Researchers from the University of Sydney have reported that three acidic cannabinoids found in cannabis reduced seizures in a mouse model of Dravet syndrome, an intractable form of childhood epilepsy. Published in the British Journal of Pharmacology, the study used the Scn1a+/− mouse model of Dravet syndrome to investigate the cannabis plant for phytocannabinoids with anticonvulsant effects against hyperthermia‐induced seizures. The most promising, cannabigerolic acid (CBGA), was further examined against spontaneous seizures and survival in Scn1a+/− mice and in electroshock seizure models. Pharmacological effects of CBGA were surveyed across multiple drug targets. The initial screen identified three phytocannabinoids with novel anticonvulsant properties: CBGA, cannabidivarinic acid and cannabigerovarinic acid. CBGA was most potent and potentiated the anticonvulsant effects of clobazam against hyperthermia‐induced and spontaneous seizures, and was anticonvulsant in the maximal electroshock seizure threshold test. However, CBGA was proconvulsant in the 6 Hz threshold test, and a high dose increased spontaneous seizure frequency in Scn1a+/− mice. CBGA was found to interact with numerous epilepsy‐relevant targets, including GPR55, TRPV1 channels and GABAA receptors. “We have assessed the cannabinoids one by one and now we are exploring what happens when you put them all back together. There remains a real possibility that all these individual anticonvulsant cannabinoids might work better when combined,” the authors said.
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