Minor cannabinoids may have a major impact on epilepsy treatment
Cannabis, often referred to as marijuana, has been utilized by humans for thousands of years for medical purposes … and beyond. You’ve probably heard of tetrahydrocannabinol (THC, that same well-known psychoactive component of marijuana that makes people feel ‘high’) and cannabidiol (CBD), a major phytocannabinoid which has proven to be such an effective anticonvulsant that in 2018 the FDA approved it (Epidiolex, a purified form of CBD) for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome, two rare and severe forms of epilepsy.
The success of CBD inspired scientists to address whether other less well characterized phytocannabinoids might similarly have anti-seizure properties. Indeed, besides THC and CBD, more than 100 other phytocannabinoids have been identified in cannabis. Hidden in the green leaves are other minor cannabinoids like cannabigerolic acid (CBGA), cannabidivarinic acid (CBDVA), cannabichromenic acid (CBCA), cannabigerol (CBG) and cannabichromene (CBC) which also might have a say in how we approach epilepsy treatment in the future. These compounds have previously shown anti-convulsant properties in animal models, similar to CBD, but the molecular mode of action of these cannabinoids is poorly understood.
Some previous studies suggested that phytocannabinoids may potentially yield their anti-seizure and analgesic effects via inhibition of NaV channels. CBD, for example, has been shown to modulate epilepsy-relevant NaV channels but the interaction of other non-psychoactive phytocannabinoids with sodium channels remained unexplored until now.
The recent study from Steven Petrou Group shed light on the NaV-dependent pharmacology of five non-psychoactive phytocannabinoids (CBGA, CBDVA, CBG, CBCA, and CBC) for four NaV channel isoforms (NaV1.1, NaV1.2, NaV1.6, and NaV1.7) associated with epilepsy and pain.
With the use of the automated patch clamp system, the Patchliner, the authors revealed that CBD and CBGA non-selectively inhibited all channel subtypes examined, whereas CBDVA was selective for NaV1.6. The other cannabinoids, CBG, CBCA, and CBC were a bit shy in showing much effect.
In conclusion, this study has identified two minor phytocanabinoids, CBGA and CBDVA, as NaV inhibitors, and nudged us closer to perhaps a broader spectrum of cannabis-based anti-epileptic treatments.
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Learn more about the uses of automated patch-clamp systems for your research here.