Cannabis has been used for centuries to treat
seizures. Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised interest in cannabis-based
antiepileptic therapies. In this study, we review current understanding of the
endocannabinoid system, characterize the pro- and anticonvulsive effects of
cannabinoids [e.g., Δ9-tetrahydrocannabinol and
cannabidiol (CBD)], and highlight scientific evidence from pre-clinical and clinical trials of
cannabinoids in
epilepsy. These studies suggest that CBD avoids the psychoactive effects of the
endocannabinoid system to provide a well-tolerated, promising therapeutic for the treatment of
seizures, while whole-plant cannabis can both contribute to and reduce
seizures. Finally, we discuss results from a new multicenter, open-label study using CBD in a population with treatment-resistant
epilepsy. In all, we seek to evaluate our current understanding of
cannabinoids in
epilepsy and guide future basic science and clinical studies.