A patient with drug-resistant epilepsy who self-medicated with cannabis experienced dramatic seizure reduction and cognitive improvement, with blood levels suggesting the rare cannabinoid CBDV may have contributed through effects on GABA receptors.
Read this if you follow cannabinoid research for epilepsy or are interested in cannabinoids beyond THC and CBD.
CBDV enhanced inhibitory GABA signaling in human epileptic brain tissue
What the researchers found
A patient with symptomatic partial epilepsy who had failed numerous medications and surgical treatments began self-medicating with cannabis. The clinical improvement was dramatic: seizure frequency decreased substantially and cognitive function recovered.
Blood analysis revealed significant levels of cannabidivarin (CBDV), a relatively rare minor cannabinoid, alongside CBD and THC. The clinical improvement appeared to parallel high CBDV plasma concentrations.
To investigate CBDV's potential mechanism, the researchers performed electrophysiology experiments on human hippocampal tissue from four epilepsy surgery patients. They found that prolonged CBDV exposure reduced the "rundown" of GABA-A receptor currents, essentially helping inhibitory signaling maintain its strength over time. This finding was confirmed in tissue from a patient with Rasmussen encephalitis.
This suggests CBDV may combat seizures by enhancing the brain's inhibitory GABA system, a mechanism distinct from CBD's known actions.
Why it matters
While CBD (as Epidiolex) has gained attention for epilepsy, this study suggests another cannabinoid, CBDV, may also have anticonvulsant properties through a different mechanism. If confirmed, CBDV could expand the cannabinoid toolkit for treatment-resistant epilepsy.
The numbers in context
One patient with drug-resistant partial epilepsy. Failed countless pharmacological and surgical treatments. Dramatic seizure reduction and cognitive improvement with cannabis. CBDV detected in blood. GABA-A receptor rundown reduced by CBDV exposure in tissue from 4 TLE patients and 1 RE patient.
How the study worked
Case report with clinical monitoring (EEG, seizure diaries) and serial blood cannabinoid measurements. Complementary electrophysiology experiments using human epileptic hippocampal tissue transplanted into Xenopus oocytes to test CBDV effects on GABA-A receptor currents.
What this study cannot tell us
Single case report cannot establish efficacy. The patient used whole-plant cannabis, so effects cannot be attributed solely to CBDV. The electrophysiology experiments used an artificial expression system. CBDV availability and dosing for clinical use are not established.
How to read the evidence
Case report with complementary basic science providing mechanistic plausibility. Novel finding but very preliminary.
When this study was published
Published in 2016. CBDV research for epilepsy has continued, including preclinical studies by pharmaceutical companies.
The bigger picture
The endocannabinoid system contains dozens of compounds beyond THC and CBD. This study highlights CBDV as a potentially important anticonvulsant cannabinoid with a unique mechanism of action, suggesting that the therapeutic potential of cannabis extends well beyond its most famous components.
Questions still open
- Would purified CBDV be effective as an anticonvulsant? How does CBDV's mechanism complement CBD's for seizure control? Could cannabis varieties bred for high CBDV content be developed for epilepsy treatment?
Common questions
What is CBDV and could it help epilepsy?
Is CBDV different from CBD for seizures?
Read the original research
Cannabis in epilepsy: From clinical practice to basic research focusing on the possible role of cannabidivarin.
Epilepsia open, 1(3-4), 145-151
Citation
Morano, Alessandra; Cifelli, Pierangelo; Nencini, Paolo; Antonilli, Letizia; Fattouch, Jinane; Ruffolo, Gabriele; Roseti, Cristina; Aronica, Eleonora; Limatola, Cristina; Di Bonaventura, Carlo; Palma, Eleonora; Giallonardo, Anna Teresa. (2016). Cannabis in epilepsy: From clinical practice to basic research focusing on the possible role of cannabidivarin.. Epilepsia open, 1(3-4), 145-151. https://doi.org/10.1002/epi4.12015
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