Cannabidiol reduces seizures and associated behavioral comorbidities in a range of animal seizure and epilepsy models

Pabitra Hriday Patra, Melissa Barker-Haliski, H Steve White, Benjamin J Whalley, Sarah Glyn, Haramrit Sandhu, Nicholas Jones, Michael Bazelot, Claire M Williams, Alister James McNeish

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

OBJECTIVE: Epilepsy is a progressive neurological disease characterized by recurrent seizures and behavioral comorbidities. We investigated the antiseizure effect of cannabidiol (CBD) in a battery of acute seizure models. Additionally, we defined the disease-modifying potential of chronic oral administration of CBD on associated comorbidities in the reduced intensity status epilepticus-spontaneous recurrent seizures (RISE-SRS) model of temporal lobe epilepsy (TLE).

METHODS: We evaluated the acute antiseizure effect of CBD in the maximal electroshock seizure, 6-Hz psychomotor seizure, and pentylenetetrazol acute seizure tests, as well as the corneal kindling model of chronic seizures in mice following intraperitoneal administration. Median effective or behavioral toxic dose was determined in both mice and rats. Next, we tested an intravenous preparation of CBD (10 mg/kg single dose) in a rat model of pilocarpine-induced status epilepticus. We defined the effect of chronic CBD administration (200 mg/kg orally) on spontaneous seizures, motor control, gait, and memory function in the rat RISE-SRS model of TLE.

RESULTS: CBD was effective in a battery of acute seizure models in both mice and rats following intraperitoneal administration. In the pilocarpine-induced status epilepticus rat model, CBD attenuated maximum seizure severity following intravenous administration, further demonstrating CBD's acute antiseizure efficacy in this rat model. We established that oral CBD attenuated the time-dependent increase in seizure burden and improved TLE-associated motor comorbidities of epileptic rats in the RISE-SRS model without affecting gait. Chronic administration of CBD after the onset of SRS ameliorated reference memory and working memory errors of epileptic animals in a spatial learning and memory task.

SIGNIFICANCE: The present study illustrates that CBD is a well-tolerated and effective antiseizure agent and illustrates a potential disease-modifying effect of CBD on reducing both seizure burden and associated comorbidities well after the onset of symptomatic seizures in a model of TLE.

Original languageEnglish
Pages (from-to)303-314
Number of pages12
JournalEpilepsia
Volume60
Issue number2
Early online date26 Dec 2018
DOIs
Publication statusPublished - 6 Feb 2019

Bibliographical note

© 2018 The Authors Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

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