MAR 29, 2018 1:30 PM PDT

Cannabidiol Treatment of Epilepsy and Autism Through Restoration of GABAergic Signaling

Speaker
  • Senior Fellow, Department of Pharmacology, University of Washington
    Biography
      Dr. Josh Kaplan, Ph.D., is a senior fellow in the Department of Pharmacology at the University of Washington. He earned his Ph.D. in Behavioral Neuroscience at Oregon Health & Science University in 2015 studying the neural mechanisms underlying risk for developing alcohol use disorders, after which he moved north to Seattle where he researches the therapeutic potential of cannabis and the endocannabinoid system. Dr. Kaplan uses behavioral neuroscience and neurophysiology to better understand the therapeutic efficacy of cannabis as well as it's neural mechanism.

    Abstract

    Cannabidiol (CBD) has emerged as a promising anti-epileptic drug in otherwise treatment-resistant genetic epileptic disorders. However, the clinical trials have been limited by their use of CBD only as an add-on therapy, their lack of assessment of CBD on comorbid phenotypes, and their lack of insight into CBD’s therapeutic mechanism. To address these limitations, we tested CBD’s effects on behavior and physiology in our genetic mouse model of Dravet Syndrome (DS). DS is a severe childhood epileptic disorder characterized by treatment resistant epilepsy, as well as cognitive and social deficits consistent with autism. Our DS mice recapitulate these core behavioral phenotypes and are thus a powerful precision medicine tool to test the efficacy of CBD as a monotherapy in DS. We find that acute CBD administration reduced the thermally-induced seizures that model febrile seizures in the early stage of DS. Twice-daily CBD administration also reduced the frequency of spontaneous seizures that characterize the later stages of DS.

    These anti-epileptic effects were associated with an enhancement in GABAergic signaling in the dentate gyrus of the hippocampus, which is mediated by CBD antagonism of GPR55 signaling. Furthermore, we find that CBD rescued social interaction deficits and abnormal social responses in our DS mice. Together, our data suggest that CBD is an effective monotherapy against epileptic seizures and autism in DS. Our results also reveal that GPR55 signaling is an important target for CBD’s therapeutic benefits.

    Learning Objectives:

    •  Be able to describe cannabidiol's benefits as a monotherapy in treating epilepsy and autism
    •  Understand the cellular mechanism by which cannabidiol rescues brain function that's disrupted   by genetic mutations
       

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