A new study from the Lambert Initiative has found that boosting the endocannabinoid system impacts seizures in two phases according to a mouse model of childhood epilepsy Dravet Syndrome.
Consequently, compounds that increase endocannabinoid tone could be developed as novel treatments for the condition.
Dravet Syndrome is a treatment-resistant childhood epilepsy with multiple seizure types. In Australia, it is one of two indications for which certain CBD medications are approved as a form of treatment.
Principal investigator Associate Professor Jonathon Arnold said: “Many in the community suggest that cannabis may yield its therapeutic properties by correcting deficiencies in the endocannabinoid system.
“The endocannabinoid system is a naturally occurring signalling system that exists in our brain and bodies to control normal physiological functions and is sensitive to the effects of plant cannabinoids including THC and CBD.
“Given that cannabis and CBD are being used to treat intractable epilepsies like Dravet Syndrome, we decided to explore whether deficiencies in the endocannabinoid system occur in a mouse model and whether boosting endocannabinoid signalling has anti-seizure effects.”
The study used one drug that increases endocannabinoid concentration and another that makes the CB1 cannabinoid receptor more sensitive to activation.
While the drugs did indeed have anti-seizure effects on one type of seizure, the team observed that over-stimulating the endocannabinoid system with high doses could also trigger seizures.
Speaking on the findings, Professor Arnold added: “We found evidence that the gene for the cannabinoid CB1 receptor might be influencing the severity of how Dravet Syndrome presents.
“While 80% of children with [the condition] have a mutation in the SCN1A gene, not all those who have the mutation exhibit the devastating seizure symptoms observed.
“This suggests that there are other genes that influence how severe the symptoms are. We found mice who were susceptible to seizures had lower levels of the cannabinoid CB1 receptor gene than mice that were seizure-resistant, which is consistent with the gene for the CB1 receptor being a potential genetic modifier.
“The results suggest that pharmacologically boosting the endocannabinoid system might be examined as a new means to treat Dravet Syndrome.”
However, Professor Arnold warned: “We also found a potential liability of this strategy, where overstimulating the endocannabinoid system could make things worse”, adding further human studies are required.