CBDv Drug Bank

Drugbank

Generic Name

DrugBank Accession Number

DB14050

Background

Cannabidivarin, also known as cannabidivarol or CBDV, is a non-psychoactive cannabinoid found within Medical Cannabis. It is one of over 100 cannabinoids identified from the Cannabis plant that can modulate the physiological activity of cannabis, or marijuana 3. Compared to its homolog, Cannabidiol, CBDV is shortened by two methyl (CH2) groups on its side chain. Notably, both Cannabidiol and CBDV have demonstrated anticonvulsant activity in animal and human models and are demonstrating promising clinical trial results 2,4,5,6. Other cannabinoids with some evidence of anti-epileptic activity include Tetrahydrocannabivarin (THCV) and Δ9-tetrahydrocannabinolic acid.

While the primary components 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 investigational cannabinoids with anticonvulsant action mostly use mechanisms that do not involve these two endocannabinoid receptors.

The anti-epileptic activity of CBD and CBDV is thought to be modulated by their effects on transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor, which is a member of a large family of ion channels that are involved in the onset and progression of several types of epilepsy. CBD and CBDV have been shown to dose-dependently activate and then desensitize TRPV1 as well as TRPV2 and TRPA1 channels 4,7,8. Desensitization of these ion channels is a potential mechanism by which these molecules cause a reduction of neuronal hyperexcitability that contributes to epileptic activity and seizures.

CBDV has also 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). The clinical implications of this are unclear however, as this interaction has not been shown to affect CBDV's anticonvulsant activity.

Cannabidivarin is being actively developed by GW Pharmaceuticals as the experimental compound GWP42006 as it has "shown the ability to treat seizures in pre-clinical models of epilepsy with significantly fewer side effects than currently approved anti-epileptic drugs" 13. Unfortunately, as of February 2018, GW Pharmaceuticals announced that their Phase 2a placebo-controlled study of CBDV for focal seizure did not reach its primary endpoints. They will continue to study its use in epilepsy, however, and are expanding their investigations to include its potential use in Autism Spectrum Disorder, Rett syndrome and Fragile X among others.

In October 2017 CBDV was given orphan designation by the European Medicines Agency for use in Rett Syndrome and again in February 2018 for treatment of Fragile X Syndrome.

Type

Small Molecule

Groups

Investigational

Weight

• Average: 286.415
• Monoisotopic: 286.193280077

Chemical Formula

C₁₉H26O2

Synonyms

• cannabidivarine
• Cannabidivarol
• CBD-V
• CBDV

PHARMACOLOGY

Indication

Cannabidivarin does not currently have any FDA or Health Canada approved indications, however in October 2017 CBDV was given orphan designation by the European Medicines Agency for use in Rett Syndrome and again in February 2018 for treatment of Fragile X Syndrome.

Pharmacodynamics

Not Available

Mechanism of action

The anti-epileptic activity of CBD and CBDV is thought to be modulated by their effects on transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor, which is part of a large family of ion channels that are involved in the onset and progression of several types of epilepsy. CBD and CBDV have been shown to dose-dependently activate and then desensitize TRPV1 as well as TRPV2 and TRPA1 channels 4,7,8. Desensitization of these ion channels is a potential mechanism by which these molecules cause a reduction of neuronal hyperexcitability that contributes to epileptic activity and seizures.

CBDV has also been shown to inhibit the activity of diacylglycerol (DAG) lipase-α, the primary synthetic enzyme of the endocannabinoid, 2-arachidonoylglycerol (2-AG) 1,10. The clinical implications of this are unclear however, as this interaction has not been shown to affect CBDV's anticonvulsant activity.

Absorption

Like Δ9-THC, CBDV has low water solubility and poor oral bioavailability (~6% in humans), making oral administration an unfavourable method of delivery. Despite this, CBDV has relatively rapid absorption with peak concentrations seen around 2 h after oral administration in animal pharmacokinetic studies.

Orally administered CBDV in mice was found to have a plasma Cmax of 0.47ug/mL and Tmax of 30 minutes, and a brain Cmax of 0.94ug/mL and Tmax of 60 minutes.

Volume of distribution

Due to its lipophilicity, CBDV has been shown to cross the blood brain barrier.

Protein binding

Not Available

Metabolism

Significant first-pass metabolism by the liver results in erratic absorption from the GI tract, low bioavailability, and unreliable pharmacokinetics.

Route of elimination

Not Available

Half-life

Orally administered CBDV in mice was found to have a plasma elimination half life of 222 minutes, and a brain elimination half life of 204 minutes.

Clearance

Not Available

Toxicity

Not Available

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

INTERACTIONS

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• APPROVED
• VET APPROVED
• NUTRACEUTICAL
• ILLICIT
• WITHDRAWN
• INVESTIGATIONAL
• EXPERIMENTAL
• ALL DRUGS