Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome

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(Kaplan, et al. 2017) Parents often report “improved behavior” or “improved cognition” when they initiate cannabidiol (CBD) treatment in their children with Dravet syndrome, with and without improved seizure control. This project sought to measure the effect of CBD on seizure control, autistic-like behaviors, and specific neuron action.

They found that when mice were given CBD one hour before thermally induced seizures, the seizures were shorter and less severe than in the mice who did not receive CBD. To see if CBD reduced spontaneous seizures, they administered CBD twice daily to mice with DS (from Scn1a mutations) during the period of maximum seizure risk and found that it did indeed reduce the frequency of seizures by roughly 70%.

In a standard three-chamber test for sociability, mice may exhibit autistic-like behavior by spending more time in the chamber with a novel object or the center chamber than the chamber with a new mouse. In this test, mice with DS exhibit autistic-like behavior and a low dose of CBD caused the DS mice to perform similarly to their typical peers. A high dose of CBD, however, did not show a similar benefit. Another test, in which a mouse is introduced to a new mouse and scientists measure the number of times the mouse interacts with the new mouse and how often it retreats from the novel mouse. Mice with DS initiate the same number of interactions with the new mouse, but retreat defensively more often than typical mice. A low dose of CBD reduced the number of defensive retreats in the DS mice. Unfortunately, the high dose required for seizure control did not produce the social improvements the low dose did.

In studying the mechanism for reducing seizures, the authors found that CBD improved inhibitory neuron function, and this action could be replicated by a GPR55 antagonist, suggesting another potential therapeutic option.

Kaplan JS, Stella N, Catterall WA, Westenbroek RE. Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome. Proc Natl Acad Sci U S A. 2017 Oct 17;114(42):11229-11234. doi: 10.1073/pnas.1711351114. Epub 2017 Oct 2. PubMed PMID: 28973916; PubMed Central PMCID: PMC5651774.
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