Cannabidiol attenuates seizures and EEG abnormalities in Angelman syndrome model mice
Bin Gu, … , Paul R. Carney, Benjamin D. Philpot
Bin Gu, … , Paul R. Carney, Benjamin D. Philpot
Published December 2, 2019; First published September 10, 2019
Citation Information: J Clin Invest. 2019;129(12):5462-5467. https://doi.org/10.1172/JCI130419.
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Categories: Concise Communication Neuroscience

Cannabidiol attenuates seizures and EEG abnormalities in Angelman syndrome model mice

Abstract

Angelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, lack of speech, ataxia, EEG abnormalities, and epilepsy. Seizures in individuals with AS are common, debilitating, and often drug resistant. Thus, there is an unmet need for better treatment options. Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, has shown antiseizure activity and behavioral benefits in preclinical and clinical studies for some disorders associated with epilepsy, suggesting that the same could be true for AS. Here, we show that acute CBD (100 mg/kg) treatment attenuated hyperthermia- and acoustically induced seizures in a mouse model of AS. However, neither acute CBD nor a 2-week-long course of CBD administered immediately after a kindling protocol could halt the proepileptogenic plasticity observed in AS model mice. CBD had a dose-dependent sedative effect but did not have an impact on motor performance. CBD abrogated the enhanced intracortical local field potential power, including the delta and theta rhythms observed in AS model mice, indicating that CBD administration could also help normalize the EEG deficits observed in individuals with AS. We believe our results provide critical preclinical evidence supporting CBD treatment of seizures and alleviation of EEG abnormalities in AS and will thus help guide the rational development of CBD as a treatment for AS.

Authors

Bin Gu, Manhua Zhu, Madison R. Glass, Marie Rougié, Viktoriya D. Nikolova, Sheryl S. Moy, Paul R. Carney, Benjamin D. Philpot

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Figure 3

CBD has moderate sedative effects in AS model mice.

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CBD has moderate sedative effects in AS model mice. (A and B) WT and AS ...
(A and B) WT and AS model mice were subjected to an open-field test to assess (A) horizontal (distance traveled) and (B) vertical (rears) movement 1 hour after injection of vehicle or CBD. (C and D) Latency to fall from an accelerating rotarod in each trial of (C) acquisition and (D) retest session. Vehicle or CBD was injected i.p. 1 hour prior to the acquisition session. (E) Number of marbles buried by WT and AS model mice treated i.p. with vehicle or CBD 1 hour prior to the test. Note that none of the 10 AS model mice treated with 100 mg/kg CBD buried a marble during the test. Data represent the mean ± SEM. n = 6–11 mice/group. #P < 0.05 and ##P < 0.01 compared with vehicle-treated WT mice; *P < 0.05 and **P < 0.01 compared with vehicle-treated AS mice; 2-way ANOVA with Tukey’s post hoc test.