Photopharmacology is a highly novel approach in the field of neurosciences and has never been
adopted with the aim to treat epileptic seizures. It allows precise spatiotemporal intervention by
combining smart drug design with implantation of an optic fiber in the seizure focus.
Photopharmacology might become superior to opto- and chemogenetics because it does not
require genetic engineering of the brain tissue. We here propose a pioneering proof-of-principle
study in mice for the application of photoswitchable cannabinoids for treating focal epilepsies. The
choice for cannabinoids as treatment option is based on the rising evidence that cannabinoids can
combat treatment-resistant epilepsies and because we have access to exclusive and potent
photoswitchable cannabinoids. We will use in vitro electrophysiology in slices combined with in vivo
investigations towards the anticonvulsant effects of the photoswitchable cannabinoids in acute
mouse seizure models and in a well-validated epilepsy model for refractory seizures. Moreover, we
hypothesize that these photoswitchable ligands have a reduced side effect profile and will study
their effects on motor and memory function.