Synthetic cannabinoids for use in therapy and for enhancement of wellbeing

Abstract

The present disclosure relates to a non-therapeutic use of a synthetic cannabinoid metabolite; a synthetic cannabinoid metabolite for use in therapy; a non-therapeutic method of enhancing wellbeing of a subject comprising administering a synthetic cannabinoid metabolite to a subject; a composition comprising a synthetic cannabinoid metabolite; a consumable comprising a synthetic cannabinoid metabolite or composition; and a delivery system comprising the consumable.

Description

SYNTHETIC CANNABINOIDS FOR USE IN THERAPY AND FOR ENHANCEMENT OF WELLBEINGFIELD OF INVENTION

[0001] The present disclosure relates to a non-therapeutic use of a synthetic cannabinoid metabolite; a synthetic cannabinoid metabolite for use in therapy; a non-therapeutic method of enhancing wellbeing of a subject comprising administering a synthetic cannabinoid metabolite to a subject; a composition comprising a synthetic cannabinoid metabolite; a consumable comprising a synthetic cannabinoid metabolite or composition; and a delivery system comprising the consumable.BACKGROUND OF THE INVENTION

[0002] Cannabinoids have been shown to have a variety of therapeutic effects. For example, cannabidiol (CBD) has been implemented in the treatment of the symptoms of epilepsy, multiple sclerosis (MS) arthritis, migraine, bacterial infection, anxiolytic, inflammation; cannabichromene (CBC) has been implemented in the treatment of symptoms of pain, inflammation, neuroprotection, cancer, bacterial infection; and cannabidvarin (CBDV) has been implemented in the treatment of symptoms of seizures, autism, muscular dystrophy.

[0003] Cannabinoids are also used recreationally. There has been a recent surge in commercial consumer products containing cannabinoids including products such as concentrated plant extracts, oral supplements, foods, candies, beverages, topicals, vapes and eliquids. Cannabis comprises a multitude of different cannabinoids, each of which have different effects on the brain and body. Tetrahydrocannabinol (THC) and CBD are the main cannabinoids present in cannabis, of which THC is primarily responsible for the ‘high’ associated with recreational cannabis usage.

[0004] It would be desirable to provide consumers with new uses of cannabinoids and products comprising cannabinoids or related compounds.SUMMARY OF THE INVENTION

[0005] In accordance with some embodiments described herein, there is provided a non- therapeutic use of a synthetic cannabinoid metabolite for the enhancement of wellbeing of a subject.

[0006] In accordance with some embodiments described herein, there is provided a synthetic cannabinoid metabolite for use in therapy.

[0007] In an embodiment, said synthetic cannabinoid metabolite is used in combination with one or more cannabinoids and / or one or more additional cannabinoid metabolites.

[0008] In accordance with some embodiments described herein, there is provided a non- therapeutic method of enhancing the wellbeing of a subject, wherein said method comprises administering a synthetic cannabinoid metabolite as described herein, or a combination of synthetic cannabinoid metabolite(s) and cannabinoids as disclosed herein to the subject.

[0009] In accordance with some embodiments described herein, there is provided a composition comprising a synthetic cannabinoid metabolite.

[0010] In an embodiment, the composition further comprises one or more cannabinoids and / or one or more additional cannabinoid metabolites.

[0011] In accordance with some embodiments described herein, there is provided a consumable comprising a synthetic cannabinoid metabolite as disclosed herein, or a combination of synthetic cannabinoid metabolite(s) and cannabinoids as disclosed herein, or a composition as disclosed herein.

[0012] In accordance with some embodiments described herein, there is provided a delivery system comprising the consumable as disclosed herein.BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Embodiments of the invention will now be described, by way of example only, with reference to accompanying drawings, in which:

[0014] Figure 1 : shows 5-OH-CBC and CBC activation of Cannabinoid type 2 receptor (CB2R). Briefly, the calcium response of Chinese hamster ovary cells (CHO) expressing CB2R (CHO- CB2R cells) treated with 1uM, 5uM and 10uM CBC (data points shown by diamonds) or its metabolite 5-OH-CBC (data points shown by triangles). 5-OH-CBC shows a greater concentration-dependent maximal response compared to CBC. This experiment was performed in triplicate and compound concentration is expressed on a logarithmic scale. Each data point represents the mean + / - sem.DEFINITIONS

[0015] This disclosure is not limited by the exemplary methods and materials disclosed herein, and any methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of this disclosure.

[0016] The headings provided herein are not limitations of the various aspects or embodiments of this disclosure which can be had by reference to the specification as a whole. Accordingly, the terms defined immediately below are more fully defined by reference to the specification as a whole.

[0017] As used herein, “cannabinoid metabolite” refers to derivatives of native cannabinoids. The metabolite may be a primary metabolite or a secondary metabolite of the native form of the cannabinoid from which it is derived.

[0018] It is intended that the cannabinoid metabolite is a synthetic cannabinoid metabolite. However, the synthetic cannabinoid metabolite may be provided in combination with one or more cannabinoids in their native form and one or more additional cannabinoid metabolites. The additional cannabinoid metabolites may be naturally derived (i.e. compounds naturally produced during metabolism of a native cannabinoid in a subject), or may also be synthetic cannabinoid metabolites.

[0019] As used herein, “synthetic” refers to ‘man-made’ compounds, e.g. those synthesised by in vitro methods. However, “synthetic” compounds may also include “biosynthetic” compounds, for example compounds that are produced in a living organism, or a laboratory process modelled after the synthesis pathway in a living organism. “Biosynthetic” compounds may include those compounds that are produced by or in, for example, a plant, bacteria, fungi, etc., e.g. following genetic engineering to insert the relevant gene(s) to result in the expression of the desired synthetic compound. The synthetic compound is not endogenously produced in a human or animal.

[0020] As used herein “native” or “native form” refers to compounds produced in nature. For example, in the context of this disclosure, the native form of cannabinoids are those cannabinoids found in cannabis plants and other plant species. Other “native forms” of cannabinoids are endogenous cannabinoids, also known as endocannabinoids which are produced endogenously by a subject.

[0021] As used herein, “subject” refers to the recipient of the synthetic cannabinoid metabolite. The “subject” may be human or animal. In some embodiments, the subject is human. In some embodiments, the subject is an animal. Where the subject is an animal, the animal may be mammalian, avian, reptilian, amphibian, invertebrate or aquatic (fish). Where the animal is a mammalian animal, the mammalian animal may be a monotreme (such as a platypus or echidna), marsupial (such as a kangaroo, wallaby, wambat, etc ), or a placental mammal (such as a primate - monkeys, apes; canine - dogs, wolves, foxes, etc; feline - domestic cats, lions, tigers, etc,)

[0022] As used herein, “wellbeing” refers to the state of being comfortable, healthy, or happy. “Wellbeing” may also be referred to as “wellness” and used interchangeably. Thus, “enhancement of wellbeing” refers to the enhancement / improvement or perceived enhancement / improvement of a subject’s health, happiness or feeling of comfort. The feeling of the “enhancement of wellbeing” is unique to each subject. Thus, a subject is considered to have achieved an “enhancement of wellbeing” if they feel that some aspect of their health or mental state has improved following use of the synthetic cannabinoid metabolite.

[0023] As used herein, “analog” refers to a structural analog, e.g. a compound that has a structure that is related to another compound, but differing from it in respect to a certain component, such as one or more atoms, functional groups or substructures.

[0024] A “homolog” is a type of analog, wherein the homolog is a chemical compound from a series of compounds that differ only in the number of repeated structural units.

[0025] As used herein, the terms "flavour" and "flavourant" refer to materials which, where local regulations permit, may be used to create a desired taste, aroma or other somatosensorial sensation in a product for adult consumers. They may include naturally occurring flavour materials, botanicals, extracts of botanicals, synthetically obtained materials, or combinationsthereof (e.g., tobacco, cannabis, licorice (liquorice), hydrangea, eugenol, Japanese white bark magnolia leaf, chamomile, fenugreek, clove, maple, matcha, menthol, Japanese mint, aniseed (anise), cinnamon, turmeric, Indian spices, Asian spices, herb, Wintergreen, cherry, berry, red berry, cranberry, peach, apple, orange, mango, clementine, lemon, lime, tropical fruit, papaya, rhubarb, grape, durian, dragon fruit, cucumber, blueberry, mulberry, citrus fruits, Drambuie, bourbon, scotch, whiskey, gin, tequila, rum, spearmint, peppermint, lavender, aloe vera, cardamom, celery, cascarilla, nutmeg, sandalwood, bergamot, geranium, khat, naswar, betel, shisha, pine, honey essence, rose oil, vanilla, lemon oil, orange oil, orange blossom, cherry blossom, cassia, caraway, cognac, jasmine, ylang-ylang, sage, fennel, wasabi, piment, ginger, coriander, coffee, hemp, a mint oil from any species of the genus Mentha, eucalyptus, star anise, cocoa, lemongrass, rooibos, flax, ginkgo biloba, hazel, hibiscus, laurel, mate, orange skin, rose, tea such as green tea or black tea, thyme, juniper, elderflower, basil, bay leaves, cumin, oregano, paprika, rosemary, saffron, lemon peel, mint, beefsteak plant, curcuma, cilantro, myrtle, cassis, valerian, pimento, mace, damien, marjoram, olive, lemon balm, lemon basil, chive, carvi, verbena, tarragon, limonene, thymol, camphene), flavour enhancers, bitterness receptor site blockers, sensorial receptor site activators or stimulators, sugars and / or sugar substitutes (e.g., sucralose, acesulfame potassium, aspartame, saccharine, cyclamates, lactose, sucrose, glucose, fructose, sorbitol, or mannitol), and other additives such as charcoal, chlorophyll, minerals, botanicals, or breath freshening agents. They may be imitation, synthetic or natural ingredients or blends thereof. They may be in any suitable form, for example, liquid such as an oil, solid such as a powder, or gas.

[0026] Other definitions of terms may appear throughout the specification. Before the exemplary aspects and embodiments are described in more detail, it is important to understand that this disclosure is not limited to particular aspects or embodiments described, which as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects or embodiments only, and is not intended to be limiting, since the scope of the present disclosure will be limited only by the appended claims.

[0027] It must be noted that as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a cannabinoid” or “a cannabinoid metabolite” includes a plurality of such candidate agents and equivalents thereof known to those skilled in the art, and so forth.DETAILED DESCRIPTION OF THE INVETION

[0028] In one aspect, there is provided a non-therapeutic use of a synthetic cannabinoid metabolite for the enhancement of wellbeing of a subject.

[0029] In one aspect, there is provided a synthetic cannabinoid metabolite for use in therapy.

[0030] In an embodiment, said synthetic cannabinoid metabolite is a metabolite of one of the following cannabinoids: cannabichromene (CBC), cannabidiol (CBD), Cannabidvarin (CBDV), cannabigerol (CBG), tetrahydrocannabinol (THC), or analogs or homologs thereof,

[0031] In a further embodiment, the synthetic cannabinoid metabolite is a metabolite of CBC, or homolog or analog thereof.

[0032] In yet a further embodiment, the synthetic cannabinoid metabolite is a metabolite ofCBC.

[0033] In a further embodiment, the synthetic cannabinoid metabolite is a metabolite of CBD, or homolog or analog thereof.

[0034] In yet a further embodiment, the synthetic cannabinoid metabolite is a metabolite ofCBD.

[0035] In a further embodiment, the synthetic cannabinoid metabolite is a metabolite of CBDV, or homolog or analog thereof.

[0036] In yet a further embodiment, the synthetic cannabinoid metabolite is a metabolite of CBDV.

[0037] In a further embodiment, the synthetic cannabinoid metabolite is a metabolite of CBG, or homolog or analog thereof.

[0038] In yet a further embodiment, the synthetic cannabinoid metabolite is a metabolite of CBG.

[0039] In a further embodiment, the synthetic cannabinoid metabolite is a metabolite of THC, or homolog or analog thereof.

[0040] In yet a further embodiment, the synthetic cannabinoid metabolite is a metabolite of THC, delta-8-THC, or delta-9-THC.

[0041] In an embodiment, said synthetic cannabinoid metabolite is selected from the group comprising: 5-OH-CBC; 7-OH-CBD; and 7-OH-CBDV.

[0042] In an embodiment, the synthetic cannabinoid metabolite is 5-OH-CBC.

[0043] In an embodiment, the synthetic cannabinoid metabolite is 7-OH-CBD.

[0044] In an embodiment, the synthetic cannabinoid metabolite is 7-OH-CBDV.

[0045] In an embodiment, said synthetic cannabinoid metabolite is used in combination with one or more cannabinoids and / or one or more additional cannabinoid metabolites.

[0046] In a further embodiment, said cannabinoid or additional cannabinoid metabolite is selected from the group comprising: CBD, CBC, CBDV, CBG, THC, and any analog, homolog, or metabolite thereof; and wherein said additional cannabinoid metabolite is different to the first synthetic cannabinoid metabolite. Suitably, at least one of the additional cannabinoid metabolites may be different to the first synthetic cannabinoid metabolite.

[0047] In an embodiment, the additional cannabinoid metabolite is a synthetic cannabinoid metabolite, wherein said additional synthetic cannabinoid metabolite is different to the first synthetic cannabinoid metabolite.

[0048] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is CBD, or any analog, homolog, or metabolite thereof.

[0049] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is CBD.

[0050] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is CBC, or any analog, homolog, or metabolite thereof.

[0051] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is CBC.

[0052] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is CBDV, or any analog, homolog, or metabolite thereof.

[0053] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is CBDV.

[0054] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is CBG, or any analog, homolog, or metabolite thereof.

[0055] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is CBG.

[0056] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is THC, or any analog, homolog, or metabolite thereof.

[0057] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is THC.

[0058] In a further embodiment, said additional cannabinoid metabolite is selected from the group comprising: 7-OH-CBD; 7-OH-CBDV; and 5-OH-CBC; and wherein said additional cannabinoid metabolite is different to the first synthetic cannabinoid metabolite.

[0059] In yet a further embodiment, said additional cannabinoid metabolite is 7-OH-CBD.

[0060] In yet a further embodiment, said additional cannabinoid metabolite is 7-OH-CBDV.

[0061] In yet a further embodiment, said additional cannabinoid metabolite is 5-OH-CBC.

[0062] Consumption of the synthetic cannabinoid metabolite either alone or in combination with one or more cannabinoids and / or one or more additional cannabinoid metabolites may have greater potency than the native form of the cannabinoid alone, thus a lower concentration of the synthetic cannabinoid metabolite may be used to achieve the same effect as the native form of the cannabinoid. The synthetic cannabinoid metabolite may have a faster action than the native form of the cannabinoid because there is no need for the synthetic cannabinoid metabolite to be metabolised after consumption to produce the desired effect.Non-therapeutic use

[0063] As disclosed herein, there is provided a non-therapeutic use of a synthetic cannabinoid metabolite for the enhancement of wellbeing of a subject.

[0064] In an embodiment, the enhancement of wellbeing comprises at least one of the group comprising: improved sleep quality; feeling refreshed; and feeling less tired.

[0065] In a further embodiment, the enhancement of wellbeing comprises improved sleep quality or feeling less tired.

[0066] In a further embodiment, the enhancement of wellbeing comprises improved sleep quality.

[0067] In a further embodiment, the enhancement of wellbeing comprises feeling refreshed.

[0068] In a further embodiment, the enhancement of wellbeing comprises feeling less tired.Therapeutic use

[0069] As disclosed herein, there is provided a synthetic cannabinoid metabolite for use in therapy.

[0070] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of one or more of epilepsy, multiple sclerosis, arthritis, migraine, bacterial infection, stress, anxiety, depression, inflammation, pain, neuroprotection, cancer, seizures, autism, muscular dystrophy, irritable bowel syndrome, blood pressure, diabetes, itching, insomnia, attention disorders, Parkinson’s disease, schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, Alzheimer’s disease, frontotemporal dementia, and Crohn’s disease.

[0071] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of pain, anxiety, depression, inflammation or irritable bowel syndrome.In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of one or more of epilepsy, MS, arthritis, migraine, bacterial infection, anxiety, and inflammation.

[0072] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of one or more of pain, inflammation, neuroprotection, cancer, and bacterial infection.

[0073] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of one or more of seizures, autism, and muscular dystrophy.

[0074] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of one or more of Parkinson’s disease, neuroprotection, pain, depression, bipolar disorder, major depressive disorder, post-traumatic stress disorder, Alzheimer’s disease, frontotemporal dementia and diabetes.

[0075] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of one or more of depression, bipolar disorder, major depressive disorder, post-traumatic stress disorder, anxiety, pain, and insomnia.

[0076] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of one or more of insomnia, stress, post-traumatic stress disorder, anxiety, attention disorders, and depression.

[0077] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of one or more of insomnia, Crohn’s disease, irritable bowel syndrome and pain.

[0078] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of one or more of inflammation, irritable bowel syndrome, and Crohn’s disease.

[0079] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of diabetes and / or blood pressure.

[0080] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of inflammation and / or irritable bowel syndrome.

[0081] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of pain and / or itching.

[0082] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of diabetes.

[0083] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of pain.

[0084] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of epilepsy.

[0085] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of multiple sclerosis.

[0086] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of arthritis.

[0087] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of migraine.

[0088] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of bacterial infection.

[0089] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of stress.

[0090] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of anxiety.

[0091] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of depression.

[0092] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of inflammation.

[0093] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of neuroprotection.

[0094] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of cancer.

[0095] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of seizures.

[0096] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of autism.

[0097] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of muscular dystrophy.

[0098] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of irritable bowel syndrome.

[0099] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of blood pressure.

[0100] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of itching.

[0101] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of insomnia.

[0102] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of attention disorders.

[0103] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of Parkinson’s disease.

[0104] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of schizophrenia.

[0105] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of bipolar disorder.

[0106] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of major depressive disorder.

[0107] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of post-traumatic stress disorder.

[0108] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of Alzheimer’s disease.

[0109] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of, frontotemporal dementia.

[0110] In an embodiment, the synthetic cannabinoid metabolite is for use in the treatment of Crohn’s disease.

[0111] The skilled person will understand that treatment of the conditions disclosed herein by the synthetic cannabinoid metabolite as disclosed herein, may comprise managing and / or alleviating the symptoms of the condition and / or curing the condition. The provision of thesynthetic cannabinoid metabolite for use in the treatment of any of the conditions disclosed herein may be in conjunction with other therapies required for the treatment of said condition. The synthetic cannabinoid metabolite may have a complementary effect on the other therapies used to treat any of the conditions disclosed herein. The synthetic cannabinoid metabolite may be used to alleviate symptoms caused by other therapies used in the treatment of any of the conditions disclosed herein.Method

[0112] In one aspect, there is provided a non-therapeutic method of enhancing the wellbeing of a subject, wherein said method comprises administering a synthetic cannabinoid metabolite as disclosed herein, or a combination of synthetic cannabinoid metabolite(s) and cannabinoids as disclosed herein to the subject.

[0113] In one embodiment, the non-therapeutic method of enhancing wellbeing of a subject comprises administering a synthetic cannabinoid metabolite as disclosed herein to the subject.

[0114] In one embodiment, the non-therapeutic method of enhancing wellbeing of a subject comprises administering a combination of synthetic cannabinoid metabolite(s) and cannabinoids as disclosed herein to the subject.Composition

[0115] In one aspect, there is provided a composition comprising a synthetic cannabinoid metabolite.

[0116] In an embodiment, said synthetic cannabinoid metabolite is a metabolite of CBC, or a metabolite of an analog or homolog of CBC.

[0117] In an embodiment, said synthetic cannabinoid metabolite is a metabolite of CBC.

[0118] In a further embodiment, said synthetic cannabinoid metabolite is 5-OH-CBC.

[0119] In an embodiment, said synthetic cannabinoid metabolite is a metabolite of CBD, or a metabolite of an analog or homolog of CBD.

[0120] In an embodiment, said synthetic cannabinoid metabolite is a metabolite of CBD.

[0121] In a further embodiment, said synthetic cannabinoid metabolite is 7-OH-CBD.

[0122] In an embodiment, said synthetic cannabinoid metabolite is a metabolite of CBDV, or a metabolite of an analog or homolog of CBDV.

[0123] In an embodiment, said synthetic cannabinoid metabolite is a metabolite of CBDV.

[0124] In a further embodiment, said synthetic cannabinoid metabolite is 7-OH-CBDV.

[0125] In an embodiment, said synthetic cannabinoid metabolite is a metabolite of CBG, or a metabolite of an analog or homolog of CBG.

[0126] In an embodiment, said synthetic cannabinoid metabolite is a metabolite of CBG.

[0127] In an embodiment, said synthetic cannabinoid metabolite is a metabolite of THC, or a metabolite of an analog or homolog of THC.

[0128] In an embodiment, said synthetic cannabinoid metabolite is a metabolite of THC.

[0129] In an embodiment, the composition further comprises one or more cannabinoids and / or one or more additional cannabinoid metabolites.

[0130] In a further embodiment, said cannabinoid or additional cannabinoid metabolite is selected from the group comprising: CBD, CBC, CBDV, CBG, THC, and any analog, homolog, or metabolite thereof; and wherein said additional cannabinoid metabolite is different to the first synthetic cannabinoid metabolite.

[0131] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is CBD, or any analog, homolog, or metabolite thereof.

[0132] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is CBD.

[0133] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is CBC, or any analog, homolog, or metabolite thereof.

[0134] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is CBC.

[0135] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is CBDV, or any analog, homolog, or metabolite thereof.

[0136] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is CBDV.

[0137] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is CBG, or any analog, homolog, or metabolite thereof.

[0138] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is CBG.

[0139] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is THC, or any analog, homolog, or metabolite thereof.

[0140] In yet a further embodiment, said cannabinoid or additional cannabinoid metabolite is THC.

[0141] In a further embodiment, said additional cannabinoid metabolite is selected from the group comprising: 7-OH-CBD; 7-OH-CBDV; and 5-OH-CBC; and wherein said additional cannabinoid metabolite is different to the first synthetic cannabinoid metabolite.

[0142] In yet a further embodiment, said additional cannabinoid metabolite is 7-OH-CBD.

[0143] In yet a further embodiment, said additional cannabinoid metabolite is 7-OH-CBDV.

[0144] In yet a further embodiment, said additional cannabinoid metabolite is 5-OH-CBC.

[0145] In a further embodiment of the composition: i) said one or more cannabinoids is selected from the group consisting of: CBD, CBC, CBDV CBG, THC, and any analog or homolog thereof; and / or ii) said one or more additional cannabinoid metabolites is selected form the group consisting of: 7-OH-CBD, 7-OH-CBDV and 5-OH-CBC.

[0146] In a further embodiment of the composition: i) said one or more cannabinoids is selected from the group consisting of: CBD, CBC, CBDV CBG, and THC; and / or ii) said one or more additional cannabinoid metabolites is selected form the group consisting of: 7-OH-CBD, 7-OH-CBDV and 5-OH-CBC.

[0147] In an embodiment, the composition additionally comprises one or more flavours.

[0148] In an embodiment, the flavour comprises menthol, spearmint and / or peppermint.

[0149] In an embodiment, the flavour comprises flavour components of cucumber, blueberry, citrus fruits and / or redberry.

[0150] In an embodiment, the flavour comprises eugenol.

[0151] In an embodiment, the flavour comprises flavour components extracted from tobacco.

[0152] In an embodiment, the flavour comprises flavour components extracted from cannabis.

[0153] In an embodiment, the flavour may comprise a sensate, which is intended to achieve a somatosensorial sensation which are usually chemically induced and perceived by the stimulation of the fifth cranial nerve (trigeminal nerve), in addition to or in place of aroma or taste nerves, and these may include agents providing heating, cooling, tingling, numbing effect. A suitable heat effect agent may be, but is not limited to, vanillyl ethyl ether and a suitable cooling agent may be, but not alimited to eucolyptol, WS-3.

[0154] In a further embodiment, the one or more flavours comprises an aroma.

[0155] In an embodiment, the composition comprises: i) a synthetic metabolite of CBC; ii) one or more cannabinoids and / or one or more additional cannabinoid metabolites as disclosed herein; and optionally iii) one or more flavours as disclosed herein.

[0156] In a further embodiment, the synthetic metabolite of CBC is 5-OH-CBC.

[0157] In an embodiment, the composition comprises: i) a synthetic metabolite of CBD; ii) one or more cannabinoids and / or one or more additional cannabinoid metabolites as disclosed herein; and optionally iii) one or more flavours as disclosed herein.

[0158] In a further embodiment, the synthetic metabolite of CBD is 7-OH-CBD.

[0159] In an embodiment, the composition comprises: i) a synthetic metabolite of CBDV; ii) one or more cannabinoids and / or one or more additional cannabinoid metabolites as disclosed herein; and optionally iii) one or more flavours as disclosed herein.

[0160] In a further embodiment, the synthetic metabolite of CBDV is 7-OH-CBDV.

[0161] In an embodiment, the composition is used for the non-therapeutic enhancement of wellbeing of a subject.

[0162] In an embodiment, the composition is for use in therapy.

[0163] The skilled person will understand that the non-therapeutic and therapeutic uses of the composition may be any of those as disclosed herein for the synthetic cannabinoid metabolite and / or the combination of synthetic cannabinoid metabolite(s) and cannabinoids as disclosed herein.Consumable

[0164] In one aspect, there is provided a consumable comprising a synthetic cannabinoid metabolite as disclosed herein, or a combination of synthetic cannabinoid metabolite(s) and cannabinoids as disclosed herein, or a composition as disclosed herein.

[0165] A consumable is an article comprising or consisting of aerosol-generating material, part or all of which is intended to be consumed during use by a user. A consumable may comprise one or more other components, such as an aerosol-generating material storage area, an aerosol-generating material transfer component, an aerosol generation area, a housing, a wrapper, a mouthpiece, a filter and / or an aerosol-modifying agent. A consumable may also comprise an aerosol generator, such as a heater, that emits heat to cause the aerosolgenerating material to generate aerosol in use. The heater may, for example, comprise combustible material, a material heatable by electrical conduction, or a susceptor.

[0166] A consumable may also be an article that does not comprise an aerosol-generating material. Instead, the consumable comprises an article, part or all of which is intended to be consumed during use by a user, such as gums, patches, or inhalable powders.Delivery system

[0167] In one aspect, there is provided a delivery system comprising the consumable as disclosed herein.

[0168] As used herein, the term “delivery system” is intended to encompass systems that deliver at least one substance to a user, and includes:

[0169] combustible aerosol provision systems, such as cigarettes, cigarillos, cigars, and tobacco for pipes or for roll-your-own or for make-your-own cigarettes (whether based on tobacco, tobacco derivatives, expanded tobacco, reconstituted tobacco, tobacco substitutes or other smokable material);

[0170] non-combustible aerosol provision systems that release compounds from an aerosol-generating material without combusting the aerosol-generating material, such as electronic cigarettes, tobacco heating products, and hybrid systems to generate aerosol using a combination of aerosol-generating materials; and

[0171] aerosol-free delivery systems that deliver the at least one substance to a user orally, nasally, transdermally or in another way without forming an aerosol, including but not limited to, lozenges, gums, patches, articles comprising inhalable powders, and oral products such as oral tobacco which includes snus or moist snuff, wherein the at least one substance may or may not comprise nicotine.

[0172] In an embodiment, the delivery system is a combustible aerosol provision system, a non-combustible aerosol provision system, or an aerosol-free delivery system.

[0173] According to the present disclosure, a “combustible” aerosol provision system is one where a constituent aerosol-generating material of the aerosol provision system (or component thereof) is combusted or burned during use in order to facilitate delivery of at least one substance to a user.

[0174] In an embodiment, the delivery system is a combustible aerosol provision system, such as a system selected from the group consisting of a cigarette, a cigarillo and a cigar.

[0175] According to the present disclosure, a “non-combustible” aerosol provision system is one where a constituent aerosol-generating material of the aerosol provision system (or component thereof) is not combusted or burned in order to facilitate delivery of at least one substance to a user.

[0176] In an embodiment, the delivery system is a non-combustible aerosol provision system, such as a powered non-combustible aerosol provision system.

[0177] In an embodiment, the non-combustible aerosol provision system is an electronic cigarette, also known as a vaping device or electronic nicotine delivery system (END), although it is noted that the presence of nicotine in the aerosol-generating material is not a requirement.

[0178] In an embodiment, the non-combustible aerosol provision system is an aerosolgenerating material heating system, also known as a heat-not-burn system. An example of such a system is a tobacco heating system.

[0179] In an embodiment, the non-combustible aerosol provision system is a hybrid system to generate aerosol using a combination of aerosol-generating materials, one or a plurality of which may be heated. Each of the aerosol-generating materials may be, for example, in the form of a solid, liquid or gel and may or may not contain nicotine. In some embodiments, the hybrid system comprises a liquid or gel aerosol-generating material and a solid aerosolgenerating material. The solid aerosol-generating material may comprise, for example, tobacco or a non-tobacco product.

[0180] Typically, the non-combustible aerosol provision system may comprise a non- combustible aerosol provision device and a consumable for use with the non-combustible aerosol provision device.

[0181] In an embodiment, the consumable for use with the non-combustible aerosol provision device is a consumable as disclosed herein.

[0182] In an embodiment, the disclosure relates to consumables comprising aerosol-generating material and the composition as disclosed herein, configured to be used with non-combustible aerosol provision devices. These consumables are sometimes referred to as articles throughout the disclosure.

[0183] In an embodiment, the non-combustible aerosol provision system, such as a noncombustible aerosol provision device thereof, may comprise a power source and a controller. The power source may, for example, be an electric power source or an exothermic power source. In some embodiments, the exothermic power source comprises a carbon substrate which may be energised so as to distribute power in the form of heat to an aerosol-generating material or to a heat transfer material in proximity to the exothermic power source.

[0184] In an embodiment, the non-combustible aerosol provision system may comprise an area for receiving the consumable, an aerosol generator, an aerosol generation area, a housing, a mouthpiece, a filter and / or an aerosol-modifying agent.

[0185] In an embodiment, the consumable for use with the non-combustible aerosol provision device may comprise aerosol-generating material and the composition as disclosed herein, an aerosol-generating material storage area, an aerosol-generating material transfer component, an aerosol generator, an aerosol generation area, a housing, a wrapper, a filter, a mouthpiece, and / or an aerosol-modifying agent.

[0186] In an embodiment, the delivery system is an aerosol-free delivery system that delivers at least one substance to a user orally, nasally, transdermally or in another way without forming an aerosol, including but not limited to, lozenges, gums, patches, articles comprising inhalable powders, and oral products such as oral tobacco which includes snus or moist snuff, wherein the at least one substance may or may not comprise nicotine.

[0187] In a further embodiment, the aerosol-free delivery system is an edible, a lozenge, a gum, a patch, an inhalable powder, a beverage, a shot, an oil, a supplement or an oral product.

[0188] The various aspects and / or embodiments described herein are presented only to assist in understanding and teaching the claimed features. These aspects and / or embodiments are provided as a representative sample of aspects and / or embodiments only, and are not exhaustive and / or exclusive. It is to be understood that advantages, embodiments, examples, functions, features, structures, and / or other aspects described herein are not to be considered limitations on the scope of the invention as defined by the claims or limitations on equivalents to the claims, and that other embodiments may be utilised and modifications may be made without departing from the scope of the claimed invention. Various embodiments of the invention may suitably comprise, consist of, or consist essentially of, appropriate combinations of the disclosed elements, components, features, parts, steps, means, etc, other than those specifically described herein. In addition, this disclosure may include other inventions not presently claimed, but which may be claimed in future.

[0189] The invention will now be described with reference to the following non-limiting examples.EXAMPLESExample 1 : CBC and 5-OH-CBCMethods

[0190] CBC and 5-OH-CBC synthesis and purification

[0191] CBC was acquired from Sanobiotec and 5-OH-CBC was chemically synthesized at a multi-gram scale using proprietary methods.Assay of Cannabinoid type 2 receptor (CB2R) binding

[0192] Competition binding experiments were performed incubating a maximum concentration of 1000nM of WIN 55,212-2 and 1uM, 5uM, and 10uM of CBC and 5-OH-CBC with membranes extracted by WuXi AppTec. Bound and free radioactivity were separated by filtering the reaction mixture through GF / B plates. The3H trapped on the filter was counted using Perkin Elmer MicroBeta2 Reader. Data was analyzed using Prism 5.Assay of Cannabinoid type 2 receptor (CB2R) function

[0193] Changes in calcium using a proprietary assay kit (Fluo-4 Direct Calcium Assay Kit, #F10471) were measured. CHO cells expressing CB2 receptor were cultured on a 384-well cell plate. Cells were treated with 1uM, 5uM, or 10uM CBC, 5-OH-CBC or 10uM CP55940 in triplicate. The cells were incubated with Fluo-4-Direct calcium reagent solution for 50 minutes at 37°C and 5% (vol / vol) CO2. Fluorescence dye was used to measure the response of calcium flux. Data was analyzed using Prism.ResultsRadioligand-based assays of agonist binding to CB2R

[0194] The effect of CBC and 5-OH-CBC on agonist binding to CB2R was tested using a classical radioligand-binding assay and incubated with [3H]-WIN 55,212-2. Both CBC and 5- OH-CBC demonstrated binding to CB2R.Response of CBC and 5-OH-CBC at CB2R

[0195] CP55940, CB2R agonist, produced an increase in fluorescence in CHO cells with an EC50 of 143.3nM. Both CBC and 5-OH-CBC demonstrated agonistic activity at CB2R (Fig.1). CBC produced an increase in fluorescence with an EC50 greater than 10uM. 5-OH-CBC produced an increase in fluorescence with an EC50 of 1.97uM. The metabolite, 5-OH-CBC, appeared more potent than CBC.

[0196] The dose-response curve (Figure 1) demonstrates the maximum change in fluorescence induced by each compound. Each data point represents the mean + / - s.e.m. of one experiment performed in triplicate.

[0197] The principal finding of the work is that 5-OH-CBC, the primary P450 metabolite, has higher activity on CB2R than CBC.Example 2. Cannabinoid metabolite efficacy

[0198] In silico predictive models will be used to screen the efficacy of other cannabinoid metabolites on cannabinoid receptors. In brief, a library with the 3D structures of cannabinoid metabolites will be obtained by publicly available repositories such as (ZINC, PUBCHEM) whenever available or drawn on chemical software (MOE, Chemdraw). The crystal structure of cannabinoid receptor 1 and 2 will be obtained from a publicly available repository (PDB). This structure will be protonated in the Molecular Operating Environment (MOE) and the active site will be defined around the bound CBD in the crystal structure. The library will be screened to generate 50 docking scores and poses using the Molecular Operating Environment (MOE) (Chemical Computing Group Inc, Montreal, Quebec, Canada) software. The free energy of binding will be calculated from the contributions of the hydrophobic, ionic, hydrogen bond, and van der Waals interactions between the receptor and the ligand. Docking poses will be ranked by the binding free energy calculation in the S field, with the expectation that the cannabinoid metabolites will perform better than native compound, such as shown in Fig.1 for 5-OH-CBC.

Claims

CLAIMS1. Non-therapeutic use of a synthetic cannabinoid metabolite for the enhancement of wellbeing of a subject.

2. A synthetic cannabinoid metabolite for use in therapy.

3. The synthetic cannabinoid metabolite for use of claim 2 for use in the treatment of one or more of pain, anxiety, depression, inflammation or irritable bowel syndrome.

4. The synthetic cannabinoid metabolite according to claim 1 or the synthetic cannabinoid metabolite for use according to claims 2 or claim 3, wherein said synthetic cannabinoid metabolite is a metabolite of one of the following cannabinoids: cannabichromene (CBC), cannabidiol (CBD), Cannabidvarin (CBDV) cannabigerol (CBG), tetrahydrocannabinol (THC), or analogs or homologs thereof.

5. The synthetic cannabinoid metabolite or the synthetic cannabinoid metabolite for use according to claim 4, wherein said synthetic cannabinoid metabolite is a metabolite of CBC.

6. The synthetic cannabinoid metabolite according to any one of claims 1 , 4 and 5 or the synthetic cannabinoid metabolite for use according to any one of claims 2-5, wherein said synthetic cannabinoid metabolite is selected from the group comprising: 5-OH-CBC; 7-OH- CBD; and 7-OH-CBDV.

7. The synthetic cannabinoid metabolite according to any one of claims 1 and 4-6 or the synthetic cannabinoid metabolite for use according to any one of claims 2-6, wherein said synthetic cannabinoid metabolite is 5-OH-CBC.

8. The synthetic cannabinoid metabolite according to any one of claims 1 and 4-7 or the synthetic cannabinoid metabolite for use according to any one of claims 2-7, wherein said synthetic cannabinoid metabolite is used in combination with one or more cannabinoids and / or one or more additional cannabinoid metabolites.

9. The synthetic cannabinoid metabolite or the synthetic cannabinoid metabolite for use according to claim 8, wherein said cannabinoid or additional cannabinoid metabolite is selected from the group comprising: CBD, CBC, CBDV, CBG, THC, and any analog, homolog, or metabolite thereof; and wherein said additional cannabinoid metabolite is different to the first synthetic cannabinoid metabolite.

10. The synthetic cannabinoid metabolite or the synthetic cannabinoid metabolite for use according to claim 8 or claim 9, wherein said additional cannabinoid metabolite is selected from the group comprising: 7-OH-CBD; 7-OH-CBDV; and 5-OH-CBC; and wherein said additional cannabinoid metabolite is different to the first synthetic cannabinoid metabolite.

11. The synthetic cannabinoid metabolite according to any one of claims 1 and 4-10, wherein the enhancement of wellbeing comprises at least one of the group comprising: improved sleep quality; feeling refreshed; and feeling less tired.

12. The synthetic cannabinoid metabolite according to claim 11, wherein the enhancement of wellbeing comprises improved sleep quality or feeling less tired.

13. A non-therapeutic method of enhancing the wellbeing of a subject, wherein said method comprises administering a synthetic cannabinoid metabolite as described in any one of claims 1 and 4-7 or, a combination of synthetic cannabinoid metabolite(s) and cannabinoids as described in any one of claims 8-10 to the subject.

14. A composition comprising a synthetic cannabinoid metabolite.

15. A composition according to claim 14, wherein said synthetic cannabinoid metabolite is a metabolite of CBC.

16. A composition according to claim 14 or claim 15, wherein said synthetic cannabinoid metabolite is 5-OH-CBC.

17. A composition according to any one of claims 14-16, further comprising one or more cannabinoids and / or one or more additional cannabinoid metabolites.

18. A composition according to claim 17, wherein: i) said one or more cannabinoids is selected from the group consisting of: CBD, CBC, CBDV and CBG; and / or ii) said one or more additional cannabinoid metabolites is selected form the group consisting of: 7-OH-CBD, 7-OH-CBDV and 5-OH-CBC.

19. The composition according to any one of claims 14-18, wherein the composition additionally comprises one or more flavours.

20. The composition according to claim 19, wherein one or more flavours comprises an aroma.

21. A consumable comprising a synthetic cannabinoid metabolite as described in any one of claims 1-7, or a combination of synthetic cannabinoid metabolite(s) and cannabinoids as described in any one of claims 8-10, or a composition according to any one of claims 14-20.

22. A delivery system comprising the consumable according to claim 21.

23. The delivery system according to claim 22, wherein the delivery system is a combustible aerosol provision system, a non-combustible aerosol provision system, or an aerosol-free delivery system.

24. A delivery system according to claim 23, wherein the aerosol-free delivery system is an edible, a lozenge, a gum, a patch, an inhalable powder, a beverage, a shot, an oil, a supplement or an oral product.

Images