Cellular and molecular mechanisms underlying the anti-epileptic effects of non-psychoactive cannabinoids

The pharmacological effects of many components of cannabis are not mediated by the mammalian endocannabinoid system and lack the psychoactive effects of endocannabinoid system modulators. However, during the last decade, we have demonstrated that some of these plant cannabinoids, most notably cannabidiol and cannabidivarin (CBD & CBDV), exert significant anticonvulsant and antiepileptic effects in preclinical models. Whilst our findings support ongoing and planned human adult and paediatric clinical trials in people with epilepsy, the mechanism(s) by which these compounds exert their beneficial effects remains unknown.
The successful applicant will employ network level (multi-electrode array) and single cell electrophysiological recording methods with multi-photon microscopy in a number of acute slice preparations from relevant models of disease to elucidate the underlying mechanism of CBDV and CBD’s antiepileptic actions. This project will be informed by ongoing clinical findings via an industrial supervisor who has an established and successful relationship with both academic supervisors. Furthermore, the project forms part of a wider preclinical investigation and so the successful applicant will form part of, and be supported by, a wider research team based at University of Reading and other academic sites. Both academic supervisors and industrial sponsors are committed to the publication of the project’s findings, as our previous track record attests. All equipment, expertise and facilities necessary for the conduct of the project have been fully funded or are already in place. Appropriate training will be given as necessary.