After years of anecdotal claims about its benefits, the cannabis derivative cannabidiol reduced seizure frequency 39 percent for patients with Dravet syndrome—a rare, severe form of epilepsy—in the first large-scale, randomized clinical trial for the compound. The New England Journal of Medicine published the findings online May 24.

“Cannabidiol should not be viewed as a panacea for epilepsy, but for patients with especially severe forms who have not responded to numerous medications, these results provide hope that we may soon have another treatment option,” says lead investigator Orrin Devinsky, MD, professor of neurology, neurosurgery, and psychiatry and director of the Comprehensive Epilepsy Center at NYU Langone Medical Center. “We still need more research, but this new trial provides more evidence than we have ever had of cannabidiol’s effectiveness as a medication for treatment-resistant epilepsy.”

Cannabidiol, or CBD, is a compound in the cannabis plant that does not contain psychoactive properties that induce a high. The study included a liquid pharmaceutical formulation of CBD, called Epidiolex^®, which is manufactured by GW Pharmaceuticals and has not yet received U.S. Food and Drug Administration approval. GW Pharmaceuticals funded the clinical trial.

For the study, 120 children and adolescents with Dravet syndrome between the ages of 2 and 18 years were randomized across 23 sites in the United States and Europe to receive either CBD 20 mg/kg or placebo, added to their existing treatment over a 14-week period. Seizure frequency was tracked for one month prior to the study for baseline readings and during the course of the study.

Specifically, seizure frequency dropped 39 percent in the CBD-treated group from a median of nearly 12 convulsive seizures per month before the study to about six; three patients’ seizures stopped entirely. In the placebo group, there was a 13 percent reduction in seizures from about 15 monthly seizures to 14. The difference in the degree of seizure reduction between the CBD group and the placebo group was both statistically significant and clinically consistent.

Side effects, experienced by 93.4 percent of patients in the CBD group and 74.6 percent of those treated with placebo, were generally reported as mild or moderate in severity. The most common side effects in the CBD group were vomiting, fatigue, and fever. Eight participants from the CBD group withdrew from the trial due to side effects compared to one participant in the placebo group.

The new study confirms results from a December 2015 open-label, expanded access trial led by Dr. Devinsky that reported reductions in seizure frequency. In that program, both the researchers and patient’s families knew they were receiving CBD, which may have introduced a bias into the results. This new randomized, controlled clinical study eliminated those concerns, as participants did not know if they were on CBD or placebo, nor did their physicians, say the study authors.

Future research will look at whether safety and tolerability might be improved and whether efficacy of CBD can be maintained at lower doses. Longer-term studies of CBD for Dravet syndrome, as well as for other forms of treatment-resistant epilepsy, are also underway.

In addition to Dr. Devinsky, the co-authors in this study are J. Helen Cross, PhD, FRCPCH; Linda Laux, MD; Eric Marsh, MD; Ian Miller, MD; Rima Nabbout, MD; Ingrid E. Scheffer, MD, PhD; Elizabeth Thiele, MD; and Stephen Wright, MD, on behalf of The Cannabidiol in Dravet Syndrome Study Group. Judith Bluvstein, MD, and Daniel Friedman, MD, also served as co-authors at the NYU Langone site involved in the study.