WO2022011460A1 - Transmucosal cannabis compositions with enhanced permeation properties - Google Patents

Abstract

The present disclosure provides a composition comprising a cannabinoid for administration to a mucosal surface of a subject that, upon administration to the subject, demonstrates improvements compared to known cannabis compositions for example in terms of increased transmucosal permeation of the composition, reduced onset time, less variable response between subjects, more particularly in terms of onset time and/or cannabinoid-effect intensity, or any combinations thereof. This is achieved by making a composition comprising a cannabinoid component and a monohydric alcohol, where the monohydric alcohol is in an amount sufficient to obtain the desired effect while being below a threshold amount, the threshold amount being an amount beyond which the monohydric alcohol causes a significant stinging sensation upon contacting the mucosal surface of the subject. Such composition can be used for therapeutic or recreational applications.

Description

TRANSMUCOSAL CANNABIS COMPOSITIONS WITH ENHANCED PERMEATION

PROPERTIES

TECHNICAL FIELD

[0001] This application generally relates to the field of cannabis compositions and, more specifically, to compositions including a cannabinoid that are designed for increased transmucosal absorption.

BACKGROUND

[0002] Cannabis produces desirable psychoactive and/or physiological effects associated with a feeling of physical and/or emotional satisfaction and/or can be useful in the treatment of variety of diseases and conditions (e.g., pain, anxiety, inflammatory disorders, immune disorders, metabolic disorders, and the like).

[0003] Administration of cannabis has evolved over time from inhalation of combustible by products (/. e. , smoking or vaping) to other preferred routes of administration, such as for example, via transmucosal delivery. Cannabis formulations intended for transmucosal delivery, e.g., by spraying, dropping or pipetting, are typically formulated as oil formulations (e.g., with a carrier oil) or as aqueous formulations (e.g., as an emulsion). However, cannabis formulations intended for transmucosal delivery have presented practical disadvantages, which may limit user experience and/or impair user compliance.

[0004] For example, it has been observed that absorption of cannabis formulations via transmucosal delivery results in highly variable responses between subjects, more particularly in terms of the onset time and/or the intensity for the desirable physiological effects and/or therapeutic effects. Such variability causes significant problems when there is a need to adjust the dose as one needs to increment over a wide range of potential doses to reach the desired effect. This is in addition to the inherent biologically highly variable response of cannabinoids between subjects.

[0005] There remains a need for cannabinoid compositions for transmucosal administration which addresses at least some of the above-mentioned shortcomings. SUMMARY

[0006] This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This Summary is not intended to identify key aspects or essential aspects of the claimed subject matter.

[0007] As embodied and broadly described herein, the present disclosure relates to a composition comprising (i) a cannabinoid component including a cannabinoid, and (ii) a monohydric alcohol. The monohydric alcohol is in an amount sufficient to obtain an improvement compared to other oil-based composition comprising a cannabinoid, while being below a threshold amount. The composition is a liquid composition for administration to the mucosal surface of the subject.

[0008] For example, the threshold amount can be an amount beyond which the monohydric alcohol causes a significant stinging sensation upon contacting a mucosal surface of a subject.

[0009] For example, the threshold amount can be an amount beyond which the monohydric alcohol significantly destabilizes the cannabinoid component in the composition.

[0010] For example, the improved cannabinoid-associated effect can be an increased transmucosal permeation of the composition, a faster onset time, less variable onset time and/or cannabinoid-effect intensity across users, or any combinations thereof.

[0011] As embodied and broadly described herein, the present disclosure relates to a composition comprising a cannabinoid component including a cannabinoid, and a monohydric alcohol in an amount sufficient to increase transmucosal permeation of the cannabinoid while being below a threshold amount, the threshold amount being an amount beyond which the monohydric alcohol causes a significant stinging sensation upon contacting a mucosal surface of a subject, the composition being a liquid composition for administration to the mucosal surface of the subject.

[0012] As embodied and broadly described herein, the present disclosure relates to a composition comprising a cannabinoid component comprising a cannabinoid, and a monohydric alcohol in an amount sufficient to (i) increase transmucosal permeation of the composition, (ii) reduce variability of a cannabinoid-associated effect between a plurality of users, preferably reduce variability of onset time and/or reduce variability of cannabinoid-effect intensity across users, and (iii) optionally, maintain stability of the cannabinoid component over a period of at least 5 days, preferably at least 6 days, more preferably at least 7 days, even more preferably 8 days, yet even more preferably 9 days, the composition being a liquid composition for administration to a mucosal surface of a user.

[0013] In some embodiments, the composition may have one or more of the following features:

• the monohydric alcohol includes ethanol.

• the monohydric alcohol is present in an amount of about 30 wt.% or less, preferably about 20 wt.% or less, more, more preferably from about 5 wt.% to about 20 wt.%, even more preferably from about 5 wt.% to about 15 wt.%, even more preferably from about 10 wt.% to about 15 wt.%. .

• the cannabinoid includes tetrahydrocannabinoid (THC).

• the THC includes one or more of the following compounds: Dd-tetrahydrocannabinol

(Dd-THC), A9-cis-tetrahydrocannabinol (cis-THC), A9-tetrahydrocannabinol (A9-THC), A9-tetrahydrocannabinolic acid A (THCA-A), D10-tetrahydrocannabinol (DIO-THC), tetrahydrocannabivarin (THCV), A9-tetrahydrocannabinol-C4, D9- tetrahydrocannabinolic acid-C4 (THCA-C4), and synhexyl (n-hexyl-A3THC).

• the THC is Dd-tetrahydrocannabinol (Dd-THC), A9-tetrahydrocannabinol (A9-THC), or a combination thereof.

• the cannabinoid includes cannabidiol (CBD).

• CBD includes one or more of the following compounds: A2-cannabidiol, A5-cannabidiol

(2-(6-isopropenyl-3-methyl-5-cyclohexen-l-yl)-5-pentyl-l,3-benzenediol); A4-cannabidiol (2-(6-isopropenyl-3-methyl-4-cyclohexen-l-yl)-5-pentyl-l,3-benzenediol); A3-cannabidiol (2-(6-isopropenyl-3-methyl-3-cyclohexen-l-yl)-5-pentyl-l,3-benzenediol); D3,7- cannabidiol (2-(6-isopropenyl-3-methylenecyclohex-l-yl)-5-pentyl-l,3-benzenediol); D2- cannabidiol (2-(6-isopropenyl-3-methyl-2-cyclohexen-l-yl)-5-pentyl-l,3-benzenediol); D1 -cannabidiol (2-(6-isopropenyl-3-methyl-l-cyclohexen-l-yl)-5-pentyl-l,3-benzenediol); and (7) A6-cannabidiol (2-(6-isopropenyl-3-methyl-6-cyclohexen-l-yl)-5-pentyl-l,3- benzenediol).

• the CBD is A2-cannabidiol.

• the cannabinoid includes a mixture of THC and CBD in a (w/w) ratio of between about 1 :1000 and about 1000:1.

• the cannabinoid is present in an amount of from about 0.001 mg/mLto about 100 mg/ml_, preferably from about 0.1 mg/ml_ to about 50 mg/ml_.

• the cannabinoid is an isolated cannabinoid having a purity of 50-60%, or > 80%, or > 95%.

• the composition further comprises a flavour agent and/or a flavour enhancer. • the flavour agent includes a terpene.

• the flavour enhancer is an extract from a natural source or an artificial flavour enhancer.

• the flavour enhancer is selected from the group consisting of cinnamon, cucumber, mint, orange, lime, citrus, cookie dough, chocolate, vanilla, jasmine, lychee, almond, banana, grape, pear, pineapple, pine, oak, apple, pumpkin, grapefruit, watermelon, cotton sugar, durian, longan, taro, sapote, toffee nut, caramel, lotus, mango, mangosteen, coconut, coffee, strawberry, passion fruit, blueberry, raspberry, kiwi, walnut, cocoa, cherimoya, custard apple, papaya, fig, plum, nectarine, peaches, guava, honeydew, jackfruit, kumquat, loquat, palm, pomelo, persimmon, quince, cassia, sage, marjoram, lemon, orange, and tamarind flavour, or any combinations thereof.

• the flavour agent and/or flavour enhancer is present in an amount of < 12 wt.%, or < 10 wt.%, or < 8 wt.%, or < 5 wt.%.

• the cannabinoid component further comprises a carrier oil.

• the carrier oil is selected from borage oil, coconut oil, cottonseed oil, soybean oil, safflower oil, sunflower oil, castor oil, corn oil, olive oil, palm oil, peanut oil, almond oil, sesame oil, rapeseed oil, peppermint oil, poppy seed oil, canola oil, palm kernel oil, hydrogenated soybean oil, hydrogenated vegetable oils, glycerin/glycerol, glyceryl esters of saturated fatty acids, glyceryl behenate, glyceryl distearate, glyceryl isostearate, glyceryl laurate, glyceryl monooleate, glyceryl, monolinoleate, glyceryl palmitate, glyceryl palmitostearate, glyceryl ricinoleate, glyceryl stearate, polyglyceryl 10-oleate, polyglyceryl 3-oleate, polyglyceryl 4-oleate, polyglyceryl 10-tetralinoleate, behenic acid, medium-chain triglycerides (MCT), long chain triglycerides (LCT), and any combination thereof.

• the carrier oil is MCT oil.

• the composition is an oil-based composition and the carrier oil is present in an amount of about 50 wt.% or more, preferably from about 50 wt.% to about 90 wt.%.

• the composition is a water-based composition in the form of an emulsion and the composition further comprises an emulsifier and water.

• the emulsifier includes a polysorbate-type non-ionic surfactant.

• the emulsifier is selected from polyoxyethylene monostearate (PEG 400 Monostearate), polyoxyethylene monooleate (PEG 400 Monoleate), polyoxyethylene sorbitan monolaurate (Tween^® 20), polyoxyethylene sorbitan monolaurate (Tween^® 21), polyoxyethylene sorbitan monopalmitate (Tween^® 40), polyoxyethylene sorbitan monostearate (Tween^® 60), polyoxyethylene sorbitan monostearate (Tween^® 61), polyoxyethylene sorbitan tristearate (Tween^® 65), polyoxyethylene sorbitan monooleate (Tween^® 80), polyoxyethylene sorbitan monooleate (Tween 81), polyoxyethylene sorbitan trioleate (Tween^® 85), polyoxyethylene-(15)-stearic acid (Pegosperse 1500MS), polyoxyethylene-(20)-stearyl alcohol (Brij 78), polyoxyethylene-(23)-lauryl alcohol (Brij 35), (Lutensol ON 60), PEG-40 hydrogenated castor oil (Cremophor/Kolliphor RH 40), PEG-35 castor oil (Cremophor EL), Solutol HS-15, and any combinations thereof.

• wherein the cannabinoid component in the water-based composition further comprises a carrier oil, preferably as defined above.

• the water-based composition comprises the carrier oil in an amount of from about 5 wt.% to about 20 wt.%.

• the emulsion has a D₉₀ of about 200 nm or less, preferably of about 150 nm or less, more preferably of about 120 nm or less.

• the emulsion has a particle size distribution of from about 20 nm to about 120 nm, preferably from about 30 nm to about 80 nm, more preferably from about 40 nm to about 60 nm.

[0014] As embodied and broadly described herein, the present disclosure relates to a cannabis product for administration to a mucosal surface of a subject, the product comprising a container enclosing the composition as described herein and an outlet nozzle for administration of the composition to the mucosal surface of the subject.

[0015] In some embodiments, the cannabis product may have one or more of the following features:

• a pump-action delivery system for delivery of the composition to the mucosal surface of the subject.

• being for administration of the composition to the mucosal surface of the subject by spraying, dropping or pipetting.

• being for administration of the composition to the buccal cavity of the subject.

[0016] As embodied and broadly described herein, the present disclosure relates to a method for reducing cannabinoid-associated effect variability between users, comprising providing the cannabis composition as described above, and administering the composition to a user mucosal surface.

[0017] In some embodiments, the method may have one or more of the following features:

• the composition is enclosed in a cannabis article configured for administration of the composition to a user mucosal surface.

• the composition is administered by pipetting or dropping.

• the composition is administered with a spray or mist administration device. • the administration device is a vaporizer or atomizer.

• the composition is administered via nasal, oral, vaginal, ocular or rectal administration route. Preferably, the composition is administered to the mucosal surface via nasal routes, oral routes, or both.

• reducing the cannabinoid-associated effect variability between users includes reducing onset time and/or cannabinoid-effect intensity.

[0018] All features of exemplary embodiments that are described in this disclosure and are not mutually exclusive can be combined with one another. Elements of one embodiment can be utilized in the other embodiments without further mention. Other aspects and features of the present invention will become apparent to those ordinarily skilled in the art upon review of the following description of specific embodiments in conjunction with the accompanying Figures.

BRIEF DESCRIPTION OF THE DRAWINGS

[0019] A detailed description of specific exemplary embodiments is provided herein below with reference to the accompanying drawings in which:

[0020] FIG. 1A shows charted self-reported onset times for Elixir™ THC (circles) and the composition of Example 2 (“Distillate Tincture”, squares) results in a simple diagram, with the average onset time indicated by the horizontal line. The results show an overall reduction in onset time for a composition in accordance with the present disclosure, as well as narrower distribution of plotted onset times, indicating improved consistency in onset across users.

[0021] FIG. 1B shows the results of FIG. 1 A, with the 25^th percentile (bottom line of box), 75^th percentile (top line of box), median (“middle” line in box), as well as maximum and minimum values (whiskers) for each dataset indicated.

[0022] FIG. 2 shows charted self-reported onset times for a distillate oil-based spray without ethanol and with ethanol, with the average onset time indicated by the horizontal line as well its standard error of the mean (SEM).

[0023] FIG. 3 shows charted self-reported onset times for a distillate water-based spray (nanoemulsion) without ethanol and with ethanol, with the average onset time indicated by the horizontal line as well its standard error of the mean (SEM).

[0024] In the drawings, exemplary embodiments are illustrated by way of example. It is to be expressly understood that the description and drawings are only for the purpose of illustrating certain embodiments and are an aid for understanding. They are not intended to be a definition of the limits of the invention. DETAILED DESCRIPTION

[0025] A detailed description of one or more embodiments of the invention is provided below along with accompanying figures that illustrate the principles of the invention. The invention is described in connection with such embodiments, but the invention is not limited to any embodiment. The scope of the invention is limited only by the claims. Numerous specific details are set forth in the following description to provide a thorough understanding of the invention. These details are provided for the purpose of non-limiting examples and the invention may be practiced according to the claims without some or all these specific details. Technical material that is known in the technical fields related to the invention has not been described in detail so that the invention is not unnecessarily obscured.

[0026] The present inventors have surprisingly and unexpectedly designed a composition comprising a cannabinoid for administration to a mucosal surface of a subject that, upon administration to the subject, demonstrates improvements compared to known oil-based cannabis compositions for mucosal administration (e.g., compared to the Elixir™ oral spray product from Hexo Corporation Inc., Canada) or compared to known cannabis tincture oral compositions (e.g., Sativex™ oromucosal spray, GW Pharmaceuticals pic, UK.) that typically include 50 vol% ethanol. While cannabis tinctures have been reported to relieve pain in some chronic diseases, patients have developed oral burning sensation, stinging or white lesions and burns often leading to discontinuation of the medication (Scully, C. “Cannabis; adverse effects from an oromucosal spray.” Br Dent J 203, E12 (2007).

[0027] Such improvements, for example, can be an increased transmucosal permeation of the composition, a faster onset time, less variable onset time and/or cannabinoid-effect intensity across users, or any combinations thereof. This is achievable with compositions that comprise (i) a cannabinoid component including a cannabinoid and (ii) a monohydric alcohol, where the monohydric alcohol is in an amount sufficient to obtain an improvement compared to other oil- based composition comprising a cannabinoid, while being below a threshold amount. The composition is a liquid composition for administration to the mucosal surface of the subject.

[0028] For example, the threshold amount can be an amount beyond which the monohydric alcohol causes a significant stinging sensation upon contacting a mucosal surface of a subject. Indeed, a monohydric alcohol such as ethanol when contacting a mucosal surface of a subject may produce a hot stinging sensation when used in certain concentrations (also referred to herein as a “burning sensation”). The stinging sensation may cause undesirable user experience as well as negatively affect transmucosal delivery. For instance, in the case of oral administration, the stinging sensation so produced may cause reflex swallowing - thus, reducing transmucosal absorption because a proportion of the dose may then be involuntarily swallowed by stimulation of the swallowing reflex. The composition of the present disclosure may advantageously improve compliance (e.g. temporary abstinence from swallowing in the case of oral administration) and thus may improve transmucosal absorption.

[0029] For example, the threshold amount can be an amount beyond which the monohydric alcohol significantly destabilizes the cannabinoid component in the composition. For example, the present inventors also surprisingly discovered that presence of a monohydric alcohol in water-based nanoemulsions allows for increased permeation of the cannabinoids without significantly disrupting the nanoemulsion (e.g., less than about 65% increase in particle size over a period of at least 5, 6, 7, 8, or 9 days), which was surprising at least because monohydric alcohols such as ethanol are known to destabilize nanostructures of emulsions.

[0030] Furthermore, while ethanol has been used to increase permeation of molecules through mucosal membranes, ethanol was not known to the inventors knowledge to affect permeation of nanoparticles such as the droplets of a nanoemulsion, as these droplets are believed to be absorbed through mucosal membranes via a different mechanism than molecules.

Cannabinoid Component includes a cannabinoid

[0031] The composition of the present disclosure comprises a “cannabinoid component” that includes a cannabinoid.

[0032] As used herein, the term “cannabinoid” generally refers to any chemical compound that acts upon a cannabinoid receptor such as CB1 and CB2. Examples of cannabinoids include, but are not limited to, cannabichromanon (CBCN), cannabichromene (CBC), cannabichromevarin (CBCV), cannabicitran (CBT), cannabicyclol (CBL), cannabicyclovarin (CBLV), cannabidiol (CBD, defined below), cannabidiolic acid (CBDA), cannabidiol monomethylether (CBDM), cannabidiol-C4 (CBD-C4), cannabidiorcol (CBD-C1), cannabidiphorol (CBDP), cannabidivarin (CBDV), cannabielsoin (CBE), cannabifuran (CBF), cannabigerol (CBG), cannabigerol monomethylether (CBGM), cannabigerolic acid (CBGA), cannabigerovarin (CBGV), cannabinodiol (CBND), cannabinodivarin (CBVD), cannabinol

(CBN), cannabinol methylether (CBNM), cannabinol propyl variant (CBNV), cannabinol-C2 (CBN-C2), cannabinol-C4 (CBN-C4), cannabiorcol (CBN-C1), cannabiripsol (CBR), cannabitriol

(CBO), cannabitriolvarin (CBTV), cannabivarin (CBV), dehydrocannabifuran (DCBF), A7-cis-iso tetrahydrocannabivarin, tetrahydrocannabinol (THC, defined below), A9-tetrahydrocannabinolic acid (THC-A) including either or both isomers 2-COOH-THC (THC A- A) and 4-COOH-THC (THCA-B), A9-tetrahydrocannabiorcol (THC-C1), tetrahydrocannabivarinic acid (THCVA), tetrahydrocannabivarin (THCV), ethoxy-cannabitriolvarin (CBTVE), trihydroxy-A9- tetrahydrocannabinol (triOH-THC), 10-ethoxy-9hydroxy-A6a-tetrahydrocannabinol, 8,9- dihydroxy-A6a-tetrahydrocannabinol, 10-oxo-A6a-tetrahydrocannabionol (OTHC), 3, 4,5,6- tetrahydro-7-hydroxy-a-a-2-trimethyl-9-n-propyl-2, 6-methano-2H-1-benzoxocin-5-methanol (OH-iso-HHCV), A6a,10a-tetrahydrocannabinol (A6a,10a-THC), Dd-tetrahydrocannabivarin (Dd-THCV), A9-tetrahydrocannabiphorol (D9-THOR), A9-tetrahydrocannabutol (A9-THCB), derivatives of any thereof, and combinations thereof. Further examples of suitable cannabinoids are discussed in at least WO2017/190249 and U.S. Patent Application Pub. No. US2014/0271940, which are each incorporated by reference herein in their entirety.

[0033] Cannabidiol (CBD) means one or more of the following compounds: A2-cannabidiol, A5-cannabidiol (2-(6-isopropenyl-3-methyl-5-cyclohexen-l-yl)-5-pentyl-l,3-benzenediol); D4- cannabidiol (2-(6-isopropenyl-3-methyl-4-cyclohexen-l-yl)-5-pentyl-l,3-benzenediol); D3- cannabidiol (2-(6-isopropenyl-3-methyl-3-cyclohexen-l-yl)-5-pentyl-l,3-benzenediol); D3,7- cannabidiol (2-(6-isopropenyl-3-methylenecyclohex-l-yl)-5-pentyl-l,3-benzenediol); D2- cannabidiol (2-(6-isopropenyl-3-methyl-2-cyclohexen-l-yl)-5-pentyl-l,3-benzenediol); D1- cannabidiol (2-(6-isopropenyl-3-methyl-l-cyclohexen-l-yl)-5-pentyl-l,3-benzenediol); and D6- cannabidiol (2-(6-isopropenyl-3-methyl-6-cyclohexen-l-yl)-5-pentyl-l,3-benzenediol). In a preferred embodiment, and unless otherwise stated, CBD means A2-cannabidiol.

[0034] Tetrahydrocannabinol (THC) means one or more of the following compounds: D8- tetrahydrocannabinol (Dd-THC), Dd-tetrahydrocannabivahn (Dd-THCV), A9-cis- tetrahydrocannabinol (cis-THC), A9-tetrahydrocannabinol (D9-THO), D10-tetrahydrocannabinol (DIO-THC), A9-tetrahydrocannabinol-C4 (THC-C4), A9-tetrahydrocannabinolic acid-C4 (THCA- C4), synhexyl (n-hexyl-A3THC). In a preferred embodiment, and unless otherwise stated, THC means one or more of the following compounds: A9-tetrahydrocannabinol and D8- tetrahydrocannabinol.

[0035] Synthetic cannabinoids and semisynthetic cannabinoids encompass a variety of distinct chemical classes, for example and without limitation: the classical cannabinoids structurally related to THC, the non-classical cannabinoids (cannabimimetics) including the aminoalkylindoles, 1 ,5-diarylpyrazoles, quinolines, and arylsulfonamides as well as eicosanoids related to endocannabinoids.

[0036] In many cases, a cannabinoid can be identified because its chemical name will include the text string “*cannabi*”. However, there are a number of cannabinoids that do not use this nomenclature, such as for example those described herein. [0037] Within the context of this disclosure, where reference is made to a particular cannabinoid, each of the acid and/or decarboxylated forms are contemplated as both single molecules and mixtures. In addition, salts of cannabinoids are also encompassed, such as salts of cannabinoid carboxylic acids.

[0038] As well, any and all isomeric, enantiomeric, or optically active derivatives are also encompassed. In particular, where appropriate, reference to a particular cannabinoid includes both the “A Form” and the “B Form”. For example, it is known that THCA has two isomers, THCA-A in which the carboxylic acid group is in the 1 position between the hydroxyl group and the carbon chain (A Form) and THCA-B in which the carboxylic acid group is in the 3 position following the carbon chain (B Form).

[0039] In an embodiment, the cannabinoid is a cannabinoid dimer. The cannabinoid may be a dimer of the same cannabinoid (e.g., THC-THC) or different cannabinoids. In an embodiment, the cannabinoid may be a dimer of THC, including for example cannabisol.

[0040] In an embodiment, the cannabinoid is THC (Dd-THC and/or DQ-THC), CBD, CBG, CBN, THCV, CBC, or any combinations thereof, in similar or different amounts.

[0041] In an embodiment, the cannabinoid is THC.

[0042] In an embodiment, the cannabinoid is CBD.

[0043] As is known in the art, various cannabinoids can be used in combination to achieve a desired effect in a user. Certain specific ratios of cannabinoids may be useful to produce the feeling of physical and/or emotional satisfaction and/or may be useful in the treatment or management of specific diseases or conditions.

[0044] In some embodiments, the cannabinoid component includes or is a mixture of THC and CBD.

[0045] For example, the mixture of THC and CBD may be characterized with a w/w ratio of THC to CBD of between about 1:1000 and about 1000:1. Preferably, the (w/w) ratio of THC to CBD may be about 1 :1000, about 1 :900, about 1 :800, about 1:700, about 1 :600, about 1:500, about 1 :400, about 1:300, about 1 :250, about 1:200, about 1 :150, about 1 :100, about 1 :90, about 1 :80, about 1 :70, about 1 :60, about 1 :50, about 1 :45, about 1 :40, about 1 :35, about 1 :30, about 1 :29, about 1 :28, about 1 :27, about 1 :26, about 1 :25, about 1 :24, about 1:23, about 1 :22, about 1 :21, about 1 :20, about 1 :19, about 1 :18, about 1 :17, about 1 :16, about 1 :15, about 1 :14, about 1 :13, about 1 :12, about 1 :11, about 1:10, about 1 :9, about 1 :8, about 1 :7, about 1 :6, about

1 :5, about 1:4.5, about 1 :4, about 1 :3.5, about 1:3, about 1 :2.9, about 1 :2.8, about 1 :2.7, about 1 :2.6, about 1:2.5, about 1 :2.4, about 1 :2.3, about 1:2.2, about 1:2.1 , about 1 :2, about 1 :1.9, about 1 :1.8, about 1 :1.7, about 1 :1.6, about 1:1.5, about 1 :1.4, about 1 :1.3, about 1 :1.2, about 1 :1.1, about 1:1 , about 1.1 :1, about 1.2:1 , about 1.3:1 , about 1.4:1 , about 1.5:1 , about 1.6:1 , about 1.7:1 , about 1.8:1 , about 1.9:1 , about 2:1 , about 2.1:1 , about 2.2:1 , about 2.3:1, about 2.4:1, about 2.5:1 , about 2.6:1 , about 2.7:1 , about 2.8:1 , about 2.9:1, about 3:1, about 3.5:1 , about 4:1, about 4.5:1, about 5:1, about 6:1, about 7:1, about 8:1, about 9:1 , about 10:1 , about

11 :1 , about 12:1 , about 13:1 , about 14:1 , about 15:1 , about 16:1 , about 17:1 , about 18:1, about

19:1 , about 20: 1 , about 21 :1 , about 22: 1 , about 23: 1 , about 24: 1 , about 25: 1 , about 26: 1 , about

27:1 , about 28:1 , about 29:1 , about 30:1 , about 35:1 , about 40:1 , about 45:1 , about 50:1, about

60:1 , about 70:1 , about 80:1 , about 90:1 , about 100:1 , about 150:1, about 200:1, about 250:1 , about 300:1 , about 400:1 , about 500:1 , about 600:1 , about 700:1 , about 800:1 , or about 900:1.

[0046] In some embodiments, the composition includes the cannabinoid in a concentration of about 0.001 mg/ml_ or more. In a non-limiting example, the composition may comprise the cannabinoid in an amount of from about 0.001 mg/ml_ to about 100 mg/ml_, including any amount therebetween or any ranges therein. For example, and without wishing to be limiting, the composition may comprise the cannabinoid in an amount of from about 0.002 mg/ml_ to about 100 mg/ml_, from about 0.1 mg/mLto about 75 mg/ml_, or from about 0.1 mg/ml_ to about 50 mg/ml_, or from about 0.1 mg/ml_ to about 25 mg/ml_, including any amount therebetween or any ranges therein. The person of skill will be able to design a composition having a desired cannabinoid content without undue effort, based on the teachings described herein.

[0047] In some embodiments, the composition includes the cannabinoid in an amount of from about 1 wt.% to about 50 wt.% (the weight percentage being of the cannabinoid relative to total weight of the composition), including any amount therebetween or any ranges therein. For example, the composition includes the cannabinoid in an amount of from about 2.5 wt.% to about 50 wt.%, including any amount therebetween or any ranges therein, such as from about 5 wt.% to about 30 wt.% or from about 7.5 wt.% to about 25 wt.%, including any amount therebetween or any ranges therein.

[0048] Cannabinoids may be obtained from any suitable source material including, but not limited to, cannabis or hemp plant material (e.g., flowers, seeds, trichomes, and kief from cannabis plants) or manufactured (for example cannabinoids produced in yeast, for example as described in WO WO2018/148848). The term “cannabis plant(s)” encompasses wild type Cannabis (including but not limited to the species Cannabis sativa, Cannabis indica and Cannabis ruderalis) and also variants thereof, including cannabis chemovars (or “strains”) that naturally contain different amounts of the individual cannabinoids. [0049] In some embodiments, the cannabinoid is obtained from a cannabis extract (e.g., resin, wax, concentrate, and distillate).

[0050] As used herein, a “cannabis extract” refers to an extract obtained from a cannabis plant material according to any procedure known in the art; such extracts yield cannabinoids in pure or isolated form. For example, a cannabis extract may be obtained by a process including an extraction step from plant materials using for example organic solvent extraction, such as extraction with C0₂, butane, ethanol, and the like. For example, a cannabis extract may be obtained by a process including an extraction step from plant materials using for example heat decarboxylation to convert cannabinoids in their acid forms to neutral forms followed by or after C0₂ extraction (under sub-critical or super-critical conditions), providing a crude extract. The crude extract may then be “winterized,” that is, extracted with ethanol to remove lipids and waxes, as described for example in US 7,700,368, US 2004/0049059, and US 2008/0167483, which are incorporated herein by reference. Optionally, the method for obtaining the cannabis extract may further include purification steps such as a distillation step to further purify, isolate, or crystallize one or more cannabinoids, which is referred to herein as a “distillate”; US20160346339, which is incorporated herein by reference, describes a process for extracting cannabinoids from cannabis plant material using solvent extraction followed by filtration, and evaporation of the solvent in a distiller to obtain a distillate. The distillate may be further cut with one or more terpenes. The distillate may be further purified, for example using chromatographic and other separation methods known in the art, to obtain an “isolate.” In some embodiments, pure or isolated cannabinoids, such as those provided in a cannabis extract, may be combined with water, lipids, hydrocarbons, or mixtures thereof.

[0051] The cannabinoid may be an isolated cannabinoid, for example having 50-75% purity (as in the case of a crude C0₂ extract), or > 80% purity (as in the case of a distillate), or >95% purity (as in the case of an isolate). For example, and without wishing to be limiting, the cannabinoid may have a purity such as 50%-60%, or >65%, or >70%, or > 75%, or > 80%, or > 90%, or > 95%, or > 98%, or > 98%, or > 99%, or > 99.5%.

[0052] In an embodiment, the composition may include up to 10% by weight cannabinoid. In select embodiments, the composition may include from about 0.01% by weight to about 10% by weight, more particularly from about 0.1% by weight to about 8% by weight, even more particularly from about 0.5% by weight to about 5% by weight, and even more particularly still from about 1.0% by weight to about 3% by weight of cannabinoid. In select embodiments, the composition may include about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10% by weight of cannabinoid. [0053] In one particularly suitable embodiment, the composition includes about 25 mg/mL total cannabinoids.

[0054] In select embodiments, the cannabinoid component includes one or more cannabinoid distillates and isolates, and in particular, the cannabinoid component includes CBD distillates and/or isolates; THC distillates and/or isolates; or a combination of THC and CBD distillates and/or isolates. In some embodiments, the cannabinoid component includes THC distillates and/or isolates.

[0055] In select embodiments of the composition disclosed herein, the cannabinoids may be introduced in the form of pure cannabinoids or as a cannabis concentrate. As used herein, “pure cannabinoids” is meant to refer to a single cannabinoid or a mixture of different cannabinoids that is free of other compounds. The pure cannabinoids may be contained in solution in a diluent or other medium or may be a liquid or solid form of the pure cannabinoids absent any diluent. In an embodiment, the pure cannabinoids are synthetic or semi-synthetic cannabinoids. Nonlimiting exemplary embodiments of a cannabis concentrate include a cannabinoid distillate, a cannabinoid isolate, a cannabis oil, or any other type of extract containing one or more cannabinoids.

Other ingredients of the cannabinoid component

[0056] In some embodiments, the cannabinoid component may comprise other ingredients, including but not limited to one or more carrier oils, one or more terpenes, one or more emulsifiers, one or more flavor enhancer and/or flavor agent, or any combination thereof.

[0057] As used herein, the term “carrier oil” refers to any suitable carrier oil. Non-limiting examples of carrier oils include borage oil, coconut oil, cottonseed oil, soybean oil, safflower oil, sunflower oil, castor oil, corn oil, olive oil, palm oil, peanut oil, almond oil, sesame oil, rapeseed oil, peppermint oil, poppy seed oil, canola oil, palm kernel oil, hydrogenated soybean oil, hydrogenated vegetable oils, glyceryl esters of saturated fatty acids, glyceryl behenate, glyceryl distearate, glyceryl isostearate, glyceryl laurate, glyceryl monooleate, glyceryl, monolinoleate, glyceryl palmitate, glycerin/glycerol, glyceryl palmitostearate, glyceryl ricinoleate, glyceryl stearate, polyglyceryl 10-oleate, polyglyceryl 3-oleate, polyglyceryl 4-oleate, polyglyceryl 10- tetralinoleate, behenic acid, medium-chain triglycerides (MCT), long chain triglycerides (LCT), and any combination thereof. Preferably, the carrier oil is MCT.

[0058] In select embodiments, the carrier oil can reduce the viscosity of the cannabinoids and/or provide other suitable properties. Further, at least in the case of solid cannabinoids (e.g., crystalline CBD), the carrier oil aids in its dissolution of the cannabinoid. [0059] In an embodiment, a combination of carrier oils may be used in the composition described herein. When more than one carrier is used, they may be used at any amount relative to the other. In an embodiment, a first carrier oil and a second carrier oil may be used at a ratio between 10:1 and 1 :10 by weight to each other. In an embodiment, the two carrier oils may be used at about a ratio of 3:1 , 2:1 , 1 :1 , 1 :2 or 1 :3 by weight to each other. In an embodiment, the two carrier oils may be used at about a 1 : 1 by weight ratio to each other.

[0060] In an embodiment, the carrier oil may contribute to providing rapid onset of the cannabinoid in the composition described herein. The carrier oil may improve the rate of absorption and/or onset of a medicinal, therapeutic and/or recreational effect of the cannabinoid. In an embodiment, the rapid onset occurs within 60 minutes, within 30 minutes, with 15 minutes, or less from administration of the composition to a subject.

[0061] In select embodiments, the compositions are oil-based compositions and include the carrier oil in an amount of about 50 wt.% or more, preferably from about 50 wt.% to about 90 wt.%, including any amounts therein or any ranges therefrom. For example, the oil-based compositions may include the carrier oil in an amount of about 50 wt.%, about 60 wt.%, about 70 wt.%, about 80 wt.%, or about 90 wt.%.

[0062] In select embodiments, the compositions are water-based compositions in the form of an emulsion. In such embodiments, the compositions can include the carrier oil in an amount of about 40 wt.% or less, preferably from about 5 wt.% to about 20 wt.%. For example, the water- based compositions may include the carrier oil in an amount of about 5 wt.%, about 10 wt.%, about 15 wt.%, or about 20 wt.%.

[0063] As used herein, the term “terpenes” refers to refer to a class of chemical components comprised of the fundamental building block of isoprene, which can be linked to form linear structures or rings. Terpenes may include hemiterpenes (single isoprenoid unit), monoterpenes (two units), sesquiterpenes (three units), diterpenes (four units), sesterterpenes (five units), triterpenes (six units), and so on. At least some terpenes are expected to interact with, and potentiate the activity of, cannabinoids. Examples of terpenes known to be extractable from cannabis include aromadendrene, bergamottin, bergamotol, bisabolene, borneol, 4-3-carene, caryophyllene, cineole/eucalyptol, p-cymene, dihydroj asmone, elemene, farnesene, fenchol, geranylacetate, guaiol, humulene, isopulegol, limonene, linalool, menthone, menthol, menthofuran, myrcene, nerylacetate, neomenthylacetate, ocimene, perillylalcohol, phellandrene, pinene, pulegone, sabinene, terpinene, terpineol, 4-terpineol, terpinolene, and derivatives thereof. Additional examples of terpenes include nerolidol, phytol, geraniol, alpha- bisabolol, thymol, genipin, astragaloside, asiaticoside, camphene, beta-amyrin, thujone, citronellol, 1 ,8-cineole, cycloartenol, and derivatives thereof.

[0064] As used herein, the term “emulsifier” refers to a compound that can stabilize the cannabinoid in the water-based composition described herein, forming an emulsion.

[0065] In some embodiments, the emulsion is in the form of a nanoemulsion. As used herein, the term “nanoemulsion” means an emulsion which is mainly constituted of particles having a particle size distribution which is less than about 1000 nm. In other words, the emulsion is made of at least 95%, or at least 96%, or at least 97%, or at least 98%, or at least 99% of particles in the nanometric range (i.e., from Oto 1000 nm). For example, the nanoemulsion described herein has Dgo of about 200 nm or less, preferably of about 150 nm or less, more preferably of about 120 nm or less. For example, the nanoemulsion described herein has a particle size distribution of from about 20 nm to about 120 nm, preferably from about 30 nm to about 80 nm, more preferably from about 40 nm to about 60 nm.

[0066] The term “particle size”, as used herein, refers to a volume based particle size measured, for example, by dynamic light scattering (DLS) which is a non-invasive, well- established technique for measuring the size and size distribution of molecules and particles typically in the submicron region. The DLS instrument has a laser light source which is used to illuminate the particles. Then, the generated scattered light fluctuates at a speed depending on the particle size. With the velocity of the Brownian motion, derived from the analysis of these fluctuations, and the Stokes-Einstein equation, particle size can be obtained. The particle size is reported as a volume equivalent sphere diameter.

[0067] Examples of suitable emulsifiers include, but are not limited to, polysaccharide-based emulsifiers, protein-based emulsifiers, small molecule surfactants, and mixtures thereof.

[0068] Examples of suitable polysaccharide-based emulsifiers include, but are not limited to, gum arabic, modified starches such as octenyl succinate modified starches, modified cellulose such as methyl cellulose, hydroxypropyl cellulose, methyl hydroxypropyl cellulose, and carboxymethylcellulose, certain types of pectin such as beet pectin, soy soluble polysaccharide, corn fiber gum, and mixtures thereof.

[0069] Examples of suitable protein-based emulsifiers include, but are not limited to, globular proteins such as whey protein and whey protein ingredients such as whey protein concentrate, whey protein isolate, and highly purified protein fractions such as b-lactoglobulin and a- lactalbumin, flexible proteins such as gelatin and caseins such as sodium caseinate, calcium caseinate, and purified protein fractions, such as b-casein. Milk-derived proteins (e.g., caseins, in either monomeric or micellar form, or whey proteins) may be used to form dairy emulsions. Milk proteins function as surface active ingredients in emulsions because of their amphiphilic structure, and they contribute to the stability of the emulsion droplets by a combination of electrostatic and steric stabilization mechanisms.

[0070] Examples of small molecule surfactants include, but are not limited to, polysorbate- type non-ionic surfactant, sugar esters such as sucrose monopalmitate, sucrose monostearate, sucrose distearate, sucrose polystearate, quillaja saponin (Q-Naturale™) and components thereof, sorbitan esters (Spans™) such as Span 20 (sorbitan monolaurate), Span 40 (sorbitan monopalmitate), Span 60 (sorbitan monostearate), Span 80 (sorbitan monooleate).

[0071] Emulsifiers such as lecithin, gum arabic, and octenyl succinate starches produce an emulsion with a negative charge on the surface of the droplet, which attracts pro-oxidant metal ions. This can be overcome using proteins, typically those derived from milk or soya.

[0072] In some embodiments, the emulsifier includes a polysorbate-type non-ionic surfactant. For example, polyoxyethylene monostearate (PEG 400 Monostearate), polyoxyethylene monooleate (PEG 400 Monoleate), polyoxyethylene sorbitan monolaurate (Tween^® 20), polyoxyethylene sorbitan monolaurate (Tween^® 21), polyoxyethylene sorbitan monopalmitate (Tween^® 40), polyoxyethylene sorbitan monostearate (Tween^® 60), polyoxyethylene sorbitan monostearate (Tween^® 61), polyoxyethylene sorbitan tristearate (Tween^® 65), polyoxyethylene sorbitan monooleate (Tween^® 80), polyoxyethylene sorbitan monooleate (Tween 81), polyoxyethylene sorbitan trioleate (Tween^® 85), polyoxyethylene-(15)-stearic acid (Pegosperse 1500MS), polyoxyethylene-(20)-stearyl alcohol (Brij 78), polyoxyethylene-(23)-lauryl alcohol (Brij 35), (Lutensol ON 60), PEG-40 hydrogenated castor oil (Cremophor/Kolliphor RH 40), PEG-35 castor oil (Cremophor EL), Solutol HS-15 and a combination thereof. Preferably, the emulsifier includes polyoxyethylene sorbitan monooleate (Tween^® 80).

[0073] In some embodiments, the emulsifier includes a mixture of a polysorbate-type nonionic surfactant and another emulsifier, such as lecithin.

[0074] Other emulsifiers can be used and will be apparent to the person of skill and for conciseness sake, will not be further described here.

[0075] The person skilled in the art would be familiar with formulating cannabinoid emulsions and would be aware of suitable amounts/ratios of the at least one emulsifier. For example, the cannabinoid composition may include up to about 10% by weight emulsifier. In an embodiment, the cannabinoid composition includes the emulsifier in an amount of from about 0.01% by weight to 10% by weight, more particularly from about 0.1% by weight to about 8% by weight, even more particularly from about 0.5% by weight to about 5% by weight, and even more particularly still from about 1.0% by weight to about 3% by weight. In select embodiments, the cannabinoid composition may include the emulsifier in an amount of about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10% by weight.

[0076] In some embodiments, the cannabinoid composition of the present disclosure may include a ratio by weight of emulsifier to cannabinoid of from 10:1 to 1 :10, including any ratio value therein or any range of ratio values there in-between. For example, the ratio of emulsifier to cannabinoid may be of about 3:1 , about 2:1 , about 1:1 , about 1 :2, about 1 :3, and the like.

[0077] In some embodiments, the cannabinoid composition may include a ratio by weight of emulsifier to carrier oil of from 5:1 to 1 :1, including any ratio value therein or any range of ratio values there in-between. For example, the ratio of emulsifier to carrier oil may be of about 3:1 , about 2:1 , about 1:1 , about 1:2, about 1 :3, and the like. Preferably, the ratio of emulsifier to carrier oil is of about 2:1 .

[0078] The reader will readily understand that in some embodiments, the cannabinoid component may include other ingredients in addition to the above described additional ingredients.

The composition includes a monohvdric alcohol

[0079] The composition of the present disclosure further comprises a monohydric alcohol in an amount sufficient to increase transmucosal permeation of the composition while being below a threshold amount, the threshold amount being an amount beyond which the monohydric alcohol causes a significant stinging sensation upon contacting a mucosal surface of a subject.

[0080] In some embodiments, the monohydric alcohol is present in an amount of about 30 wt.% or less, preferably about 20 wt.% or less. For example, the composition may include the monohydric alcohol in an amount of from about 5 wt.% to about 30 wt.%, more preferably from about 5 wt.% to about 20 wt.%, even more preferably from about 5 wt.% to about 15 wt.%, yet even more preferably from about 10 wt.% to about 15 wt.%, including any values therein. For example, the composition may include the monohydric alcohol in an amount of about 5 wt.%, about 10 wt.%, about 15 wt.%, or about 20 wt.%.

[0081] In some embodiments, the monohydric alcohol includes ethanol. Preferably, the monohydric alcohol is ethanol.

[0082] Contrary to known cannabis tinctures (e.g., SATIVEX™, oromucosal spray, GW Pharmaceuticals, UK) that typically contain 50 vol.% ethanol, the herein described compositions have significant lower amounts of monohydric alcohol and yet, still demonstrate improved transmucosal absorption.

[0083] In some embodiments, the composition may include water in an amount of < 2 wt.%, or < 1.5 wt.%, or < 1.2 wt.%, or < 1 wt.%, or < 0.5 wt.%. In some embodiments, the composition may be water-free.

Additional ingredients of the composition

[0084] It is desirable that the composition of the present disclosure, particularly if intended for oral administration, does not have a disagreeable taste. As used herein, the term “taste” means a perception arising because of the interaction of molecules or ions with taste receptors in the mouth. In the context of the present disclosure, a disagreeable taste can be a taste that is perceived such as, for example but not limited to, unpleasant, sharp, bitter, or synthetic. For example, the composition containing cannabinoids may be perceived to have a synthetic or bitter taste.

[0085] Accordingly, the composition may contain an effective amount of a flavor agent to mask the disagreeable taste. The composition may include the flavor agent in an amount of < 10 wt.% , or < 8 wt.%, or < 5 wt.%. For example, the flavor agent may be present in an amount of from about 0.01 wt.% to about 10 wt.%, preferably from about 0.01 wt.% to about 4 wt.%, preferably from about 0.1 wt.% to about 3 wt.%, preferably from about 0.5 wt.% to about 2 wt.%, or a combination thereof.

[0086] In some embodiments, the flavor agent may be one or more terpene as described above.

[0087] In some embodiments, the composition may contain an effective amount of a flavor enhancer. For example, the flavor enhancer may be a natural extract or a synthetic extract.

[0088] The composition may include the flavor enhancer in an amount of from about 0.01 wt.% to about 5 wt.%, preferably from about 0.01 wt.% to about 1 wt.%.

[0089] In some embodiments, the flavor enhancer may be selected from the group consisting of extracts of cinnamon, monk fruit, cucumber, mint, orange, lime, citrus, cookie dough, chocolate, vanilla, jasmine, lychee, almond, banana, grape, pear, pineapple, pine, oak, apple, pumpkin, grapefruit, watermelon, cotton sugar, durian, longan, taro, sapote, toffee nut, caramel, lotus, mango, mangosteen, coconut, coffee, strawberry, passion fruit, blueberry, raspberry, kiwi, walnut, cocoa, cherimoya, custard apple, papaya, fig, plum, nectarine, peaches, guava, honeydew, jackfruit, kumquat, loquat, palm, pomelo, persimmon, quince, and tamarind, or any combinations thereof.

[0090] Other examples of suitable flavor enhancer include, but are not limited to, mint oils, wintergreen, clove bud oil, cassia, sage, parsley oil, marjoram, lemon, orange, propenyl guaethol, heliotropine, 4-cis-heptenal, diacetyl, methyl-p-tert-butyl phenyl acetate, methyl salicylate, ethyl salicylate, 1-menthyl acetate, oxanone, a-irisone, methyl cinnamate, ethyl cinnamate, butyl cinnamate, ethyl butyrate, ethyl acetate, methyl anthranilate, iso-amyl acetate, iso-amyl butyrate, allyl caproate, eugenol, eucalyptol, thymol, cinnamic alcohol, octanol, octanal, decanol, decanal, phenylethyl alcohol, benzyl alcohol, a-terpineol, linalool, limonene, citral, neral, geranial, geraniol nerol, maltol, ethyl maltol, anethole, dihydroanethole, carvone, menthone, beta-damascenone, ionone, gamma-decalactone, gamma-nonalactone, y- undecalactone, or any combinations thereof.

Packaging of the composition

[0091] In some embodiments, the composition of the present disclosure may be included in an article of manufacture comprising a dispenser, such as for example a spray dispenser or mist dispenser, which may use mechanical and/or electric means to dispense the composition. As a result, it is desirable that the composition of the present disclosure can be formulated for delivery to, for example, the nasal and/or oral cavity, using spray devices or mist dispenser devices known in the art such as for example, via a pump action or pressurized administration vessel such as an aerosol spray (e.g., compressed air-, jet-, ultrasonic-, and piezoelectric nebulizers available from Pfeiffer and Valois). Such devices are familiar to the skilled artisan and can provide metered doses of the compositions, such as for example, single or multiple dosing, as desired.

[0092] In some embodiments, the formulation of the composition is such that it provides a fine micellized mist spray comprising the cannabinoid suitable for mucosal delivery for effective transdermal absorption across the mucosa. Without wishing to be bound by theory, the fine mist ensures maximum surface coverage and therefore optimum delivery via transmucosal delivery, for example via the nasal and/or oral mucosa.

In some embodiments, the composition is packaged into a cannabis product configured for administration to a mucosal surface of a subject. For example, the product can comprise a container enclosing the composition and an outlet nozzle for administration of the composition to the mucosal surface of the subject. For example, the cannabis product can be an oral spray, preferably a sublingual liquid spray form and/or a buccal liquid spray form. [0093] In some embodiments, procedures may be employed during manufacturing of the composition to reduce or avoid contamination with bacteria, yeast, or mold. For example, the composition may be processed and/or made such that there is less than 100,000 CFU of total viable aerobic bacteria count; less than 100,000 CFU/g of total yeast and mold count, preferably less than 10,000 CFU/g; less than 1000 CFU of bile-tolerant gram negative bacteria; less than 1000 CFU/g of total conforms count, preferably less than 100 CFU/g; or any combinations thereof.

[0094] It will be readily apparent to the person of skill how to implement such procedures using known techniques in the art (such as pasteurization, etc.) and as such, and for conciseness sake, will not be further discussed here.

Use of the composition

[001] Cannabis compositions described herein can be used for recreational and/or medicinal uses. For example, the cannabis compositions can be used to achieve a desired effect in a user, such as a psychoactive effect, a physiological effect, or a treatment of a condition. By “psychoactive effect”, it is meant a substantial effect on mood, perception, consciousness, cognition, or behavior of a subject resulting from changes in the normal functioning of the nervous system. By “physiological effect”, it is meant an effect associated with a feeling of physical and/or emotional satisfaction. By “treatment of a condition”, it is meant the treatment or alleviation of a disease or condition by absorption of cannabinoid(s) at sufficient amounts to mediate the therapeutic effects.

[0095] The methods according to the present disclosure comprise administering to a mucosa surface of a subject, preferably a nasal and/or oral mucosa (e.g., sublingual), an effective amount of the composition according to the present disclosure.

[0096] The terms “treating”, “treatment” and the like are used herein to mean obtaining a desired pharmacologic and/or physiologic effect. The effect may be prophylactic, in terms of completely or partially preventing a disease, condition, or symptoms thereof, and/or may be therapeutic in terms of a partial or complete cure for a disease or condition and/or adverse effect, such as a symptom, attributable to the disease or disorder. “Treatment” as used herein covers any treatment of a disease or condition of a mammal, such as a dog, cat or human, preferably a human.

[0097] In certain embodiments, the disease or condition is selected from the group consisting of: pain, anxiety, an inflammatory disorder, a neurological disorder, a psychiatric disorder, a malignancy, an immune disorder, a metabolic disorder, a nutritional deficiency, an infectious disease, a gastrointestinal disorder, and a cardiovascular disorder. Preferably the disease or condition is pain. In other embodiments, the disease or condition is associated with the feeling of physical and/or emotional satisfaction. In the context of these methods, it is preferable that the cannabinoid composition provides substantially no psychoactive effect or no psychoactive effect.

[0098] In the context of recreational use, the “effective amount” administered and rate and time-course of administration, will depend on the desired effect associated with a feeling of physical and/or emotional satisfaction in the subject.

[0099] In the context of health and wellness, the “effective amount” administered and rate and time-course of administration will depend on the nature and severity of the disease or condition being treated and typically also takes into consideration the condition of the individual subject, the method of administration and the like.

[0100] In one broad aspect, the present disclosure further relates to a method for reducing cannabinoid-associated effect variability between users. The method includes providing a cannabis composition for administration to a mucosal surface of a user. The cannabis composition has been described elsewhere herein and for conciseness sake will not be further described here. Preferably, the composition is enclosed in a cannabis article configured for administration of the composition to a mucosal surface of the user (e.g., sublingual). The method may further include administration of the composition to the mucosal surface. The composition may be administered by hand (e.g., pipetting or dropping) or applied utilizing a spray or mist apparatus, such as for example, a vaporizer or atomizer. The scope of the present disclosure should be considered to cover one or more distinct applications of the composition or the continuous release of a composition via a vaporizer, mist generator, or other type of atomizer. The composition may be administered via nasal or oral (e.g., buccal administration or sublingual administration), vaginal, ocular or rectal administration route. Preferably, the composition is administered to the mucosal surface via nasal routes, oral routes, or both.

[0101] The oral mucosa route of administration is attractive because it is a non-invasive route of administration, with the advantage of avoiding the first-pass metabolism, sustained action and ease of use. The sublingual mucosa (i.e., mouth) and buccal mucosa (i.e., inside of the cheeks) are preferred due to the fact that permeability is greater there and it is possible to realize transmucosal absorption of the cannabinoid administration, resulting in a systemic effect. Preferably, the administered cannabinoids are absorbed transmucosally in the oral cavity within about 90 minutes, about 60 minutes, about 40 minutes, about 30 minutes, about 20 minutes, about 15 minutes, or about 10 minutes after administration. For example, the subject may experience an onset of the effect associated with the cannabinoid in an average time as low as about 10 minutes.

[0102] The compositions of the present disclosure may thus also provide faster onset of a desirable psychoactive and/or physiological effect in a subject, particularly compared to art- known comparative compositions. Advantageously, the compositions of the present disclosure may provide a less variable onset time across subjects, thus providing a more consistent and reliable onset of the desired psychoactive and/or physiological effect.

[0103] The present disclosure further relates to a kit or commercial package comprising the composition of the present disclosure and instructions for use.

Methods of manufacture

[0104] In another broad aspect, the present disclosure relates to methods for producing a liquid composition containing a cannabinoid for administration to a mucosal surface of a subject. The method includes mixing a cannabinoid component as described herein with a monohydric alcohol, where the monohydric alcohol is in an amount sufficient to obtain the desired effect while being below a threshold amount, as described elsewhere in this text. The method optionally includes adding the herein described flavour agent and/or flavour enhancer.

[0105] In another broad aspect, the present disclosure relates to methods for producing an article of manufacture for administration of a composition containing a cannabinoid to a mucosal surface of a user. The method includes mixing a cannabinoid component as described herein with a monohydric alcohol, where the monohydric alcohol is in an amount sufficient to obtain the desired effect while being below a threshold amount, as described elsewhere in this text. The person of skill will readily understand that when the composition is a water-based composition, the method may include an emulsification step (or a self-emulsification step) with the addition of one or more emulsifier(s) thus forming an emulsion, e.g., a nanoemulsion. Emulsification processes are known in the art and for conciseness sake will not be further described here (e.g., the reader can refer to W02020037413, WO/2020/037411, WO/2020/037412, WO/2020/037408, WO/2020/037410, and WO/2020/037409, which are each herein incorporated by reference in their entirety).

[0106] The method can further include filling a liquid reservoir of the article of manufacture (e.g., a spraying, dropping, mist-generating, or pipetting article). The person of skill will readily realize that the step of filling the liquid reservoir may be performed by the same person formulating the composition or may be performed by another individual, for example. In the latter case, the method of the present disclosure may include a further step of releasing the composition such that another individual receiving the composition can proceed to fill the liquid reservoir with the composition.

EXAMPLES

[0107] The following examples describe some exemplary modes of making and practicing certain compositions that are described herein. These examples are for illustrative purposes only and are not meant to limit the scope of the compositions and methods described herein.

Example 1 - General formulation of oil-based compositions

[0108] In this example, oil-based compositions were prepared with a cannabinoid component comprising 25-50 mg/mL of a cannabinoid and with a monohydric alcohol in accordance with embodiments of the present disclosure.

[0109] The cannabinoid component was first provided. A distillate comprising THC, CBD, or a mixture thereof (prepared in-house at the Applicant’s facilities) was dispensed in carrier oil, then heated to 70-80°C and stirred until homogenous (e.g., 5-10 minutes). Carrier oils used in these compositions included MCT oil, extra virgin olive oil, and/or hempseed oil. The resulting cannabinoid component was cooled to room temperature. Ethanol (USP grade > 94%) was then added to the cannabinoid component. The resulting composition was then stirred for 5 minutes. If included, natural flavor agents and flavor enhancers were then added and stirred until homogenous (e.g., 2-3 minutes). Turbidity and/or ethanol-caused burning sensation was improved by letting the composition equilibrate over a period of at least 24h. The quantities of components used is listed in Table 1 below.

Table 1

Example 2 - Specific flavored oil-based compositions

[0110] In this example, several flavored oil-based compositions were prepared in accordance with the process set forth in Example 1. The compositions were strawberry, lemon-lime and peppermint flavored compositions. The ingredients are listed in Tables 1.1 to 1.3 below.

Table 1.1

Table 1.2

Table 1.3

All three flavors of CBD distillate oil-based spray corresponding to compositions made according to Tables 1.1 - 1.3 were well received by subjects testing the three sprays, with no reporting of a stinging sensation.

Example 3 - Specific unflavored oil-based composition

[0111] In this example, a specific oil-based composition was prepared with a cannabinoid component including a THC distillate and with ethanol as monohydric alcohol in accordance with the process set forth in Example 1.

[0112] Quantities of components used are listed in Table 2 below. Table 2

[0113] The final composition was equilibrated for 3-4 days prior to use in Example 3.

Example 3 - First sensory trial with oil-based compositions

[0114] The composition of Example 2 was incorporated into a spraying device, which was configured to provide a dosage of 2.5 mg of THC per spray. As a reference, a comparative commercially available spray device comprising an oil-based composition including a THC concentrate (cannabis extract obtained with C0₂ extraction) was also provided (Elixir™ THC spray, HEXO; 25 mg/mL THC and >95 wt.% MCT oil).

[0115] A panel of participants tested the compositions (9 participants with the composition of Example 2 and 10 participants with the comparative commercial composition) and self- administered 4 sprays to limit the daily dose to 10 mg of THC, keeping the dosage the same across the products. The participants were asked to fast 2 hours prior to and following the product administration to the buccal cavity. Participants were provided a journal to record adverse events.

[0116] The participants also reported not feeling any significant stinging sensation with the composition of Example 2. Participants noted an improved taste and mouthfeel of the composition of Example 2 over the commercial composition. Additionally, participants voluntarily reported (as an adverse event) on the onset of the compositions. Generally, a faster onset with the composition of Example 2 relative to the commercial composition. Specifically, the average onset time of about 65 minutes (median onset time of about 52 minutes) with the commercial composition was reduced to about 39 minutes (median onset time of about 36 minutes) for the composition of Example 2. Further, there was reduced variation in onset time between the participants when using the composition of Example 2 relative to the comparative composition. As can be seen in Figs. 1A and B, the commercial composition resulted in onset times spanning more than two hours, between 20 to 150 minutes, whereas the range resulting for the composition of Example 2 narrowed to between 10 to 100 minutes. Example 4 - Second sensory trial with oil-based compositions

[0117] In this example, oil-based compositions were prepared with a cannabinoid component comprising a THC distillate and with ethanol as monohydric alcohol (“test composition”), or without ethanol (“reference composition”).

[0118] The quantities of components used for the test and reference compositions are listed in Table 3 below.

Table 3

[0119] The test and reference compositions according to Table 3 were each incorporated into respective spraying devices, which were configured to provide a dosage of 5 mg of THC per spray.

[0120] A panel of participants tested the test and reference compositions (8 participants with each composition) and self-administered 2 sprays to limit the daily dose to 10 mg of THC, keeping the dosage the same across the products. Participants were provided a journal to record adverse events and only included persons who were not heavy cannabis consumers.

[0121] Participants noted a pleasant taste and mouthfeel of the compositions. Both sprays scored very well in terms of mouthfeel and taste, with the spray with ethanol presenting a trend towards a lighter mouthfeel and sweeter taste over the spray without ethanol. Additionally, participants voluntarily reported (as an adverse event) on the onset of the sprays.

[0122] Table 4 and Fig. 2 shows the results on the onset times for the spray with and without ethanol. In the results, participants who did not feel any subjective effects were excluded. Generally, a faster onset with the composition of the spray with ethanol was reported relative to the spray without ethanol. Specifically, the average onset time of about 21 minutes (median onset time of about 25 minutes) with the spray without ethanol was reduced to about 13 minutes (median onset time of about 14 minutes) for the spray with ethanol. Further, there was reduced variation in onset time between the participants when using the spray with ethanol relative to the spray without ethanol, with the standard error of the mean (SEM), reducing from 4.2 for the spray without ethanol to 0.81 for the spray with ethanol. As can be seen in Fig. 2, the composition without ethanol resulted in onset times between 7 and 30 minutes, whereas the range resulting for the composition with ethanol narrowed to between 10 to 15 minutes.

Table 4

[0123] In the results of Table 4, the mean onset time is reported ± the standard error of the mean and a one-tailed, unpaired Student t-test was used to find the significance, with p = 0.0405.

Example 5 - General formulation of water-based compositions

[0124] In this example, water-based compositions in the form of a nanoemulsion were prepared with a cannabinoid component comprising 25-50 mg/ml_ of a cannabinoid and with a monohydric alcohol in accordance with embodiments of the present disclosure.

[0125] The cannabinoid component was first provided. For example, the ingredients making up the cannabinoid component are mixed under suitable conditions to ensure substantial mixing. For example, such suitable conditions may include heating on a hot plate to 80 °C with a stir bar at medium agitation for about 5 minutes, but the reader will appreciate that other conditions may be implemented to obtain similar results.

[0126] The water phase was then provided. For example, the ingredients making up the water phase are mixed under suitable conditions to ensure substantial mixing. For example, such suitable conditions may include adding surfactant and/or emulsifier to water and mixing on stirring plate at medium speed until complete dissolution, and then heating on a hot plate to °40 C with a stir bar at medium agitation for about 5 minutes. Again, the reader will appreciate that other conditions may be implemented to obtain similar results.

[0127] The cannabinoid component was then added stepwise into the water phase while mixing at about 5000 rpm with a L5M-A lab homogenizer (Silverson, USA). After mixing, the resulting solution was homogenized with a PandaPLUS 2000 valve homogenizer (GEA, USA) to obtain a nanoemulsion characterized with a particle size of from about 60 nm to 90 nm, as measured with a DLS particle size analyzer (Anton Parr, Canada). [0128] The monohydric alcohol was then added to the nanoemulsion and mixed on a stirring plate at medium speed for about 5 to 10 minutes.

[0129] The ingredients are listed in the following table 5.

Table 5

Example 6 - Specific water-based compositions.

[0130] In this example, several water-based compositions (numbered 001 to 010) were prepared in accordance with the process set forth in Example 5 and the composition components thereof are set forth in table 6.

Table 6

[0131] The particle size of the resulting nanoemulsions prior to addition of the monohydric alcohol was measured with DLS particle size measurement and reported in the following Table 7.

Table 7

Example 7 - Specific water-based compositions.

[0132] In this example, nanoemulsion compositions were prepared in accordance with the process set forth in Example 5 and using different amounts of monohydric alcohol. The stability of the particle size in the resulting water-based compositions was tested up to 9 days postmanufacturing.

[0133] The ingredients of the water-base compositions prior to addition of the monohydric alcohol are listed in the following table 8.

Table 8

[0134] Increasing amounts of ethanol as monohydric alcohol was then added, namely 10%, 20%, 30, and 40%. The particle size (PS in nm) and polydispersity index (PD%) of the resulting nanoemulsions after addition of the monohydric alcohol was measured at T = 0 and T = 9 days post-manufacturing with DLS particle size measurement and reported in the following table 9.

Table 9

[0135] As seen from these results, the nanoemulsion particle size is substantially stable up to 9 days post-manufacturing with up to 30% ethanol content. In other words, over a period of at least 5, 6, 7, 8, or 9 days, the nanoemulsion particle size varies by about 65% or less (e.g., the largest variation seen here being 64% with a starting particle size of 104 nm and a particle size after 9 days of 164 nm - 104 / 164 * 100 = 64%). Example 8 - Specific water-based compositions

[0136] In this example, water-based compositions were prepared according to the process set forth in Example 5 using ethanol as monohydric alcohol. The ingredients of the water-base formulations are listed in the following table 10.

Table 10

[0137] The oil phase was added in a step-wise manner (e.g., dropwise) to the water phase and mixed between 20-25 °C.

Example 8 - Sensory trial using water-based compositions

[0138] In this example, water-based compositions were prepared with a cannabinoid component comprising THC and with ethanol as monohydric alcohol (“test composition”), or without ethanol (“reference composition”).

[0139] The quantities of components used for the test and reference compositions are listed in Table 11

Table 11

[0140] Both the test and the reference compositions demonstrated a nanoparticle size of about 70 nm. The test and reference compositions according to Table 11 were each incorporated into respective spraying devices, which were configured to provide a dosage of 2.5 mg of THC per spray.

[0141] A panel of participants tested the test and reference compositions (the same 9 participants tested each composition on subsequent days) and self-administered 4 sprays sublingually to limit the daily dose to 10 mg of THC, keeping the dosage the same across the products. A total of 8/9 were able to evaluate both samples (1 participant lost to follow-up due to schedule conflict). Participants were provided a journal to record adverse events and only included persons who were not heavy cannabis consumers.

[0142] Participants noted a pleasant taste and mouthfeel of the compositions. Both sprays scored very well in terms of mouthfeel. Participants on both sensory days provided interesting insight into the onset and experience of the spray prototypes when reporting adverse events (AE).

[0143] Reviewing the self-reported AE data revealed the following:

Table 12: Comparison of Self-reported Onset Time by Spray

One-tailed, unpaired Student t-test

** for this analysis, participants who did not feel any subjective effects were excluded (1 participant in the test composition group was excluded)

[0144] Anecdotally all participants reported that the intensity of the THC-associated effect (“high”) was lower for the comparison composition (nanoemulsion spray without ethanol) versus the test composition (nanoemulsion spray with ethanol).

[0145] These results suggest that presence of the monohydric alcohol (here being ethanol) in the nanoemulsion spray provided a significantly faster onset time. Possibly, more significant than this, the results suggest a tighter, more consistent reported onset time between subjects, as can be better seen in FIG. 3. [0146] In other words, these results suggest that adding a monohydric alcohol in an amount below a threshold amount, the threshold amount being an amount beyond which the monohydric alcohol causes a significant stinging sensation upon contacting a mucosal surface of a subject, resulted in a composition that can provide a faster onset of a desirable psychoactive and/or physiological effect in a subject, particularly compared to art-known comparative compositions. These results also suggest that the composition can further provide a less variable onset time across subjects, thus providing a more consistent and reliable onset of the desired psychoactive and/or physiological effect.

[0147] Other examples of implementations will become apparent to the reader in view of the teachings of the present description and as such, will not be further described here.

[0148] Note that titles or subtitles may be used throughout the present disclosure for convenience of a reader, but in no way these should limit the scope of the invention. Moreover, certain theories may be proposed and disclosed herein; however, in no way they, whether they are right or wrong, should limit the scope of the invention so long as the invention is practiced according to the present disclosure without regard for any particular theory or scheme of action.

[0149] All references cited throughout the specification are hereby incorporated by reference in their entirety for all purposes.

[0150] Reference throughout the specification to “some embodiments”, and so forth, means that a particular element (e.g., feature, structure, and/or characteristic) described in connection with the invention is included in at least one embodiment described herein, and may or may not be present in other embodiments. In addition, it is to be understood that the described inventive features may be combined in any suitable manner in the various embodiments.

[0151] It will be understood by those of skill in the art that throughout the present specification, the term “a” used before a term encompasses embodiments containing one or more to what the term refers. It will also be understood by those of skill in the art that throughout the present specification, the term “comprising”, which is synonymous with “including,” “containing,” or “characterized by,” is inclusive or open-ended and does not exclude additional, un-recited elements or method steps.

[0152] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. In the case of conflict, the present document will control. [0153] As used in the present disclosure, the terms “around”, “about” or “approximately” shall generally mean within the error margin generally accepted in the art. Hence, numerical quantities given herein generally include such error margin such that the terms “around”, “about” or “approximately” can be inferred if not expressly stated.

[0154] Although various embodiments of the disclosure have been described and illustrated, it will be apparent to those skilled in the art considering the present description that numerous modifications and variations can be made. The scope of the invention is defined more particularly in the appended claims.

Claims

CLAIMS:

1. A composition comprising a) a cannabinoid component comprising a cannabinoid, and b) a monohydric alcohol in an amount sufficient to increase transmucosal permeation of the composition while being below a threshold amount, the threshold amount being an amount beyond which the monohydric alcohol causes a significant stinging sensation upon contacting a mucosal surface of a subject, the composition being a liquid composition for administration to the mucosal surface of the subject.

2. A composition comprising a) a cannabinoid component comprising a cannabinoid, and b) a monohydric alcohol in an amount sufficient to (i) increase transmucosal permeation of the composition, (ii) reduce variability of a cannabinoid-associated effect between a plurality of users, preferably reduce variability of onset time and/or reduce variability of cannabinoid-effect intensity across users, and (iii) optionally, maintain stability of the cannabinoid component over a period of at least 5 days, preferably at least 6 days, more preferably at least 7 days, even more preferably 8 days, yet even more preferably 9 days, the composition being a liquid composition for administration to a mucosal surface of a user.

3. The composition of claim 1 or 2, wherein the monohydric alcohol includes ethanol, preferably is ethanol.

4. The composition of claim 1 to 3, wherein the monohydric alcohol is present in an amount of about 30 wt.% or less, preferably about 20 wt.% or less, more preferably from about 5 wt.% to about 20 wt.%, even more preferably from about 5 wt.% to about 15 wt.%, even more preferably from about 10 wt.% to about 15 wt.%.

5. The composition of any one of claims 1 to 4, wherein the cannabinoid includes tetrahydrocannabinoid (THC).

6. The composition of claim 5, wherein the THC includes one or more of the following compounds: Dd-tetrahydrocannabinol (Dd-THC), A9-cis-tetrahydrocannabinol (cis-THC), D9- tetrahydrocannabinol (A9-THC), A9-tetrahydrocannabinolic acid A (THCA-A), D10- tetrahydrocannabinol (DIO-THC), tetrahydrocannabivarin (THCV), A9-tetrahydrocannabinol- C4, A9-tetrahydrocannabinolic acid-C4 (THCA-C4), and synhexyl (n-hexyl-A3THC).

7. The composition of claim 5, wherein the THC is Dd-tetrahydrocannabinol (Dd-THC), A9-tetrahydrocannabinol (D9-THO), or a combination thereof.

3. The composition of any one of claims 1 to 7, wherein the cannabinoid includes cannabidiol (CBD).

9. The composition of claim 8, wherein the CBD includes one or more of the following compounds: A2-cannabidiol, A5-cannabidiol (2-(6-isopropenyl-3-methyl-5-cyclohexen-l-yl)-5- pentyl-l,3-benzenediol); A4-cannabidiol (2-(6-isopropenyl-3-methyl-4-cyclohexen-l-yl)-5-pentyl-

1.3-benzenediol); A3-cannabidiol (2-(6-isopropenyl-3-methyl-3-cyclohexen-l-yl)-5-pentyl-l,3- benzenediol); A3,7-cannabidiol (2-(6-isopropenyl-3-methylenecyclohex-l-yl)-5-pentyl-l,3- benzenediol); A2-cannabidiol (2-(6-isopropenyl-3-methyl-2-cyclohexen-l-yl)-5-pentyl-l,3- benzenediol); D1 -cannabidiol (2-(6-isopropenyl-3-methyl-l-cyclohexen-l-yl)-5-pentyl-l,3- benzenediol); and (7) A6-cannabidiol (2-(6-isopropenyl-3-methyl-6-cyclohexen-l-yl)-5-pentyl-

1.3-benzenediol).

10. The composition of claim 9, wherein the CBD is A2-cannabidiol.

11. The composition according to any one of claims 1 to 10, wherein the cannabinoid is a mixture of THC and CBD.

12. The composition of any one of claims 1 to 11 , wherein the cannabinoid is present in an amount of from about 0.001 mg/ml_ to about 100 mg/ml_, preferably from about 0.1 mg/ml_ to about 50 mg/ml_.

13. The composition of any one of claims 1 to 12, wherein the cannabinoid is an isolated cannabinoid having a purity of 50%-75%, or > 80%, or > 95%.

14. The composition of any one of claims 1 to 13, further comprising a flavour agent and/or a flavour enhancer.

15. The composition of claim 14, wherein the flavour agent includes a terpene.

16. The composition of claim 14, wherein the flavour enhancer is an extract from a natural source or an artificial flavour enhancer.

17. The composition of claim 16, wherein the flavour enhancer is selected from the group consisting of cinnamon, cucumber, mint, orange, lime, citrus, cookie dough, chocolate, vanilla, jasmine, lychee, almond, banana, grape, pear, pineapple, pine, oak, apple, pumpkin, grapefruit, watermelon, cotton sugar, durian, longan, taro, sapote, toffee nut, caramel, lotus, mango, mangosteen, coconut, coffee, strawberry, passion fruit, blueberry, raspberry, kiwi, walnut, cocoa, cherimoya, custard apple, papaya, fig, plum, nectarine, peaches, guava, honeydew, jackfruit, kumquat, loquat, palm, pomelo, persimmon, quince, cassia, sage, marjoram, lemon, orange, and tamarind flavour, or any combinations thereof.

18. The composition of any one of claims 14 to 17, wherein the flavour agent and/or flavour enhancer is present in an amount of < 12 wt.%, or < 10 wt.%, or < 8 wt.%, or < 5 wt.%.

19. The composition of any one of claims 1 to 18, wherein the cannabinoid component further comprises a carrier oil.

20. The composition of claim 19, wherein the carrier oil is selected from borage oil, coconut oil, cottonseed oil, soybean oil, safflower oil, sunflower oil, castor oil, corn oil, olive oil, palm oil, peanut oil, almond oil, sesame oil, rapeseed oil, peppermint oil, poppy seed oil, canola oil, palm kernel oil, hydrogenated soybean oil, hydrogenated vegetable oils, glycerin / glycerol, glyceryl esters of saturated fatty acids, glyceryl behenate, glyceryl distearate, glyceryl isostearate, glyceryl laurate, glyceryl monooleate, glyceryl, monolinoleate, glyceryl palmitate, glyceryl palmitostearate, glyceryl ricinoleate, glyceryl stearate, polyglyceryl 10-oleate, polyglyceryl 3- oleate, polyglyceryl 4-oleate, polyglyceryl 10-tetralinoleate, behenic acid, medium-chain triglycerides (MCT), long chain triglycerides (LCT), and any combination thereof.

21. The composition of claim 20, wherein the carrier oil is MCT oil.

22. The composition according to any one of claims 19 to 21 , wherein the composition is an oil-based composition and the carrier oil is present in an amount of about 50 wt.% or more, preferably from about 50 wt.% to about 90 wt.%.

23. The composition of any one of claims 1 to 18, wherein the composition is a water-based composition in the form of an emulsion and the composition further comprises an emulsifier and water.

24. The composition of claim 23, wherein the emulsifier includes a polysorbate-type nonionic surfactant.

25. The composition of claim 23, wherein the emulsifier is selected from polyoxyethylene monostearate (PEG 400 Monostearate), polyoxyethylene monooleate (PEG 400 Monoleate), polyoxyethylene sorbitan monolaurate (Tween^® 20), polyoxyethylene sorbitan monolaurate (Tween^® 21), polyoxyethylene sorbitan monopalmitate (Tween^® 40), polyoxyethylene sorbitan monostearate (Tween^® 60), polyoxyethylene sorbitan monostearate (Tween^® 61), polyoxyethylene sorbitan tristearate (Tween^® 65), polyoxyethylene sorbitan monooleate (Tween^® 80), polyoxyethylene sorbitan monooleate (Tween 81), polyoxyethylene sorbitan trioleate (Tween^® 85), polyoxyethylene-(15)-stearic acid (Pegosperse 1500MS), polyoxyethylene-(20)-stearyl alcohol (Brij 78), polyoxyethylene-(23)-lauryl alcohol (Brij 35), (Lutensol ON 60), PEG-40 hydrogenated castor oil (Cremophor/Kolliphor RH 40), PEG-35 castor oil (Cremophor EL), Solutol HS-15, and any combinations thereof.

26. The composition of any one of claims 23 to 25, wherein the cannabinoid component further comprises a carrier oil.

27. The composition of claim 26, wherein the carrier oil is selected from borage oil, coconut oil, cottonseed oil, soybean oil, safflower oil, sunflower oil, castor oil, corn oil, olive oil, palm oil, peanut oil, almond oil, sesame oil, rapeseed oil, peppermint oil, poppy seed oil, canola oil, palm kernel oil, hydrogenated soybean oil, hydrogenated vegetable oils, glycerin / glycerol, glyceryl esters of saturated fatty acids, glyceryl behenate, glyceryl distearate, glyceryl isostearate, glyceryl laurate, glyceryl monooleate, glyceryl, monolinoleate, glyceryl palmitate, glyceryl palmitostearate, glyceryl ricinoleate, glyceryl stearate, polyglyceryl 10-oleate, polyglyceryl 3- oleate, polyglyceryl 4-oleate, polyglyceryl 10-tetralinoleate, behenic acid, medium-chain triglycerides (MCT), long chain triglycerides (LCT), and any combination thereof.

28. The composition of claim 27, wherein the carrier oil is MCT oil.

29. The composition of any one of claims 26 to 28, wherein the carrier oil is present in the composition in an amount of from about 5 wt.% to about 20 wt.%.

30. The composition of claim 23 to 29, wherein the emulsion has a D₉₀ of about 200 nm or less, preferably of about 150 nm or less, more preferably of about 120 nm or less.

31. The composition of claim 23 to 29, wherein the emulsion has a particle size distribution of from about 20 nm to about 120 nm, preferably from about 30 nm to about 80 nm, more preferably from about 40 nm to about 60 nm.

32. A cannabis product for administration to a mucosal surface of a subject, the product comprising a container enclosing the composition of any one of claims 1 to 31 , and an outlet nozzle for administration of the composition to the mucosal surface of the subject.

33. The product of claim 32, comprising a pump-action delivery system for delivery of the composition to the mucosal surface of the subject.

34. The product of claim 32, being for administration of the composition to the mucosal surface of the subject by spraying, dropping or pipetting.

35. The product of any one of claims 32 to 34, being for administration of the composition to the buccal cavity of the subject.

36. A method for reducing cannabinoid-associated effect variability between users, comprising providing the composition of any one of claims 1 to 31, for administration of the composition to a user mucosal surface.

37. The method of claim 36, further comprising enclosing the composition in a cannabis article configured for administration of the composition to the user mucosal surface.

38. The method of claim 36 or 37, wherein the method further comprises administration of the composition to the user mucosal surface.

39. The method of claim 38, wherein the composition is administered by pipetting or dropping, or a spray or mist administration device.

40. The method of claim 38 or 39, wherein the composition is administered via nasal, oral, vaginal, ocular, or rectal administration route, or any combination thereof.

41. The method of any one of claims 36 to 40, wherein reducing the cannabinoid- associated effect variability between users includes reducing variability of onset time and/or cannabinoid-effect intensity.