Significance:
Medicinal cannabis use is booming despite limited preclinical evidence and mechanistic insight. Recent clinical trials of cannabidiol (CBD) in Dravet syndrome (DS) support its clinical efficacy for reduction of seizure frequency and invite study of its benefits for additional DS symptoms. We demonstrate here that treatment with CBD is beneficial for seizure frequency, duration, and severity and for autistic-like social deficits in a mouse model of DS. CBD rescue of DS symptoms is associated with increased inhibitory neurotransmission, potentially mediated by antagonism of the lipid-activated G protein-coupled receptor GPR55. These studies lend critical support for treatment of seizures in DS with CBD, extend the scope of CBD treatment to autistic-like behaviors, and provide initial mechanistic insights into CBD’s therapeutic actions.
