Cannabidiol effect in pentylenetetrazole-induced seizures depends on PI3K

Background The phytocannabinoid cannabidiol (CBD) has previously shown to have anticonvulsant effects in preclinical and clinical studies. Recently, CBD has been approved to treat certain types of drug-resistant epileptic syndromes. However, the underlying mechanism of action remains unclear. The phosphatidylinositol 3-kinase (PI3K) signaling pathway has been proposed to modulate seizures and might be recruited by CBD. Thus, we tested the hypothesis that the anticonvulsant effect of CBD involves PI3K in a seizure model induced by pentylenetetrazole ( PTZ). Methods We employed pharmacological and genetic approaches to inhibit PI3K and quantified its effects on seizure duration, latency, and number. Results PI3K genetic ablation increased the duration and number of seizures. CBD inhibited PTZ-induced seizures in mice. Genetic deletion of PI3K or pretreatment with the selective inhibitor LY294002 prevented CBD effects. Conclusion Our data strengthen the hypothesis that the CBD anticonvulsant effect requires the PI3K signaling pathway.