Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures

Abstract

Cannabis sativa has been associated with contradictory effects upon seizure states despite its medicinal use by numerous people with epilepsy. We have recently shown that the phytocannabinoid cannabidiol (CBD) reduces seizure severity and lethality in the well-established in vivo model of pentylenetetrazole-induced generalised seizures, suggesting that earlier, small-scale clinical trials examining CBD effects in people with epilepsy warrant renewed attention. Here, we report the effects of pure CBD (1, 10 and 100mg/kg) in two other established rodent seizure models, the acute pilocarpine model of temporal lobe seizure and the penicillin model of partial seizure. Seizure activity was video recorded and scored offline using model-specific seizure severity scales. In the pilocarpine model CBD (all doses) significantly reduced the percentage of animals experiencing the most severe seizures. In the penicillin model, CBD (≥ 10 mg/kg) significantly decreased the percentage mortality as a result of seizures; CBD (all doses) also decreased the percentage of animals experiencing the most severe tonic-clonic seizures. These results extend the anti-convulsant profile of CBD; when combined with a reported absence of psychoactive effects, this evidence strongly supports CBD as a therapeutic candidate for a diverse range of human epilepsies.

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

“…It produces antiepileptiform and anticonvulsant effects in in vitro and in vivo models (406,407). CBD regulation of Ca 2ϩ homeostasis via several mechanisms may contribute to these actions, particularly for partial or generalized seizures.…”

Cannabidiol exerts antiepileptic effects by restoring hippocampal interneuron functions in a temporal lobe epilepsy model

“…http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2424, Δ 9 ‐THC) that act through cannabinoid type‐1 (http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=56) receptors (Consroe and Wolkin, 1977; Consroe et al, 1982; Kogan and Mechoulam, 2007; Jones et al, 2010; 2012), making the cannabinoid system an interesting and novel therapeutic target for epilepsy. These observations have been corroborated by recent human clinical studies, where CBD reduced the convulsive seizure frequency by 50%, giving hope for patient groups with uncontrollable epilepsy where other drug treatments have failed, namely, in a complex childhood epilepsy disorder associated with high mortality rate, Dravet syndrome (Devinsky et al, 2017).…”

Cannabidiol provides viable treatment opportunity for multiple neurological pathologies of autism spectrum disorder

“…Animalspossessing such genetic modifications also exhibit CNS hyperexcitability, enhanced seizure susceptibility and/ or spontaneous recurrent seizures. CBD exhibits potent anti-epileptic features in both clinical and preclinical studies [8,[16][17][18][19][20][21]. Notably, CBD significantly reduced the frequency of total seizures of all types in a recent clinical trial for the treatment of drug-resistant seizures in Dravet syndrome [8].…”