Background: Epilepsy is one of the most prevalent neurological disorders, affecting approximately 50 million individuals globally. Cannabidiol (CBD) has demonstrated efficacy in reducing seizure frequency among patients with drug-resistant epilepsy. However, the precise mechanisms of action and their interactions with the endocannabinoid system remain inadequately understood. Method: The study conducted a systematic review of the literature on the effects of CBD on epilepsy. A systematic literature review was conducted to identify preclinical and cohort studies involving both pediatric and adult patients. The search was performed across Medline (via PubMed), Scopus, Embase, Web of Science, and CINAHL, with the search period ending in August 2024. Data extraction and synthesis were performed, including study design, sample size, participants, treatment used, mechanisms, and findings. Result: Several studies have shown that CBD has antipsychotic, antidepressant, and anxiolytic properties due to its inhibition of Fatty Acid Amide Hydrolase (FAAH), 5-Hydroxytryptamine (serotonin) receptor 1A (5-HT1A), and Transient Receptor Potential Vanilloid 1 (TRPV1) receptors. CBD has been studied for its effect on epilepsy-related receptors and channels and is an effective treatment for drug-resistant seizures in patients with Lennox-Gastaut Syndrome (LGS) and Dravet Syndrome (DS). Gamma-Aminobutyric Acid Type A Receptor (GABAAR) dysfunction leads to neurological and psychiatric disorders and different drug effects. CBD and 2-Arachidonoylglycerol (2-AG) are positive allosteric modulators of GABAARs. CBD and Cannabidivarin (CBDV) have been shown to activate and desensitize TRPV1 both in vitro and in vivo, which may explain why CBD is such an effective antiepileptic drug. CBD is rapidly absorbed and reaches maximum plasma concentrations in children and adults 0.5-6 hours after ingestion. The oral bioavailability of CBD is low (6-10%) and increases when administered with a high-fat, high-calorie meal. CBD inhibits Cytochrome P450 (CYP)2C19 and CYP3A4, increasing N-desmethylclobazam (N-CLB) and drowsiness in patients with epileptic encephalopathy. CBD has been used in the treatment of refractory epilepsy in recent years. Conclusion: Epilepsy is a chronic hyperexcitability disorder caused by various defects in the brain's neuronal networks. CBD may be able to treat epilepsy by modulating the endocannabinoid system, thereby counteracting some of the functional effects of CB1 receptor activation in the central nervous system.
Shafiei et al. (Fri,) studied this question.