The Anticonvulsant Potential of Cannabidivarinic Acid (CBDVA): Preclinical Data and Mechanism of Action
Introduction
The ongoing search for safer and more effective anticonvulsant therapies continues to fuel scientific interest in the non-intoxicating cannabinoids from the cannabis plant. While Cannabidiol (CBD) and Cannabidivarin (CBDV) have received considerable attention for their anticonvulsant properties, emerging research is spotlighting their acidic precursors, most notably Cannabidivarinic Acid (CBDVA).
CBDVA is the carboxylic acid form of CBDV, found in the raw cannabis plant before decarboxylation (a process typically triggered by heat) converts it to its neutral counterpart. As an unprocessed phytocannabinoid, CBDVA belongs to the group of propyl cannabinoids, defined by having a three-carbon (propyl) side chain rather than the five-carbon side chain found in pentyl cannabinoids like CBD.
Key to CBDVA’s emerging profile is its ability to interact with neurological pathways tied to seizure activity while avoiding the intoxicating effects of THC. Initial findings suggest that CBDVA modulates a variety of targets within both endocannabinoid and non-endocannabinoid systems. This distinction may allow it to deliver therapeutic effects with fewer side effects than conventional antiepileptic drugs (AEDs), which are often associated with adverse events such as fatigue, liver toxicity, and behavioral changes.
The growing interest in CBDVA is further supported by regulatory progress in the cannabis-derived pharmaceutical space. The approval of Epidiolex (a CBD-based drug by GW Pharmaceuticals) for treatment-resistant epilepsies like Dravet syndrome and Lennox-Gastaut syndrome set an important precedent. This breakthrough has redirected scientific attention toward similar, less explored cannabinoids. Investigative work, especially by cannabis pharmaceutical pioneers like GW Pharmaceuticals (now part of Jazz Pharmaceuticals), highlights CBDVA’s potential role in preclinical epilepsy models.
As research into acidic cannabinoids advances, CBDVA is emerging as a compound with distinct therapeutic potential. Professionals in the medical, cannabis, and pharmaceutical industries would benefit from understanding its unique profile, which could lead to transformative product development and expanded clinical research opportunities.
Preclinical Studies and Mechanism of Action
A growing body of preclinical studies points to the promise of CBDVA as a potential anticonvulsant agent. One noteworthy study from GW Pharmaceuticals was published in the British Journal of Pharmacology in 2012. This study evaluated various cannabis-derived compounds, including CBDVA, in rodent models of seizures and epilepsy. Findings from tests like the pentylenetetrazol (PTZ) and mesial temporal lobe epilepsy models showed that CBDVA reduced seizure severity and frequency in a dose-dependent manner. These early preclinical results suggest CBDVA could be a future novel antiepileptic compound.
Mechanistically, CBDVA exerts its effects through interactions with several neural receptors and pathways:
– It does not significantly act on the CB1 receptor, associated with cannabis’ psychoactive effects.
– Instead, it modulates transient receptor potential (TRP) channels, particularly TRPV1 and TRPA1. These ion channels are essential in pain processing, inflammation, and neuronal excitability. TRPV1 (commonly known as the capsaicin receptor) is particularly important in epilepsy because it manages calcium flow in neurons, affecting both excitability and neurotransmitter release.
– CBDVA may also modulate GPR55, a G-protein-coupled receptor implicated in neurological inflammation and hyperexcitability. Antagonizing GPR55 has been proposed as an effective strategy for preventing seizures. Similar to CBD and CBDV, there is early evidence suggesting CBDVA may act as a GPR55 antagonist, helping suppress neural overactivity that triggers seizures.
Epigenetic Mechanisms and Gene Expression
In addition to its receptor-based activity, a novel pathway through which CBDVA might exert anticonvulsant effects is via epigenetic modulation. An exploratory analysis shared at the 2019 International Cannabinoid Research Society (ICRS) Conference found that CBDVA may influence gene methylation in neural tissue. This type of gene regulation, without altering the DNA sequence, may be critical in long-term seizure control. Altered gene expression is often observed in patients with refractory epilepsy, and agents capable of modulating it epigenetically could offer groundbreaking benefits.
Safety and Toxicological Profile
Safety is a cornerstone of any antiepileptic treatment, and early findings are encouraging. In rodent models, therapeutic doses of CBDVA did not produce any significant liver toxicity, sedation, or behavioral abnormalities. This safety profile positions CBDVA as a potential monotherapy or adjunct therapy in patients who do not tolerate traditional antiepileptic drugs well.
Given these distinct pharmacological traits—targeting TRP channels, GPR55 antagonism, and potential epigenetic modulation—CBDVA demonstrates a multifaceted method of action that separates it from other cannabinoids, including those already FDA-approved for epilepsy therapy.
Conclusion
Although clinical trials on Cannabidivarinic Acid (CBDVA) are still forthcoming, its strong performance in preclinical models makes it a compelling target for continued research. Its apparent ability to modulate neural excitability through TRP channels, inhibit GPR55 activity, and potentially regulate gene expression marks it as a compound with multiple therapeutic avenues. Combined with its non-psychoactive nature and favorable safety profile, CBDVA could become a valuable addition to the cannabinoid pharmaceutical toolkit—especially for treating forms of epilepsy unresponsive to conventional medications.
For medical professionals, researchers, and cannabis formulators, understanding CBDVA’s unique chemical and biological characteristics is key to harnessing its future therapeutic power.
References
Concise Summary
Cannabidivarinic Acid (CBDVA), the raw acid precursor of CBDV, shows significant promise as a non-psychoactive anticonvulsant in preclinical research. Unlike THC, CBDVA primarily targets TRP channels and acts as a GPR55 antagonist, both of which are implicated in seizure control. Emerging studies suggest CBDVA could also influence epigenetic mechanisms involved in epilepsy. With no observed toxicity in animal models and multifaceted mechanisms of action, CBDVA is being positioned as a next-generation therapeutic cannabinoid. Its favorable safety profile and potential to address treatment-resistant epilepsy make it a key candidate for clinical trials and product development in cannabinoid-focused neurology.
