FDA Approves Landmark Marijuana-Derived Drug First Tested at UCSF

a bottle of Epidolex sits in front of boxes of the drug
The FDA has approved the durg Epidiolex, which is derived from marijuana, for two forms of epilepsy.

For the first time, a drug derived from marijuana has been approved by the Food and Drug Administration, and it may soon offer relief to children with hard-to-treat seizures. In 2013, UCSF Benioff Children’s Hospital San Francisco became the first site to administer the drug in a child, and as of this week, the FDA has approved its use in two rare and devastating forms of epilepsy.

“Everybody knew that this could be a good medication for seizures, but still, nobody tried,” said Maria Roberta Cilio, MD, PhD, director of research at the UCSF Pediatric Epilepsy Center. Cilio was the senior author of a multi-center study testing the safety and efficacy of the new drug, Epidiolex, in children and young adults. The study provided evidence that Epidiolex should be considered for FDA approval.

“UCSF was very brave to support me,” Cilio said. “We pioneered with this drug.”

Eleven epilepsy centers across the nation administered Epidiolex to 162 participants over 12 weeks. The participants all had severe, childhood-onset, treatment-resistant epilepsy. The results, published in The Lancet Neurology in 2015, showed that the treatment was well-tolerated by patients and reduced the frequency of their seizures. Participants had a median 36.5 percent reduction in monthly motor seizures, which affect muscle activity, with a median monthly frequency of motor seizures falling from 30 a month to 15.8 over the course of the trial.

In the last month of the trial, six patients were free of all motor seizures and nine more were free of all seizure types. At the start of the study, some of these seizure-free patients regularly had hundreds of seizures a day and wound up in the emergency room every three weeks or so, said Cilio.

Unclear How CBD Works on Seizures

Maria Roberta Cilio, MD, PhD
Maria Roberta Cilio, MD, PhD

Epidiolex is a purified form of cannabis devoid of the plant’s main psychoactive component, tetrahydrocannabinol, or THC. The liquid medication mostly consists of cannabidiol, or CBD, a component of marijuana that produces anticonvulsant effects without an accompanying “high.”

It’s still unclear the mechanism by which CBD alleviates seizures, Cilio said, but basic research studies have consistently shown that it does, while THC can sometimes cause seizures. Like any other antiepileptic drug, CBD oil works better for some patients than others and can sometimes be made more effective if combined with other medications. Now that Epidiolex is approved, more studies are needed to understand how it stifles seizures at a molecular level and which patients could benefit most.

Currently medical marijuana is legal in 30 states and Washington, D.C. The FDA previously has approved the drugs Marinol, Syndros and Cesamet, which use synthetic forms of THC, but this is the first time it’s approved a drug derived from the cannabis plant.

CBD oils containing different percentages of CBD and THC are already legal for medical use in some states, including Georgia, Iowa and Oklahoma, but only for treatment of specific conditions and often only with an official registration card. The quality and dosage of those drugs have not been vetted by the FDA.

In contrast, Epidiolex has been shown to be reliable and relatively safe through years of rigorous testing. It now stands as the only FDA-approved treatment for Dravet syndrome, a genetic disorder that can cause daily seizures, sometimes in the hundreds. It is also approved for Lennox-Gastaut syndrome, which is difficult to control with standard epilepsy medications and therapies.

Children with Dravet syndrome begin having seizures before their first birthdays, and those with Lennox-Gastaut often start showing symptoms as toddlers. Epidiolex is a now an option for these children and their families.

“I’m glad this drug was finally approved – the early years were not easy,” said Cilio, referring to the regulatory hurdles of working with a Schedule 1 classified substance. The next challenge will be better understanding the drug’s mechanism of action, she said.

“This is just the beginning.”