Grant: CIHR Fellowship

Epilepsy and seizures affect 50 million people worldwide, and approximately 30% of these patients do not respond to currently available medication. Cannabidiol (CBD), a non-psychoactive component of Cannabis sativa L., is a novel anti-seizure therapeutic and has recently been FDA-approved for the treatment of Dravet and Lennox-Gastaut syndromes, two rare intractable forms of epilepsy. However, how CBD acts on neurons and synapses to decrease seizures remains mysterious. To address this gap in knowledge, we will study the cellular, synaptic and network signaling mechanisms of CBD in the hippocampus, a brain region often affected in patients living with epilepsies. Our most recent efforts have revealed how CBD affects different population of neurons in the hippocampus. We find that CBD differentially acts on a subset of inhibitory neurons to dampen the propagation of high-frequency activity. Here, we will investigate the molecular mechanisms of CBD in this population of neuron, and determine how the specific modulation of these neurons can mimic the effects of CBD. Our multidisciplinary approaches will allow to dissect CBD's mechanism of action, and to specifically pinpoint the neuronal targets allowing for the anti-epileptic effects of CBD. The ultimate goal is to bridge how CBD modulates synapses and neurons to its anti-epileptic effects, aiming to stimulate the development of novel therapeutic strategies.