Add-On Cannabidiol for Treatment-Resistant Drop Seizures in Lennox-Gastaut Syndrome

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Cannabidiol may be effective as add-on treatment for drop seizures associated with Lennox-Gastaut syndrome.

Cannabidiol is a safe, tolerable, and effective short-term adjunct treatment option for patients with Lennox-Gastaut syndrome-associated drop seizures whose disease does not respond adequately to antiepileptic drugs, according to findings from a randomized, double-blind trial published in the Lancet.

Patients with treatment-resistant Lennox-Gastaut syndrome and associated drop seizures were included in this trial (N=171). Participants were treated at 24 different centers across the United States, Poland, and The Netherlands and had evidence of slow (<3 Hz) spike-and-wave patterns on electroencephalogram. In addition, participants had clinical evidence of >1 generalized seizure type for ≥6 months, had no response to ≥2 antiepileptic drugs (median, 6 drugs), and had ≥2 drop seizures per week during a 4-week baseline period. Using baseline data, the investigators evaluated the change in monthly drop seizure frequency for each participant at 14 weeks.

Investigators randomly assigned participants to receive either 20 mg/kg oral cannabidiol daily (n=86) or matched placebo (n=85) for a total of 14 weeks. Cannabidiol was considered add-on therapy because participants were taking conventional antiepileptic therapies during the study period.

Participants assigned to cannabidiol experienced a greater percentage reduction in monthly drop seizure frequency compared with those in the placebo arm (43.9% [interquartile range -69.6 to -1.9] vs 21.8% [interquartile range -45.7 to 1.7], respectively), with an estimated median difference between groups of -17.21% (95% CI, -30.32 to -4.09; P =.0135). Although adverse events were higher among those receiving cannabidiol vs placebo (86% vs 69%, respectively), the events were considered mild or moderate in severity.

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As cannabidiol was used in addition to conventional antiepileptic drugs in this study population, the findings may have been reflective of unadjusted drug-drug interactions. Greater insight into the long-term effects of add-on cannabidiol in patients with drop seizures is needed to determine whether the recommendations from these findings can be safely incorporated into clinical care.

The findings that cannabidiol reduced the median frequency of total seizures as well as non-drop seizures during the 14-week study period suggest “that add-on cannabidiol might have broad spectrum effects on seizure reduction,” effects of which need further exploration in longitudinal randomized trials.


Thiele EA, Marsh ED, French JA, et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10125):1085-1096.