CBDV is a minor cannabinoid with activity in animal models of epilepsy, autism spectrum disorders, and neuropathic pain. Several clinical trials have been initiated in these conditions.

Cannabidivarin (CBDV) was discovered in 1969. And then (like almost every other minor cannabinoid) came a long, boring break where nothing happened for several decades. But in the last few years, CBDV research has really taken off.

Although CBDV has little affinity for CB 1 or CB 2 receptors, it demonstrated activity in animal models of epilepsy, autism, and neuropathic pain. Unlike other minor cannabinoids, CBDV progressed relatively quickly into clinical trials in multiple conditions. Read on to see where these currently stand.

Seizure

CBDV was anticonvulsant in several rodent models of seizure and reduced epilepsy-related gene expression, although the active doses were quite high (50-200 mg/kg). As a followup study, CBDV-rich cannabis extracts also had anticonvulsant activity. Some further data can be seen in the patent for CBDV and seizures.

The mechanism of anti-seizure activity is not totally clear. We know that it is not mediated by the CB 1 receptor. Although CBDV activated and rapidly desensitized TRPV1, this did not appear to be a relevant mechanism either.

One study showed the mechanism of CBDV was related to the inhibitory GABA A receptor (this study also confirmed that the TRPV1 receptor was not involved). Notably, CBDV exerted its maximal effect in this model at the low concentration of 50 nM.

Moving on to clinical data:

A 2016 case study was quite compelling (for a case study). An epilepsy patient showed marked improvement after starting homemade oral cannabis preparations. Blood levels of THC, CBD, and CBDV were tracked as the patient tried different strains. The largest improvements were seen when CBDV blood levels were highest.

GW Pharma carried out the first controlled clinical trial of CBDV between 2015 and 2017 in patients with inadequately controlled focal seizures. Part A assessed pharmacokinetics of CBDV in combination with different types of anti-epileptic drugs (AEDs), whereas Part B focused on the safety and efficacy of CBDV in combination with AEDs.

Although full results have not yet been published, a February, 2018 press release told us that the trial was negative: “In the trial’s preliminary top-line results, both active and placebo arms showed similar reductions in focal seizures of approximately 40 percent.”

They note that the placebo response rate was much higher than expected (I really hate when this happens.) GW Pharma still includes CBDV and seizure on their pipeline page, but it is not yet clear what their next steps will be.

Autism Spectrum Disorders

There is little published research on CBDV and autism spectrum disorders (ASDs), but that doesn’t mean that the studies haven’t been done. Instead we can look to the GW Pharma patent for CBDV and autism and their website:

“GW has evaluated the cannabinoids CBD and CBDV in both general and syndromic pre-clinical models of ASDs yielding promising signals on cognitive and social functioning endpoints as well as repetitive behaviors.”

There are currently two active clinical trials related to autism:

This is primarily a brain imaging study that will assess changes in brain biochemistry, activity, and connectivity after single 600 mg doses of CBD and CBDV. It will be carried out in healthy men with and without autism spectrum disorder. It started in August, 2016 and although enrollment appears to be complete, it is still ongoing.

This trial aims to study the efficacy and safety of CBDV in children with ASD. It is a Phase 2, double-blind, randomized, placebo-controlled trial that includes 12 weeks of treatment. Patients enrolled on the active arm will receive 10 mg/kg/day of CBDV. This study is planned to start in December, 2018 and will run for several years.

In addition to the above studies, there is a small physician-led expanded access program in 10 patients to treat seizures associated with autism .

Rett Syndrome

Rett Syndrome is a rare neurological disorder caused by mutations in the X chromosome. It is characterized by impairments in cognitive, sensory, emotional, motor and autonomic functions.

CBDV rescued behavioural alterations and brain atrophy in a model of Rett syndrome. GW Pharma plans to commence an open-label study (in early 2019 from the most recent announcement I could find), followed by a Phase 2, placebo-controlled trial in this condition.

Importantly, GW Pharma has received orphan drug designation from the FDA for testing CBDV in this condition. If you are not familiar with this process, it encourages companies to develop drugs in rare diseases (that might not otherwise be profitable) by providing various financial incentives.

Neuropathic Pain

No preclinical studies have actually been published on CBDV and pain that I could find. However, there is some data in a GW Pharma patent showing that CBDV has significant activity in a mouse model of neuropathic pain.

One clinical study was started in 2015 in HIV-associated neuropathic pain:

The clinical trial registry states that this study is still ongoing (although it may not be up to date) and I was not able to find any preliminary results.

There is currently no mention of CBDV and neuropathic pain in the GW Pharma pipeline page, so it is not clear what future plans they have for this.

Other Activities of CBDV

•CBDV is an inverse agonist of GPR6

•CBDV is a GPR55 antagonist

•CBDV activated TRPV4 channels

•CBDV reduced nausea, although only at a very high dose (200 mg/kg)

•CBDV prevented loss of motor function in a model of Duchenne muscular dystrophy