In a randomized, double-blind, placebo-controlled clinical trial—the gold-standard design—a component of marijuana called cannabidiol (CBD) reduced seizures in children with a rare and devastating form of epilepsy.

The results, published in the New England Journal of Medicine, provide the first solid evidence that marijuana can be used to treat epilepsy, something some patient groups and advocates have argued for years. It also adds to mounting data supporting the medicinal value of the controversial plant. The Drug Enforcement Administration currently lists marijuana as a Schedule I drug, a type of drug with no accepted medical use but a high potential for abuse.

landmark review of marijuana research , released in January by the National Academies of Science, Engineering, and Medicine, concluded that marijuana can effectively treat chronic pain in some patients. But for other conditions, including epilepsy, the data is still inconclusive. Earlier trials on epilepsy, for instance, were small or suboptimal and provided mixed results.

For the new high-quality trial, neurologist Orrin Devinsky of New York University Langone Medical Center and colleagues enrolled 120 US and European kids, aged 2 to 18 (average age of 9.8). All of the kids had a rare form of epilepsy, called Dravet syndrome, and suffered from drug-resistant seizures. Dravet syndrome is a life-long intractable condition generally caused by a mutation in the SCN1A gene. This gene is critical for proper electrical signaling in the brain because it contributes to voltage-gated sodium ion channels in neurons. Dravet syndrome affects only about one in 16,000 people. Between 10 and 20 percent of those affected don’t survive to adulthood.

The 120 participants in the study were, on average, taking three drugs to try to control their seizures. For the first four weeks of the trial, the researchers tracked each participant’s seizure frequency as a baseline. The kids were then randomly assigned to take either CBD—a non-psychoactive component of marijuana taken as an oil—or a placebo for 14 weeks along with their normal drug regimen. The kids and their caretakers didn’t know if they were taking CBD or a placebo.

Data high

In the end, the group of kids taking CBD saw their average number of convulsive seizures drop from 12.4 per month to 5.9. The placebo group’s average only dropped from 14.9 to 14.1 seizures per month. Parsing the data further, the researchers found that 43 percent of those taking CBD saw their seizure rate at least halved, while only 27 percent of the placebo group saw the same. Three of the participants taking CBD became completely free of seizures, but none in the placebo group did. Caregivers were also nearly twice as likely to report that the participant’s overall condition improved while taking CBD compared with placebo.

But these benefits had costs. Ninety-three percent of those taking CBD reported side effects, while only 75 percent of placebo participants made similar reports. The most common side effects reported in the CBD group (and at much higher rates than the placebo group) were sleepiness, diarrhea, and loss of appetite. Other side effects included fatigue, vomiting, raised body temperature, lethargy, upper respiratory tract infections, and elevated liver enzymes. Eight participants taking CBD withdrew from the trial due to the side effects, as did one in the placebo group.

But some of the side effects may have been due to drug combinations, not CBD alone. For instance, kids in the CBD group who were also taking the epilepsy drug valproate were the only ones to experience liver problems as a side effect.

The researchers note that some of the side effects had the potential to “unblind” participants, clueing them in to their treatment group. But when the researchers did extra analysis of the data from the kids that seemed to benefit from CBD, there was no link between improvement and common CBD side-effect reporting. This hints that those participants may not have figured it out.

Still, the authors concluded that they’ll need more data to determine the long-term efficacy and safety. But the trial definitely showed that CBD reduced seizures in kids with Dravet syndrome.

The trial was sponsored by GW Pharmaceuticals, which has branded its CBD oil Epidiolex. The company has already received a “Fast Track” designation from the Food and Drug Administration to hasten its approval process, which will begin later this year. Currently there are no FDA-approved drugs specifically for Dravet syndrome.

"This trial represents the beginning of solid evidence for the use of cannabinoids in epilepsy," Samuel F. Berkovic, of the Epilepsy Research Centre at the University of Melbourne, wrote in an accompanying editorial. "After an era dominated by anecdote and obfuscated by medicolegal issues and emotionally infused debate, more scientific studies are under way."

NEJM, 2017. DOI: 10.1056/NEJMoa1611618 (About DOIs).