WO2021127559A1

WO2021127559A1 - Compositions comprising cannabinoid anions and anti-nucleating agents

Info

Publication number: WO2021127559A1
Application number: PCT/US2020/066206
Authority: WO
Inventors: C. Russell Thomas; Douglas G. METCALF
Original assignee: Natural Extraction Systems LLC
Current assignee: Natural Extraction Systems LLC
Priority date: 2019-12-19
Filing date: 2020-12-18
Publication date: 2021-06-24
Anticipated expiration: 2022-06-19

Abstract

Various aspects of this patent document relate to compositions comprising cannabinoid anions and excipients that act as anti-nucleating agents.

Description

COMPOSITIONS COMPRISING CANNABINOID ANIONS AND ANTI-NUCLEATING AGENTS

CROSS-REFERENCE TO RELATED APPLICATIONS

This patent application claims priority to U.S. Provisional Patent Application No. 62/950,826, filed December 19, 2019, which is incorporated by reference in its entirety.

BACKGROUND

Cannabinoids display poor bioavailability and pharmacokinetics when administered orally in part because cannabinoids are hydrophobic and tend to aggregate. Cannabinoid formulations with improved bioavailability and pharmacokinetics are desirable.

SUMMARY

Various aspects of this patent document relate to the discovery that cannabinoids can be deprotonated to produce cannabinoid anions that carry negative charges that repel each other to minimize aggregation and improve bioavailability and pharmacokinetics. U.S. Patent No. 10,609,944 B1 discloses this initial discovery. This subsequent patent document discloses the subsequent discovery that bioavailability and pharmacokinetics as well as manufacturing methods can be further optimized by the introduction of an excipient that can act as an anti-nucleating agent to inhibit the aggregation of the neutrally-charged conjugate acid of a cannabinoid anion.

DETAILED DESCRIPTION

Various aspects of this patent document relate to a composition comprising a cannabinoid anion and an excipient.

In all embodiments, the cannabinoid anion is not a carboxylate. Various cannabinoid anions are described, for example, in PCT Patent Application Publication No. WO 2020/123976 Al, which is incorporated by reference for the cannabinoid anions that it names (which the PCT publication refers to as “anionic cannabinoid molecules”). Generally applicable methods to produce cannabinoid anions are described in WO 2020/123976 Al and U.S. Patent No. 10,555,914 B2.

In some embodiments, the cannabinoid anion is 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2- en-l-yl]-3-hydroxy-5-alkylphenolate. In some specific embodiments, the cannabinoid anion is 2- [(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5-pentylphenolate. In some specific embodiments, the cannabinoid anion is 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en- l-yl]-3-hydroxy-5-propylphenolate.

In some embodiments, the cannabinoid anion is 2-(3,7-dimethylocta-2,6-diene-l-yl)-3-hydroxy- 5-alkylphenolate. In some specific embodiments, the cannabinoid anion is 2-(3,7-dimethylocta-2,6- diene-l-yl)-3-hydroxy-5-pentylphenolate. In some specific embodiments, the cannabinoid anion is 2-(3,7-dimethylocta-2,6-diene-l-yl)-3-hydroxy-5-propylphenolate.

In some embodiments, the cannabinoid anion is (6aR,10aR)-3-alkyl-6,6,9-trimethyl-6a,7,8,10a- tetrahydro-6H-benzo[c]chromen-l-oxide. In some specific embodiments, the cannabinoid anion is (6aR,10aR)-3-pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-l-oxide. In some specific embodiments, the cannabinoid anion is the cannabinoid anion is (6aR,10aR)-3 -propyl- 6, 6, 9-trimethyl-6a, 7,8,10a-tetrahydro-6H-benzo[c]chromen-l -oxide.

“Alkyl” refers to a branched or unbranched hydrocarbon chain comprising exactly 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 carbon atoms that is optionally substituted by phenyl or cycloalkyl.

“Substituted by phenyl or cycloalkyl” refers to the substitution of one hydrogen atom of a hydrocarbon chain with phenyl or the substitution of at least one hydrogen atom of a hydrocarbon chain with a cycloalkyl, respectively. When a hydrocarbon chain is substituted with a cycloalkyl, then either (i) a single hydrogen atom of the hydrocarbon chain is substituted with the cycloalkyl such that the cycloalkyl does not include any carbon atom of the hydrocarbon chain, or (ii) two hydrogen atoms of the hydrocarbon chain are substituted with the cycloalkyl such that the cycloalkyl comprises one or more carbon atoms of the hydrocarbon chain. The carbon atoms of phenyl or cycloalkyl are counted when counting the carbon atoms of a hydrocarbon chain that is substituted by phenyl or cycloalkyl, for example, such that 2-phenylethyl comprises exactly 8 carbon atoms and adamantyl comprises exactly 10 carbon atoms.

“Cycloalkyl” refers to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and adamantyl.

In some embodiments, alkyl is selected from methyl; ethyl; propyl; butyl; pentyl; hexyl; heptyl; octyl; nonyl; decyl; prop-2-yl; but-2-yl; pent-2-yl; hex-2 -yl; hept-2-yl; octan-2-yl; nonan-2-yl; decan-2-yl; 2-methylpropyl; 2-methylbutyl; 2-methylpentyl; 2-methylhexyl; 2-methylheptyl; 2- methyloctyl; 2-methylnonyl; 2-methyldecyl; 2-methylprop-2-yl; 2-methylbut-2-yl; 2-methylpent-2- yl; 2-methylhex-2-yl; 2-methylhept-2-yl; 2-methyloctan-2-yl; 2-methylnonan-2-yl; 2-methyldecan- 2-yl; 3-methylbut-2-yl; 3-methylpent-2-yl; 3-methylhex-2-yl; 3-methylhept-2-yl; 3-methyloctan-2- yl; 3-methylnonan-2-yl; 3-methyldecan-2-yl; 2,3-dimethylbut-2-yl; 2,3-dimethylpent-2-yl; 2,3- dimethylhex-2-yl; 2,3-dimethylhept-2-yl; 2,3-dimethyloctan-2-yl; 2,3-dimethylnonan-2-yl; 2,3- dimethyldecan-2-yl; cyclopropyl; 1-methylcyclopropyl; 1-ethylcyclopropyl; 1-propylcyclopropyl; 1-butylcyclopropyl; 1-pentylcyclopropyl; 1 -hexyl cyclopropyl; 1 -heptyl cyclopropyl; 1- octylcyclopropyl; 1-nonylcyclopropyl; cyclobutyl; 1-methylcyclobutyl; 1-ethylcyclobutyl; 1- propylcyclobutyl; 1 -butyl cyclobutyl; 1-pentylcyclobutyl; 1-hexylcyclobutyl; 1-heptylcyclobutyl; 1- octylcyclobutyl; cyclopentyl; 1-methylcyclopentyl; 1-ethylcyclopentyl; 1-propylcyclopentyl; 1- butylcyclopentyl; 1-pentylcyclopentyl; 1-hexylcyclopentyl; 1-heptylcyclopentyl; cyclohexyl; 1- methylcyclohexyl; 1-ethylcyclohexyl; 1 -propyl cyclohexyl; 1-butylcyclohexyl; 1-pentylcyclohexyl; 1-hexylcyclohexyl; ethenyl; prop-l-enyl; but-l-enyl; pent-l-enyl; hex-l-enyl; hept-l-enyl; octan-1- enyl; nonan-l-enyl; decan-l-enyl; ethynyl; prop-l-ynyl; but-l-ynyl; pent-l-ynyl; hex-l-ynyl; hept- 1-ynyl; octan-l-ynyl; nonan-l-ynyl; decan-l-ynyl; 2-phenylethyl; and adamantyl. In some specific embodiments, alkyl is methyl, ethyl, propyl, butyl, pentyl, hexyl, or heptyl. In preferred embodiments, alkyl is propyl or pentyl.

In some embodiments, the composition comprises the cannabinoid anion at a concentration of at least 10 milligrams per liter and no greater than 100 grams per liter.

In some embodiments, the composition comprises the cannabinoid anion at a concentration of at least 10 parts per million and no greater than 10 percent by mass.

In some embodiments, the composition comprises the cannabinoid anion at a concentration of at least 10 parts per million and no greater than 10 percent by mass; and the composition comprises the excipient at a concentration of at least 10 parts per million and no greater than 10 percent by mass.

In some embodiments, the excipient has the formula CxHyOz; x is an integer of at least 4 and no greater than 21; y is an integer of at least 4 and no greater than 28; z is an integer of at least 1 and no greater than 7; y is no greater than x+10; and z is less than x.

In some embodiments, the excipient has the formula CxHyOz x is an integer of at least 4 and no greater than 21; y is an integer of at least 3 and no greater than 27; z is an integer of at least 1 and no greater than 7; y is no greater than x+10; and z is less than x.

In some embodiments, the excipient is selected from acetanisole, acetylpropionyl, alkannin, allyl hexanoate, alpha-tocopherol, alpha-tocotrienol, amyl acetate, anethole, 4-anisaldehyde, anisol, benzaldehyde, benzyl acetate, benzylacetone, benzyl cinnamate, beta-tocopherol, beta-tocotrienol, n-butyl acetate, butylated hydroxyanisole, butylated hydroxytoluene, n-butyl butyrate, butylphthalide, capsaicin, capsanthin, capsorubin, cholic acid, cinnamaldehyde, cis-3-hexen-l-ol, cuminaldehyde, curcumin, cyclotene, delta-decalactone, delta-nonalactone, delta-octalactone, delta- tocopherol, delta-tocotrienol, dihydrojasmone, eriodictyol, estragole, ethyl acetate, ethyl benzoate, ethyl butyrate, ethyl cinnamate, ethyl decadienoate, ethyl heptanoate, ethyl maltol, ethyl methylphenylglycidate, ethylparaben, ethyl pentanoate, ethyl propionate, ethyl salicylate, ethylvanillin, eugenol, ferulate, fructone, furaneol, furfural, gamma-decalactone, gamma- nonalactone, gamma-tocopherol, gamma-tocotrienol, glyceryl diacetate, glyceryl monoacetate, glycyrrhizin, heptyl acetate, heptylparaben, 3-hexanol, hexyl acetate, hexyl cinnamaldehyde, homoeriodictyol, indanthrone blue, isoamyl acetate, isobutyl acetate, isovaleraldehy dejasmine lactone, maltol, manzanate, massoia lactone, menthol, menthone, menthoxypropanediol, menthyl isovalerate, methyl anthranilate, methyl butyrate, methylparaben, methyl propionate, methyl salicylate, octyl acetate, ortho-vanillin, pentyl butyrate, pentyl pentanoate, propyl acetate, propylparaben, raspberry ketone, resveratrol, salicylaldehyde, sedanolide, sterubin, sotolon, tert- butylhydroquinone, tetrahydrofurfuryl acetate, tetrahydrofurfuryl alcohol, tetrahydrofurfuryl butyrate, tetrahydrofurfuryl cinnamate, tetrahydrofurfuryl propionate, triacetin, triethyl citrate, vanillin, wine lactone, and a conjugate base of any one of the preceding molecules. In some specific embodiments, the excipient is selected from cinnamaldehyde, curcumin, ethyl salicylate, limonene, menthol, menthone, methyl salicylate, raspberry ketone, vanillin, wine lactone, and a conjugate base of any one of the foregoing. In some very specific embodiments, the excipient is selected from curcumin, limonene, menthol, methyl salicylate, raspberry ketone, and a conjugate base of any one of the foregoing.

“Conjugate base” as used in this patent document refers to the anionic form of a molecule that lacks a charge; a conjugate base is produced by removing a proton from the molecule under alkaline conditions such that the conjugate base carries a net charge of negative one.

In some embodiments, the composition comprises the excipient at a concentration of at least 10 parts per million and no greater than 10 percent by mass.

In some embodiments, the composition comprises a cannabinoid. In some specific embodiments, the composition comprises a neutrally-charged cannabinoid. In some very specific embodiments, the composition comprises a neutrally-charged cannabinoid, and the cannabinoid anion is the conjugate base of the neutrally-charged cannabinoid. In all embodiments, the cannabinoid lacks a carboxyl group (for example, -C(=0)OH).

“Neutrally-charged” refers to a molecule that has a net charge of zero.

In some embodiments, the cannabinoid anion is the conjugate base of a neutrally-charged cannabinoid; and the excipient acts as an anti-nucleating agent in relation to the neutrally-charged cannabinoid such that the excipient inhibits the aggregation of the neutrally-charged cannabinoid.

In some embodiments, the cannabinoid anion is the conjugate base of a neutrally-charged cannabinoid that has a solubility in water at 37 degrees Celsius; the cannabinoid anion is dissolved in a solvent; the solvent has a molarity of the cannabinoid anion; and the molarity of the cannabinoid anion in the solvent is greater than the solubility of the neutrally-charged cannabinoid in water at 37 degrees Celsius. In some specific embodiments, the molarity of the cannabinoid anion in the solvent is at least 10 times greater than the solubility of the neutrally-charged cannabinoid in water at 37 degrees Celsius. In some very specific embodiments, the molarity of the cannabinoid anion in the solvent is at least 100 times greater than the solubility of the neutrally- charged cannabinoid in water at 37 degrees Celsius. In some even more specific embodiments, the molarity of the cannabinoid anion in the solvent is at least 1000 times greater than the solubility of the neutrally-charged cannabinoid in water at 37 degrees Celsius.

“Dissolved” refers to a solute that is solvated in a liquid phase; a chemical species that is present within a phase that is dispersed within a liquid phase, such as the dispersed phase of an emulsion, is not dissolved in the liquid phase; a chemical species that is non-covalently bound to any chemical species that is a solid in the absence of a liquid phase, such as a cyclodextrin, is not dissolved.

In some specific embodiments, the cannabinoid is 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-

2-en-l-yl]-5-alkylbenzene-l,3-diol, and the cannabinoid anion is 2-[(lR,6R)-6-isopropenyl-3- methylcyclohex-2-en-l-yl]-3-hydroxy-5-alkylphenolate. In some very specific embodiments, the cannabinoid is 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-5-pentylbenzene-l,3-diol, and the cannabinoid anion is 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5- pentylphenolate. In some very specific embodiments, the cannabinoid is 2-[(lR,6R)-6-isopropenyl-

3-methylcyclohex-2-en-l-yl]-5-propylbenzene-l,3-diol, and the cannabinoid anion is 2-[(lR,6R)-6- isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5-propylphenolate.

In some specific embodiments, the cannabinoid is 2-(3,7-dimethylocta-2,6-diene-l-yl)-5- alkylbenzene-l,3-diol, and the cannabinoid anion is 2-(3,7-dimethylocta-2,6-diene-l-yl)-3-hydroxy- 5-alkylphenolate. In some very specific embodiments, the cannabinoid is 2-(3,7-dimethylocta-2,6- diene-l-yl)-5-pentylbenzene-l,3-diol, and the cannabinoid anion is 2-(3,7-dimethylocta-2,6-diene- l-yl)-3-hydroxy-5-pentylphenolate. In some very specific embodiments, the cannabinoid is 2 -(3, 7- dimethylocta-2,6-diene-l-yl)-5-propylbenzene-l,3-diol, and the cannabinoid anion is 2-(3,7- dimethylocta-2,6-diene-l-yl)-3-hydroxy-5-propylphenolate.

In some specific embodiments, the cannabinoid is (6aR,10aR)-3-alkyl-6,6,9-trimethyl- 6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-l-ol, and the cannabinoid anion is the cannabinoid anion is (6aR, 10aR)-3-alkyl-6,6,9-trimethyl-6a,7,8, 10a-tetrahydro-6H-benzo[c]chromen-l -oxide. In some very specific embodiments, the cannabinoid is (6aR,10aR)-3-pentyl-6,6,9-trimethyl- 6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-l-ol, and the cannabinoid anion is the cannabinoid anion is (6aR,10aR)-3-pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-l-oxide.

In some very specific embodiments, the cannabinoid is (6aR,10aR)-3-propyl-6,6,9-trimethyl- 6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-l-ol, and the cannabinoid anion is the cannabinoid anion is (6aR, 10aR)-3-propyl-6,6,9-trimethyl-6a,7,8, 10a-tetrahydro-6H-benzo[c]chromen-l -oxide.

In some preferred embodiments, the composition comprises the cannabinoid and the cannabinoid anion at a ratio of at least 1 : 100,000 and no greater than 10: 1 by mole. In some specific preferred embodiments, the composition comprises the cannabinoid and the cannabinoid anion at a ratio of at least 1 : 10,000 and no greater than 1 : 1 by mole. In some very specific preferred embodiments, the composition comprises the cannabinoid and the cannabinoid anion at a ratio of at least 1 : 1,000 and no greater than 1 : 1 by mole.

In some embodiments, the composition comprises a cation.

In some embodiments, the cation is selected from lithium cation (Li+); potassium cation (K+), sodium cation (Na+), calcium cation (Ca++), magnesium cation (Mg++), iron (II) cation (Fe++), iron (III) cation (Fe+++), zinc cation (Zn++), manganese (II) cation (Mn++), copper (I) cation (Cu+), copper (II) cation (Cu++), ammonium cation (NH4+), protonated lysine, protonated hydroxylysine, protonated arginine, protonated ethanolamine, choline, and protonated sphingosine. In some specific embodiments, the cation is potassium cation or sodium cation. In some very specific embodiments, the cation is potassium cation.

In some embodiments, the composition comprises the cation at a greater concentration by mole than the cannabinoid anion. In some embodiments, the composition comprises the cannabinoid anion at a greater concentration by mass than the cation. In some very specific embodiments, the composition comprises the cation at a greater concentration by mole than the cannabinoid anion; and the composition comprises the cannabinoid anion at a greater concentration by mass than the cation.

In some embodiments, the composition comprises the cation at a concentration of at least 5 parts per million and no greater than 5 percent by mass.

In some embodiments, the composition comprises a solvent. In some specific embodiments, the composition comprises a solvent; and the cannabinoid anion is a solute that is dissolved in the solvent. In some specific embodiments, the composition comprises a solvent and a cation; and the cation is a solute that is dissolved in the solvent. In some very specific embodiments, the composition comprises a solvent and a cation; and the cannabinoid anion and the cation are solutes that are dissolved in the solvent.

In some embodiments, the solvent is selected from water, ethanol, propane- 1,2-diol, propane- 1, 3-diol, propane- 1,2, 3 -triol, and butane- 1, 3 -diol. In some specific embodiments, the solvent is water or propane- 1,2, 3 -triol. In some very specific embodiments, the solvent is propane- 1,2, 3 -triol. In some specific embodiments, the composition comprises the solvent at a concentration of at least 50 percent by mass. In some specific embodiments, the composition comprises the solvent at a concentration of at least 50 percent by mass and no greater than 99 percent by mass.

In some embodiments, the composition comprises a solvent and a cosolvent. In some specific embodiments, the composition comprises the solvent at a greater concentration by mass than the cosolvent. In some very specific embodiments, the composition comprises the cosolvent at a greater concentration by mass than the cannabinoid anion.

In some embodiments, the solvent is selected from water, propane- 1,2-diol, propane- 1, 3 -diol, propane- 1,2, 3 -triol, and butane- 1,3 -diol; and the cosolvent is ethanol. In some specific embodiments, the solvent is propane-1, 2, 3-triol; and the cosolvent is ethanol. In some very specific embodiments, the solvent is propane-1, 2, 3-triol; the cosolvent is ethanol; and the composition further comprises water.

In some embodiments, the composition comprises the cosolvent at a concentration of no greater than 0.5 percent by mass.

In some embodiments, the composition comprises the cosolvent at a concentration of at least 0.1 percent by mass.

In some embodiments, the composition comprises the cosolvent at a concentration of at least 20 percent and no greater than 49 percent by mass.

In some specific embodiments, the composition comprises propane-1, 2, 3-triol at a concentration of at least 50 percent by mass; and the composition comprises the cannabinoid anion at a concentration of at least 100 milligram per liter and no greater than 100 grams per liter.

In some embodiments, the composition comprises water at a concentration of at least 0.1 percent by mass. In some specific embodiments, the composition comprises water at a concentration of at least 50 percent and no greater than 99.8 percent by mass. In some very specific embodiments, the composition comprises water at a concentration of at least 90 percent by mass; and the composition comprises the cannabinoid anion at a concentration of at least 10 milligrams per liter and no greater than 10 grams per liter.

In some embodiments, the composition comprises a liquid phase. In some specific embodiments, the cannabinoid anion is a solute that is dissolved in the liquid phase. In some very specific embodiments, the cannabinoid anion and the cation are solutes that are dissolved in the liquid phase.

In some embodiments, the liquid phase is a liquid that comprises the solvent. In some specific embodiments, the liquid phase is a liquid that comprises the solvent and the cosolvent. In some very specific embodiments, the liquid phase is a liquid that comprises the solvent, the cosolvent, and water.

In some embodiments, the composition comprises ethanol at a concentration of at least 50 parts per million and no greater than 49 percent by mass.

In some embodiments, the composition comprises hydroxide, ethoxide, and 2,3- dihydroxypropane-1 -oxide. In some embodiments, the composition comprises hydroxide, ethoxide, and l,3-dihydroxypropane-2-oxide.

Various aspects of this patent document relate to a composition described anywhere in this patent document. Various aspects of this patent document relate to a composition described anywhere in this patent document for use as a medicament. Various aspects of this patent document relate to a composition described anywhere in this patent document for to manufacture a medicament.

Various aspects of this patent document relate to a method to consume a cannabinoid, comprising providing a composition described anywhere in this patent document, and orally administering the composition to a subject.

Various aspects of this patent document relate to a method to consume a cannabinoid, comprising providing a composition described anywhere in this patent document; contacting the composition with a second composition that comprises water at a concentration of at least 98 percent by mass to produce a beverage; and orally administering the beverage to a subject.

In some embodiments, the subject is a bee, fish, chicken, rodent, lagomorph, feline, canine, porcine, ovine, caprine, lama, vicugna, bovine, equine, or primate. In some specific embodiments, the subject is a Felis catus, Canis familiaris, Sus scrofa domesticus, Bos taurus, Equus ferns caballus, or Homo sapien. In some very specific embodiments, the subject is a human.

Various aspects of this patent document relate to a method to dissolve a cannabinoid anion in water, comprising providing a composition described anywhere in this patent document; and contacting the composition with a second composition that comprises water at a concentration of at least 98 percent by mass to dissolve the cannabinoid anion in water.

Various combinations of the features disclosed in this patent document will be evident to those of ordinary skill, and these combinations are expressly contemplated. This patent document discloses each linguistic and grammatical combination of features disclosed anywhere in the patent document as though any specific combination were disclosed in the same sentence except for combinations that lack internal consistency, which will be apparent to those of ordinary skill.

“Comprising” and “comprise(s)” refer to open-ended sets. A composition comprising a cannabinoid anion, for example, can also comprise a cannabinoid and a cation.

EXEMPLIFICATION

The following examples set forth selected commercially-viable embodiments, and these embodiments do not limit the scope of this patent document or any claim that matures from this patent document.

Example 1. Compositions comprising menthol and methyl salicylate

A composition was prepared comprising 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l- yl]-5-pentylbenzene-l,3-diol; 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5- pentylphenolate; potassium cation; propane-1, 2, 3-triol; ethanol; and water using methods adapted from Ti.S. Patent No. 10,555,914 B2. The composition contained the 2-[(lR,6R)-6-isopropenyl-3- methylcyclohex-2-en-l-yl]-5-pentylbenzene-l,3-diol and the 2-[(lR,6R)-6-isopropenyl-3- methylcyclohex-2-en-l-yl]-3-hydroxy-5-pentylphenolate at a ratio of at least 1:100,000 and no greater than 1:1 by mole. The composition contained the 2-[(lR,6R)-6-isopropenyl-3- methylcyclohex-2-en-l-yl]-3-hydroxy-5-pentylphenolate at a concentration of at least 10 milligrams per liter and no greater than 100 grams per liter; the potassium cation at a concentration of at least 5 parts per million and no greater than 5 percent by mass; the propane-1, 2, 3-triol at a concentration of at least 50 percent by mass; the ethanol at a concentration of at least 20 percent and no greater than 49 percent by mass; and the water at a concentration of at least 0.1 percent by mass. The composition contained the potassium cation at a greater concentration by mole than the 2- [(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5-pentylphenolate and the 2- [(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5-pentylphenolate at a greater concentration by mass than the potassium cation. The composition contained the ethanol at a greater concentration by mass than the [(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-3- hydroxy-5-pentylphenolate. The composition contained a liquid phase that was a liquid comprising the propane- 1,2, 3-triol, the ethanol, and the water, wherein the 2-[(lR,6R)-6-isopropenyl-3- methylcyclohex-2-en-l-yl]-3-hydroxy-5-pentylphenolate and the potassium cation were solutes that were dissolved in the liquid phase. The composition also contained hydroxide; ethoxide; 2,3- dihydroxypropane-1 -oxide; and l,3-dihydroxypropane-2-oxide. The molarity of the 2-[(lR,6R)-6- isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5-pentylphenolate in the liquid phase was greater than the solubility of the 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-5- pentylbenzene-l,3-diol in water at 37 degrees Celsius.

The composition of the preceding paragraph was divided into three aliquots. No excipient was added to the first aliquot. Menthol was added to the second aliquot at a concentration of at least 10 parts per million and no greater than 10 percent by mass. Methyl salicylate was added to the third aliquot at a concentration of at least 10 parts per million and no greater than 10 percent by mass.

Relative to the first aliquot, the menthol appeared to act as an anti-nucleating agent in relation to the 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-5-pentylbenzene-l,3-diol such that the menthol inhibited the aggregation of the 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-5- pentylbenzene-l,3-diol in the second aliquot. Mixing the first aliquot with water resulted in aggregation, for example, whereas mixing the second aliquot with water reduced aggregation relative to the first aliquot. Consumption of the second aliquot resulted in more significant subjectively-reported physiological effects than consumption of the first aliquot, which suggests that reducing aggregation increases efficacy.

Relative to the first aliquot, the methyl salicylate appeared to act as an anti-nucleating agent in relation to the 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-5-pentylbenzene-l,3-diol such that the methyl salicylate inhibited the aggregation of the 2-[(lR,6R)-6-isopropenyl-3- methylcyclohex-2-en-l-yl]-5-pentylbenzene-l,3-diol in the third aliquot. Mixing the first aliquot with water resulted in aggregation, for example, whereas mixing the third aliquot with water reduced aggregation relative to the first aliquot. Consumption of the third aliquot resulted in more significant subjectively-reported physiological effects than consumption of the first aliquot, which suggests that reducing aggregation increases efficacy.

Example 2. Compositions comprising curcumin

A composition comprising the conjugate base(s) of curcumin was prepared using methods adapted from U.S. Patent No. 10,555,914 B2. The composition comprised 2-[(lR,6R)-6- isopropenyl-3-methylcyclohex-2-en-l-yl]-5-pentylbenzene-l,3-diol; 2-[(lR,6R)-6-isopropenyl-3- methylcyclohex-2-en-l-yl]-3-hydroxy-5-pentylphenolate; the conjugate base(s) of curcumin; potassium cation; propane-1, 2, 3-triol; ethanol; and water. The composition contained the 2- [(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-5-pentylbenzene-l,3-diol and the 2-[(lR,6R)- 6-isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5-pentylphenolate at a ratio of at least 1 : 100,000 and no greater than 1 : 1 by mole. The composition contained the 2-[(lR,6R)-6- isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5-pentylphenolate at a concentration of at least 10 milligrams per liter and no greater than 100 grams per liter; the conjugate base(s) of curcumin at a concentration of at least 10 parts per million and no greater than 10 percent by mass; the potassium cation at a concentration of at least 5 parts per million and no greater than 5 percent by mass; the propane- 1,2, 3 -triol at a concentration of at least 50 percent by mass; the ethanol at a concentration of at least 20 percent and no greater than 49 percent by mass; and the water at a concentration of at least 0.1 percent by mass. The composition contained the potassium cation at a greater concentration by mole than the 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-3- hydroxy-5-pentylphenolate and the 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-3- hydroxy-5-pentylphenolate at a greater concentration by mass than the potassium cation. The composition contained the ethanol at a greater concentration by mass than the [(lR,6R)-6- isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5-pentylphenolate. The composition contained a liquid phase that was a liquid comprising the propane- 1,2, 3 -triol, the ethanol, and the water, wherein the 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5-pentylphenolate and the potassium cation were solutes that were dissolved in the liquid phase. The composition also contained hydroxide; ethoxide; 2,3 -dihydroxypropane-1 -oxide; and l,3-dihydroxypropane-2-oxide. The molarity of the 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5- pentylphenolate in the liquid phase was greater than the solubility of the 2-[(lR,6R)-6-isopropenyl- 3-methylcyclohex-2-en-l-yl]-5-pentylbenzene-l,3-diol in water at 37 degrees Celsius.

Relative to the first aliquot described in Example 1, the conjugate base(s) of curcumin appeared to act as an anti -nucleating agent in relation to the 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2- en-l-yl]-5-pentylbenzene-l,3-diol such that the conjugate base(s) of curcumin inhibited the aggregation of the 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-5-pentylbenzene-l,3- diol. Mixing the first aliquot described in Example 1 with water resulted in aggregation, for example, whereas mixing the composition described in the preceding paragraph with water reduced aggregation relative to the first aliquot. Consumption of the composition described in the preceding paragraph resulted in more significant subjectively-reported physiological effects than consumption of the first aliquot described in Example 1, which suggests that reducing aggregation increases efficacy.

Example 3. Compositions comprising raspberry ketone and limonene

The composition described in Example 2 was added to distilled water that was alkalized using potassium hydroxide. Three 1 -gallon batches of water were produced. The conjugate base of raspberry ketone was added to a first batch, a flavoring composition comprising limonene was added to the second batch, and no additional excipient was added to the third batch.

The first batch was a composition comprising 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2- en-l-yl]-5-pentylbenzene-l,3-diol; 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-3- hydroxy-5-pentylphenolate; the conjugate base of raspberry ketone; potassium cation; propane- 1, 2, 3-triol; ethanol; and water. The composition contained the 2-[(lR,6R)-6-isopropenyl-3- methylcyclohex-2-en-l-yl]-5-pentylbenzene-l,3-diol and the 2-[(lR,6R)-6-isopropenyl-3- methylcyclohex-2-en-l-yl]-3-hydroxy-5-pentylphenolate at a ratio of at least 1:100,000 and no greater than 1:1 by mole. The composition contained the 2-[(lR,6R)-6-isopropenyl-3- methylcyclohex-2-en-l-yl]-3-hydroxy-5-pentylphenolate at a concentration of at least 10 milligrams per liter and no greater than 100 grams per liter; the conjugate base of raspberry ketone at a concentration of at least 10 parts per million and no greater than 10 percent by mass; the potassium cation at a concentration of at least 5 parts per million and no greater than 5 percent by mass; the ethanol at a concentration of no greater than 0.5 percent by mass; and the water at a concentration of at least 50 percent and no greater than 99.8 percent by mass. The composition contained the potassium cation at a greater concentration by mole than the 2-[(lR,6R)-6- isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5-pentylphenolate and the 2-[(lR,6R)-6- isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5-pentylphenolate at a greater concentration by mass than the potassium cation. The composition contained the ethanol at a greater concentration by mass than the [(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5- pentylphenolate. The composition contained a liquid phase that was a liquid comprising the propane- 1,2, 3-triol, the ethanol, and the water, wherein the 2-[(lR,6R)-6-isopropenyl-3- methylcyclohex-2-en-l-yl]-3-hydroxy-5-pentylphenolate and the potassium cation were solutes that were dissolved in the liquid phase. The composition also contained hydroxide; ethoxide; 2,3- dihydroxypropane-1 -oxide; and l,3-dihydroxypropane-2-oxide. The molarity of the 2-[(lR,6R)-6- isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5-pentylphenolate in the liquid phase was greater than the solubility of the 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-5- pentylbenzene-l,3-diol in water at 37 degrees Celsius.

Example 4. Compositions comprising 2-(3,7-dimethylocta-2,6-diene-l-yl)-3-hydroxy-5- pentylphenolate and curcumin

A composition comprising 2-(3,7-dimethylocta-2,6-diene-l-yl)-3-hydroxy-5-pentylphenolate and the conjugate base(s) of curcumin was prepared using a strategy similar to those described in Examples 1 and 2. The composition comprised 2-(3,7-dimethylocta-2,6-diene-l-yl)-5- pentylbenzene-l,3-diol; 2-(3,7-dimethylocta-2,6-diene-l-yl)-3-hydroxy-5-pentylphenolate; the conjugate base(s) of curcumin; potassium cation; propane-1, 2, 3-triol; ethanol; and water. The composition contained the 2-(3,7-dimethylocta-2,6-diene-l-yl)-5-pentylbenzene-l,3-diol and the 2- (3,7-dimethylocta-2,6-diene-l-yl)-3-hydroxy-5-pentylphenolate at a ratio of at least 1:100,000 and no greater than 1:1 by mole. The composition contained the 2-(3,7-dimethylocta-2,6-diene-l-yl)-3- hydroxy-5-pentylphenolate at a concentration of at least 10 milligrams per liter and no greater than 100 grams per liter; the conjugate base(s) of curcumin at a concentration of at least 10 parts per million and no greater than 10 percent by mass; the potassium cation at a concentration of at least 5 parts per million and no greater than 5 percent by mass; the propane-1, 2, 3-triol at a concentration of at least 50 percent by mass; the ethanol at a concentration of at least 20 percent and no greater than 49 percent by mass; and the water at a concentration of at least 0.1 percent by mass. The composition contained the potassium cation at a greater concentration by mole than the 2-(3,7- dimethylocta-2,6-diene-l-yl)-3-hydroxy-5-pentylphenolate and the 2-(3,7-dimethylocta-2,6-diene-

1-yl)-3-hydroxy-5-pentylphenolate at a greater concentration by mass than the potassium cation.

The composition contained the ethanol at a greater concentration by mass than the 2-(3,7- dimethylocta-2,6-diene-l-yl)-3-hydroxy-5-pentylphenolate. The composition contained a liquid phase that was a liquid comprising the propane-1, 2, 3-triol, the ethanol, and the water, wherein the

2-(3,7-dimethylocta-2,6-diene-l-yl)-3-hydroxy-5-pentylphenolate and the potassium cation were solutes that were dissolved in the liquid phase. The composition also contained hydroxide; ethoxide; 2,3 -dihydroxypropane-1 -oxide; and l,3-dihydroxypropane-2-oxide. The molarity of the 2-(3,7-dimethylocta-2,6-diene-l-yl)-3-hydroxy-5-pentylphenolate in the liquid phase was greater than the solubility of the 2-(3,7-dimethylocta-2,6-diene-l-yl)-5-pentylbenzene-l,3-diol in water at 37 degrees Celsius.

A composition comprising 2-(3,7-dimethylocta-2,6-diene-l-yl)-3-hydroxy-5-pentylphenolate and the conjugate base(s) of curcumin was prepared using a strategy similar to that described in Example 3. The composition contained the 2-(3,7-dimethylocta-2,6-diene-l-yl)-5-pentylbenzene- 1,3-diol and the 2-(3,7-dimethylocta-2,6-diene-l-yl)-3-hydroxy-5-pentylphenolate at a ratio of at least 1 : 100,000 and no greater than 1 : 1 by mole. The composition contained the 2-(3,7- dimethylocta-2,6-diene-l-yl)-3-hydroxy-5-pentylphenolate at a concentration of at least 10 milligrams per liter and no greater than 100 grams per liter; the conjugate base(s) of curcumin at a concentration of at least 10 parts per million and no greater than 10 percent by mass; the potassium cation at a concentration of at least 5 parts per million and no greater than 5 percent by mass; the ethanol at a concentration of no greater than 0.5 percent by mass; and the water at a concentration of at least 50 percent and no greater than 99.8 percent by mass. The composition contained the potassium cation at a greater concentration by mole than the 2-(3,7-dimethylocta-2,6-diene-l-yl)-3- hydroxy-5-pentylphenolate and the 2-(3,7-dimethylocta-2,6-diene-l-yl)-3-hydroxy-5- pentylphenolate at a greater concentration by mass than the potassium cation. The composition contained the ethanol at a greater concentration by mass than the 2-(3,7-dimethylocta-2,6-diene-l- yl)-3-hydroxy-5-pentylphenolate. The composition contained a liquid phase that was a liquid comprising the propane- 1,2, 3 -triol, the ethanol, and the water, wherein the 2-(3,7-dimethylocta-2,6- diene-l-yl)-3-hydroxy-5-pentylphenolate and the potassium cation were solutes that were dissolved in the liquid phase. The composition also contained hydroxide; ethoxide; 2,3-dihydroxypropane-l- oxide; and l,3-dihydroxypropane-2-oxide. The molarity of the 2-(3,7-dimethylocta-2,6-diene-l-yl)- 3-hydroxy-5-pentylphenolate in the liquid phase was greater than the solubility of the 2-(3,7- dimethylocta-2, 6-diene- l-yl)-5-pentylbenzene-l, 3 -diol in water at 37 degrees Celsius.

Example 5. Compositions comprising (6aR,10aR)-3-pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro- 6H-benzo[c]chromen-l -oxide and curcumin

A composition comprising (6aR,10aR)-3-pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H- benzo[c]chromen-l-oxide and the conjugate base(s) of curcumin was prepared using a strategy similar to those described in Examples 1 and 2. The composition comprised (6aR,10aR)-3 -pentyl-

6.6.9-trimethyl-6a, 7,8,10a-tetrahydro-6H-benzo[c]chromen-l-ol; (6aR,10aR)-3-pentyl-6,6,9- trimethyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-l -oxide; the conjugate base(s) of curcumin; potassium cation; propane-1, 2, 3-triol; ethanol; and water. The composition contained the (6aR,10aR)-3-pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-l-ol and the (6aR,10aR)-3-pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-l-oxide at a ratio of at least 1 : 100,000 and no greater than 1 : 1 by mole. The composition contained the (6aR,10aR)-3- pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-l-oxide at a concentration of at least 10 milligrams per liter and no greater than 100 grams per liter; the conjugate base(s) of curcumin at a concentration of at least 10 parts per million and no greater than 10 percent by mass; the potassium cation at a concentration of at least 5 parts per million and no greater than 5 percent by mass; the propane- 1,2, 3 -triol at a concentration of at least 50 percent by mass; the ethanol at a concentration of at least 20 percent and no greater than 49 percent by mass; and the water at a concentration of at least 0.1 percent by mass. The composition contained the potassium cation at a greater concentration by mole than the (6aR,10aR)-3-pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro- 6H-benzo[c]chromen-l -oxide and the (6aR,10aR)-3-pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro- 6H-benzo[c]chromen-l -oxide at a greater concentration by mass than the potassium cation. The composition contained the ethanol at a greater concentration by mass than the (6aR,10aR)-3 -pentyl-

6.6.9-trimethyl-6a, 7,8, 10a-tetrahydro-6H-benzo[c]chromen-l-oxide. The composition contained a liquid phase that was a liquid comprising the propane-1, 2, 3-triol, the ethanol, and the water, wherein the (6aR,10aR)-3-pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-l- oxide and the potassium cation were solutes that were dissolved in the liquid phase. The composition also contained hydroxide; ethoxide; 2,3 -dihydroxypropane-1 -oxide; and 1,3- dihydroxypropane-2-oxide. The molarity of the (6aR,10aR)-3-pentyl-6,6,9-trimethyl-6a,7,8,10a- tetrahydro-6H-benzo[c]chromen-l-oxide in the liquid phase was greater than the solubility of the (6aR,10aR)-3-pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-l-ol in water at 37 degrees Celsius.

A composition comprising (6aR,10aR)-3-pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H- benzo[c]chromen-l-oxide and the conjugate base(s) of curcumin was prepared using a strategy similar to that described in Example 3. The composition contained the (6aR,10aR)-3-pentyl-6,6,9- trimethyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-l-ol and the (6aR,10aR)-3-pentyl-6,6,9- trimethyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-l -oxide at a ratio of at least 1:100,000 and no greater than 1:1 by mole. The composition contained the (6aR,10aR)-3-pentyl-6,6,9-trimethyl- 6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-l -oxide at a concentration of at least 10 milligrams per liter and no greater than 100 grams per liter; the conjugate base(s) of curcumin at a concentration of at least 10 parts per million and no greater than 10 percent by mass; the potassium cation at a concentration of at least 5 parts per million and no greater than 5 percent by mass; the ethanol at a concentration of no greater than 0.5 percent by mass; and the water at a concentration of at least 50 percent and no greater than 99.8 percent by mass. The composition contained the potassium cation at a greater concentration by mole than the (6aR,10aR)-3-pentyl-6,6,9-trimethyl-6a,7,8,10a- tetrahydro-6H-benzo[c]chromen-l-oxide and the (6aR,10aR)-3-pentyl-6,6,9-trimethyl-6a,7,8,10a- tetrahydro-6H-benzo[c]chromen-l-oxide at a greater concentration by mass than the potassium cation. The composition contained the ethanol at a greater concentration by mass than the (6aR,10aR)-3-pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-l-oxide. The composition contained a liquid phase that was a liquid comprising the propane- 1,2, 3-triol, the ethanol, and the water, wherein the (6aR,10aR)-3-pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H- benzo[c]chromen-l-oxide and the potassium cation were solutes that were dissolved in the liquid phase. The composition also contained hydroxide; ethoxide; 2,3 -dihydroxypropane-1 -oxide; and l,3-dihydroxypropane-2-oxide. The molarity of the (6aR,10aR)-3-pentyl-6,6,9-trimethyl- 6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-l -oxide in the liquid phase was greater than the solubility of the (6aR,10aR)-3-pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen- l-ol in water at 37 degrees Celsius.

Claims

What is claimed is:

1. A composition, comprising a cannabinoid, a cannabinoid anion, an excipient, a cation, a solvent, a cosolvent, and water, wherein: the cannabinoid is 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-5-pentylbenzene-l,3- diol; the cannabinoid anion is 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5- pentylphenolate; the excipient is selected from cinnamaldehyde, curcumin, ethyl salicylate, limonene, menthol, menthone, methyl salicylate, raspberry ketone, vanillin, wine lactone, and a conjugate base of any one of the foregoing; the cation is selected from potassium cation (K+) and sodium cation (Na+); the solvent is propane-1, 2, 3-triol; the cosolvent is ethanol; and the composition comprises the cannabinoid and the cannabinoid anion at a ratio of at least 1 : 100,000 and no greater than 1 : 1 by mole.

2. A composition, comprising a cannabinoid, a cannabinoid anion, an excipient, a cation, a solvent, a cosolvent, and water, wherein: the cannabinoid is 2-(3,7-dimethylocta-2,6-diene-l-yl)-5-pentylbenzene-l,3-diol; the cannabinoid anion is 2-(3,7-dimethylocta-2,6-diene-l-yl)-3-hydroxy-5-pentylphenolate; the excipient is selected from cinnamaldehyde, curcumin, ethyl salicylate, limonene, menthol, menthone, methyl salicylate, raspberry ketone, vanillin, wine lactone, and a conjugate base of any one of the foregoing; the cation is selected from potassium cation (K+) and sodium cation (Na+); the solvent is propane-1, 2, 3-triol; the cosolvent is ethanol; and the composition comprises the cannabinoid and the cannabinoid anion at a ratio of at least 1 : 100,000 and no greater than 1 : 1 by mole.

3. A composition, comprising a cannabinoid, a cannabinoid anion, an excipient, a cation, a solvent, a cosolvent, and water, wherein: the cannabinoid is (6aR,10aR)-3-pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H- benzo[c]chromen- 1 -ol; the cannabinoid anion is (6aR,10aR)-3-pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H- benzo[c]chromen- 1 -oxide; the excipient is selected from cinnamaldehyde, curcumin, ethyl salicylate, limonene, menthol, menthone, methyl salicylate, raspberry ketone, vanillin, wine lactone, and a conjugate base of any one of the foregoing; the cation is selected from potassium cation (K+) and sodium cation (Na+); the solvent is propane-1, 2, 3-triol; the cosolvent is ethanol; and the composition comprises the cannabinoid and the cannabinoid anion at a ratio of at least 1 : 100,000 and no greater than 1 : 1 by mole.

4. A composition, comprising a cannabinoid, a cannabinoid anion, an excipient, a cation, a solvent, a cosolvent, and water, wherein: the cannabinoid is 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-5-propylbenzene-l,3- diol; the cannabinoid anion is 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5- propylphenolate; the excipient is selected from cinnamaldehyde, curcumin, ethyl salicylate, limonene, menthol, menthone, methyl salicylate, raspberry ketone, vanillin, wine lactone, and a conjugate base of any one of the foregoing; the cation is selected from potassium cation (K+) and sodium cation (Na+); the solvent is propane-1, 2, 3-triol; the cosolvent is ethanol; and the composition comprises the cannabinoid and the cannabinoid anion at a ratio of at least 1 : 100,000 and no greater than 1 : 1 by mole.

5. A composition, comprising a cannabinoid, a cannabinoid anion, an excipient, a cation, a solvent, a cosolvent, and water, wherein: the cannabinoid is 2-(3,7-dimethylocta-2,6-diene-l-yl)-5-propylbenzene-l,3-diol; the cannabinoid anion is 2-(3,7-dimethylocta-2,6-diene-l-yl)-3-hydroxy-5-propylphenolate; the excipient is selected from cinnamaldehyde, curcumin, ethyl salicylate, limonene, menthol, menthone, methyl salicylate, raspberry ketone, vanillin, wine lactone, and a conjugate base of any one of the foregoing; the cation is selected from potassium cation (K+) and sodium cation (Na+); the solvent is propane-1, 2, 3-triol; the cosolvent is ethanol; and the composition comprises the cannabinoid and the cannabinoid anion at a ratio of at least 1 : 100,000 and no greater than 1 : 1 by mole.

6. A composition, comprising a cannabinoid, a cannabinoid anion, an excipient, a cation, a solvent, a cosolvent, and water, wherein: the cannabinoid is (6aR,10aR)-3-propyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H- benzo[c]chromen- 1 -ol; the cannabinoid anion is (6aR,10aR)-3-propyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H- benzo[c]chromen- 1 -oxide; the excipient is selected from cinnamaldehyde, curcumin, ethyl salicylate, limonene, menthol, menthone, methyl salicylate, raspberry ketone, vanillin, wine lactone, and a conjugate base of any one of the foregoing; the cation is selected from potassium cation (K+) and sodium cation (Na+); the solvent is propane-1, 2, 3-triol; the cosolvent is ethanol; and the composition comprises the cannabinoid and the cannabinoid anion at a ratio of at least 1 : 100,000 and no greater than 1 : 1 by mole.

7. A composition, comprising a cannabinoid, a cannabinoid anion, an excipient, a cation, a solvent, a cosolvent, and water, wherein: the cannabinoid is 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-5-alkylbenzene-l,3-diol; the cannabinoid anion is 2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5- alkylphenolate; the cation is selected from lithium cation (Li+); potassium cation (K+), sodium cation (Na+), calcium cation (Ca++), magnesium cation (Mg++), iron (II) cation (Fe++), iron (III) cation (Fe+++), zinc cation (Zn++), manganese (II) cation (Mn++), copper (I) cation (Cu+), copper (II) cation (Cu++), ammonium cation (NH4+), protonated lysine, protonated hydroxylysine, protonated arginine, protonated ethanolamine, choline, and protonated sphingosine; the solvent is selected from propane- 1,2-diol, propane-1, 3-diol, and propane-1, 2, 3-triol; the cosolvent is ethanol; and the composition comprises the cannabinoid and the cannabinoid anion at a ratio of at least 1 : 100,000 and no greater than 1 : 1 by mole.

8. A composition, comprising a cannabinoid, a cannabinoid anion, an excipient, a cation, a solvent, a cosolvent, and water, wherein: the cannabinoid is 2-(3,7-dimethylocta-2,6-diene-l-yl)-5-alkylbenzene-l,3-diol; the cannabinoid anion is 2-(3,7-dimethylocta-2,6-diene-l-yl)-3-hydroxy-5-alkylphenolate; the cation is selected from lithium cation (Li+); potassium cation (K+), sodium cation (Na+), calcium cation (Ca++), magnesium cation (Mg++), iron (II) cation (Fe++), iron (III) cation (Fe+++), zinc cation (Zn++), manganese (II) cation (Mn++), copper (I) cation (Cu+), copper (II) cation (Cu++), ammonium cation (NH4+), protonated lysine, protonated hydroxylysine, protonated arginine, protonated ethanolamine, choline, and protonated sphingosine; the solvent is selected from propane- 1,2-diol, propane-1, 3-diol, and propane-1, 2, 3-triol; the cosolvent is ethanol; and the composition comprises the cannabinoid and the cannabinoid anion at a ratio of at least 1 : 100,000 and no greater than 1 : 1 by mole.

9. A composition, comprising a cannabinoid, a cannabinoid anion, an excipient, a cation, a solvent, a cosolvent, and water, wherein: the cannabinoid is (6aR,10aR)-3-alkyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen- l-ol; the cannabinoid anion is (6aR,10aR)-3-alkyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H- benzo[c]chromen- 1 -oxide; the cation is selected from lithium cation (Li+); potassium cation (K+), sodium cation (Na+), calcium cation (Ca++), magnesium cation (Mg++), iron (II) cation (Fe++), iron (III) cation (Fe+++), zinc cation (Zn++), manganese (II) cation (Mn++), copper (I) cation (Cu+), copper (II) cation (Cu++), ammonium cation (NH4+), protonated lysine, protonated hydroxylysine, protonated arginine, protonated ethanolamine, choline, and protonated sphingosine; the solvent is selected from propane- 1,2-diol, propane-1, 3-diol, and propane-1, 2, 3-triol; the cosolvent is ethanol; and the composition comprises the cannabinoid and the cannabinoid anion at a ratio of at least 1 : 100,000 and no greater than 1 : 1 by mole.

10. The composition of any one of claims 7-9, wherein the excipient is selected from acetanisole, acetylpropionyl, alkannin, allyl hexanoate, alpha-tocopherol, alpha-tocotrienol, amyl acetate, anethole, 4-anisaldehyde, anisol, benzaldehyde, benzyl acetate, benzyl acetone, benzyl cinnamate, beta-tocopherol, beta-tocotrienol, n-butyl acetate, butylated hydroxyanisole, butylated hydroxytoluene, n-butyl butyrate, butylphthalide, capsaicin, capsanthin, capsorubin, cholic acid, cinnamaldehyde, cis-3-hexen-l-ol, cuminaldehyde, curcumin, cyclotene, delta-decalactone, delta- nonalactone, delta-octal actone, delta-tocopherol, delta-tocotrienol, dihydrojasmone, eriodictyol, estragole, ethyl acetate, ethyl benzoate, ethyl butyrate, ethyl cinnamate, ethyl decadienoate, ethyl heptanoate, ethyl maltol, ethyl methylphenylglycidate, ethylparaben, ethyl pentanoate, ethyl propionate, ethyl salicylate, ethylvanillin, eugenol, ferulate, fructone, furaneol, furfural, gamma- decalactone, gamma-nonal actone, gamma-tocopherol, gamma-tocotrienol, glyceryl diacetate, glyceryl monoacetate, glycyrrhizin, heptyl acetate, heptylparaben, 3-hexanol, hexyl acetate, hexyl cinnamaldehyde, homoeriodictyol, indanthrone blue, isoamyl acetate, isobutyl acetate, isovaleraldehyde, jasmine lactone, maltol, manzanate, massoia lactone, menthol, menthone, menthoxypropanediol, menthyl isovalerate, methyl anthranilate, methyl butyrate, methylparaben, methyl propionate, methyl salicylate, octyl acetate, ortho-vanillin, pentyl butyrate, pentyl pentanoate, propyl acetate, propylparaben, raspberry ketone, resveratrol, salicylaldehyde, sedanolide, sterubin, sotolon, tert-butylhydroquinone, tetrahydrofurfuryl acetate, tetrahydrofurfuryl alcohol, tetrahydrofurfuryl butyrate, tetrahydrofurfuryl cinnamate, tetrahydrofurfuryl propionate, triacetin, triethyl citrate, vanillin, wine lactone, and a conjugate base of any one of the preceding molecules.

11. The composition of any one of claims 1-10, comprising the cannabinoid anion at a concentration of at least 10 milligrams per liter and no greater than 100 grams per liter.

12. The composition of any one of claims 1-11, comprising the solvent at a concentration of at least 50 percent by mass.

13. The composition of any one of claims 1-12, comprising the water at a concentration of at least 0.1 percent by mass.

14. The composition of any one of claims 1-11, comprising the water at a concentration of at least 50 percent and no greater than 99.8 percent by mass.

15. The composition of claim 14, comprising the cosolvent at a concentration of no greater than 0.5 percent by mass.

16. The composition of any one of claims 1-15, comprising the cosolvent at a concentration of at least 0.1 percent by mass.

17. The composition of any one of claims 1-14, comprising the cosolvent at a concentration of at least 20 percent and no greater than 49 percent by mass.

18. The composition of any one of claims 1-17, comprising the cation at a greater concentration by mole than the cannabinoid anion.

19. The composition of any one of claims 1-18, comprising the cannabinoid anion at a greater concentration by mole than the cation.

20. The composition of any one of claims 1-19, comprising a liquid phase, wherein the liquid phase is a liquid that comprises the solvent, the cosolvent, and the water; and the cannabinoid anion and the cation are solutes that are dissolved in the liquid phase.

21. A composition, comprising a cannabinoid anion and an excipient, wherein the excipient has the formula CxHyOz; x is an integer of at least 4 and no greater than 21; y is an integer of at least 4 and no greater than 28; z is an integer of at least 1 and no greater than 7; y is no greater than x+10; and z is less than x.

22. A composition, comprising a cannabinoid anion and an excipient, wherein the excipient has the formula CxHyOz

x is an integer of at least 4 and no greater than 21; y is an integer of at least 3 and no greater than 27; z is an integer of at least 1 and no greater than 7; y is no greater than x+10; and z is less than x.

23. A composition, comprising a cannabinoid anion and an excipient, wherein the excipient is selected from acetanisole, acetylpropionyl, alkannin, allyl hexanoate, alpha-tocopherol, alpha- tocotrienol, amyl acetate, anethole, 4-anisaldehyde, anisol, benzaldehyde, benzyl acetate, benzylacetone, benzyl cinnamate, beta-tocopherol, beta-tocotrienol, n-butyl acetate, butylated hydroxyanisole, butylated hydroxytoluene, n-butyl butyrate, butylphthalide, capsaicin, capsanthin, capsorubin, cholic acid, cinnamaldehyde, cis-3-hexen-l-ol, cuminaldehyde, curcumin, cyclotene, delta-decalactone, delta-nonalactone, delta-octalactone, delta-tocopherol, delta-tocotrienol, dihydrojasmone, eriodictyol, estragole, ethyl acetate, ethyl benzoate, ethyl butyrate, ethyl cinnamate, ethyl decadienoate, ethyl heptanoate, ethyl maltol, ethyl methylphenylglycidate, ethylparaben, ethyl pentanoate, ethyl propionate, ethyl salicylate, ethylvanillin, eugenol, ferulate, fructone, furaneol, furfural, gamma-decalactone, gamma-nonalactone, gamma-tocopherol, gamma- tocotrienol, glyceryl diacetate, glyceryl monoacetate, glycyrrhizin, heptyl acetate, heptylparaben, 3- hexanol, hexyl acetate, hexyl cinnamaldehyde, homoeriodictyol, indanthrone blue, isoamyl acetate, isobutyl acetate, isovaleraldehy dejasmine lactone, maltol, manzanate, massoia lactone, menthol, menthone, menthoxypropanediol, menthyl isovalerate, methyl anthranilate, methyl butyrate, methylparaben, methyl propionate, methyl salicylate, octyl acetate, ortho-vanillin, pentyl butyrate, pentyl pentanoate, propyl acetate, propylparaben, raspberry ketone, resveratrol, salicylaldehyde, sedanolide, sterubin, sotolon, tert-butylhydroquinone, tetrahydrofurfuryl acetate, tetrahydrofurfuryl alcohol, tetrahydrofurfuryl butyrate, tetrahydrofurfuryl cinnamate, tetrahydrofurfuryl propionate, triacetin, triethyl citrate, vanillin, wine lactone, and a conjugate base of any one of the preceding molecules.

24. The composition of any one of claims 21-23, comprising a solvent, wherein the cannabinoid anion is a solute that is dissolved in the solvent.

25. The composition of claim 24, wherein the solvent is water, ethanol, propane- 1,2-diol, propane- 1, 3-diol, propane- 1,2, 3 -triol, or butane- 1,3 -diol.

26. The composition of claim 24 or 25, wherein the solvent is water or propane-1, 2, 3-triol.

27. The composition of any one of claims 24-26, comprising a cosolvent, wherein the composition comprises the solvent at a greater concentration by mass than the cosolvent; and the composition comprises the cosolvent at a greater concentration by mass than the cannabinoid anion.

28. The composition of claim 27, wherein the solvent is water or propane-1, 2, 3-triol; and the cosolvent is ethanol.

29. The composition of any one of claims 21-28, comprising the cannabinoid anion at a concentration of at least 10 parts per million and no greater than 10 percent by mass; and comprising the excipient at a concentration of at least 10 parts per million and no greater than 10 percent by mass.

30. The composition of claims 21-29, comprising a cation selected from potassium cation (K+), sodium cation (Na+), calcium cation (Ca++), magnesium cation (Mg++), iron (II) cation (Fe++), iron (III) cation (Fe+++), zinc cation (Zn++), manganese (II) cation (Mn++), copper (I) cation (Cu+), copper (II) cation (Cu++), ammonium cation (NH4+), protonated lysine, protonated hydroxylysine, protonated arginine, protonated ethanolamine, and choline.

31. The composition of claim 30, comprising the cation at a concentration of at least 5 parts per million and no greater than 5 percent by mass.

32. A composition comprising a cannabinoid anion, a cation, a solvent, a cosolvent, and an excipient, wherein: the composition comprises the cannabinoid anion at a concentration of at least 10 parts per million and no greater than 10 percent by mass; the composition comprises the cation at a concentration of at least 5 parts per million and no greater than 5 percent by mass; the solvent is either water or propane-1, 2, 3-triol; the composition comprises the solvent at a concentration of at least 50 percent by mass and no greater than 99 percent by mass; the cannabinoid anion is a solute that is dissolved in the solvent; the cation is a solute that is dissolved in the solvent; the cosolvent is ethanol; the composition comprises the ethanol at a concentration of at least 50 parts per million and no greater than 49 percent by mass; the excipient is acetanisole, acetylpropionyl, alkannin, allyl hexanoate, alpha-tocopherol, alpha- tocotrienol, amyl acetate, anethole, 4-anisaldehyde, anisol, benzaldehyde, benzyl acetate, benzylacetone, benzyl cinnamate, beta-tocopherol, beta-tocotrienol, n-butyl acetate, butylated hydroxyanisole, butylated hydroxytoluene, n-butyl butyrate, butylphthalide, capsaicin, capsanthin, capsorubin, cholic acid, cinnamaldehyde, cis-3-hexen-l-ol, cuminaldehyde, curcumin, cyclotene, delta-decalactone, delta-nonalactone, delta-octal actone, delta-tocopherol, delta-tocotrienol, dihydrojasmone, eriodictyol, estragole, ethyl acetate, ethyl benzoate, ethyl butyrate, ethyl cinnamate, ethyl decadienoate, ethyl heptanoate, ethyl maltol, ethyl methylphenylglycidate, ethylparaben, ethyl pentanoate, ethyl propionate, ethyl salicylate, ethylvanillin, eugenol, ferulate, fructone, furaneol, furfural, gamma-decalactone, gamma-nonalactone, gamma-tocopherol, gamma-tocotrienol, glyceryl diacetate, glyceryl monoacetate, glycyrrhizin, heptyl acetate, heptylparaben, 3-hexanol, hexyl acetate, hexyl cinnamaldehyde, homoeriodictyol, indanthrone blue, isoamyl acetate, isobutyl acetate, isovaleraldehy dejasmine lactone, maltol, manzanate, massoia lactone, menthol, menthone, menthoxypropanediol, menthyl isovalerate, methyl anthranilate, methyl butyrate, methylparaben, methyl propionate, methyl salicylate, octyl acetate, ortho-vanillin, pentyl butyrate, pentyl pentanoate, propyl acetate, propylparaben, raspberry ketone, resveratrol, salicylaldehyde, sedanolide, sterubin, sotolon, tert-butylhydroquinone, tetrahydrofurfuryl acetate, tetrahydrofurfuryl alcohol, tetrahydrofurfuryl butyrate, tetrahydrofurfuryl cinnamate, tetrahydrofurfuryl propionate, triacetin, triethyl citrate, vanillin, wine lactone, or a conjugate base of any one of the preceding molecules; and the composition comprises the excipient at a concentration of at least 10 parts per million and no greater than 10 percent by mass.

33. The composition of claim 32, wherein the cation is potassium cation (K+), sodium cation (Na+), calcium cation (Ca++), magnesium cation (Mg++), iron (II) cation (Fe++), iron (III) cation (Fe+++), zinc cation (Zn++), manganese (II) cation (Mn++), copper (I) cation (Cu+), copper (II) cation (Cu++), ammonium cation (NH₄+), protonated lysine, protonated hydroxylysine, protonated arginine, protonated ethanolamine, or choline.

34. The composition of any one of claims 29-33, wherein the cation is potassium cation or sodium cation.

35. The composition of any one of claims 1-20 and 30-34, comprising the cation at a greater concentration by mole than the cannabinoid anion; and comprising the cannabinoid anion at a greater concentration by mass than the cation.

36. The composition of any one of claims 20-35, wherein the cannabinoid anion is 2-[(lR,6R)-6- isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5-propylphenolate or 2-[(lR,6R)-6- isopropenyl-3-methylcyclohex-2-en-l-yl]-3-hydroxy-5-pentylphenolate.

37. The composition of any one of claims 20-35, wherein the cannabinoid anion is 2-(3,7- dimethylocta-2,6-diene-l-yl)-3-hydroxy-5-propylphenolate or 2-(3,7-dimethylocta-2,6-diene-l-yl)- 3-hydroxy-5-pentylphenolate.

38. The composition of any one of claims 20-35, wherein the cannabinoid anion is (6aR,10aR)-3- propyl-6,6,9-trimethyl-6a,7,8, 10a-tetrahydro-6H-benzo[c]chromen-l -oxide or (6aR, 10aR)-3 -pentyl- 6, 6, 9-trimethyl-6a, 7,8,10a-tetrahydro-6H-benzo[c]chromen-l -oxide.

39. The composition of any one of claims 1-38, wherein the excipient is selected from cinnamaldehyde, curcumin, ethyl salicylate, limonene, menthol, menthone, methyl salicylate, raspberry ketone, vanillin, wine lactone, and a conjugate base of any one of the foregoing.

40. The composition of any one of claims 1-39, wherein the excipient is selected from curcumin, limonene, menthol, methyl salicylate, and raspberry ketone.

41. The composition of any one of claims 1-20 and 24-40, wherein: the cannabinoid anion is the conjugate base of a neutrally-charged cannabinoid that has a solubility in water at 37 degrees Celsius; the cannabinoid anion is dissolved in the solvent; the solvent has a molarity of the cannabinoid anion; and the molarity of the cannabinoid anion in the solvent is greater than the solubility of the neutrally- charged cannabinoid in water at 37 degrees Celsius.

42. The composition of claim 41, wherein the molarity of the cannabinoid anion in the solvent is at least 100 times greater than the solubility of the neutrally-charged cannabinoid in water at 37 degrees Celsius.

43. The composition of any one of claims 1-42, wherein the cannabinoid anion is the conjugate base of a neutrally -charged cannabinoid; and the excipient acts as an anti-nucleating agent in relation to the neutrally-charged cannabinoid such that the excipient inhibits the aggregation of the neutrally-charged cannabinoid.

44. The composition of any one of claims 1-43, comprising hydroxide, ethoxide, and 2,3- dihydroxypropane-1 -oxide.

45. The composition of any one of claims 1-44, comprising hydroxide, ethoxide, and 1,3- dihydroxypropane-2-oxide.

46. The composition of any one of claims 1-45, for use as a medicament.

47. Use of the composition of any one of claims 1-45 to manufacture a medicament.

48. A method to consume a cannabinoid, comprising providing a composition according to any one of claims 1-46; and orally administering the composition to a subject.

49. A method to consume a cannabinoid, comprising: providing a composition according to any one of claims 1-46; contacting the composition with a second composition that comprises water at a concentration of at least 98 percent by mass to produce a beverage; and orally administering the beverage to a subject.

50. A method to dissolve a cannabinoid anion in water, comprising: providing a composition according to any one of claims 1-46; and contacting the composition with a second composition that comprises water at a concentration of at least 98 percent by mass to dissolve the cannabinoid anion in water.