The US Food and Drug Administration (FDA) has given approval for studies to begin on a medicinal form of marijuana for the treatment of intractable epilepsy in children.

The drug, cannabidiol (Epidiolex, GW Pharmaceuticals) is the largest nonpsychoactive component of the cannabis plant. The product has also been granted orphan drug status for the treatment of children with Dravet syndrome, a rare and severe syndrome of infantile-onset, genetic, drug-resistant epilepsy.

One of the investigators in the study, Orrin Devinksy, MD, New York University School of Medicine, New York, told Medscape Medical News that this is the first formal study of cannabidiol, although there have been anecdotal reports of "miraculous" benefits with similar products in severe epilepsy. Many of these reports have been featured as part of media coverage profiling parents lobbying to get access to this treatment for their children.

Dr. Devinksy noted that GW Pharmaceuticals already has approval and is marketing a drug containing 50% cannabidiol and 50% delta-9 tetrahydrocannabinol (THC, a psychoactive ingredient of marijuana) under the brand name Sativex in the United Kingdom, several European countries, Canada, and New Zealand to treat spasticity in multiple sclerosis (MS). It is also being developed to treat neuropathic pain in MS as well as cancer pain.

"The company is now also making pure cannabidiol, which is to be tested in our epilepsy study," he added.

Dramatic Effects in Anecdotal Reports

"We still don't know for sure that it works in epilepsy," he noted. "There have been very promising results in animal studies. In addition, marijuana growers have developed strains high in cannabidiol and patients are reporting dramatic benefits with these in reducing epileptic seizures, but there is no controlled data to eliminate the placebo effect and bias, which could be enormous."

He explained that placebo response rates are generally higher in pediatric studies because parents appear to be more willing to see benefits in their children.

Dr. Devinksy reported that THC has been shown to be associated with psychiatric disorders and a permanent reduction in short-term memory in children. "So if you are considering using products containing THC, the benefits would have to outweigh the risks. If a child was having 100 seizures a day, then its use might be justified, but it would not be warranted for milder epilepsy."

He added: "Cannabidiol does not have psychoactive properties and its safety profile seems quite good. As cannabidiol makes up half the contents of Sativex, which is being taken by many tens of thousands of patients, and we anticipate that cannabidiol will have a better safety profile, we do not expect there to be major safety issues."

He noted that strains of marijuana with cannabidiol-to-THC ratios of 20:1 have been tolerated well and reported to improve cognitive function and behavioral function in children in anecdotal reports.

The initial FDA-approved study of cannabidiol will assess dose tolerability in an open-label design, with blood counts, liver function, and attentiveness all carefully monitored. Although safety is the primary outcome, frequency of seizures will also be measured.

This first study will take place at 5 sites, with 25 patients at each site, all with epilepsy refractory to current treatment. Most of the participants will be children with Dravet syndrome, but there will also be some children with other severe forms of epilepsy and some young adults. "From this study we will select an optimal dose with which to go into a placebo-controlled efficacy trial," Dr. Devinksy commented.

He added: "We have been inundated with applicants. We will largely select from patients who have been in our practice for a long time, but we will also take some other very severe cases." The study will start in January, with initial results available after 2 to 3 months.