The Interplay between the Endocannabinoid System, Epilepsy and Cannabinoids

Abstract

Epilepsy is a neurological disorder that affects approximately 50 million people worldwide. There is currently no definitive epilepsy cure. However, in recent years, medicinal cannabis has been successfully trialed as an effective treatment for managing epileptic symptoms, but whose mechanisms of action are largely unknown. Lately, there has been a focus on neuroinflammation as an important factor in the pathology of many epileptic disorders. In this literature review, we consider the links that have been identified between epilepsy, neuroinflammation, the endocannabinoid system (ECS), and how cannabinoids may be potent alternatives to more conventional pharmacological therapies. We review the research that demonstrates how the ECS can contribute to neuroinflammation, and could therefore be modulated by cannabinoids to potentially reduce the incidence and severity of seizures. In particular, the cannabinoid cannabidiol has been reported to have anti-convulsant and anti-inflammatory properties, and it shows promise for epilepsy treatment. There are a multitude of signaling pathways that involve endocannabinoids, eicosanoids, and associated receptors by which cannabinoids could potentially exert their therapeutic effects. Further research is needed to better characterize these pathways, and consequently improve the application and regulation of medicinal cannabis.

Cannabis, More Than the Euphoria: Its Therapeutic Use in Drug-Resistant Epilepsy

“…The ECS, which modulates neuronal excitability, has been shown to be dysfunctional in patients with epilepsy [26]. This system comprises two receptors CB1 and CB2 and is activated by endogenous cannabinoids such as anandamide and 2-arachidonoyl glycerol (2-AG) when there is an excessive neuronal activity [27,28].…”

“…A further study by Wallace et al showed that CB1 receptors mediate the anticonvulsant effect of THC, while CBD was not shown to have a similar effect [32]. Cheung et al found that the therapeutic use of THC as an anticonvulsant has been limited due to its psychoactive properties and the possibility of drug tolerance [26]. Its long-term safety is hence a cause for concern [26].…”

“…Cheung et al found that the therapeutic use of THC as an anticonvulsant has been limited due to its psychoactive properties and the possibility of drug tolerance [26]. Its long-term safety is hence a cause for concern [26]. CBD, the non-psychoactive component, has a low affinity for CB1 and CB2 receptors [26].…”

“…Its long-term safety is hence a cause for concern [26]. CBD, the non-psychoactive component, has a low affinity for CB1 and CB2 receptors [26]. Its anticonvulsant properties occur through a variety of mechanisms.…”

Cannabidiol Treatment for Refractory Epilepsies in Pediatrics

“…The discovered role of the endocannabinoid system in epileptogenesis has provided the basis to investigate the pharmacological use of exogenously produced cannabinoids, to treat epilepsy (Cheung et al, 2019;Huntsman et al, 2020).…”