Possible mechanisms of action of cannabidiol in the epilepsies: a review

Abstract

Background: Cannabidiol (CBD) is a compound of Cannabis Sativa plant that has been studied since the 1970s for its effectiveness in the treatment of refractory epilepsies. With the discovery of the endocannabinoid system, most recent studies have been dedicated to elucidating its mechanisms of action. Objective: To review scientific articles in order to enlightening the antiepileptic cannabidiol’s mechanisms of action. Methods: Literature review on both PubMed and Google Scholar searching for the terms: “epilepsy”, “cannabidiol” and “mechanism of action”. Results: We found that cannabidiol has a lot of mechanisms of action which can explain its effectiveness, among which stand out: endocannabinoid system facilitation, by inhibition of recaption and hydrolysis of anandamide as well as by the facilitation of its synthesis and release. These processes must result in the indirect activation of CB1 and CB2 receptors. Furthermore, CBD promotes the activation of mTOR and PI3K proteins intracellular pathway, with subsequent reduction of glutamatergic release. Conclusions: The general hypothesis is that cannabidiol has antiepileptic effectiveness, even in cases of refractory epilepsies, precisely for showing several mechanisms of action. We emphasize, however, the necessity of more researches in this area for further enlightenment of theses possible mechanisms of action and the applicability in the treatment of epilepsies.