

[0028] The term "Cannabis plant" as used herein generally refers to a plant that is part of a genus of flowering plants in the Cannabaceae family and may include three species or subspecies: sativa, indica, and ruderalis. A cannabis plant may include several different parts, including nodes, stems, fan leaves, and flowers. The flowers of a cannabis plant may be male or female. A female flower may include a flower, a pistil, a cola, a trichome, and a calyx.

[0029] The term "cannabinoid" as used herein generally refers to cannabinoid compounds that have been isolated or identified in the cannabis plant. Cannabinoid compounds can act on cannabinoid receptors in cells. Cannabinoids can alter physiological processes, including altering neurotransmitter release in the brain, appetite, pain sensation, mood, and memory. Cannabinoid compounds are known to be involved in the regulation of cannabinoid function, such as the release of cannabinoids in the brain, the release of cannabinoids in the brain, and the release of cannabinoids in the brain. 21 It can also be said to have a terpenophenol core.

[0030] As used herein, the term "carboxylated cannabinoid" generally refers to compounds that have been isolated or identified in the cannabis plant and that have a carboxylic acid moiety (i.e., -COOH). Carboxylated cannabinoids can be said to be tetrahydrocannabinolic acid.

[0031] The term "decarboxylated cannabinoids" as used herein generally refers to cannabinoid compounds that previously had a carboxylic acid moiety (e.g., a carboxylated cannabinoid) and have undergone a chemical reaction that no longer has the carboxylic acid moiety. Decarboxylated cannabinoids may be natural compounds or may be present in the cannabis plant. Decarboxylated cannabinoids may also be synthesized or produced by synthetic methods. Decarboxylated cannabinoids are cannabinoids that have a Δ 9 It can be said to be tetrahydrocannabinol.

[0032] As used herein, the term "terpenoid" generally refers to an organic compound composed of isoprene units, each of which has the formula C5H8. The isoprene units may be linked by covalent bonds. Terpenoids are compounds of the formula (C5H8) n where n is an integer of 1 or greater, such as 2, 3, 4, 5, or greater. Terpenoids are monoterpenoids (C 10 skeleton), sesquiterpenoids (C 15 skeleton), diterpenoids (C20 skeleton), or triterpenoid (C 30 Terpenoids may have beneficial effects on a subject and may be used as dietary supplements or nutritional supplements.

[0033] The term "terpenoid degradation products" as used herein generally refers to organic compounds that are products of reactions performed on terpenoids. Terpenoids may be decomposed into multiple fragments, and each fragment may be considered a terpenoid degradation product. Terpenoid degradation products may be formed during reactions such as heating, burning, or smoking of terpenoid compounds or compositions containing terpenoids. Terpenoid degradation products may be formed by application of heat at least about 50°C, 75°C, 100°C, 200°C, 300°C, 400°C, 500°C, 600°C, 700°C, 800°C, 900°C, 1000°C, or higher. Terpenoid degradation products may not have the beneficial properties of the terpenoids from which they are derived.

[0034] Cannabinoid compounds can be divided into 10 subclasses, including cannabigerols, cannabichromenes, cannabidiols, delta-9-tetrahydrocannabinols, delta-8-tetrahydrocannabinols, cannabicyclols, cannabielsoins, cannabinols and cannabinodiols, cannabidiols, and other cannabinoids.

[0035] Non-limiting examples of cannabinoid compounds of the cannabigerol class include cannabigerolic acid (CBGA), cannabigerolic acid monomethyl ether (CBGAM), cannabigerol (CBG), cannabigerol monomethyl ether (CBGM), cannabigerovaric acid (CBGVA), and cannabigerovarin (CBGV).

[0036] Non-limiting examples of cannabichromene class cannabinoid compounds include cannabichromene acid (CBCA), cannabichromene (CBC), cannabichromevarinic acid (CBCVA), and cannabichromevarin (CBCV).

[0037] Non-limiting examples of cannabinoid compounds of the cannabidiol class include cannabidiol acid (CBDA), cannabidiol (CBD), cannabidiol monomethyl ether (CBDM), cannabidiol-C4 (CBD-C4), cannabidivaric acid (CBDVA), cannabidivarin (CBDV), and cannabidiolcol (CBD-C1).

[0038] Non-limiting examples of cannabinoid compounds of the delta-9-tetrahydrocannabinol class include delta-9-tetrahydrocannabinolic acid A (THCA-A), delta-9-tetrahydrocannabinolic acid B (THCA-B), delta-9-tetrahydrocannabinol (THC), delta-9-tetrahydrocannabinolic acid-C4 (THCA-C4), delta-9-tetrahydrocannabinol-C4 (THC-C4), delta(dena)-9-tetrahydrocannabivarin (THCV), delta-9-tetrahydrocannabiorcholic acid (THCA-C1), delta-9-tetrahydrocannabiorcholic acid (THC-C1), and delta-7-cis-iso-tetrahydrocannabivarin.

[0039] Non-limiting examples of cannabinoid compounds of the delta-8-tetrahydrocannabinol class include delta-8-tetrahydrocannabinolic acid (Δ 8 -THCA) and delta-8-tetrahydrocannabinol (Δ 8 -THC).

[0040] Non-limiting examples of cannabinoid compounds of the cannabicyclol class include cannabicycloronic acid (CBLA), cannabicyclol (CBL), and cannabicyclovaline (CBLV).

[0041] Non-limiting examples of cannabielsoin class cannabinoid compounds include cannabielsonic acid A (CBEA-A), cannabielsonic acid B (CBEA-B), and cannabielsoin (CBE).

[0042] Non-limiting examples of cannabinoid compounds of the cannabinol and cannabinodial classes include cannabinolic acid (CBNA), cannabinol (CBN), cannabinol methyl ether (CBNM), cannabinol-C4 (CBN-C4), cannabivarin (CBV), cannabinol-C2 (CBN-C2), cannabiolkol (CBN-C1), cannabinodial (CBND), and cannabinodivalin (CBVD).

[0043] Non-limiting examples of cannabinoid compounds of the cannabidiol class include cannabidiol (CBT), 10-ethoxy-9-hydroxy-delta-6a-tetrahydrocannabinol, 8,9-dihydroxy-delta-6a-tetrahydrocannabinol, cannabidiol valine (CBTV), and ethoxy-cannabidiol valine (CBTVE).

[0044] Non-limiting examples of cannabinoid compounds of the other cannabinoid class include dehydrocannabifuran (DCBF), cannabifuran (CBF), cannabichromanone (CBCN), cannabicitran (CBT), 10-oxo-delta-6a-tetrahydrocannabinol (OTHC), delta-9-cis-tetrahydrocannabinol (cis-THC), 3,4,5,6-tetrahydro-7-hydroxy-alpha-alpha-2-trimethyl-9-n-propyl-2,6-methano-2H-1-benzoxine-5-methanol (OH-iso-HHCV), cannabilipsol (CBR), and trihydroxy-delta-9-tetrahydrocannabinol (triOH-THC).

[0045] Terpenoid compounds that have been isolated from the essential oil of the cannabis plant include myrcene, limonene, linalool, trans-ocimene, beta-pinene, alpha-pinene, beta-caryophyllene, delta-3-carene, trans-gamma-bisabolene, trans-alpha-farnesene, beta-fenchol, beta-phellandrene, alpha-humulene (alpha-caryophyllene), guajole, alpha-guayene, alpha-eudesmol, terpinolene, alpha-selinene, alpha-terpineol, fenchone, and can. phene, cis-sabinene hydrate, cis-ocimene, beta-eudesmol, beta-selinene, alpha-trans-bergamotene, gamma-eudesmol, borneol, cis-beta-farnesene, gamma-curcumene, cis-gamma-bisabolene, alpha-thujene, epi-alpha-bisabolol, ipsdienol, alpha-ilangene, beta-elemene, alpha-cis-bergamotene, gamma-muurolene, alpha-cadinene, alpha-longipinene, and caryophyllene oxide.

[0046] Nitrogen-containing compounds have been isolated from cannabis plants. Spermidine-type alkaloids isolated from cannabis sativa include cannabisativine and anhydrocannabisativine. Other nitrogen-containing compounds isolated from cannabis plants include, but are not limited to, n-trans-feruloyityramine, np-coumaroyltyramine, n-trans-caffeoyltyramine, glossamide, cannabidiin A, cannabidiin B, cannabidiin C, and cannabidiin D.

[0047] Flavonoids are compounds that can be plant or fungal secondary metabolites. In general, flavonoids are classified into C 15 Flavonoids including apigenin, luteolin, kaempferol, quercetin, orientin, vitexin, cannflavin A, and cannflavin B have been identified in the cannabis plant.

[0048] Additional compounds that have been isolated from the Cannabis plant include unsaturated fatty acids and non-cannabinoid phenols, including, but not limited to, linoleic acid, alpha-linolenic acid, oleic acid, cannabispirane, isocannabispirane, cannabistilbene I, cannabistilbene II, cannithrene 1, and cannithrene 2. composition

[0049] The present disclosure relates to mixtures of carboxylated and decarboxylated cannabinoids. and one or more terpenoids. The composition may comprise a decarboxylated cannabinoid (e.g., Δ 9 tetrahydrocannabinol) and carboxylated cannabinoids (e.g., tetrahydrocannabinolic acid).

[0050] The composition may comprise a ratio of decarboxylated cannabinoids to carboxylated cannabinoids of at least about 0.01:1, 0.05:1, 0.1:1, 0.5:1, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 20:1, 30:1, 40:1, 50:1, 60:1, 70:1, 80:1, 90:1, 100:1, or higher. The ratio of decarboxylated cannabinoids to carboxylated cannabinoids may also be described as a single value of at least about 0.01, 0.05, 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, or higher. The ratio of decarboxylated to carboxylated cannabinoids in the compositions or unit doses of the present disclosure may differ from the ratio of the products isolated directly from natural sources. For example, decarboxylated cannabinoids (e.g., Δ 9 The ratio of decarboxylated cannabinoids (e.g., Δ tetrahydrocannabinol) to carboxylated cannabinoids (e.g., tetrahydrocannabinolic acid) when isolated from a natural source such as a cannabis plant may be 0.05:1. After carrying out the methods described herein, decarboxylated cannabinoids (e.g., Δ 9 The ratio of tetrahydrocannabinol) to carboxylated cannabinoids (e.g., tetrahydrocannabinolic acid) may be 1:1, 2:1, 5:1, or higher.

[0051] Δ 9 Any of the ingredients described herein, including tetrahydrocannabinol, may be used in the compositions in free form, isolated form, purified from natural sources, and / or purified or prepared from synthetic sources. Natural sources may be animal or plant sources. The ingredients may be at least about 95, 97, 99, 99.5, 99.9, 99.99, or 99.999% pure.

[0052] Doses of the present disclosure, which may be unit doses, may contain greater than about 1 milligram (mg), 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, or 100 mg of a cannabinoid compound. Doses of the compositions of the present disclosure, which may be unit doses, may contain about 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, or 100 mg of a cannabinoid compound. Doses of the compositions of the present disclosure, which may be unit doses, may contain less than about 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, or 100 mg of a cannabinoid compound.

[0053] Δ 9 The unit dose of tetrahydrocannabinol can be at least about 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, or 1000 mg. 9 The unit dose of tetrahydrocannabinol is about 1 mg to about 20 mg, 3 mg to about 15, 5 mg g to about 10 mg. 9The dose of tetrahydrocannabinol may be at least about 0.001 mole (mol), 0.005 mol, 0.01 mol, 0.015 mol, 0.02 mol, 0.03 mol, 0.04 mol, 0.05 mol, 0.06 mol, 0.07 mol, 0.08 mol, 0.09 mol, 0.1 mol, 0.2 mol, 0.3 mol, 0.4 mol, 0.5 mol, or more Δ 9 May contain tetrahydrocannabinol.

[0054] A unit dose may contain at least about 10 milligrams (mg), 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, or 1000 mg of tetrahydrocannabinolic acid.

[0055] A unit dose may contain at least about 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, or 1000 mg of a terpenoid.

[0056] The unit dose may be substantially free of terpenoid degrading compounds. The unit dose may contain less than about 1000 mg, 900 mg, 800 mg, 700 mg, 600 mg, 500 mg, 400 mg, 300 mg, 200 mg, 100 mg, 50 mg, 40 mg, 30 mg, 20 mg, or 10 mg of terpenoid degrading compounds. The unit dose may contain less than about 1000 mg, 900 mg, 800 mg, 700 mg, 600 mg, 500 mg, 400 mg, 300 mg, 200 mg, 100 mg, 50 mg, 40 mg, 30 mg, 20 mg, or 10 mg of a plurality of terpenoid degrading compounds. A unit dose may contain less than about 10%, 5%, 4%, 3%, 2%, 1%, 0.1%, or 0.01% by weight of terpenoid degrading compounds. A unit dose may contain less than about 10%, 5%, 4%, 3%, 2%, 1%, 0.1%, or 0.01% by volume of terpenoid degrading compounds. A unit dose may contain at most about 1000 mg, 900 mg, 800 mg, 700 mg, 600 mg, 500 mg, 400 mg, 300 mg, 200 mg, 100 mg, 50 mg, 40 mg, 30 mg, 20 mg, or 10 mg of terpenoid degrading compounds.

[0057] The unit dose may be substantially free of acids that can be used to convert carboxylated cannabinoids to decarboxylated cannabinoids. The unit dose may contain less than about 1000mg, 900mg, 800mg, 700mg, 600mg, 500mg, 400mg, 300mg, 200mg, 100mg, 50mg, 40mg, 30mg, 20mg, or 10mg of acids. The unit dose may contain less than about 1000mg, 900mg, 800mg, 700mg, 600mg, 500mg, 400mg, 300mg, 200mg, 100mg, 50mg, 40mg, 30mg, 20mg, or 10mg of acids. A unit dose may contain less than about 10%, 5%, 4%, 3%, 2%, 1%, 0.1%, or 0.01% by weight of acid. A unit dose may contain less than about 10%, 5%, 4%, 3%, 2%, 1%, 0.1%, or 0.01% by volume of acid. A unit dose may contain at most about 1000 mg, 900 mg, 800 mg, 700 mg, 600 mg, 500 mg, 400 mg, 300 mg, 200 mg, 100 mg, 50 mg, 40 mg, 30 mg, 20 mg, or 10 mg of acid.

[0058] A unit dose of the composition of the present disclosure may result in a certain amount of blood concentration, plasma concentration, or blood content of a compound in the composition after a given period of time. The blood content that may be achieved by a unit dose of the composition may be measured from a blood sample, plasma sample, urine sample, saliva swab, subject's breath, or other bodily fluid sample.

[0059] A unit dose of cannabinoid can result in a blood concentration of the cannabinoid of at least about 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 300, 400, 500 nanograms per milliliter (ng / mL), or more. Alternatively, the unit dose of the cannabinoid may result in a blood concentration of the cannabinoid of at most about 500, 400, 300, 200, 190, 180, 170, 160, 150, 140, 130, 120, 110, 100, 90, 80, 70, 60, 50, 40, 30, 20, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0.5 ng / mL. The unit dose of the cannabinoid may result in a blood concentration of the cannabinoid of at least about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 ng / mL, or more. A unit dose of cannabinoid may result in a blood concentration of the cannabinoid of 10-200 ng / mL, 50-190 ng / mL, or 90-170 ng / mL.

[0060] The daily dose of cannabinoids is adjusted to maintain blood levels of cannabinoids at or above about 0.5ng / mL, 0.75ng / mL, 1ng / mL, 1.25ng / mL, 1.5ng / mL, 1.75ng / mL, 2ng / mL, 2.5ng / mL, 3ng / mL, 4ng / mL, 5ng / mL, 10ng / mL, 20ng / mL, 30ng / mL, 40ng / mL, 50ng / mL, 60ng / mL , 70ng / mL, 80ng / mL, 90ng / mL, 100ng / mL, 110ng / mL, 120ng / mL, 130ng / mL, 140ng / mL, 150ng / mL, 160ng / mL, 170ng / mL, 180ng / mL, 190ng / mL, 200ng / mL, 300ng / mL, 400ng / mL, 500ng / mL, or higher. A unit dose of cannabinoid may result in a blood concentration of cannabinoid of 10-200ng / mL, 50-190ng / mL, or 90-170ng / mL.

[0061] Cannabinoid blood levels may peak about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, or 20 minutes after the first administration of the cannabinoid. Cannabinoid blood levels may remain detectable for about 1 minute, 2 minutes, 5 minutes, 10 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 18 hours, 24 hours, or 36 hours after the last administration of the cannabinoid.

[0062] The compositions of the present disclosure can be used in combination therapy.Combination therapy can be administered by combination treatment regimen.Combination treatment regimen can include treatment regimen that administration of the compound described herein or its pharmaceutically acceptable salt is started before, during or after treatment with a second agent, and can continue during or after the end of treatment with the second agent.The second agent used in combination can be administered simultaneously with the first agent during the treatment period, or at different times and / or at shorter or longer intervals.

[0063] The compositions of the present disclosure may include two or more compounds. The compositions of the present disclosure may include two or more compounds.

[0064] The compositions of the present disclosure can be used in conjunction with an opioid. After being administered, it can act on opioid receptors.The combination of the composition of the present disclosure and opioids can produce synergistic effects in subjects.In combination therapy, the number and severity of observed side effects can be reduced compared to when the compound or composition is administered as a single drug.

[0065] The compositions of the present disclosure can be used in conjunction with a chemotherapeutic agent (e.g., paclitaxel, docetaxel, doxorubicin, bortezomib, gemcitabine, cisplatin) or chemotherapy treatment. The chemotherapeutic agent or treatment can be radiation, hormonal therapy, targeted therapy, or cytotoxic drugs. When used in conjunction with a chemotherapy treatment, the composition and the chemotherapy treatment can exhibit synergistic effects.

[0066] Combination compositions may be formulated to achieve a given, desired, or predetermined molar or mass ratio between two or more compounds of the composition. The molar ratio may be adjusted to compensate for the bioavailability, uptake, or metabolic processes of one or more components of the combination composition. For example, if a component has low bioavailability, the molar amount of that component may be increased relative to other components in the combination composition. The circulating molar or mass ratio may be achieved within about 0.1, 0.5, 0.75, 1, 3, 5, or 10, 12, 24, or 48 hours after administration. The circulating molar or mass ratio may be maintained for about 0.1, 1, 2, 5, 10, 12, 18, 24, 36, 48, 72, or 96 hours, or longer. Dosage Form

[0067] The compositions described herein can be formulated into a variety of different dosage forms. The compositions can be in oral dosage form. For example, the compositions can be used orally, such as in the form of tablets, capsules, pills, granules, emulsions, gels, capsuled beads, powders, suspensions, liquids, semi-liquids, semi-solids, syrups, slurries, chewable forms, caplets, soft gelatin capsules, lozenges, or solutions. Alternatively, the compositions can be formulated for inhalation or intravenous delivery. When the compositions are in solution form, they can be formulated as nasal sprays or for injection. Alternatively, the compositions can be in liquid compositions suitable for oral consumption.

[0068] The composition may be formulated on a solid or semi-solid support. The composition may be formulated on or in a polymeric material (e.g., silicone) and may be used as an injectable polymeric material (e.g., silicone) to prevent blood loss during traumatic injury or surgery. The polymeric material may be a biopolymer. The biopolymer may be biodegradable or may be absorbed by the subject over a period of time.

[0069] The polymeric material may promote wound healing, help reduce the perceived pain of the subject, exhibit antibacterial properties such as slowing down the growth of microorganisms, or promote the overall homeostatic balance in or around the wound or in the whole subject.The polymeric material may reduce shock, trauma, or oxidative stress in or around the wound area or in the whole subject.The polymeric material may also be used as a vehicle for delivering therapeutic materials.In some cases, the composition of the present disclosure and the second therapeutic material may be formulated on the polymeric material that is used before, during, or after a surgical procedure or trauma.

[0070] The compositions can be formulated for use during and after surgical procedures, such as on medical devices. The medical devices can be sutures, plugs, sutures, implants, or prostheses. The compositions can be formulated on materials that are biodegradable or absorbable and can degrade in the body after at least about 1 day, 2 days, 3 days, 7 days, 1 month, 2 months, or longer. Alternatively, the medical devices (e.g., sutures and plugs) can be non-biodegradable. Or may be non-absorbable. The composition may facilitate slow release of the compound of the composition, which may be desired. The composition may be formulated on a medical device that is implanted in a subject during surgery, and may release one or more components over a period of 1, 4, 6, 8, 12, 16, 20, 24, 36, 48, or more.

[0071] The compositions described herein can be used to enhance the success or outcome of implant or prosthetic procedures. For example, the compositions can be administered before, during, or after an implant procedure. The implants can be used to replace missing biological structures, support damaged structures, or augment existing structures. In some embodiments, the implants can be subcutaneous. In some embodiments, the implants can be percutaneous. The implants can include, for example, cardiovascular implants, orthopedic implants, contraceptive implants, cosmetic implants, prosthetics, and ophthalmic implants. In some cases, the implants can be neural laces, can be implanted in the head cavity, or can be in or near the brain. In some cases, the compositions described herein can benefit neuroplasticity and positively alter the brain's ability to change over time. The compositions formulated for inhalation can be packaged as an inhaler or nebulizer. The inhaler can be designed to dispense 0.25, 0.5, or 1 unit dose per inhalation. The inhaler may comprise a canister that holds the subject composition formulated for inhalation, a metering valve that allows a metered amount of the formulation to be dispensed with each actuation, and an actuator or mouthpiece that allows the device to actuate and direct the subject composition to the lungs of the subject. The formulated composition may include a liquefied gas propellant and possibly a stabilizing excipient. The actuator may comprise a mating firing nozzle that connects to the canister and a dust cap to prevent contamination of the actuator. Upon actuation, the subject composition may volatilize, resulting in the formation of droplets of the subject composition. The droplets may evaporate rapidly, resulting in micrometer-sized particles that may then be inhaled by the subject.

[0072] Compositions of the present disclosure suitable for oral administration include liquid dosage forms (e.g., suspensions or slurries) and oral solid dosage forms (e.g., tablets and bulk powders), which may be presented as discrete dosage forms such as capsules, cachets, tablets, or liquids or aerosol sprays, each containing a predetermined amount of the active ingredient as a powder or granules, solution, suspension in an aqueous or non-aqueous liquid, oil-in-water emulsion, or water-in-oil liquid emulsion. Oral dosage forms may be formulated as tablets, pills, dragees, capsules, emulsions, lipophilic and hydrophilic suspensions, liquids, gels, syrups, slurries, suspensions, to be consumed orally by the individual, patient, or subject to be treated. Such dosage forms may be prepared by any of the methods of formulation. For example, the active ingredient may be combined with a carrier that is in the nature of one or more required ingredients. Capsules suitable for oral administration include push-fit capsules made of gelatin, as well as soft sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. Push-fit capsules may contain the active ingredient mixed with a filler such as lactose, a binder such as starch, and / or a lubricant such as talc or magnesium stearate, and optionally a stabilizer. Compositions for oral use may be obtained by mixing the composition with a solid excipient, optionally grinding the resulting mixture, adding suitable auxiliary agents, if desired, and processing the granular mixture to obtain tablets or dragee cores. The excipients may be sugars, including lactose, sucrose, mannitol, or sorbitol, cellulose preparations, for example, corn starch, wheat starch, rice starch, potato starch, gelatin, tragacanth gum, methylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, and / or fillers such as polyvinylpyrrolidone (PVP). The prepared compositions may be prepared by mixing the active ingredient evenly and homogeneously with liquid carriers or finely divided solid carriers or both, and then, if necessary, mixing the product. It can be prepared by shaping into a desired appearance. For example, a tablet can be prepared by compression or molding, optionally with one or more accessory ingredients. Compressed tablets can be prepared by compressing in a suitable machine the active ingredient in a free-flowing form, such as a powder or granules, optionally mixed with an excipient, such as, but not limited to, a binder, a lubricant, an inert diluent, and / or a surfactant or dispersant. Molded tablets can be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent.

[0073] Liquid forms into which the formulations disclosed herein may be incorporated for oral or injectable administration include aqueous solutions, suitably flavored syrups, aqueous or oily suspensions, and flavored emulsions including edible oils such as cottonseed oil, sesame oil, coconut oil, peanut oil, and the like, as well as elixirs and similar pharmaceutical vehicles. Suitable dispersing or suspending agents for aqueous suspensions include synthetic natural gums, for example, tragacanth, acacia, alginate, dextran, sodium carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone, or gelatin.

[0074] Liquid preparations for oral administration may take the form of, for example, solutions, syrups, or suspensions, or may appear as a dry product for reconstitution with water or other suitable vehicle before use. Such liquid preparations may be prepared by conventional procedures with pharma- ceutically acceptable additives, such as suspending agents (e.g., sorbitol syrup, methylcellulose, hydrogenated edible fats), emulsifying agents (e.g., lecithin or acacia), non-aqueous vehicles (e.g., almond oil, oily esters, ethyl alcohol), preservatives (e.g., methyl or propyl p-hydroxybenzoate or sorbic acid), artificial or natural colorants and / or sweeteners, etc.

[0075] The present disclosure further encompasses anhydrous compositions and dosage forms containing active ingredients, since water may accelerate the degradation of some compounds. To characterize properties such as shelf life and stability of formulations over time, water (e.g., 5%) can be added, for example, to mimic long-term storage. The anhydrous compositions and dosage forms of the present disclosure can be prepared using anhydrous or low moisture content ingredients and low moisture or humidity conditions. The compositions and dosage forms of the present disclosure containing lactose can be made anhydrous if substantial contact with moisture and / or humidity is expected during production, packaging, and / or storage. The anhydrous compositions can be prepared and stored such that their anhydrous nature is maintained. Thus, the anhydrous compositions can be packaged using materials that prevent exposure to water, such as those that can be included in a suitable formulary kit. Examples of suitable packaging materials include, but are not limited to, hermetically sealed foils, plastics, unit dose containers, blister packs, and strip packs.

[0076] The components described herein can be combined with pharmaceutical carriers according to conventional pharmaceutical compounding techniques to form a homogeneous mixture. The carriers can take a wide variety of forms, depending on the form of preparation desired for administration. When preparing compositions for oral dosage forms, pharmaceutical vehicles such as water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents, etc., can be used as carriers for oral liquid preparations (such as suspensions, solutions, elixirs, etc.) or aerosols, or carriers such as starch, sugar, microcrystalline cellulose, diluents, granulating agents, lubricants, binders, disintegrating agents, etc., with or without the use of lactose, can be used for oral solid preparations. For solid oral preparations, suitable carriers include, for example, powders, capsules, and tablets. If desired, tablets can be coated by standard aqueous or nonaqueous techniques.

[0077] Some examples of materials that can be pharma- ceutically acceptable carriers include: (1) lactose, glucose, (2) sugars such as corn starch and potato starch; (3) cellulose and its derivatives such as sodium carboxymethylcellulose, ethyl cellulose, and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients such as cocoa butter and suppository wax; (9) oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; (10) glycosides such as propylene glycol. (11) polyols, such as glycerin, sorbitol, mannitol, and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar, (14) buffers, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid, (16) pyrogen-free water, (17) isotonic saline, (18) Ringer's solution, (19) ethyl alcohol, (20) phosphate buffer solution, and (21) other compatible non-toxic substances used in pharmaceutical formulations.

[0078] Binders suitable for use in the dosage form include, but are not limited to, corn starch, potato starch or other starches, gelatin, natural and synthetic gums such as acacia, sodium alginate, alginic acid, other alginates, powdered tragacanth, guar gum, cellulose and its derivatives (e.g., ethyl cellulose, cellulose acetate, calcium carboxymethylcellulose, sodium carboxymethylcellulose), polyvinylpyrrolidone, methylcellulose, pregelatinized starch, hydroxypropyl methylcellulose, microcrystalline cellulose, and mixtures thereof.

[0079] Lubricants that can be used in forming the compositions and dosage forms of the present disclosure include, but are not limited to, calcium stearate, magnesium stearate, mineral oil, light mineral oil, glycerin, sorbitol, mannitol, polyethylene glycol, other glycols, stearic acid, sodium lauryl sulfate, talc, hydrogenated vegetable oils (e.g., peanut oil, cottonseed oil, sunflower oil, sesame oil, olive oil, corn oil, soybean oil), zinc stearate, ethyl oleate, ethylaureate, agar, or mixtures thereof. Additional lubricants include, for example, syloid silica gel, agglomerated aerosol of synthetic silica, or mixtures thereof. Lubricants may be added, for example, in an amount of less than about 1 weight percent of the composition.

[0080] Lubricants may be used in conjunction with tissue barriers, including, but not limited to, polysaccharides, polyglycans, seprafilm, interceed, and hyaluronic acid.

[0081] The use of a disintegrant in the compositions of the present disclosure can provide tablets that disintegrate when exposed to an aqueous environment. Too much disintegrant can produce tablets that may disintegrate in the bottle. Too little can be insufficient for disintegration to occur, and thus alter the rate and extent of release of the active ingredient from the dosage form. Thus, a dosage form of the compounds disclosed herein can be formed using a sufficient amount of disintegrant that is not too little or too much and adversely alters the release of the active ingredient. The amount of disintegrant used can vary based on the type of formulation and the mode of administration, and can be readily determined by one of ordinary skill in the art. About 0.5 to about 15 weight percent of disintegrant, or about 1 to about 5 weight percent of disintegrant can be used in the pharmaceutical composition. Disintegrants that can be used in forming the compositions and dosage forms of the present disclosure include, but are not limited to, agar, alginic acid, calcium carbonate, microcrystalline cellulose, croscarmellose sodium, crospovidone, polacrilin potassium, sodium starch glycolate, potato or tapioca starch, other starches, pregelatinized starch, other starches, clays, other algins, other celluloses, gums, or mixtures thereof.

[0082] Examples of fillers suitable for use in the compositions and dosage forms disclosed herein include, but are not limited to, talc, calcium carbonate (e.g., granules or powder), microcrystalline cellulose, Included are powdered cellulose, dextrates, kaolin, mannitol, silicic acid, sorbitol, starch, pregelatinized starch, and mixtures thereof.

[0083] In some cases, aqueous suspensions and / or elixirs may be desirable for oral administration, in which the active ingredient may be combined with various sweeteners or flavorings, coloring substances or dyes, if desired, emulsifying and / or suspending agents, and diluents such as water, ethanol, propylene glycol, glycerin, or combinations thereof.

[0084] Tablets may be uncoated or may be coated to delay disintegration and absorption in the digestive tract, thereby providing a sustained action over a longer period. For example, a time-delay material such as glyceryl monostearate or glyceryl distearate may be used. Preparations for oral use may be presented as hard gelatin capsules in which the active ingredient is mixed with an inert solid diluent, such as calcium carbonate, calcium phosphate, or kaolin, or as soft gelatin capsules in which the active ingredient is mixed with water or an oil medium, such as peanut oil, liquid paraffin, or olive oil.

[0085] In one embodiment, the composition may contain a solubilizer to ensure good solubilization and / or dissolution of the disclosed compound and minimize precipitation of the disclosed compound.This may be particularly important for compositions that are used parenterally, such as compositions for injection.Solubilizers can also be added to increase the solubility of other components, such as hydrophilic drugs and / or surfactants, or to maintain the composition as a stable or homogeneous solution or dispersion.

[0086] The composition may further comprise one or more pharma- ceutically acceptable additives or pharma-ceutically acceptable excipients.Such additives and excipients include, but are not limited to, detackifiers, antifoaming agents, buffers, polymers, antioxidants, preservatives, chelating agents, viscomodulators, tonicifiers, flavorings, colorings, flavorings, opacifiers, suspending agents, binders, fillers, plasticizers, lubricants, and mixtures thereof.Non-exhaustive examples of excipients include monoglycerides, magnesium stearate, edible modified starch, gelatin, microcrystalline cellulose, glycerin, stearic acid, silica, yellow wax, lecithin, hydroxypropyl cellulose, croscarmellose sodium, and crospovidone.

[0087] In some embodiments, the compounds or compositions described herein may be formulated or administered in combination with one or more other active ingredients. In some cases, the cannabinoid composition may be administered with a psychedelic compound to enhance treatment. Enhancement of treatment may involve the activation of the endocannabinoid system, neuroplasticity, neural trimming, and the like. trimming), antipsychotic effects, anxiolytic effects, enhanced neurogenesis, or a combination of these.

[0088] In some cases, the cannabinoid compositions described herein may be used in combination with psychedelic compounds such as 3,4-methylenedioxymethamphetamine (MDMA), psilocybin, lysergic acid diethylamide (LSD), etc. In some cases, the cannabinoid compositions may be used in combination with a psychedelic-assisted treatment program, which may aid in overall effectiveness.

[0089] The compositions described herein can also be formulated as extended release, slow release, sustained release, or timed release, such that one or more components are released over time. The disclosed compositions may have a half-life of at least about 1 minute, 10 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, or longer. Delayed release can be achieved by formulating one or more components in a matrix of various materials or by microencapsulation (e.g., microencapsulation in a material with a predetermined degradation rate or a material with pores with a pore size that allows for controllable release). The composition can be formulated to release one or more components over 1, 4, 6, 8, 12, 16, 20, 24, 36, or 48 hours. The release of one or more components may be at a constant rate or at a variable rate.

[0090] The compositions described herein may be formulated as matrix pellets, in which particles of the subject composition are embedded in a matrix of water-insoluble plastic and encapsulated in a membrane of water-insoluble plastic containing embedded lactose particles, to bring and maintain the plasma level of the subject composition within the targeted therapeutic range. The compositions may also be formulated as sustained or controlled release capsules or tablets. Sustained or controlled release tablets can be formed by coating a core granule consisting mainly of the subject composition with a layer of a coating film consisting of a hydrophobic material and a plastic excipient, and optionally containing an enteric polymeric material, to form a coated granule, and then compressing the coated granule with a disintegrating excipient. Such sustained or controlled release capsules or tablets can release the composition in a substantially sustained or controlled manner over a given period of time, for example, at a substantially constant release rate over a period of at least 0.1 hours, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 24 hours, or longer. Such sustained or controlled release capsules or tablets may enable at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or more of the composition to be released over a period of at least 0.1 hours, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 24 hours or more.

[0091] The controlled release dosage form provided herein can be used to release one or more cofactors in the dosage form at a slower rate than observed for the immediate release formulation of the same amount of components.The rate of change in biological sample can be measured as the change in concentration over a specified period of time from administration relative to the maximum concentration for the controlled release formulation, and is less than about 80%, 70%, 60%, 50%, 40%, 30%, 20%, or 10% of the rate of the immediate release formulation.The rate of concentration change over time can be less than about 80%, 70%, 60%, 50%, 40%, 30%, 20%, or 10% of the rate for the immediate release formulation.

[0092] The rate of concentration change over time can be slowed down by extending the time to maximum concentration in a relatively proportional manner. For example, extending the time to maximum concentration by two times can slow down the rate of concentration change by approximately half. As a result, one or more cofactors can be provided to reach their maximum concentration at a rate that is significantly slower than an immediate release dosage form. The compositions of the present disclosure can be formulated to achieve a 24-hour, 16-hour, 8-hour, 4-hour, 2-hour, or at least 1-hour change in maximum concentration. The associated slowdown in the rate of concentration change can be about 0.05, 0.10, 0.25, 0.5, or at least 0.8-fold. This can be achieved by releasing less than about 30%, 50%, 75%, 90%, or 95% of one or more cofactors into circulation within one hour of such administration.

[0093] A controlled release formulation may exhibit a plasma concentration curve with an initial slope (e.g., from 2 hours post-administration to 4 hours post-administration) that is less than 75%, 50%, 40%, 30%, 20%, or 10% of the slope for an immediate release formulation of the same dose of the same cofactor.

[0094] The release rate of a cofactor measured in a dissolution study can be less than about 80%, 70%, 60%, 50%, 40%, 30%, 20%, or 10% of the rate for an immediate release formulation of the same cofactor over the first 1, 2, 4, 6, 8, 10, or 12 hours.

[0095] The controlled release formulations provided herein can be in a variety of formats. The formulations can be in oral dosage forms, including, but not limited to, liquid dosage forms (e.g., suspensions and slurries) and oral solid dosage forms (e.g., tablets and bulk powders), such as those described herein.

[0096] Tablets or pills can be coated or otherwise formulated to obtain dosage forms that provide the advantage of sustained action. For example, a tablet or pill can include an inner dosage and an outer dosage component, the latter in the form of an envelope over the former. The two components can be separated by an enteric layer that serves to resist disintegration in the stomach and allows the inner component to pass intact into the duodenum or to be delayed in release. Such enteric layers or coatings can use a variety of materials, including some polymeric acids and mixtures of polymeric acids with materials such as shellac, cetyl alcohol, and cellulose acetate. Formulations that include multiple cofactors can have different cofactors that are released at different rates or at different times. For example, there can be additional layers in which the cofactors are interspersed with the enteric layer.

[0097] The composition can be formulated as a food composition. For example, the composition can be a beverage or other liquid, solid food, semi-solid food, with or without a food carrier. For example, the composition can be a black tea supplemented with any of the compositions described herein. The composition can also be a dairy product supplemented with any of the compositions described herein. The composition can be formulated as a food composition. For example, the composition can be a beverage, solid food, semi-solid food, or food carrier.

[0098] Liquid food carriers such as beverages, for example in the form of supplemented juice, coffee, tea, soda, flavored water, etc., can be used. For example, the beverage may include the formulation and liquid components such as various deodorants or natural carbohydrates present in conventional beverages. Examples of natural carbohydrates include, but are not limited to, monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, conventional sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol and erythritol. Natural deodorants such as thaumatin, stevia extract, rebaudioside A, glycyrrhizin, and synthetic deodorants such as saccharin and aspartame may be used. Agents such as flavoring agents, coloring agents, etc. may be used. For example, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal adhesives, pH controlling agents, stabilizers, preservatives, glycerin, alcohol, or carbonizing agents may be used. Fruits and vegetables may also be used in the preparation of foods and beverages, including the formulations discussed herein.

[0099] Alternatively, the composition may be a snack bar supplemented with any of the compositions described herein. For example, the snack bar may be a chocolate bar, a granola bar, or a trail mix bar. In yet another embodiment, the dietary supplement or food composition is formulated to have a suitable and desirable taste, mouthfeel, and viscosity for consumption. Any suitable food carrier may be used in the food composition. Food carriers of the present disclosure include virtually any food. Examples of such food carriers include, but are not limited to, food bars (granola bars, protein bars, candy bars, etc.) Food products include, for example, cereal products (oatmeal, breakfast cereals, granola, etc.), bakery products (bread, donuts, crackers, bagels, pastries, cakes, etc.), beverages (dairy drinks, sports drinks, fruit juices, alcoholic drinks, bottled water, etc.), pasta, grains (rice, corn, oats, rye, wheat, flour, etc.), egg products, snacks (candy, chips, gum, chocolate, etc.), meat, fruit, and vegetables. In one embodiment, the food carriers used herein can mask undesirable flavors (e.g., bitterness). In desired cases, the food compositions provided herein exhibit a more desirable mouthfeel and aroma than any of the components described herein. For example, liquid food carriers can be used in accordance with the present disclosure to provide the food compositions in the form of beverages such as supplemented juices, coffees, teas, etc. Solid food carriers can be used in accordance with the present disclosure to provide the food compositions in the form of dietary supplements such as supplemented snack bars, pastas, breads, etc. Alternatively, semi-solid food carriers can be used in accordance with the present disclosure to provide the food composition in the form of a gum, or chewing candy or snack. method

[0100] In some embodiments, the present disclosure provides methods for converting a carboxylated cannabinoid to a decarboxylated cannabinoid. Such conversion may include removal of a carboxylic acid group from the carboxylated cannabinoid.

[0101] In some embodiments, the present disclosure provides a method of supplementing cannabinoid compounds and terpenoids to a subject in need thereof, comprising administering a unit dose of a composition described herein.

[0102] The method of converting carboxylated cannabinoids to decarboxylated cannabinoids may be a chemical reaction. The chemical reaction conditions may include a catalyst, such as an acid, to promote the conversion of carboxylated cannabinoids to decarboxylated cannabinoids. The acid used may be a weak acid. The acid may have a pKa of at most about 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0, -1, -2, -3, -4, -5, -6, -7, -8, -9, -10 or lower. The acid may have a pKa of at least about -10, -9, -8, -7, -6, -5, -4, -3, -2, -1, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or higher. The acid may have a pKa that is about -10 to about 10, about -7 to about 7, about -3 to about 7, about -1 to about 7, about 3 to about 7, or about 4 to about 6, or about 5 to 7. In some embodiments, the acid has a pKa of at most about 20, 15, 10, or 5. In some embodiments, the acid has a pKa of at least about -10, -5, 0, 5, or higher. The acid may be a weak acid. The acid may be a strong acid. The acid may be an organic acid. The acid may include a carboxylic acid moiety. The acid may have a molecular weight of less than about 500 daltons, 400 daltons, 300 daltons, 200 daltons, 100 daltons, 90 daltons, 80 daltons, 70 daltons, 60 daltons, 50 daltons, 40 daltons, or less.

[0103] Carboxylated cannabinoids (e.g., tetrahydrocannabinolic acid) are converted to decarboxylated cannabinoids (e.g., Δ 9 The amount of acid used to convert carboxylated cannabinoids to decarboxylated cannabinoids (tetrahydrocannabinol) can be selected so that the acid is catalytic (i.e., catalyzes the conversion of carboxylated cannabinoids to decarboxylated cannabinoids). The amount of acid can be at least about 0.01 grams (g), 0.1 g, 0.5 g, 1 g, 2 g, 5 g, 10 g, 20 g, 30 g, 40 g, 50 g, 60 g, 70 g, 80 g, 90 g, 100 g, or more.

[0104] Acids that can be used to convert carboxylated cannabinoids to decarboxylated cannabinoids include lactic acid, citric acid, malic acid, acetic acid, benzoic acid, butyric acid, ascorbyl phosphate, and acetic acid. The acid may include one or more members selected from the group consisting of acetic acid, lactic acid, tartaric acid, tannic acid, and oxalic acid. The acid may be an edible acid. The acid may be naturally occurring, isolated from a natural source, or synthetically produced. Depending on which acid is used, the acid may be diluted (e.g., with water) to obtain an acidic solution having a pKa that may be suitable for converting carboxylated cannabinoids to decarboxylated cannabinoids.

[0105] The conversion can be carried out in a laboratory, a production facility, a home, or a doctor's office, and can be carried out in the hands of a technician, a physician, or a purchaser or user of a kit described herein.

[0106] The conversion of carboxylated cannabinoids to decarboxylated cannabinoids may be at temperatures of at most 500° C., 400° C., 300° C., 200° C., 100° C., 75° C., 50° C., 40° C., or 30° C. The conversion may not require an external heat source or additional heating to carry out the reaction that turns the carboxylated cannabinoids into decarboxylated cannabinoids.

[0107] Carboxylated cannabinoids can be converted to decarboxylated by contacting the carboxylated cannabinoids with an acid. This can be done by blending, mixing, stirring, or any combination thereof. The conversion can be carried out in a reaction vessel, such as, for example, a bowl, a round-bottom flask, a reactor, a batch reactor, a piston reactor, a catalytic reactor, a semi-batch reactor, a household vessel, etc. The reaction vessel can be configured to hold a reaction mixture. The reaction mixture can include an acid and a cannabis plant part. The cannabis plant part can contain tetrahydrocannabinolic acid.

[0108] The reaction vessel may hold at least about 1 gram (g) of starting material, 2g, 5g, 10g, 20g, 30g, 40g, 50g, 60g, 70g, 80g, 90g, 100g, or more of starting material. The starting material may be a part of a cannabis plant. The cannabis plant may contain carboxylated cannabinoids. The cannabis plant part may contain at least about 1g, 2g, 5g, 10g, 20g, 30g, 40g, 50g, 60g, 70g, 80g, 90g, 100g, or more of tetrahydrocannabinolic acid. The reaction vessel may hold a volume of at least about 1 milliliter (mL), 2 mL, 5 mL, 10 mL, 20 mL, 30 mL, 40 mL, 50 mL, 60 mL, 70 mL, 80 mL, 90 mL, 100 mL, 1 liter (L), 2 L, 5 L, 10 L, 50 L, 100 L, 1000 L, or more. The reaction vessel may be configured to provide for production of at least about 1 gram (g), 2 g, 5 g, 10 g, 20 g, 30 g, 40 g, 50 g, 60 g, 70 g, 80 g, 90 g, 100 g, or more of decarboxylated cannabinoid compound.

[0109] The reaction mixture may be subjected to separation after the reaction is complete or nearly complete. Separation of the desired decarboxylated cannabinoids from the remainder of the reaction mixture, such as the solvent, catalyst, plant material, unconverted starting materials, etc., may include filtration, extraction, centrifugation, solubilization, concentration, washing, electrolysis, adsorption, purification, chromatography, fractionation, crystallization, or combinations thereof. In some cases, the desired decarboxylated cannabinoids (e.g., Δ 9 Tetrahydrocannabinol) is separated from the reaction mixture via one, two, three, four, five, or more separation steps or procedures.

[0110] After the reaction of carboxylated cannabinoids to decarboxylated cannabinoids, There may be trace amounts of acid in the reaction mixture. There may be trace amounts of acid after isolating the desired compound from the reaction mixture. The separated or isolated decarboxylated cannabinoid may be the desired end product that can be used in a manufacturing process that is delivered to a user. The isolated decarboxylated cannabinoid may contain trace amounts of acid. Trace amounts of acid may be less than about 10,000 parts per million (ppm), 1000 ppm, 100 ppm, 10 ppm, or 1 ppm. Indications

[0111] Terpenoids can provide beneficial effects to subjects. Terpenoids can be formulated in compositions as described herein and given to subjects as nutritional or dietary supplements. The compositions can provide nutrients or compounds that are otherwise not consumed in sufficient amounts in normal diets. The compositions can contain compounds that can be beneficial to the health, physical well-being, and emotional well-being of subjects. For example, the compositions can be used as energy boosters.

[0112] The compositions of the present disclosure can be used to treat or reduce symptoms of nausea or vomiting. A subject to whom a unit dose of the composition is administered may experience relief of symptoms associated with nausea or vomiting.

[0113] The compositions of the present disclosure can be used to treat eating disorders such as anorexia, cachexia, bulimia nervosa, rumination disorders, avoidant or restrictive food consumption disorders.

[0114] The compositions of the present disclosure can be used as sleep aids or to help with symptoms of insomnia. The compositions can help a subject relax, fall asleep more quickly, improve the amount of sleep, or improve the quality of sleep.

[0115] The compositions of the present disclosure can be used to ameliorate, limit, or reverse the effects of oxidative damage or oxidative stress. An imbalance of reactive oxygen species in a subject can be corrected or ameliorated by administration of the compositions described herein.

[0116] Oxidative stress may occur before, during, and / or after surgery.Oxidative stress may be due to anesthesia used during surgery, trauma from surgery, psychological stress associated with surgery, or a combination thereof.The composition may be administered to subject before, during, or after surgery.The composition may be administered to alleviate traumatic shock that may be caused by surgery or injury.

[0117] Oxidative stress may be caused by physical or emotional stressors.The compositions of the present disclosure can be used to treat post-traumatic stress disorder (PTSD).Some symptoms of PTSD that can be alleviated by the compositions include flashbacks, nightmares, frightening thoughts, avoidance of certain thoughts or feelings, cognitive or mood symptoms such as being easily startled, feeling nervous, having difficulty sleeping, having difficulty remembering the characteristics of traumatic events, distorted feelings such as guilt or remorse, and loss of interest in pleasurable activities.

[0118] The compositions can be administered to prevent the development or limit the severity of post-traumatic stress disorder. The compositions may be administered after physical or emotional stress, such as after physical sports, contact sports, physical combat, physical conflict, military drills or training, and military combat.

[0119] The compositions of the present disclosure can be used to treat symptoms of addiction, addictive behavior, physical dependence, or psychological dependence. Symptoms may be treated, alleviated, or eliminated. Addiction may be characterized by a compulsive involvement with a stimulus. Addiction may be graded based on a severity index, such as the Addiction Severity Index (ASI). ASI severity ratings may be based on a 10-point scale ranging from 0 to 9. A rating of 0-1 may be classified as no real problem, no treatment required. A rating of 2-3 may be classified as a mild problem, where treatment may not be required. A rating of 4-5 may be classified as a moderate problem, where some treatment may be required. A rating of 6-7 may be considered a significant problem, where treatment may be required. A rating of 8-9 may be considered an extreme problem, where treatment may be absolutely required.

[0120] Examples of drug and behavioral addictions include, but are not limited to, alcoholism, cocaine addiction, smoking addiction, nicotine addiction, opiate addiction, food addiction, amphetamine addiction, and gambling addiction.

[0121] The compositions described herein can be used to alleviate smoking addiction. The compositions can be used as part of a smoking cessation program, where subjects are provided with tobacco infused with cannabinoids. For natural and gradual reduction of addiction, the compositions can also be administered by aqueous methods to allow absorption through membranes. In addition, the compositions described herein can also contribute to anxiolytic effects. For example, compositions administered in aqueous form can provide rapid anxiolytic effects through mucosal absorption to suppress addiction. The cannabinoid compositions can be part of a program to gradually reduce tobacco use.

[0122] In some cases, cannabinoid compounds may exhibit a number of different bell curves of efficacy that may vary or modulate from day to day depending on several factors of the subject, including oxidative stress.

[0123] The compositions of the present disclosure can be administered to a subject during and / or after treatment. The subject can experience a reduction in symptoms, or a reduction in severity rating according to a severity index scale (e.g., the ASI severity index).

[0124] The composition can be used to treat cancer or tumor.Liquid tumor cancer can be, for example, blood, bone marrow, and lymph node cancer, and can include, for example, leukemia, myeloid leukemia, lymphocytic leukemia, lymphoma, Hodgkin's lymphoma, melanoma, and multiple myeloma.Leukemia includes, for example, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), and hairy cell leukemia. Solid tumor cancers include, for example, prostate cancer, testicular cancer, breast cancer, brain cancer, pancreatic cancer, colon cancer, thyroid cancer, stomach cancer, lung cancer, ovarian cancer, Kaposi's sarcoma, skin cancer, squamous cell skin cancer, kidney cancer, head and neck cancer, pharyngeal cancer, squamous cell carcinoma that forms on the moist mucosal lining of the nose, oral cavity, and pharynx, bladder cancer, osteosarcoma, cervical cancer, endometrial cancer, esophageal cancer, liver cancer, and kidney cancer. The compositions described herein can be used to treat cervical cancer.

[0125] The compositions described herein can be used to treat prostate cancer.Subjects can be evaluated based on the level of prostate specific antigen, or PSA, which is a protein produced by prostate cells.The increase in the blood level of PSA can be associated with subjects having prostate cancer.

[0126] The composition can be administered to a subject who has been diagnosed with prostate cancer. In some cases, the composition can be administered to a subject who has a PSA level of greater than or equal to about 1 nanogram per milliliter (ng / mL), 2 ng / mL, 3 ng / mL, 4 ng / mL, 5 ng / mL, or 6 ng / mL. If the subject's PSA level is greater than or equal to a certain A drug holiday may be provided for administration of the composition after PSA falls below a threshold of about 20 nanograms per milliliter (ng / mL), 10 ng / mL, 5 ng / mL, 4 ng / mL, 3 ng / mL, 2 ng / mL, or 1 ng / mL. A drug holiday of the composition may be replaced with another compound or composition. For example, during a drug holiday of the composition described herein, a certain amount of delta-9-tetrahydrocannabinol (THC) may be administered. The dosage of THC may be at most about 50 mg / kg, 40 mg / kg, 30 mg / kg, 20 mg / kg, 10 mg / kg, 5 mg / kg, 4 mg / kg, 3 mg / kg, 2 mg / kg, 1 mg / kg, or less.

[0127] The compositions of the present disclosure can be used to treat eating or weight disorders, such as, for example, anorexia and cachexia. The subject may experience an increased appetite after at least a unit dose of the composition of the present disclosure. In some cases, the Δ 9 Tetrahydrocannabinol may result in an appetite enhancing effect, which may persist for an extended period of time, such as at least 1 day, 2 days, 5 days, 7 days, 1 week, 2 weeks, 1 month, 3 months, 6 months, or 12 months after the last unit dose of the composition is consumed.

[0128] The compositions of the present disclosure can be used to treat muscle-related or movement disorders, such as, for example, spasticity, tremors, ataxia, bladder control, Tourette's syndrome, dystonia, Parkinson's disease, Huntington's disease, tardive dyskinesia, etc. Spasticity may be caused by pain, bone or joint deformity, or accident or injury to the spinal cord.

[0129] The composition of the present disclosure can be used to treat pain. The pain can be acute pain. The pain can be chronic pain. The pain can be associated with a disease. The pain in a subject can be neuropathic pain, menstrual pain, chronic headache, or back pain. The pain can be due to a disease or disorder, or can be caused by injury. The pain can be caused by diseases such as cancer, chronic intestinal inflammation, neuralgia, nerve damage, diabetes, multiple sclerosis, infection, old age, etc.

[0130] The pain may be nociceptive pain (i.e., pain caused by tissue damage), neuropathic pain, or psychogenic pain. The pain may be caused by or associated with a disease (e.g., cancer, arthritis, diabetes). Alternatively, the pain may be caused by injury (e.g., sports injury, trauma). Non-limiting examples of pain that may be treated with the compositions and methods herein include neuropathic pain, including peripheral neuropathy, diabetic neuropathy, post-herpetic neuralgia, trigeminal neuralgia, back pain, neuropathy associated with cancer, neuropathy associated with HIV / AIDS, phantom limb pain, cartilage tunnel syndrome, central post-stroke pain, pain associated with chronic alcoholism, hypothyroidism, uremia, pain associated with multiple sclerosis, pain associated with spinal cord injury, pain associated with Parkinson's disease, epilepsy, osteoarthritic pain, rheumatoid arthritis pain, visceral pain, and pain associated with vitamin deficiency, as well as nociceptive pain, including pain associated with central nervous system trauma, contusion / sprain, and burn, myocardial infarction, acute pancreatitis, post-operative pain, post-traumatic pain, renal colic, pain associated with cancer, pain associated with fibromyalgia, pain associated with cartilage tunnel syndrome, and back pain.

[0131] The compositions and methods described herein can be used to reduce the level of pain in a subject. The level of pain in a subject can be reduced by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%. , at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% alleviated. The level of pain in a subject can be assessed by a variety of methods. The level of pain can be assessed by self-report (i.e., the human subject gives a verbal report of the level of pain they experience). The level of pain can also be assessed by behavioral indicators of pain, such as facial expressions, limb movements, vocalizations, restlessness, and guarding. Such types of assessments can be useful, for example, when the subject is unable to self-report (e.g., children, unconscious subjects, non-human subjects). After treatment with the composition of the present disclosure, the level of pain can be assessed in comparison to the level of pain the subject experienced before treatment with the composition.

[0132] The compositions of the present disclosure can be used to reduce intraocular pressure or fluid pressure in the eye and treat a number of diseases associated with abnormal intraocular pressure, including, but not limited to, glaucoma, iritis, and retinal detachment. The compositions may reduce intraocular pressure by 5%, 10%, 20%, 30%, 40%, 50%, or more.

[0133] The disclosed methods and compositions can be used to treat epilepsy. The compositions described herein can be used to prevent or control epileptic seizures. Epileptic seizures can be classified as tonic-clonic, tonic, clonic, myoclonic, absence, or atonic seizures. The compositions and methods herein can prevent or reduce the number of epileptic seizures experienced by a subject by at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 99%, or more.

[0134] The disclosed methods and compositions can be used to alleviate the symptoms of inflammatory diseases of the lung airways, i.e. asthma. The compositions may reduce the severity of asthma symptoms or change the severity classification, such as from severe persistent to moderate persistent to mild persistent to intermittent.

[0135] The compositions of the present disclosure can be used to alleviate symptoms associated with withdrawal from dependence on alcohol and other drugs such as benzodiazepines and opiates. The compositions can alleviate withdrawal symptoms such as sleep disorders, irritability, increased tension, anxiety, panic attacks, tremors, sweating, difficulty concentrating, confusion, memory loss, weight loss or weight gain, headaches, and muscle pain.

[0136] The compositions of the present disclosure can be used to treat psychiatric disorders including, but not limited to, sleep disorders, anxiety disorders, panic disorders, obsessive-compulsive disorders, bipolar disorders, depression, mood disorders, personality disorders, psychotic disorders such as schizophrenia and delusional disorders. The compositions can be used to treat bipolar episodes, symptoms of which can include unusual fluctuations in mood, energy, activity levels, and inability to perform daily routines.

[0137] The compositions of the present disclosure can be used to treat autoimmune diseases or inflammation, such as, but not limited to, arthritis, lupus, vitiligo, anemia, psoriasis, scleroderma, inflammatory bowel disease, and type 1 diabetes.

[0138] The compositions can be used to treat pruritus, ADS (attention deficit syndrome), high blood pressure, tinnitus, chronic fatigue syndrome, and restless legs syndrome.

[0139] The compositions can be used to treat or alleviate the symptoms of hiccups or synchronous diaphragmatic flutter (SDF). Hiccups can be classified as acute, chronic, persistent, or intractable. In some cases, the compounds or compositions can be used to treat or alleviate the symptoms of chronic hiccups.

[0140] The compositions can be used to treat or alleviate menopausal or premenopausal symptoms, for example, by reducing the frequency and / or intensity of symptoms including hot flashes, night sweats, painful intercourse, increased anxiety or irritability, and the need to urinate more frequently.

[0141] The composition can be used to treat or sterilize wounds. The composition can be used in conjunction with citric acid or can be formulated into one composition for use in sterilizing open wounds.

[0142] The compositions described herein can be used in conjunction with venom or envenomation treatment. The compositions may be administered before, during, or after administration of an antidote or anti-venom. The compositions may be administered after exposure to a toxin or envenomation, and may be without an antidote. Administration for use with an antidote may be by injection, sublingual, oral, nasal spray, or transdermal patch. Without being bound by theory, the cannabinoid compositions may help protect tissues, the nervous system, and / or assist in regulating overall homeostasis in a subject. The cannabinoid compositions may help reduce oxidative stress, tissue damage, organ damage, or neurotrauma. The compositions may also enhance cell protection, health, and overall homeostatic balance.

[0143] In some cases, the compositions described herein may be used to treat shingles, chickenpox, measles, human papillomavirus (HPV), chronic obstructive pulmonary disease (COPD), emphysema, ilitigo, impetigo, and the like. It may also be used to treat rash, pneumonia, Listeria, Ebola, Addison's disease, Graves' disease, Sjogren's syndrome, Hashimoto's disease, autism, myasthenia gravis, pernicious anemia, or celiac disease.

[0144] In some cases, the composition may be used to treat autoimmune diseases.In some cases, the composition may be used to treat achalasia, Addison's disease, adult Still's disease, agammaglobulinemia, alopecia areata, amyloidosis, ankylosing spondylitis, anti-GBM / anti-TBM nephritis, antiphospholipid syndrome, autoimmune angioedema, autoimmune autonomic neuropathy, autoimmune encephalomyelitis, autoimmune hepatitis, autoimmune inner ear disease (AIED), autoimmune myocarditis, autoimmune oophoritis, autoimmune orchitis, autoimmune pancreatitis, autoimmune retinopathy, autoimmune urticaria, axonal and neuronal neuropathy (AMAN), Balo's disease, Behçet's disease, benign mucous membrane pemphigoid, bullous pemphigoid, Castleman's disease (CD), celiac disease, Chagas' disease, chronic inflammatory demyelinating polyneuropathy (CIDP), chronic relapsing multifocal osteomyelitis (CRMO), Churg-Strauss syndrome (CSS) or eosinophilic granulomatosis (EGPA), cicatricial pemphigoid, Cogan's syndrome, cold agglutinin disease, congenital heart block, Coxsackie myocarditis, CREST syndrome, Crohn's disease, dermatitis herpetiformis, dermatomyositis, Devic's disease (neuromyelitis optica), discoid lupus, Dressler's syndrome, endometriosis, Eosinophilic esophagitis (EoE), eosinophilic fasciitis, erythema nodosum, essential mixed cryoglobulinemia, Evans syndrome, fibromyalgia, fibrosing alveolitis, giant cell arteritis (temporal arteritis), giant cell myocarditis, glomerulonephritis, Goodpasture's syndrome, granulomatosis with polyangiitis, Graves' disease, Guillain-Barré syndrome, Hashimoto's thyroiditis, hemolytic anemia, Henoch-Schönlein purpura (HSP), herpes gestationis or pemphigoid of gestationis (PG), hidradenitis suppurativa (HS) (acne contralateral), hypogammaglobulinemia, IgA nephropathy, IgG4-related Interleukin-1 sclerosing disease, immune thrombocytopenic purpura (ITP), inclusion body myositis (IBM), interstitial cystitis (IC), juvenile arthritis, juvenile diabetes mellitus (type 1 diabetes), juvenile myositis (JM), Kawasaki disease, Lambert-Eaton syndrome, leukocytoclastic vasculitis, lichen planus, lichen sclerosus, lignified conjunctivitis, linear immunoglobulin A disease (LAD), lupus, chronic Lyme disease, Meniere's disease, microscopic polyangiitis (MPA), mixed connective tissue disease (MCTD), Mooren's ulcer, Mucha-Habermann disease, multifocal motor neuropathy (MMN) or MMNCB , multiple sclerosis, myasthenia gravis, myositis, narcolepsy, neonatal lupus, neuromyelitis optica, neutropenia, ocular cicatricial pemphigoid, optic neuritis, relapsing rheumatoid arthritis (PR), PANDAS, paraneoplastic cerebellar degeneration (PCD), paroxysmal nocturnal hemoglobinuria (PNH), Parry-Romberg syndrome, pars planitis (peripheral uveitis), Parsonnage-Turner syndrome, pemphigoid Acne, peripheral neuropathy, perivenous encephalomyelitis, pernicious anemia (PA), POEMS syndrome, polyarteritis nodosa, polyglandular syndrome type I, II, III, polymyalgia rheumatica, polymyositis, post-myocardial infarction syndrome, post-pericardiotomy syndrome, primary biliary cirrhosis, primary sclerosing cholangitis, progesterone dermatitis, psoriasis, psoriatic arthritis, pure red cell aplasia (PRCA), pyoderma gangrenosum, Raynaud's phenomenon , reactive arthritis, reflex sympathetic dystrophy, relapsing polychondritis, restless legs syndrome (RLS), retroperitoneal fibrosis, rheumatic fever, rheumatoid arthritis, sarcoidosis, Schmidt's syndrome, scleritis, scleroderma, Sjogren's syndrome, sperm and testicular autoimmunity, stiff person syndrome (SPS), subacute bacterial endocarditis (SBE), Susac's syndrome, sympathetic ophthalmia (SO), Takayasu's arteritis, temporal arteritis / giant cell arteritis, thrombocytopenic purpura (TTP), Trosa-Hunt syndrome (THS), transverse myelitis, type 1 diabetes mellitus, ulcerative colitis (UC), undifferentiated connective tissue disease (UCTD), uveitis, vasculitis, vitiligo, Hocht-Koyanagi-Harada disease, or Wegener's granulomatosis (or granulomatosis with polyangiitis (GPA)).

[0145] The composition comprising cannabinoids can be formulated as a water-soluble form.The administration of the composition in water-soluble form can allow rapid membrane absorption.The composition can be added to water supplies, for example drinking water, for protection after chemical or toxic events or exposure.

[0146] The compositions can be used to enhance neurogenesis or neural tissue growth and development in a subject. The compositions can also improve the overall performance of the nervous system, including the parasympathetic nervous system, the sympathetic nervous system, and the enteric nervous system.

[0147] The composition can be used as a supplement to protect telomeres, the end regions of chromosomes, in a subject. Protecting telomeres can protect chromosomes from deterioration.

[0148] In some cases, the compositions described herein may be used as endocannabinoid system (ECB) targeted therapeutics. The two main endocannabinoid receptors of the endocannabinoid system are CB1 and CB2.

[0149] In some cases, the compositions of the present disclosure may be used in conjunction with the study of epigenetics, i.e., heritable changes in gene function that may not involve changes in DNA sequence, or functionally relevant changes to the genome that may not involve changes in nucleotide sequence (e.g., DNA methylation, histone modifications). In some cases, epigenetic mechanisms may include factors and processes such as development (e.g., in utero, childhood), environmental factors (e.g., environmental chemicals), drugs, pharmaceuticals, aging, diet, etc.

[0150] Compositions may be administered or suggested based on epigenetic testing.In some cases, the compositions described herein can also modulate risk factors or improve disease conditions.In some cases, terpenes such as those described herein can be used to direct cannabinoids to specific CB receptor sites.The compounds disclosed herein can be used to prevent or reduce risk and harm during and after epigenetic manifestations, and can help change expression.

[0151] In some cases, if a thyroid risk factor becomes evident, a composition could be used to treat the thyroid, and then if new epigenetic manifestations appear, the same composition could be used to treat the thyroid. Different terpenes can be used to target different areas of the body.In some cases, the composition can be absorbed quickly in the body.When the composition is absorbed quickly, the same formulation can be given continuously, thereby changing the effect of cannabinoids.

[0152] In some cases, compositions may be administered or suggested based on the genetic test.

[0153] Alternatively, the compositions may be administered based on standard testing of targeted treatment protocols, where the cannabinoids and terpenes in the composition may prevent and / or treat a risk factor or disease state.

[0154] The subject may exhibit one or more symptoms. The symptoms may be selected from the group consisting of pain, stress, nausea, vomiting, insomnia, anxiety, and loss of appetite. The unit dose can be used to alleviate the symptoms in the subject, in some cases, by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, or 99%. The composition may result in the severity or number of symptoms being reduced by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, or 99%.

[0155] The unit dose may be administered at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more times per day. The subject may be medicated for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or more days, weeks, or months, or for less or more than these periods. The unit dose may be a fraction of the daily dose, such as the daily dose divided by the number of unit doses to be administered per day. The unit dose may also be a fraction of the daily dose, which is the daily dose divided by the number of unit doses to be administered per day, further divided by the number of unit doses (e.g., tablets) per administration. The number of unit doses per administration may be at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more. The number of doses per day can be at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more. The number of unit doses per day can be determined by dividing the daily dose by the unit dose, and can be at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 6, 17, 18, 19, 20, or more unit doses per day. For example, the unit dose can be about 1 / 2, 1 / 3, 1 / 4, 1 / 5, 1 / 6, 1 / 7, 1 / 8, 1 / 9, or 1 / 10 of the recommended daily dose. The unit dose can be about one-third of the daily dose and can be administered to the subject three times per day. The unit dose can be about one-half of the daily dose and can be administered to the subject twice per day. The unit dose can be about one-quarter of the daily dose and can be administered to the subject two unit doses twice per day.

[0156] The length of administration period and / or dosage can be determined by a physician or any other type of clinician.The physician or clinician can observe the subject's response to the administered composition and adjust the dosage based on the subject's outcome.For example, the dosage for the subject who shows a reduced effect in energy regulation can be increased to obtain the desired outcome.

[0157] The components of the composition may be administered simultaneously by the same route or separately. The components of the composition may be administered sequentially. The components of the composition may be administered by the same or different routes of administration.

[0158] Another aspect of the present disclosure provides for the realization of a desired effect in one or more subjects after administering the combination composition described herein for a specified period of time.For example, the beneficial effect of the composition described herein can be observed after administering the composition to a subject for 1, 2, 3, 4, 6, 8, 10, 12, 24, or 52 weeks.

[0159] In some embodiments, the present disclosure also provides methods of producing the compositions described herein. The production of the compositions described herein may involve mixing or combining two or more components.

[0160] The composition can be combined or mixed with a pharmacoactive or therapeutic agent, a carrier, and / or an excipient. Examples of such components are described herein. The combined composition can be in a unit dosage form as a tablet, capsule, gel capsule, or slow release tablet.

[0161] The compositions may be prepared such that one or more components are evenly dispersed throughout the composition to provide a solid composition containing a substantially homogeneous mixture of the component(s), such that the composition can be readily subdivided into equally effective unit dosage forms, such as tablets, pills, capsules, etc.

[0162] A unit dose of the composition may retain at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% of the one or more cannabinoids after being placed in a sealed container for a certain period of time, for example, 1 day, 7 days, 1 month, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years, or longer. A unit dose of the composition may have a shelf life of at least about 1 day, 7 days, 1 month, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years, or longer. Without being bound by theory, trace amounts of acid in the composition may contribute to and extend the shelf life of the composition.

[0163] The unit dose of the composition may be stored under conditions at least about 25° C., 30° C., 40° C., 50° C., 60° C., 70° C., or higher. The unit dose of the composition may be stored under humidity level conditions at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or higher humidity levels without substantial degradation of the cannabinoids.

[0164] The unit dose may be packaged in a container that is given to the user. The unit dose may be packaged in a tube, jar, box, vial, bag, tray, drum, bottle, syringe, or can. kit

[0165] The present disclosure also provides kits. The kits include one or more compositions described herein in suitable packaging and may further include written materials, which may include instructions for use, clinical study discussions, and side effect lists. Such kits may also include information, such as scientific literature references, package insert materials, clinical trial results, and / or summaries thereof, that indicate or demonstrate the activity and / or benefits of the compositions and / or describe dosage, administration, side effects, drug interactions, or other information useful to health care providers. Such information may be based on the results of various studies, for example, studies using laboratory animals, including in vivo models, and studies primarily involving human clinical trials. The kits may include one or more unit doses described herein. The kits may include at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 31, 60, 90, 120, 150, 180, 210, or more unit doses. The kit may include at most about 20, 15, 10, 5, 4, 3, 2, or 1 unit doses. The instructions may include dosing instructions, such as instructions to consume 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more unit doses 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more times per day. For example, the kit may be packaged according to the number of unit doses per administration as tablets, with each tablet packaged individually. As a further example, the kit may include unit doses supplied as multiple tablets (e.g., tablet pairs) individually packaged together or as whole tablets packaged together (e.g., in a bottle). As a further example, the kit may include unit doses supplied as a bottled drink, where the kit includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 24, 28, 36, 48, 72, or more bottles.

[0166] The instructions may be provided in printed form on the user interface of a user's electronic device. The instructions may also be provided on, for example, a graphical user interface or a web-based interface.

[0167] The kit may further contain another agent. The compound of the present disclosure and the agent may be provided or packaged as separate compositions in separate containers in the kit. The compound of the present disclosure and the agent may be provided or packaged as a single composition in a container in the kit. The kit may include suitable packaging materials and additional items for use (e.g., measuring cups for liquid preparations, foil wrappers to minimize exposure to air). The kits described herein may be provided, sold, and / or promoted to health providers, including physicians, nurses, pharmacists, and formulary officials. The kits may be sold directly to consumers.

[0168] The kit may include a multi-day supply of unit doses. The unit dose may be any unit dose described herein. The kit may include instructions for administering the multi-day supply of unit doses over multiple days. The multi-day supply may be a one-month supply, a 30-day supply, or a multi-week supply. The multi-day supply may be a 90-day, 180-day, 3-month, or 6-month supply. The kit may include packaged daily unit doses, such as 1, 2, 3, 4, or 5 unit dose packages. The kit may be packaged with other dietary supplements, vitamins, and meal replacement bars, mixes, and beverages.

[0169] The kit may be used to prepare a decarboxylated cannabinoid (e.g., Δ 9 The starting materials may include those that enable the user to convert the compound to tetrahydrocannabinol.

[0170] The kit may include all the necessary starting materials so that the conversion can be carried out by a user. The kit may include a carboxylated cannabinoid, an acid present to effect the conversion of the carboxylated cannabinoid to a decarboxylated cannabinoid, a reaction vessel configured to hold a reaction mixture including the acid and the carboxylated cannabinoid, and instructions for carrying out the conversion utilizing the acid. The resulting decarboxylated cannabinoid formed from the conversion has a Δ 9 Tetrahydrocannabinol may be used.

[0171] Alternatively, the kit may include some of the necessary starting materials so that the conversion can be performed by the user. The user may supplement the kit with their own supply of carboxylated cannabinoids. The kit may include an acid present to effect the conversion of the carboxylated cannabinoid to a decarboxylated cannabinoid, a reaction vessel configured to hold a reaction mixture comprising the acid and the carboxylated cannabinoid, and instructions for carrying out the conversion utilizing the acid. The carboxylated cannabinoid provided by the user may be tetrahydrocannabinolic acid.

[0172] The acid in the kit is at least about 0.01 grams (g), 0.1 g, 0.5 g, 1 g, 2 g, 5 g, 10 g, 20 g, 30 g, 40 g, 50 g, 60 g, 70 g, 80 g, 90 g, It may be present in amounts of 100g, 100g, or more.

[0173] The carboxylated cannabinoid (e.g., tetrahydrocannabinolic acid), when provided in the kit, may be present in an amount of at least about 1 gram (g), 2 g, 5 g, 10 g, 20 g, 30 g, 40 g, 50 g, 60 g, 70 g, 80 g, 90 g, 100 g, or more. The amount of decarboxylated cannabinoid formed from carrying out a reaction using the kit may be at least about 1 gram (g), 2 g, 5 g, 10 g, 20 g, 30 g, 40 g, 50 g, 60 g, 70 g, 80 g, 90 g, 100 g, or more. Computer Control System

[0174] The present disclosure provides a computer control system programmed to implement the methods of the present disclosure. Figure 1 shows a computer control system 101 programmed or otherwise configured to generate a composition comprising a mixture of carboxylated and decarboxylated cannabinoids or to provide instructions for using or generating the compositions of the present disclosure. The computer control system 101 can regulate various aspects of the methods of the present disclosure, such as the method of generating decarboxylated cannabinoids, including but not limited to the movement of the reaction vessel and agitator, packaging of unit doses of the composition, and printing of instructions for use of the composition. The computer control system 101 can be implemented in a user's electronic device or a computer system located remotely from the electronic device. The electronic device may be a mobile electronic device.

[0175] The computer system 101 includes a central processing unit (CPU, also referred to herein as "processor" and "computer processor") 105, which may be a single-core or multi-core processor, or multiple processors for parallel processing. The computer control system 101 also includes memory or memory locations 110 (e.g., random access memory, read-only memory, flash memory), an electronic storage unit 115 (e.g., hard disk), a communication interface 120 (e.g., network adapter) for communicating with one or more other systems, and peripheral devices 125, such as cache, other memory, data storage devices, and / or electronic display device adapters. The memory 110, the storage unit 115, the interface 120, and the peripheral devices 125 are in communication with the CPU 105 via a communication bus (solid lines), such as a motherboard. The storage unit 115 may be a data storage unit (or data repository) for storing data. The computer control system 101 may be operatively coupled to a computer network ("network") 130 utilizing the communication interface 120. The network 130 may be the Internet, an Internet and / or an extranet, or an intranet and / or an extranet in communication with the Internet. The network 130 may be a telecommunications and / or data network in some cases. The network 130 may include one or more computer servers, which may enable distributed computing, such as cloud computing. The network 130 may also in some cases leverage the computer system 101 to implement a peer-to-peer network, which may enable devices coupled to the computer system 101 to operate as clients or servers.

[0176] The CPU 105 may execute sequences of machine-readable instructions, which may be embodied in a program or software. The instructions may be stored in a memory location, such as the memory 110. The instructions may be directed to the CPU 105, which may subsequently program the CPU 105 to implement the methods of the present disclosure. Examples of operations performed by the CPU 105 include fetch, decode, execute, and writeback.

[0177] The CPU 105 may be part of a circuit, such as an integrated circuit. One or more other components of the system 101 may also be included in the circuit. In some cases, the circuit is an application specific integrated circuit (ASIC).

[0178] The storage unit 115 can store files such as drivers, libraries, saved programs, etc. The storage unit 115 can store user data, e.g., user settings and user programs. The computer system 101 may optionally include one or more additional data storage units external to the computer system 101, such as located on a remote server in communication with the computer system 101 via an intranet or the Internet.

[0179] The computer system 101 can communicate with one or more remote computer systems via the network 130. For example, the computer system 101 can communicate with a remote computer system of a user (e.g., a user controlling the generation of a three-dimensional object). Examples of remote computer systems include a personal computer (e.g., a portable PC), a slate or tablet PC (e.g., Apple® iPad®, Samsung® Galaxy Tab), a phone, a smartphone (e.g., Apple® iPhone®, Android-enabled devices, Blackberry®), or a personal digital assistant. A user can access the computer system 101 via the network 130.

[0180] The methods described herein may be implemented as machine-executable (e.g., computer processor) code stored in an electronic storage location of the computer system 101, such as memory 110 or electronic storage unit 115. The machine-executable or machine-readable code may be provided in the form of software. When in use, the code may be executed by the processor 105. In some cases, the code may be retrieved from the storage unit 115 and stored in the memory 110 for easy access by the processor 105. In some circumstances, the electronic storage unit 115 may not be included and the machine-executable instructions are stored in the memory 110.

[0181] The code may be precompiled and constructed for use on a machine having a processor adapted to execute the code, or it may be compiled during run-time. The code may be provided in a programming language that can be selected to allow execution by the code in precompiled or compiled form.

[0182] Aspects of the systems and methods provided herein, such as computer system 101, can be embodied in programming. Various aspects of the technology can be considered to be a "product" or "artificial product," typically in the form of machine (or processor) executable code and / or associated data carried on or embodied in some type of machine-readable medium. The machine executable code can be stored in an electronic storage unit, such as memory (e.g., read-only memory, random access memory, flash memory) or a hard disk. A "storage" type medium may provide non-transitory storage of software programming at any point in time. , computer, processor, etc., or associated modules thereof, such as part or all of the tangible memory, e.g., various semiconductor memories, tape drives, disk drives, etc. Sometimes, all or portions of the software may be communicated over the Internet or various other telecommunications networks. Such communication may, for example, allow the software to be loaded from one computer or processor to another, e.g., from a management server or host computer to a computer platform of an application server. Thus, other types of media that may carry software elements include optical waves, radio waves, and electromagnetic waves, such as those used over wired and optical landline networks, over physical interfaces between local devices, and on various air links. Physical elements that carry such waves, such as wired or wireless links, optical links, etc., may also be considered to be media that carry the software. As used herein, terms such as tangible "storage" media, i.e., computer or machine "readable media," including but not limited to non-transitory, refer to any medium that participates in providing instructions to a processor for execution.

[0183] Thus, a machine-readable medium, such as a computer-executable code, may take many forms, including, but not limited to, a tangible storage medium, a carrier wave medium, or a physical transmission medium. Non-volatile storage media include, for example, any of the storage devices in any computer, such as optical or magnetic disks, such as those shown in the drawings that can be used to implement a database, etc. Volatile storage media include dynamic memory, such as the main memory of such a computer platform. Tangible transmission media include coaxial cables; copper wire and fiber optics, including the wires that make up a bus within a computer system. Carrier wave transmission media may take the form of electric or electromagnetic signals, sound waves, or light waves, such as those generated during radio frequency (RF) and infrared (IR) data communications. Thus, common forms of computer readable media include, for example, a floppy disk, a flexible disk, a hard disk, a magnetic tape, any other magnetic medium, a CD-ROM, a DVD, or a DVD-ROM, any other optical medium, punch cards paper tape, other physical storage media having patterns of holes, RAM, ROM, PROM and EPROM, FLASH-EPROM, any other memory chip or cartridge, a carrier wave carrying data or instructions, a cable or link carrying such a carrier wave, or other medium from which programming code and / or data can be read by a computer. Many of these forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to a processor for execution. EXAMPLES

[0184] Example 1 Pain relief treatment with compositions for subjects with chronic pain Subjects (e.g., patients) suffering from chronic pain are assessed and evaluated for their pain level by the treating physician or other pain management specialist.Then, these subjects are prescribed 10mg / day of a composition comprising cannabinoids and one or more terpenoids.Subjects are then evaluated again after 2 weeks to determine whether symptoms have improved.After evaluation, dosage is increased, decreased, or remains the same depending on changes in pain level.Treatment is continued as long as necessary to affect stable resolution of chronic pain symptoms.

[0185] Example 2 Treatment of Subjects Diagnosed with Alzheimer's Disease Subjects with clinically diagnosed Alzheimer's disease were randomly assigned to Evaluate the condition.

[0186] The subject is prescribed 10mg / day of the composition, and then evaluated again after 2 weeks to determine whether symptoms have worsened.After evaluation, depending on the changes in symptoms of inattention and hyperactivity, dosage is increased, decreased, or remains the same.Treatment is continued as long as necessary to affect the symptoms of Alzheimer's disease to a stable or desired level.

[0187] Example 3 Preparation of unit doses of composition Immerse an industrial laboratory reactor in an ice bath. Charge the reactor with 100 grams of cannabis plant material, 1 mL of acetic acid, and 5 L of water. Remove the ice bath and allow the reaction to reach room temperature, then stir the reaction.

[0188] After the reaction is complete after 30 minutes, the reaction mixture is filtered to remove the water in the resulting solution. The solid is then mixed with a filler such as gelatin and placed into a capsule as a unit dose.

[0189] The unit doses are then distributed and sold to users.

[0190] Example 4 User synthesis of unit doses of composition using kits A kit is sold to a user. The kit contains all the necessary starting materials to allow the user to perform the conversion of carboxylated cannabinoids to decarboxylated cannabinoids. The kit contains 2 grams of cannabis plant material, 1 gram of citric acid, a bowl, and instructions for performing the conversion using the acid.

[0191] The user places the cannabis plant and citric acid in a bowl according to the instructions. The user then adds one cup of water according to the instructions provided with the kit. The mixture is stirred for five minutes to complete the reaction.

[0192] The methods and compositions provided herein can be combined with other methods and compositions, such as those described in PCT Patent Publication No. WO / 2016 / 094810, which is incorporated by reference in its entirety.

[0193] Although preferred embodiments of the present disclosure have been shown and described herein, it will be understood by those skilled in the art that such embodiments are provided by way of example only. Numerous variations, modifications, and substitutions will readily occur to those skilled in the art without departing from the present disclosure. It should be understood that various alternatives to the embodiments of the present disclosure described herein may be used in practicing the present disclosure. It is intended that the scope of the present disclosure be defined by the following claims, and that methods and structures within the scope of such claims and their equivalents are thereby covered.

[0194] According to a preferred embodiment of the present invention, for example, the following is provided: (Section 1) (i) a mixture of carboxylated and decarboxylated cannabinoids; and (ii) one or more terpenoids. having a wt / wt ratio of decarboxylated cannabinoids to carboxylated cannabinoids greater than 0.5; Substantially free of terpenoid degradation compounds Unit dose. (Section 2) 2. A unit dose according to claim 1, comprising at least 5 mg of decarboxylated cannabinoid. (Section 3) The decarboxylated cannabinoid is Δ 9 2. A unit dose according to claim 1, comprising tetrahydrocannabinol. (Section 4) The unit dose according to item 1, wherein the one or more terpenoids are selected from the group consisting of myrcene, limonene, linalool, trans-ocimene, beta-pinene, alpha-pinene, beta-caryophyllene, delta-3-carene, trans-gamma-bisabolene, trans-alpha-farnesene, beta-fenchol, alpha-humulene, and guajole. (Section 5) The one or more terpenoid degradation compounds are selected from the group consisting of geraniol, geranyl isobutyrate, p-cymenene, p-cymene, p-mentha-1,5,8-triene, carvone, 3-methyl-6-(1-methylethylidene)-2-cyclohexen-1-one, 3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-one, eucarvone, thymol, p-mentha-1(7),8-dien-2-ol, perillyl alcohol, camphene, beta-myrcene, alpha-phellandrene, alpha-terpinene, gamma- The unit dose according to item 1, selected from the group consisting of terpinene, terpinolene, 4-hydroxy-2-methyl-2-cyclohexenone, p-cymenene, o-cymene, 3-caren-2-one, 3-caren-5-one, 3-carene oxide, 3-carene-2,5-dione, trans-2-hydroxy-3-caren-5-one, thymol, carvacrol, 1,4-cineole, eucalyptol, 3-(1-methylethyl)-6-oxo-2-heptenal, and 3,7-dimethyl 6-oxo-2-octenal. (Section 6) 2. The unit dose of claim 1 further comprising a trace amount of acid. (Section 7) Item 1. The unit dose according to item 1, further comprising a pharma- ceutically acceptable excipient. (Section 8) The unit dose according to item 7, wherein the pharma- ceutically acceptable excipient is selected from the group consisting of binders, fillers, plasticizers, lubricants, antifoaming agents, buffers, polymers, antioxidants, preservatives, chelating agents, flavoring agents, coloring agents, flavoring agents, suspending agents, and combinations thereof. (Section 9) The unit dose according to paragraph 1 above, formulated for oral, topical, inhaled, intravenous, or intramuscular administration. (Section 10) The unit dose according to paragraph 1 above, which is in solid form. (Section 11) The unit dose according to paragraph 1 above, which is in liquid form. (Section 12) The unit dose according to paragraph 1 above may be a tablet, a chewable tablet, a capsule, a caplet, a pill, a granule, an emulsion, a gel, a spray, a plurality of beads in a capsule, a powder, a suspension, a liquid, a semi-liquid, a semi-solid, a solution, a syrup, or a slurry. (Section 13) The unit dose described in paragraph 1 above, which retains at least 80% of the cannabinoids after six months in a sealed container at a temperature of about 25°C and a relative humidity level of about 50%. (Section 14) The unit dose according to claim 1, packaged in a container selected from the group consisting of a tube, a jar, a box, a vial, a bag, a tray, a drum, a bottle, a syringe, and a can. (Section 15) A kit comprising the unit dose described in paragraph 1 above and instructions for supplementing a subject in need thereof with the mixture of carboxylated and decarboxylated cannabinoids and one or more terpenoids. (Section 16) Δ 9 1. A kit for preparing tetrahydrocannabinol, comprising: (i) incorporating at least 50% of tetrahydrocannabinolic acid into said Δ 9 an acid present in an amount effective to convert it to tetrahydrocannabinol; (ii) a reaction vessel configured to hold a reaction mixture comprising the acid and the tetrahydrocannabinolic acid; (iii) instructions for effecting said conversion using said acid; Kit including: (Section 17) Item 17. The kit according to item 16, further comprising tetrahydrocannabinolic acid. (Section 18) Item 17. The kit according to item 16, wherein the acid is a weak acid. (Section 19) Item 17. The kit according to item 16, wherein the acid has a pKa of about 3 to about 7. (Section 20) Item 17. The kit according to item 16, wherein the acid is selected from the group consisting of lactic acid, citric acid, malic acid, acetic acid, benzoic acid, ascorbic acid, tartaric acid, and oxalic acid. (Section 21) 1. A method of supplementing a subject in need thereof with one or more cannabinoids and one or more terpenoids, comprising administering to the subject: i. a mixture of carboxylated and decarboxylated cannabinoids; ii. one or more terpenoids; having a wt / wt ratio of decarboxylated cannabinoids to carboxylated cannabinoids greater than 0.5; Substantially free of terpenoid degradation compounds administering a unit dose. (Section 22) 22. The method according to claim 21, wherein the subject suffers from a symptom selected from the group consisting of pain, stress, nausea, vomiting, insomnia, anxiety, and loss of appetite. (Section 23) 22. The method of claim 21, wherein the unit dose is administered orally, topically, by inhalation, intravenously, or intramuscularly. (Section 24) 22. The method according to claim 21, wherein the unit dose is administered at least once a day. (Section 25) 22. The method of claim 21, further comprising monitoring the health or condition of the subject following administration of the unit dose to the subject. (Section 26) 1. A method for producing decarboxylated cannabinoids, comprising: (i) contacting a cannabis plant or portion thereof with an acid under conditions effective to convert carboxylated cannabinoids present in said cannabis plant to decarboxylated cannabinoids to form a reaction mixture; (ii) separating said cannabis plant or part thereof from said decarboxylated cannabinoids, thereby producing said decarboxylated cannabinoids; The method includes: (Section 27) The decarboxylated cannabinoid is Δ 9 The above, including tetrahydrocannabinol 27. The method according to item 26. (Section 28) 27. The method of claim 26, wherein the wt / wt ratio of decarboxylated cannabinoids to carboxylated cannabinoids in the reaction mixture of (ii) is greater than 0.1. (Section 29) 27. The method according to claim 26, wherein the condition is a temperature of less than 300°C. (Section 30) 29. The method of claim 28, wherein no external heating is applied during the conversion of the carboxylated cannabinoids to the decarboxylated cannabinoids. (Section 31) 27. The method according to claim 26, wherein the acid is a weak acid. (Section 32) 27. The method of claim 26, wherein the contacting comprises blending, mixing, stirring, or a combination thereof. (Section 33) 27. The method according to claim 26, wherein the separation is selected from the group consisting of filtration, extraction, centrifugation, solubilization, concentration, washing, electrolysis, adsorption, purification, chromatography, fractionation, crystallization, and combinations thereof. (Section 34) (i) carboxylated and decarboxylated cannabinoids; (ii) one or more terpenoids; (iii) Acid and having a wt / wt ratio of decarboxylated cannabinoids to carboxylated cannabinoids greater than 0.1; The acid is present in an amount effective to convert at least a portion of the carboxylated cannabinoids to decarboxylated cannabinoids. mixture. (Section 35) 35. The mixture of claim 34, wherein the carboxylated cannabinoid comprises tetrahydrocannabinolic acid. (Section 36) 34. The mixture according to claim 33, comprising at least 0.05 mol of the decarboxylated cannabinoid. (Section 37) The decarboxylated cannabinoid is Δ 9 34. The mixture according to claim 33, comprising tetrahydrocannabinol. (Section 38) Δ 9 38. The mixture of claim 37, wherein the wt / wt ratio of tetrahydrocannabinol to tetrahydrocannabinolic acid is greater than about 0.1. (Section 39) 34. The mixture according to claim 33, which is substantially free of terpenoid degrading compounds. (Section 40) 34. The mixture according to claim 33, wherein the acid is an organic acid. (Section 41) 1. A method for producing a decarboxylated cannabinoid formulation, comprising: (a) providing a reaction vessel containing a mixture, the mixture comprising: i. carboxylated and decarboxylated cannabinoids; ii. one or more terpenoids; iii. Acid and and the ratio of decarboxylated cannabinoids to carboxylated cannabinoids is wt / wt ratio is greater than 0.1, the acid is present in an amount effective to convert at least a portion of the carboxylated cannabinoids to decarboxylated cannabinoids; (b) mixing the mixture to obtain the decarboxylated cannabinoid formulation; The method includes: (Section 42) 42. The method of claim 41, wherein the decarboxylated cannabinoid preparation contains at least 5 mg of decarboxylated cannabinoid. (Section 43) The decarboxylated cannabinoid formulation is 9 42. The method according to claim 41, comprising administering to said patient tetrahydrocannabinol. (Section 44) 42. The method of claim 41, wherein the one or more terpenoids are selected from the group consisting of myrcene, limonene, linalool, trans-ocimene, beta-pinene, alpha-pinene, beta-caryophyllene, delta-3-carene, trans-gamma-bisabolene, trans-alpha-farnesene, beta-fenchol, alpha-humulene, and guajole. (Section 45) 42. The method according to claim 41, wherein the acid is a weak acid. (Section 46) 42. The method according to item 41, wherein the acid has a pKa of about 3 to about 7. (Section 47) 42. The method according to claim 41, wherein the acid is selected from the group consisting of lactic acid, citric acid, malic acid, acetic acid, benzoic acid, ascorbic acid, tartaric acid, and oxalic acid. (Section 48) (i) a mixture of carboxylated and decarboxylated cannabinoids; and (ii) one or more terpenoids. having a wt / wt ratio of decarboxylated cannabinoids to carboxylated cannabinoids greater than 0.5; Substantially free of terpenoid degradation compounds; Virtually acid-free Unit dose. (Section 49) 49. The unit dose according to claim 48, wherein the acid is a weak acid. (Section 50) 49. The unit dose according to claim 48, wherein the acid has a pKa of about 3 to about 7. (Section 51) 49. The unit dose according to claim 48, wherein the acid is selected from the group consisting of lactic acid, citric acid, malic acid, acetic acid, benzoic acid, ascorbic acid, tartaric acid, and oxalic acid.

Claims

[Claim 1] The health of the subject.

Images