Cannabidivarin

Cannabidivarin (CBDV) is a non-psychoactive plant constituent with the molecular formula C19H26O2 from the family of cannabinoids(phytocannabinoids), which occurs in various cannabis species. The substance was first identified in 1969 by Vollner et al.

Cannabidivarin is a homologue of cannabidiol (CBD), with the side chain shortened by two methylene bridges (CH2 units). Plants with relatively high CBDV contents have been found in feral populations of C. indica ( = C. sativa ssp. indica var. kafiristanica) from north-west India and in hashish from Nepal.

CBDV has anticonvulsant effects. The compound was actively developed by GW Pharmaceuticals because it has a proven neurochemical pathway for anti-epileptic and anti-convulsive effects (Amada N et al 2013).

While the major constituents of cannabis, CBD and THC, have been shown to modulate many of their physiological effects through their binding to the cannabinoid-1 (CB1R) and cannabinoid-2 (CB2R) receptors, the cannabinoids with anticonvulsant effects that have been studied mostly utilize mechanisms that do not involve these two endocannabinoid receptors. The antiepileptic effects of CBD and CBDV are thought to be modulated by their action on the transient receptor potential cation channel of subfamily V, member 1 (TRPV1), also known as the capsaicin receptor, which belongs to a large family of ion channels involved in the development and progression of various types of epilepsy (Iannotti FA et al. 2014).

CBD and CBDV have been shown to activate and then desensitize TRPV1 as well as TRPV2 and TRPA1 channels in a dose-dependent manner. Desensitization of these ion channels is a possible mechanism by which these molecules cause a reduction in neuronal hyperexcitability that contributes to epileptic activity and seizures.

CBDV has further been shown to inhibit the activity of diacylglycerol (DAG) lipase-α, the primary enzyme responsible for the synthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG).

CBDV (as well as several other cannabinoids) has shown anticonvulsant effects in animal and human models and has shown promising results in clinical trials.

CBDV continues to be studied for its use in epilepsy. In October 2017, CBDV received orphan designation from the European Medicines Agency for use in Rett syndrome and again in February 2018 for the treatment of fragile X syndrome. Another potential indication is autism spectrum.

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