CBD safe, well tolerated in focal epilepsy, efficacy not seen

Transdermal CBD was well tolerated and safe among those with drug-resistant focal epilepsy, although no efficacy was observed compared with placebo during a 12-week treatment period, researchers reported in JAMA Network Open.

“Despite the introduction of many new antiseizure medications over the past 3 decades, seizures remain uncontrolled in approximately one-third of patients,” Terence J. O’Brien, MD, MB, BS, professor and chair of neurology and head of the Central Clinical School at Monash University in Australia, and colleagues wrote. “Although the antiseizure effects of cannabidiol were noted more than 40 years ago, community and scientific interest in cannabidiol and other cannabinoids as potential treatments for drug-resistant epilepsy has intensified following demonstrations of efficacy in suppressing seizures in multiple in vivo models of epilepsy, as well as in open-label and randomized clinical trials in various patient populations.

“However, there is currently no high-level evidence for the efficacy and safety of cannabidiol as a treatment for common types of seizures affecting adults,” they said.

To investigate the efficacy, safety and tolerability of transdermal CBD in adults with drug-resistant focal epilepsy, O’Brien and colleagues conducted a randomized, double-blind, placebo-controlled clinical trial at 14 epilepsy centers in Australia and New Zealand. Researchers recruited adults with drug-resistant focal epilepsy who were receiving a stable regimen of up to three antiseizure medications.

Participants self-reported seizure frequency using a daily diary. The primary end point was the least mean difference in total seizure frequency per 28-day period during the 12-week treatment period.

A total of 188 patients (55% women; mean age, 39 years) were randomized and received 195 mg (n = 63) or 390 mg of transdermal CBD (n = 62) or placebo (n = 63) daily for 12 weeks, after which participants could enroll in an open-label extension study for up to 2 years.

At 12 weeks, researchers observed no difference in seizure frequency among the three groups (placebo: mean 2.49 seizures per 28 days; 195 mg CBD: mean 2.51 seizures; and 390 mg CBD: 2.59 seizures). However, by month 6 of the open-label extension period, 115 patients (60.8%) achieved seizure reduction of at least 50%.

Researchers noted treatment-emergent adverse events in 50.4% of patients in the CBD group compared with 41.3% in the placebo group.

“Both doses of transdermal cannabidiol showed excellent tolerability and safety, substantially better than observed in clinical trials of orally administered cannabidiol,” O’Brien and colleagues wrote. “There were no clinically meaningful changes from baseline in clinical laboratory assessments, vital signs, ECGs, physical examinations or neurological findings. The lack of abnormal liver enzymes over 18 months of the [open-label extension] study may reflect an advantage of transdermal delivery vs. oral administration.”