Cannabidiol is an effective and generally well-tolerated add-on treatment for drop seizures in patients with Lennox-Gastaut syndrome, according to research published in The Lancet.
“Patients with Lennox-Gastaut syndrome, a rare, severe form of epileptic encephalopathy, are frequently treatment resistant to available medications,” Elizabeth A. Thiele, MD, from the pediatric epilepsy program at Massachusetts General Hospital, and colleagues wrote. “No controlled studies have investigated the use of cannabidiol for patients with seizures associated with Lennox-Gastaut syndrome.”

To determine the safety and efficacy of cannabidiol as an addition to anticonvulsant therapy for drop seizures in patients with treatment-resistant Lennox-Gastaut syndrome, Thiele and colleagues conducted a double-blind, placebo-controlled trial at 24 clinical sites.

The study included 171 eligible patients from the United States, the Netherlands or Poland aged between 2 and 55 years with Lennox-Gastaut syndrome who did not respond to at least two antiepileptic drugs. Participants also had a history of slow (< 3 HZ) spike-and-wave patterns on electroencephalogram, more than one type of generalized seizure for 6 or more months and two or more drop seizures each week over the course of a 4-week baseline phase, according to the researchers.

For 14 weeks, the participants were randomly assigned to receive either 20 mg/kg of oral cannabidiol daily (n = 86) or matched placebo (n = 85). The study was discontinued by 14 patients in the cannabidiol group and one in the placebo group.

Results showed that there was a higher reduction in drop seizures with cannabidiol treatment than placebo treatment. Average drop seizures declined from 71.4 per month at the start of the study to 31.4 per month at the end in the cannabidiol group, indicating a 43.9% reduction. In the placebo group, average drop seizures declined from 74.7 per month at the start of the study to 56.3 per month at the end, indicating a 21.8% reduction. Between the two groups, there was an estimated median difference of –17.21 (95% CI, –30.32 to –4.09). The frequency of other seizures was also more likely to reduce with cannabidiol treatment. There was a 41.2% reduction in the monthly frequency of all seizures among patients taking cannabidiol, compared with a reduction of 13.7% among those taking placebo.

Adverse events were prevalent in 86% of patients taking cannabidiol and 69% of those taking placebo. Diarrhea, somnolence, pyrexia, decreased appetite and vomiting were the most common adverse events. These adverse events were mostly mild or moderate, but 12 patients in the cannabidiol group and one in the placebo group withdrew from the trial due to the side effects.


“There is an urgent need for novel treatment options for patients with Lennox-Gastaut syndrome, and we are pleased that our study has potentially found an additional option to add to patients’ existing treatment to reduce drop seizures,” Thiele said in a press release. “Our results suggest that the use of cannabidiol as an add-on therapy with other anti-epilepsy drugs might significantly reduce the frequency of drop seizures in patients with Lennox-Gastaut syndrome, which is positive news for these patients, who often do not respond to treatment.”

In a related comment, Sophia Varadkar, PhD, from the neuroscience unit at the Great Ormond Street Hospital for Children, London, wrote that the findings by Thiele and colleagues add to the evidence for treating drop seizures with cannabidiol in patients with Lennox-Gastaut syndrome and highlight the need for more studies.

“After many years without promise of new treatments in Lennox-Gastaut syndrome, this is an exciting time for patients and clinicians,” she wrote. “More data and clinical experience of cannabidiol in Lennox-Gastaut syndrome is expected… Clinical trials with cannabidiol are underway in tuberous sclerosis complex and infantile spasms, and future studies are expected in the other pharmacoresistant epilepsy syndromes.” – by Alaina Tedesco

Disclosure: Thiele reports receiving grants from GW Research Pharmaceuticals, being the principal investigator on clinical trials for GW Pharmaceuticals and Zogenix and serving as a consultant for Eisai Medical Research, Greenwich Biosciences, Ovid Therapeutics, UCB, Aquestive and Zogenix. Please see study for all other authors’ relevant financial disclosures.