The coming year is likely to include a milestone in the treatment of severe epilepsy: a formal request that the U.S. Food and Drug Administration approve a drug derived from marijuana.
Epidiolex, made from purified cannabidiol, a compound in the marijuana (cannabis) plant, will be submitted to the FDA for approval soon, says Michael Privitera, MD, director of the Epilepsy Center at the University of Cincinnati Gardner Neuroscience Institute and immediate past president of the American Epilepsy Society. He predicts the drug could be approved as early as 2018.
“Three major trials have shown positive results,” Privitera says. “This is a very important advance in the treatment of epilepsy.”
The UC Epilepsy Center was one of 20 sites involved in a Phase 3 clinical study of Epidiolex for the treatment of adults with Lennox-Gastaut syndrome, a serious type of epilepsy that usually begins in childhood and involves multiple types of seizures. People with Lennox-Gastaut can experience hundreds of seizures per week. The seizures, which come without warning, are associated with falls and developmental delay.
Two other major trials involved Epidiolex as a treatment for children with Lennox-Gastaut and Dravet syndrome. Dravet (pronounced Dra-VAY), also known as severe myoclonic epilepsy of infancy, strikes children under 2, typically starts with a high fever, and leads to uncontrollable seizures and cognitive decline. “These children typically do not respond to medication,” Privitera says. “They may lose developmental milestones or even regress in their ability to talk. It’s a terrible disorder.”
Parents of children with serious epilepsy have fueled a demand for legalization of marijuana. But Privitera continues to caution that all drugs must be proven safe, and appropriate doses must be established. “We have to treat it like any other drug,” he says. “We need to know how it works, who will be helped by it, and what side effects it may produce.”
Two important compounds in marijuana are THC (delta-9 tetrahydrocannabinol), which has “psychoactive effects,” and cannabidiol (CBD), which appears to have the most medicinal properties and does not produce psychoactive effects.
“The goal is to get a medication that works for people without making them high,” Privitera says. “You don’t want an 8-year-old who lacks seizure control to be high in class. We’re trying to extract what works for seizures and leave the other stuff behind.”
Epidiolex, the drug used in UC’s study, is made from purified CBD by GW Pharmaceuticals. It was dissolved in oil and squirted into the mouth of patients who participated in the trial. It contained no THC.
A synthetic form of THC called Marinol, which is created in a laboratory, has been approved for patients with cancer or AIDS who suffer severe appetite loss and nausea. “Marinol can make people high,” Privitera notes. A synthetic marijuana also has been approved in Europe (but not the United States) for treating spasticity in patients with multiple sclerosis.
Marijuana, including plant-based CBD, is classified by the U.S. Drug Enforcement Administration (DEA) as a Schedule I drug. The scheduling system is based on a drug’s effectiveness as a medical therapy as well as its potential for abuse and dependency. Schedule 1 drugs, which include heroin and ecstasy, are defined as having “no currently accepted medical use and a high potential for abuse.”
As a result, researchers at the UC Epilepsy Center followed stringent safety requirements in their adult Lennox-Gastaut study. “To conduct our research, I had to acquire special licensing as a ‘terminal distributor of dangerous drugs,’ plus undergo multiple DEA inspections,” Privitera says.
Privitera once quipped that the study medication was “housed in the kind of safe that the Coyote would drop on the Road Runner cartoon character. It’s a 650-pound safe that is kept in a locked room.”
Privitera and others, including the American Medical Association and the American Academy of Pediatrics, agree that reclassifying marijuana or CBD as a lesser schedule would greatly speed research.
— Cindy Starr