The psychotropic effects of cannabis may be what the historically maligned drug is best known for, yet in recent decades a growing body of evidence continues to suggest that the drug has numerous valuable properties that make it a potentially valuable therapeutic. Now, investigators from NYU School of Medicine have shown in a new large-scale, randomized, controlled trial that cannabidiol (CBD)—a compound derived from the cannabis plant that does not produce a “high”—significantly reduces the number of dangerous seizures in patients with a severe form of epilepsy called Lennox-Gastaut syndrome. Findings from the new study were published recently in the New England Journal of Medicine, in an article entitled “Effect of Cannabidiol on Drop Seizures in the Lennox–Gastaut Syndrome.”
“This new study adds rigorous evidence of cannabidiol's effectiveness in reducing seizure burden in a severe form of epilepsy and, importantly, is the first study of its kind to offer more information on proper dosing,” explained lead study investigator Orrin Devinsky, M.D., professor of neurology, neurosurgery, and psychiatry at NYU School of Medicine and director of NYU Langone's Comprehensive Epilepsy Center. “These are real medications with real side effects, and as providers, we need to know all we can about a potential treatment in order to provide safe and effective care to our patients.”
Orrin Devinsky, M.D., director of the Comprehensive Epilepsy Center at NYU Langone Health, explains the new study on cannabidiol for treatment-resistant epilepsy, and why this is an exciting time in epilepsy research. [NYU Langone Health]
In the new study, the researchers compared two doses of CBD to a placebo. The scientists reported a 41.9% reduction in “drop seizures”—a type of seizure that results in severe loss of muscle control and balance—in patients taking a 20 mg/kg per day CBD regimen, a 37.2% reduction in those on a 10 mg/kg per day CBD regimen, and a 17.2% reduction in a group given a placebo.
The study included an investigational liquid, oral formulation of CBD called Epidiolex®. The product is manufactured by GW Pharmaceuticals, which operates in the U.S. as Greenwich Biosciences—GW Pharmaceuticals funded the clinical trial.
Lennox-Gastaut syndrome is a rare and severe form of epilepsy characterized by frequent drop seizures and severe cognitive impairment. Currently, six medications are approved to treat seizures in patients with the syndrome, but disabling seizures occur in most patients despite these treatments.
In the current study, the researchers enrolled 225 patients (ages 2 to 55) with Lennox-Gastaut syndrome across 30 international sites in a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of two doses of CBD. Seventy-six patients received 20 mg/kg per day CBD, 73 received 10 mg/kg per day CBD, and 76 were given a placebo. All medications were divided into two doses per day for 14 weeks. The number of seizures was monitored beginning four weeks before the study for baseline assessment, then tracked throughout the 14-week study period and afterward for a four-week safety check.
Unfortunately, side effects occurred in 94% of patients in the 20-mg CBD group, 84% in the 10-mg CBD group, and 72% of those taking a placebo. However, side effects were generally reported as mild or moderate in severity, and those that occurred in more than 10% of patients included: sleepiness, decreased appetite, diarrhea, upper respiratory infection, fever, vomiting, nasopharyngitis, and status epilepticus. Fourteen patients taking CBD experienced dose-related elevated liver enzymes that were reversible. Seven participants from the CBD group withdrew from the trial due to side effects compared to one participant in the placebo group.
“This landmark study provides data and evidence that Epidiolex can be an effective and safe treatment for seizures seen in patients with Lennox-Gastaut syndrome, a very difficult to control epilepsy syndrome,” noted co-lead study investigator, Anup Patel, M.D., chief of neurology at Nationwide Children's Hospital.
Interestingly, a previous study led by Dr. Devinsky showed a 39% drop in seizure frequency in patients with a different rare form of epilepsy called Dravet syndrome. Those findings represented the first large-scale, randomized clinical trial for the compound. Open-label CBD studies led by Dr. Devinsky also have shown positive results for treatment-resistant epilepsies.
In April, a U.S. Food and Drug Administration advisory panel unanimously voted to recommend approval of a new drug application for Epidiolex cannabidiol oral solution, following a meeting where researchers, including Dr. Devinsky, presented their findings. The FDA will decide whether to approve the medication in late June.
“While the news gives hope for a new treatment option to the epilepsy community, more research remains imperative to better determine the effects of CBD and other similar cannabis-derived compounds on other forms of the disease and in more dosing regimens,” Dr. Devinsky concluded.