Cannabinoids in the Treatment of Epilepsy: A Review

Abstract

Cannabinoids have been studied for their role in the treatment of epilepsy for many years. The U.S. Food and Drug Administration (FDA) approved them for the treatment of some refractory syndromes in 2018. Cannabidiol and tetrahydrocannabinol are the most commonly studied cannabinoids and have been studied in great depth vis-à-vis their pharmacokinetics and pharmacodynamics. Studies have shown the efficacy of cannabinoids in the treatment of refractory epilepsy. A substantial amount of research has been performed exploring the interactions between cannabinoids and other conventional antiseizure medications. The exact mechanisms by which cannabinoids exert their effects on seizure control remain unclear and research into these mechanisms continues in great earnest. Cognitive changes from cannabinoids are constantly being studied and add to potential benefits from the use of these compounds. Cultural and social misconceptions and roadblocks about the use of cannabinoids persist and represent an ongoing obstacle to increasing research and therapeutic use of these compounds. This review focuses on all these aspects and of the use of these cannabinoids in the treatment of epilepsy and seeks to offer a fairly comprehensive description of the facets of cannabinoid therapy for refractory epilepsy.

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“…Several randomized, placebo-controlled clinical trials and retrospective studies conducted on patients with refractory epilepsy and genetic syndromes support evidence from preclinical studies and strongly indicate that CBD can reduce seizure frequency [12,67,68,[72][73][74][75][76][77][78]. The Food and Drug Administration in the USA has already approved cannabinoids for the treatment of several treatment-resistant epilepsy syndromes [68,78]. Medical cannabis, especially CBD--based therapy, could become an important addition to conventional anticonvulsive drugs used in refractory epilepsy both in children and adults as it significantly reduces seizure frequency, improves patients' quality of life and sleep patterns and does not cause severe side effects [71,79].…”

“…Several randomized, placebo-controlled clinical trials and retrospective studies conducted on patients with refractory epilepsy and genetic syndromes support evidence from preclinical studies and strongly indicate that CBD can reduce seizure frequency [12,67,68,[72][73][74][75][76][77][78]. The Food and Drug Administration in the USA has already approved cannabinoids for the treatment of several treatment-resistant epilepsy syndromes [68,78].…”

“…Although the mechanisms responsible for the anticonvulsant properties of cannabinoids remain unclear [68], the downregulation of endocannabinoid signalling associated with neuroinflammation is suggested to be a crucial factor responsible for the progression of incidence and severity of seizures [10]. Of all cannabinoids, in recent years CBD emerged as the most promising therapeutic option considering its relative safety and the lack of psychoactive effect [10,12].…”

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“…Systematic reviews have concluded that cannabinoids show limited efficacy as a monotherapy in reducing non-cancer pain [26][27][28][29][30][31][32][33], treating mental illnesses [34][35][36][37][38], and treating epilepsy [33,39,40] (with the exception of treating drug-resistant epilepsy for which there is strong evidence [14,15]), with modest improvements at best. Other systematic reviews conducted by the TGA have found that currently there is some evidence of efficacy for both THC and CBD in treatment of chronic non-cancer related pain [18] and neuropathic pain [41] (although both tend to favour THC-containing products).…”