CBDV Vs CBD: What Are the Differences?

Given the sheer volume of cannabidiol (CBD) products on the shelves of health and wellness stores worldwide, it is perhaps unsurprising that CBD is widely regarded as a cannabinoid with a great deal of therapeutic promise. Indeed, the first FDA-approved cannabis-derived medicine was a CBD product – a CBD oral spray for the treatment of two drug-resistant epilepsies. Other non-clinical studies have also indicated that the cannabinoid could be useful in tackling anxiety, inflammation, and insomnia.

By comparison, cannabidivarin (CBDV) – a cannabinoid with a remarkably similar chemical structure to CBD – has received far less attention from the public and from scientists over the years. But now, a flurry of interest in CBDV from pharmaceutical companies has thrust the compound into the spotlight.

What is CBDV?

Cannabidivarin may be the lesser known of the two cannabinoids in the public eye, but its existence has been known for decades.

First isolated in 1969, CBDV’s discovery changed the way that scientists at the time thought about cannabinoids. Previously, it was assumed that all naturally occurring cannabinoid compounds contained a pentyl (five-carbon-long) side chain in their chemical structure. But CBDV contains only a three-carbon propyl side chain. Soon after this discovery the successful isolation of CBDV, scientists would also go on to uncover and isolate tetrahydrocannabivarin (THCV), the propyl cannabinoid variant of cannabis’ main intoxicant, tetrahydrocannabinol (THC).

CBD (left) with its pentyl side chain highlighted and CBDV.

More modern research has shown that these propyl cannabinoids are more commonly found in the landrace Cannabis indica strains that originated in Asia and Africa. Landrace cannabis strains are strains that have not been extensively crossbred by humans with other cannabis plants, and so have remained genetically “pure” through the centuries of cannabis cultivation. Generally speaking, cannabis and hemp strains that are high in CBD also tend to be high in CBDV.

What is CBD? 

CBD is the major non-psychoactive cannabinoid in cannabis. Research has shown that it has therapeutic potential for conditions including epilepsy, inflammation, anxiety disorders, and a number of other common physical and neuropsychiatric conditions. It is also famed for its calming effects, which has led to a recent consumer boom in CBD isolate oils and balms. 

The potential benefits of cannabidivarin 

Unlike with THC and THCV, where the properties of each compound are dramatically different despite their near-identical chemical structures, CBD and CBDV do actually display remarkably similar therapeutic benefits. However, a few important differences uncovered by early research into CBDV has set the compound apart, and it is these properties that have stoked much of the recent interest in CBDV from pharmaceutical companies.

Nausea

A 2013 study published in the British Journal of Pharmacology tested the effects of CBDV on rats, measured against the effects of two nausea-inducing drugs that acted as CB1 receptor inverse agonists. In the first study experiment, it was determined that CBDV did not display any similar nausea-inducing effects.

But in the second experiment carried out for the study – originally designed to see whether CBDV would enhance the nausea-inducing effects of the other drugs – it was found that administering CBDV actually reduced the total amount of nausea-indicating behaviors in the rats.

This would imply that, like CBD, CBDV also has some merit for suppressing feelings of nausea. However, the anti-nausea effects of CBDV have yet to be proven in human clinical trials.

CBDV and epilepsy

CBD is known to be an effective treatment for some types of drug resistant epilepsy and the use of the cannabinoid for this purpose has been approved in the US and the European Union. Similarly, CBDV has also been investigated for use as a general anticonvulsant medication.

One 2012 study, also published in the British Journal of Pharmacology, examined the anticonvulsant effects of CBDV in vitro and in four different in vivo seizure models in mice and rats. The researchers found that CBDV alone was effective at reducing seizure in three of the four seizure models tested. Seizures in the fourth type were also significantly more attenuated when CBDV was administered as a concomitant medication alongside a known antiepileptic drug.

At the doses that were effective in this study, the researchers also noted that there were no ill-effects on normal motor function. It was an important finding, as there are concerns that other anti-epileptic drugs may negatively impact cognitive function to some extent. So with further research and investment, CBDV could present a promising alternative.

Rett Syndrome

Rett syndrome is a rare genetic disorder that affects brain development. It is caused by a genetic mutation in the MECP2 gene, which is found on the X chromosome. Rett syndrome typically affects the mental and physical development of young female children as they grow. Such children may experience difficulties with mobility, communicating with others, and may also develop seizures and breathing problems.

Treating deterioration associated with Rett syndrome is one of the most promising avenues for CBDV research. Published in the journal Neuropharmacology, treatment with CBDV in a mouse model of Rett syndrome was shown to lead to improved general health outcomes, increased sociability, improved motor coordination, and a reversal of the deterioration in brain weight seen in the mice.

Is there a future for CBDV medicines?

These potential medicinal uses of CBDV have thrust the compound back into the public eye, with big-name pharmaceutical companies now looking to pursue the development of CBDV-based medicines.

In October 2017, CBDV was given an “orphan designation” by the European Medicines Agency for use in treating Rett Syndrome. In February 2018, the EMA approved another orphan designation for CBDV, this time for the treatment of Fragile X syndrome – a genetic condition which affects brain development and can result in severe learning disability. Orphan drug designations are awarded by the EMA based on the seriousness of the health condition, its rarity in the general population, and a lack of promising treatment avenues. This designation is not the same as a marketing authorization, but it allows manufacturers of these orphan drugs to benefit from additional EMA support to encourage the drugs to be brought to market despite the small pool of patients.

GW Pharmaceuticals – the company behind Epidiolex – announced that it would be developing an experimental CBDV-based compound named GWP42006 several years ago. In 2018, the company released the results of a phase 2a placebo-controlled trial into the use of GWP42006 for focal seizures. In this trial, the drug performed no better than the placebo medication.

However, despite this result, the company has committed to keep investigating GWP42006 for use in autism spectrum disorders (ASD) and genetic developmental disorders such as Rett syndrome. Indeed, the company had planned to go ahead with a phase 2 clinical trial investigating the safety and tolerability of their CBDV drug in young people with ASD, but the trial was terminated “due to enrollment challenges during COVID-19 pandemic.” Extenuating circumstances aside, this persistent pursuit of research from such a major pharmaceutical company should at least demonstrate the existence of a very real interest in the medicinal use of CBDV.