Clinical trials of cannabidiol for epilepsy

Dravet syndrome and Lennox-Gastaut syndrome (LGS) are severe childhood-onset epilepsies that are generally refractory to medication. Dravet syndrome begins in the first 18 months of life; LGS is usually diagnosed in children ages 2 to 8. Despite trying multiple medications, children with these conditions often continue to have life-threatening seizures.

Mayo Clinic in Rochester, Minnesota, is participating in multicenter, multinational clinical trials of cannabidiol (CBD) treatment for children with Dravet syndrome and LGS. The double-blind, placebo-controlled trials are the first such studies of CBD in the United States.

"These are very important studies because we have no data on the use of CBD in carefully controlled trial designs. To date, we've only had anecdotal evidence in the popular media," says Elaine C. Wirrell, M.D., a consultant in Pediatric Neurology at Mayo Clinic's campus in Minnesota.

The medication, Epidiolex, is a pharmacy-grade product composed almost entirely of CBD with minimal tetrahydrocannabinol (THC). "It's very carefully tested — different from what's available in medical marijuana shops," Dr. Wirrell notes.

Preliminary results

Children in the studies have been placed on the medication or a placebo for 12 weeks, with both parents and physicians blinded as to whether the child is receiving active or placebo drug. After the initial 12 weeks, all children are given the opportunity to take the active medication, with parents and physicians remaining blinded to what a child received during the study period. At Mayo Clinic, 15 children and two adults with LGS and seven children with Dravet syndrome completed the double-blind, placebo-controlled portion of the trial and are now in the open-label portion.

Multicenter data from the Dravet syndrome study found that seizures were reduced by 39 percent in children treated with CBD versus only 16 percent in the placebo group. "That's a modest difference, but statistically significant," Dr. Wirrell says. "CBD is not a cure, but it could potentially be beneficial for children with Dravet syndrome."

Multicenter data from the LGS trial is still being analyzed. "Based on what we're seeing, I suspect CBD could be even more effective for patients with LGS," Dr. Wirrell says.

Clobazam dosage often needs to be reduced when CBD is added. "But otherwise, CBD doesn't react with a lot of other medications. It's pretty well-tolerated, although some of the kids at higher doses can get a little bit of sleepiness, and we've had to reduce the dose for some kids who had loose stools," Dr. Wirrell says.

If approved by the Food and Drug Administration, Epidiolex could provide a treatment option for children with devastating disease. "Kids with Dravet syndrome have recurring bouts of status epilepticus," Dr. Wirrell says. "In addition, the frequency of seizures takes a toll on children's development. As time goes on, it becomes clear that these kids aren't keeping up with their peers, and many have severe behavioral issues. These aren't kids who respond to surgery, so we don't have that option for them.

"We need to do safe and scientific studies of CBD, and get good evidence for both safety and efficacy," she adds. "That's what families deserve."