Tetrahydrocannabivarin (THCV, THV, O-4394, GWP42004) is a homologue of tetrahydrocannabinol (THC) having a propyl (3-carbon) side chain instead of pentyl (5-carbon), making it non-psychoactive in lower doses. It has been shown to exhibit neuroprotective activity, appetite suppression, glycemic control and reduced side effects compared to THC, making it a potential treatment for management of obesity and diabetes.[1] THCV was studied by Roger Adams as early as 1942.[2]
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Routes of administration | Oral, smoked, inhaled |
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Formula | C19H26O2 |
Molar mass | 286.415 g·mol−1 |
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THCV is prevalent in certain central Asian and southern African strains of Cannabis.[3][4]
Similar to THC, THCV has 7 possible double bond isomers and 30 stereoisomers (see: Tetrahydrocannabinol#Isomerism). The alternative isomer Δ8-THCV is known as a synthetic compound with a code number of O-4395,[5] but it is not known to have been isolated from Cannabis plant material.
Plants with elevated levels of propyl cannabinoids (including THCV) have been found in populations of Cannabis sativa L. ssp. indica (= Cannabis indica Lam.) from China, India, Nepal, Thailand, Afghanistan, and Pakistan, as well as southern and western Africa. THCV levels up to 20% of total cannabinoids have been reported.[2]
THCV is a cannabinoid receptor type 1 antagonist or, at higher doses, a CB1 receptor agonist and cannabinoid receptor type 2 partial agonist.[6] Δ8-THCV has also been shown to be a CB1 antagonist.[7] Both papers describing the antagonistic properties of THCV were demonstrated in murine models. THCV is an antagonist of THC at CB1 receptors and lessens the psychoactive effects of THC.[8]
THCV also acts as an agonist of GPR55 and l-α-lysophosphatidylinositol (LPI), and beyond the endocannabinoid system, THCV also activate 5-HT1A receptors to produce an antipsychotic effect, that has shown therapeutic potential for ameliorating some of the negative, cognitive and positive symptoms of schizophrenia. THCV furthermore interacts with different transient receptor potential (TRP) channels including TRPV2, which may contribute to the analgesic, anti-inflammatory and anti-cancer effects of cannabinoids and Cannabis extracts. It has also shown anti-epileptiform and anticonvulsant properties, that suggest possible therapeutic application in the treatment of pathophysiologic hyperexcitability states such as untreatable epilepsy.[9]
THCV is found to inhibit the activity of both fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MGL), even at micromolar concentrations, and thereby able to inhibit the hydrolysis of the endocannabinoids anandamide (AEA: C22H37NO2; 20:4, ω-6) besides other N-acylethanolamines and 2-Arachidonoylglycerol (2-AG: C23H38O4; 20:4, ω-6), respectively, therefore, it can also act as an indirect agonist at the cannabinoid receptors, by enhancing the activity of the endocannabinoid system (ECS).[10][11]
Unlike THC, cannabidiol (CBD), and cannabichromene (CBC), THCV doesn't begin as cannabigerolic acid (CBGA). Instead of combining with olivetolic acid to create CBGA, geranyl pyrophosphate joins with divarinolic acid, which has two fewer carbon atoms. The result is cannabigerovarin acid (CBGVA). Once CBGVA is created, the process continues exactly the same as it would for THC. CBGVA is broken down to tetrahydrocannabivarin carboxylic acid (THCVA) by the enzyme THCV synthase. At that point, THCVA can be decarboxylated with heat or UV light to create THCV.[12]
THCV is a new potential treatment against obesity-associated glucose intolerance with pharmacology different from that of CB1 inverse agonists/antagonists.[13] GW Pharmaceuticals is studying plant-derived tetrahydrocannabivarin (as GWP42004) for type 2 diabetes in addition to metformin.[14][better source needed]
THC increases appetite, which is sometimes referred to as "the munchies." THC acts as a CB1 agonist. As a CB1 antagonist, THCV has been shown to reduce appetite in murine models.[15]
THCV has been demonstrated to show anti-cancer properties in vitro on PANC-1, AsPc-1, HPAF-II, and MiaPaCa-2 cell lines. There is no record of research on in vivo models [16]
A 2:1 ratio of naturally derived THCV to THC extract (as opposed to synthetically derived sources) has been demonstrated to show energizing and motivating effects in an IRB-backed double blind placebo clinical study by Phylos Bioscience and People Science. [17][18]
It is not scheduled by Convention on Psychotropic Substances. In the United States, THCV is not specifically listed as a Schedule I drug, but "Marijuana Extract" is.[19] THCV could be considered an analog of THC, in which case, sales or possession intended for human consumption could be prosecuted under the Federal Analog Act.
THCV is not scheduled at the federal level so long as it is not derived from cannabis varieties that produce more than .3% THC on a dry weight basis in the United States.[20]
The 2018 United States farm bill legalized the production and sale of THCV if it is derived from hemp compliant with the farm bill.[21][non-primary source needed]