Cannabis derivatives and their synthetic analogs for treatment-resistant epilepsy: A systematic review and meta-analysis

Background: Cannabidiol and other synthetic analogs from the Cannabis sativa plant have been investigated as alternative for the treatment of refractory epilepsy. Objective: to assess the effects of cannabis derivatives for the treatment of refractory epilepsy. Search methods: a search of the literature was carried out in the several databases, as well as a manual search of the reference lists of relevant studies, gray literature and clinical trial registries. Selection criteria and analysis: randomized controlled trials were included, and the risk of bias was assessed using the Cochrane risk of bias tool. The certainty of the evidence was assessed using the GRADE approach. Main results: Seven randomized clinical trials were included. Cannabidiol 20 mg/kg/day and 10 mg/kg/day probably increased the frequency of participants who achieved a ≥ 50 % reduction in monthly seizures (20 mg/kg/day: Relative Risk [RR] 1.92; 95 % 95 %CI 1.49–2.46, n = 575, 4 RCTs; 10 mg/kg/day: RR 1.94; 95 %CI 1.32–2.86, n = 280, 2 RCTs, moderate certainty of evidence). The incidence of serious adverse events is probably increased with CBD 20 mg/kg/day (RR 2.30; 95 %CI 1.36–3.89, n = 583, 4 RCTs, moderate certainty of evidence), and may be increased with CBD 10 mg/kg/day (RR 1.62; 95 %CI 0.92–2.84, n = 272, 2 RCTs; low certainty of evidence). Certainty of evidence for other included interventions ranged from very low to low. Conclusions: For most included comparisons and outcomes, there were uncertainties regarding the effects of cannabinoids. Future RCTs could contribute to a better understanding of the effects of cannabinoids for refractory epilepsy.