Cannabidiol Displays Antiepileptiform and Antiseizure Properties In Vitro and In Vivo
- 11 November 2009
- journal article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET) in The Journal of pharmacology and experimental therapeutics
- Vol. 332 (2), 569-577
- https://doi.org/10.1124/jpet.109.159145
Abstract
Plant-derived cannabinoids (phytocannabinoids) are compounds with emerging therapeutic potential. Early studies suggested that cannabidiol (CBD) has anticonvulsant properties in animal models and reduced seizure frequency in limited human trials. Here, we examine the antiepileptiform and antiseizure potential of CBD using in vitro electrophysiology and an in vivo animal seizure model, respectively. CBD (0.01–100 μM) effects were assessed in vitro using the Mg2+-free and 4-aminopyridine (4-AP) models of epileptiform activity in hippocampal brain slices via multielectrode array recordings. In the Mg2+-free model, CBD decreased epileptiform local field potential (LFP) burst amplitude [in CA1 and dentate gyrus (DG) regions] and burst duration (in all regions) and increased burst frequency (in all regions). In the 4-AP model, CBD decreased LFP burst amplitude (in CA1 only at 100 μM CBD), burst duration (in CA3 and DG), and burst frequency (in all regions). CBD (1, 10, and 100 mg/kg) effects were also examined in vivo using the pentylenetetrazole model of generalized seizures. CBD (100 mg/kg) exerted clear anticonvulsant effects with significant decreases in incidence of severe seizures and mortality compared with vehicle-treated animals. Finally, CBD acted with only low affinity at cannabinoid CB1 receptors and displayed no agonist activity in [35S]guanosine 5′-O-(3-thio)triphosphate assays in cortical membranes. These findings suggest that CBD acts, potentially in a CB1 receptor-independent manner, to inhibit epileptiform activity in vitro and seizure severity in vivo. Thus, we demonstrate the potential of CBD as a novel antiepileptic drug in the unmet clinical need associated with generalized seizures.This publication has 53 references indexed in Scilit:
- Atypical Responsiveness of the Orphan Receptor GPR55 to Cannabinoid LigandsOnline Journal of Public Health Informatics, 2009
- Investigation of the effects of the novel anticonvulsant compound carisbamate (RWJ‐333369) on rat piriform cortical neurones in vitroBritish Journal of Pharmacology, 2009
- Effects of Δ9-tetrahydrocannabivarin on [35S]GTPγS binding in mouse brain cerebellum and piriform cortex membranesBritish Journal of Pharmacology, 2008
- Inhibition of Recombinant Human T-type Calcium Channels by Δ9-Tetrahydrocannabinol and CannabidiolJournal of Biological Chemistry, 2008
- The phytocannabinoid Δ9‐tetrahydrocannabivarin modulates inhibitory neurotransmission in the cerebellumBritish Journal of Pharmacology, 2008
- The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9‐tetrahydrocannabinol, cannabidiol and Δ9‐tetrahydrocannabivarinBritish Journal of Pharmacology, 2008
- The orphan receptor GPR55 is a novel cannabinoid receptorBritish Journal of Pharmacology, 2007
- Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitroBritish Journal of Pharmacology, 2007
- The Endocannabinoid System Controls Key Epileptogenic Circuits in the HippocampusNeuron, 2006
- Anticonvulsant properties of Δ9-tetrahydrocannabinol and other cannabinoidsLife Sciences, 1974