CBDV Lesser Known Cannabinoid

The Lesser-Known Cousin of CBD:
CBDV (Cannabidivarin)

When it comes to the Cannabis sativa herb, the most commonly known cannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD). These cannabinoids are responsible for the effects users experience when ingesting the plant, whether psychoactive or not. While THC is known to create a "buzz" among users, CBD is actually a non-psychoactive part of the cannabis plant and is believed to have numerous medicinal benefits, including but not limited to relieving symptoms of seizure disorders and relieving inflammation, anxiety, and nausea. Cannabidivarin (CBDV) is a homologue of CBD, only differing slightly in the chemical composition: the 5- carbon (pentyl) side chain is substituted for a 3-carbon (propyl) sidechain. Unfortunately, CBDV is a rare cannabinoid and has been reported in indica strains from northwest India, hashish strains from Nepal and China. Research revolving around CBDV is in its beginning stages but gaining momentum. While lesser known than its cousin cannabinoid, CBDV is very promising in its advantageous medicinal effects.

Cousins: CBD and CBDV

CBD and CBDV are both classified as phytocannainoids, defined as "any plant-derived natural product capable of either directly interacting with cannabinoid receptors or sharing chemical similarity with cannabinoids or both" (Gertsch). They are non-psychoactive cannabinoids, meaning that they "[do] not interfere with several psychomotor and psychological functions", stated by a 2011 review published in Current Drug Safety manual. This is because they do not use the CB1 receptors, the pathway that THC uses, which are responsible for the mind-altering effects of THC. Therefore, they do not create that familiar high often times associated with recreational marijuana. This clearly gives CBD and CBDV cannabinoids an advantage as a medicine, because they can naturally provide therapeutic healing with minimal side effects. CBDV actually prioritizes its action at TRPV1 (transient receptor potential cation channel subfamily V member 1) receptors and modulation of gene expression. CBD has also received plenty of attention because its antipsychotic effect that actually calms the nervous system.

The Entourage Effect

Cannabis may be most effective when the culmination of cannabinoids is ingested, the medicinal benefits increase. Introduced into cannabinoid science in 1998 by Shimon Ben-Shabat, with Raphael Mechoulam, the entourage effect represents a novel endogenous cannabinoid molecular regulation route. The synergy between the cannabinoids may actually imitate the body in such a mechanism that it is incredibly similar to the human body’s very own endocannabinoid system. The endocannabinoid system (ECS) consists of a group of endogenous cannabinoid receptors located throughout the brain and central and peripheral nervous systems that ultimately can affect physiological processes including appetite, pain-sensation, mood, and memory, and can even mediate the psychoactive effects that may come from the cannabis plant. Put in layman’s terms, the various cannabinoids work best combined than in isolation, perhaps fitting perfectly with Aristotle’s quote, "the whole is greater than the sum of its parts."

One of the key points of the entourage effect is the ability to minimize adverse side effects that come from other cannabinoids. By itself, CBD and CBDv each help facilitate the activity of the endocannabinoid system. Research has also shown that CBDV can be effective in minimizing the anxiety that sometimes come from THC, lowering the user’s feeling of paranoia (Russo). Meanwhile, isolation of the cannabinoids is more appealing for pharmaceutical applications.

Epilepsy Research

As of now, CBDV may prove to be the trump card when it comes to treating epilepsy. CBD has already been quite successful in this area, so it is thought that it’s analogue would be the same, if not have an even better effect.

Epilepsy currently is the most common neurological disorder, affecting over 50 million people worldwide (Iannotti). It consists of brain disorders that can range from gentler cases to more severe situations that life-threatening and disabling. The normal pattern of the neuron activity in the brain essentially becomes disturbed, which may attribute to “strange sensations, emotions, and behavior or sometimes convulsions, muscle spasms, and loss of consciousness” (NINDS). These symptoms may ultimately lead to seizures, which occur as often as one every 25 minutes. Typically, epilepsy is treated with modern medicines, surgical techniques, and other drugs, expensive and artificially generated. Drug resistance (about 35%) and poor antiepileptic drug (AED) side-effect profiles contribute to the increase of people looking for alternative forms of treating epilepsy as a much healthier and safer alternative.

Some evidence suggests that TRPV1 may contribute to the onset and progression of some forms of epilepsy. Meanwhile, CBDV exerts anticonvulsant activity in vivo and produces TRPV1-mediated intracellular calcium elevation in vitro. If the CBDV is able to activate and desensitize the TRPV1 channels, then there is potential for the treatment of neuronal hyper excitability (Iannotti). It may not just be effective in treating epilepsy, but also psychotic disorders such as schizophrenia, which traditionally has no cure, and even multiple sclerosis.

Some Italian researchers, using patch-clamp analysis, determined that “CBD and CBDV dose-dependently activate and rapidly desensitize TRPV1, as well as TRP channels of subfamily V type 2 (TRPV2) and subfamily A type 1 (TRPA1).” They proceeded to take hippocampal brain slices from the rats to stimulate an epileptic seizure and discovered that “CBDV reduced both epileptiform burst amplitude and duration”. The effects of CBDV were not reversed by IRTX, a selective TRPV1 antagonist, because the antiepileptiform effects of the CBDV are not uniquely mediated through the TRPV1 activation. Thus, they proposed in their conclusion that “CBDV effects on TRP channel should be studied further in different in vitro (cell culture) and in vivo (live) models of epilepsy”, although their current progress is very promising (Iannotti).

In an experiment conducted by Naoki Amada, epileptic seizures were induced using pentylenetrazole (PTZ). It was found that CBDV significantly decreased seizure severity and increased latency to the first seizure sign. Furthermore, CBDV responders clearly exhibited lower seizure severity and the increased onset of latency compared to the non-responders. They confirmed that PTZ-induced increases of the mRNA expression in the genes were suppressed in the CBDV responders. Therefore, the researchers came to the conclusion that they “provide[d] molecular evidence that directly supports behavioral evidence that CBDV exerts significant anticonvulsant effects via oral and other routes of administration” (Amada). These results provide significant flags for additional investigation in models of the progressive disorder and follow the longer term CBDV treatment. This was also supported by the researched conducted by Thomas Hill, where CBDV was confirmed to be an effective anticonvulsant in mice and rats.

CBDV’s Next Steps Forward

A British biopharmaceutical company, GW Pharmaceuticals, pilots the usage of CBDV as well as other cannabinoids in their medicines. Alongside their product, they continue to research potential treatments using the cannabis plant and have significantly expanded the scope of the benefits of cannabis. In April of 2015, they announced the US Patent Allowance for the use of CBDV in treating epilepsy, for the use in easing the ailments of epileptic patients and specifically for the control of generalized or temporal lobe seizures. They have proven already successful in the treatment of many patients, including children with rare and severe forms of epilepsy, and are gaining ground to this day.