Don’t Fear the Reefer—Evidence Mounts for Plant-Based Cannabidiol as Treatment for Epilepsy

Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome Devinsky O, Patel AD, Cross JH, et al; GWPCARE3 Study Group. N Engl J Med. 2018;378:1888-1897. doi:10.1056/NEJMoa1714631 Background: Cannabidiol has been used for treatment-resistant seizures in patients with severe early-onset epilepsy. We investigated the efficacy and safety of cannabidiol added to a regimen of conventional antiepileptic medication to treat drop seizures in patients with the Lennox-Gastaut syndrome, a severe developmental epileptic encephalopathy. Methods: In this double-blind, placebo-controlled trial conducted at 30 clinical centers, we randomly assigned patients with the Lennox-Gastaut syndrome (age range, 2-55 years) who had had 2 or more drop seizures per week during a 28-day baseline period to receive cannabidiol oral solution at a dose of 20 mg/kg of body weight (20-mg cannabidiol group) or 10 mg/kg (10-mg cannabidiol group) or matching placebo, administered in 2 equally divided doses daily for 14 weeks. The primary outcome was the percentage change from baseline in the frequency of drop seizures (average per 28 days) during the treatment period. Results: A total of 225 patients were enrolled; 76 patients were assigned to the 20-mg cannabidiol group, 73 to the 10-mg cannabidiol group, and 76 to the placebo group. During the 28-day baseline period, the median number of drop seizures was 85 in all trial groups combined. The median percentage reduction from baseline in drop seizure frequency during the treatment period was 41.9% in the 20-mg cannabidiol group, 37.2% in the 10-mg cannabidiol group, and 17.2% in the placebo group (P = .005 for the 20-mg cannabidiol group vs placebo group, and P = .002 for the 10-mg cannabidiol group vs placebo group). The most common adverse events among the patients in the cannabidiol groups were somnolence, decreased appetite, and diarrhea; these events occurred more frequently in the higher dose group. Six patients in the 20-mg cannabidiol group and 1 patient in the 10-mg cannabidiol group discontinued the trial medication because of adverse events and were withdrawn from the trial. Fourteen patients who received cannabidiol (9%) had elevated liver aminotransferase concentrations. Conclusions: Among children and adults with the Lennox-Gastaut syndrome, the addition of cannabidiol at a dose of 10 or 20 mg/kg/d to a conventional antiepileptic regimen resulted in greater reductions in the frequency of drop seizures than placebo. Adve