Randomized controlled trial★ Featured study

Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome.

Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, et al. · N Engl J Med · 2017

can-nabis read · published 2026-05-27

The read

The trial that put CBD in the medical mainstream. Devinsky and a multi-center team ran a 14-week placebo-controlled study of pharmaceutical-grade cannabidiol in 120 children and young adults with Dravet syndrome, a rare and brutal form of childhood epilepsy that's typically refractory to standard anticonvulsants.

Patients took either CBD at 20 mg per kilogram per day or placebo, on top of their existing seizure medications. Convulsive seizure frequency dropped by a median of 39% in the CBD group versus 13% in the placebo group. Five percent of CBD patients became completely seizure-free during the trial. None of the placebo patients did.

This was the work that drove FDA approval of Epidiolex in 2018, the first cannabis-derived medication approved in the United States. It's the cleanest evidence we have that a specific cannabinoid does a specific clinical thing under standard pharmaceutical trial conditions, with proper dosing and placebo control.

The side-effect picture was real. 93% of CBD patients had at least one adverse event versus 75% on placebo. Most common were drowsiness, decreased appetite, diarrhea, fatigue, and elevated liver enzymes. The last one matters: patients also on valproate had a measurable risk of liver-enzyme spikes that required monitoring. Eight CBD patients withdrew from the trial due to side effects.

The paper deserves the weight it carries. It doesn't generalize cleanly to other epilepsies, other CBD doses, or to over-the-counter CBD products, but for Dravet specifically the evidence is as solid as it gets.

What this paper found

39% median reduction in convulsive seizures on CBD versus 13% on placebo over 14 weeks.
5% of patients on CBD became completely seizure-free during the trial; none in the placebo group did.
Drove FDA approval of Epidiolex in 2018, the first cannabis-derived drug approved in the United States.
Cleanest RCT evidence on record for a specific cannabinoid producing a specific clinical outcome under proper trial conditions.

Where it falls short

Dravet-specific. Other epilepsy syndromes may not respond the same way to CBD.
Side effects were common: 93% of CBD patients vs 75% on placebo had at least one adverse event.
Liver-enzyme elevations required monitoring, especially in patients also taking valproate.
14-week study. Long-term efficacy and safety beyond a few months are not addressed.
Pharmaceutical-grade purified CBD at a controlled dose. Results do not translate to consumer CBD products which vary wildly in actual cannabinoid content and purity.

Original abstract

BACKGROUND: The Dravet syndrome is a complex childhood epilepsy disorder that is associated with drug-resistant seizures and a high mortality rate. We studied cannabidiol for the treatment of drug-resistant seizures in the Dravet syndrome. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 120 children and young adults with the Dravet syndrome and drug-resistant seizures to receive either cannabidiol oral solution at a dose of 20 mg per kilogram of body weight per day or placebo, in addition to standard antiepileptic treatment. The primary end point was the change in convulsive-seizure frequency over a 14-week treatment period, as compared with a 4-week baseline period. RESULTS: The median frequency of convulsive seizures per month decreased from 12.4 to 5.9 with cannabidiol, as compared with a decrease from 14.9 to 14.1 with placebo (adjusted median difference between the cannabidiol group and the placebo group in change in seizure frequency, -22.8 percentage points; 95% confidence interval [CI], -41.1 to -5.4; P=0.01). The percentage of patients who had at least a 50% reduction in convulsive-seizure frequency was 43% with cannabidiol and 27% with placebo (odds ratio, 2.00; 95% CI, 0.93 to 4.30; P=0.08). The patient's overall condition improved by at least one category on the seven-category Caregiver Global Impression of Change scale in 62% of the cannabidiol group as compared with 34% of the placebo group (P=0.02). The frequency of total seizures of all types was significantly reduced with cannabidiol (P=0.03), but there was no significant reduction in nonconvulsive seizures. The percentage of patients who became seizure-free was 5% with cannabidiol and 0% with placebo (P=0.08). Adverse events that occurred more frequently in the cannabidiol group than in the placebo group included diarrhea, vomiting, fatigue, pyrexia, somnolence, and abnormal results on liver-function tests. There were more withdrawals from the trial in the cannabidiol group. CONCLUSIONS: Among patients with the Dravet syndrome, cannabidiol resulted in a greater reduction in convulsive-seizure frequency than placebo and was associated with higher rates of adverse events. (Funded by GW Pharmaceuticals; ClinicalTrials.gov number, NCT02091375 .).

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Tagged conditions

Epilepsy →