Transdermal Cannabidiol safe but no better than placebo in drug-resistant focal epilepsy: JAMA

Australia: A new study published in the Journal of American Medical Association found that transdermal cannabidiol dosages were well accepted and safe. No significant difference in efficacy was seen between cannabidiol and placebo.

Cannabidiol has been demonstrated to be effective in randomized clinical studies for drug-resistant epilepsy in particular disorders affecting children. However, there is a paucity of high-level data regarding cannabidiol's efficacy and safety in the most frequent kind of drug-resistant epilepsy in adults, focal epilepsy. Terence J. O'Brien and colleagues designed this trial to examine the efficacy, safety, and tolerability of transdermally delivered cannabidiol in people with drug-resistant focal epilepsy.

A randomized, placebo-controlled, multicenter clinical trial was undertaken at 14 epilepsy trial centers in Australia and New Zealand for this investigation. Adults with drug-resistant focal epilepsy who were on a stable regimen of up to three antiseizure drugs took part in the study. The data was examined from July 2017 to November 2018.

Eligible participants were randomly assigned (1:1:1) to receive 195-mg or 390-mg transdermal cannabidiol or placebo twice daily for 12 weeks, following which they could participate in an open-label extension trial for up to 2 years. The frequency of seizures was self-reported that used a daily diary. During the 12-week treatment period, the primary effectiveness end point was the least squares mean difference in log-transformed total seizure frequency per 28-day period, adjusted to a shared baseline log seizure rate.

The key findings of this study were as follows:

1. The study enrolled a total of 188 patients. There was no change in seizure frequency among placebo and 195-mg or 390-mg cannabidiol at week 12 of the double-blind study.

2. By the sixth month of the open-label extension, 115 patients (60.8%) had experienced a seizure reduction of at least 50%.

3. Treatment-emergent adverse events occurred in 50.4% (63 of 125 participants) of the cannabidiol group vs 41.3% (26 of 63 participants) of the placebo group, resulting in a 9.1% treatment difference, and occurred at comparable rates in the cannabidiol groups.

Few individuals (7% [14 of 188 participants] dropped out, while the majority (98% [171 of 174 participants] completed the open-label extension.

In conclusion, although the effective therapeutic groups did not differ from the placebo groups during blinded treatment, cannabidiol-treated participants had lower long-term seizure rates than predicted in a population of adults with focal seizures.

Reference:

O'Brien TJ, Berkovic SF, French JA, et al. Adjunctive Transdermal Cannabidiol for Adults With Focal Epilepsy: A Randomized Clinical Trial. JAMA Netw Open. 2022;5(7):e2220189. doi:10.1001/jamanetworkopen.2022.20189