The definitive randomized trial proved CBD reduces seizures in Dravet syndrome by 39% vs 13% with placebo — leading directly to FDA approval of Epidiolex.
Parents of children with epilepsy, neurologists, anyone following the CBD drug development story.
39% reductionin convulsive seizure frequency vs 13% with placebo — the evidence that secured FDA approval
The Backstory
The New England Journal of Medicine doesn't publish studies about cannabis. Not because of policy — because the evidence has never been good enough. Since the journal's founding in 1812, not a single cannabis-derived drug had produced the kind of randomized, controlled, blinded data that NEJM demands.
In May 2017, that changed. Orrin Devinsky's trial of cannabidiol for Dravet syndrome was the first cannabis-derived therapy to clear the highest bar in medicine — and the paper that forced the FDA to act.
The Trial
One hundred twenty children and young adults with Dravet syndrome — a severe, SCN1A-mutation-driven epilepsy characterized by prolonged, frequent, and life-threatening seizures — were randomized across 23 sites to receive either pharmaceutical-grade CBD oral solution (Epidiolex, 20 mg/kg/day) or placebo for 14 weeks. All patients had drug-resistant seizures: they were still seizing despite being on a median of three other antiepileptic drugs.
The design was everything Charlotte's Web was not: multicenter, randomized, double-blind, placebo-controlled. No parent co-authors. No dispensary products. No hope-driven narratives. Just a molecule, a placebo, and a protocol.
CBD (Epidiolex) vs Placebo
14 Weeks in 120 Patients With Dravet Syndrome
39%
CBD seizure reduction
Median reduction in monthly convulsive seizures (from 12.4 to 5.9)
13%
Placebo seizure reduction
Median reduction in monthly convulsive seizures (from 14.9 to 14.1)
5%
Seizure-free on CBD
3 of 61 patients had zero convulsive seizures during the trial
0%
Seizure-free on placebo
No placebo patients achieved seizure freedom
43%
≥50% responders on CBD
vs 27% on placebo — a substantial proportion with meaningful improvement
Devinsky et al. (2017), N Engl J Med 376:2011-2020
The primary endpoint — change in convulsive seizure frequency — showed a clear signal. The adjusted median difference between groups was -22.8 percentage points (95% CI: -41.1 to -5.4; p=0.01). In a population where patients were already on three drugs and still seizing, this additional reduction was clinically significant.
The Numbers Behind the Numbers
The headline "39% reduction" can feel abstract. For the families in this trial, the numbers meant something concrete:
12.4 → 5.9
convulsive seizures per month — the median change in the CBD group. That's roughly 7 fewer seizures per month. For a child having a seizure every 2-3 days, that could mean entire weeks without a convulsion.
The placebo group went from 14.9 to 14.1 — essentially no change. Dravet syndrome doesn't get better on its own. Without effective treatment, these children continue to seize.
Devinsky et al. (2017), N Engl J Med
Perhaps more striking: 5% of CBD patients — 3 out of 61 — became completely seizure-free during the trial. Zero placebo patients did. In Dravet syndrome, where seizure freedom is considered nearly impossible with available drugs, this was remarkable.
And 43% of the CBD group achieved at least a 50% reduction in seizures (the standard threshold for "responder" in epilepsy trials), compared to 27% on placebo. This means that for nearly half the patients who received CBD, their seizure burden was cut in half or more — on top of whatever their existing medications were already doing.
The Side Effects Were Real
This was not a free lunch. CBD at 20 mg/kg/day produced meaningful side effects:
The liver function findings were particularly important: CBD appears to interact with valproic acid (a common antiepileptic), causing elevated liver enzymes. This drug-drug interaction became a black box warning on the Epidiolex label and requires regular liver monitoring. It's a reminder that "natural" doesn't mean "harmless" — CBD is a pharmacologically active molecule that interacts with other drugs through CYP450 enzyme pathways.
From Trial to FDA Approval
Research Timeline
The Fourteen Months That Changed Drug Policy
Devinsky trial published in NEJM
Gold-standard evidence for CBD in Dravet syndrome
FDA Advisory Committee votes unanimously to recommend approval
13-0 vote — no dissent among expert advisors
FDA approves Epidiolex
First cannabis-derived drug ever approved by the FDA
DEA reschedules Epidiolex to Schedule V
Creates legal paradox: CBD is Schedule V as Epidiolex but Schedule I as a plant extract
Epidiolex approved for Lennox-Gastaut syndrome
Second indication, based on Thiele et al. (2018) trial
Epidiolex approved for tuberous sclerosis complex
Third indication — broadening the patient population
FDA.gov; DEA scheduling records
The FDA Advisory Committee voted 13-0 to recommend approval — unanimous, which is unusual for any drug, let alone one derived from cannabis. The committee members were explicit: the evidence was strong, the unmet need was severe, and the risk-benefit ratio was favorable despite the side effects.
The DEA's subsequent rescheduling created one of the strangest legal situations in American drug policy. Epidiolex (purified CBD) was placed in Schedule V — the least restrictive category, alongside cough syrup with codeine. But CBD extracted from the cannabis plant remained Schedule I — the most restrictive category, alongside heroin. The same molecule, different legal status, depending on its source.
What This Study Doesn't Tell You
The trial was designed to answer one question: does CBD reduce convulsive seizures in Dravet syndrome? It answered that clearly. But several important questions remain:
Is whole-plant better than purified? Maa and Figi's case report argued it might be. This trial used purified CBD. Head-to-head comparisons of whole-plant extracts versus Epidiolex have not been conducted.
Does it work for other epilepsies? Epidiolex has since been approved for Lennox-Gastaut syndrome and tuberous sclerosis complex, but these are all severe, rare epilepsies. Whether CBD helps with more common forms of epilepsy remains unclear.
What about long-term use? The trial was 14 weeks. Children with Dravet syndrome need lifelong treatment. Laux's 2019 extension study provided some long-term data, but decades of follow-up data don't yet exist.
Is the dose right? Devinsky's 2018 dose-ranging study found that 10 mg/kg/day was as effective as 20 mg/kg/day with fewer side effects — suggesting the original trial may have used a higher dose than necessary.
Key Takeaways
Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome
Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, Scheffer IE, Thiele EA, Wright S (2017) · New England Journal of Medicine
Is Epidiolex the same as CBD oil I can buy online?
No. Epidiolex is pharmaceutical-grade, purified CBD with standardized dosing, manufactured under FDA oversight. Consumer CBD products vary widely in actual CBD content (some contain far less than labeled), may contain THC, and are not subject to the same quality controls. For epilepsy treatment specifically, Epidiolex's consistency and known purity matter clinically.
Can adults with epilepsy use CBD?
The trial included patients aged 2-18 years. Subsequent studies and FDA approval extended to adults. However, the strongest evidence is for Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex. Evidence for CBD in other epilepsy types is limited. Always consult a neurologist.
Why did the FDA approve this but not other cannabis products?
Epidiolex met the standard that other cannabis products haven't: randomized, double-blind, placebo-controlled evidence from adequate-sized trials. The cannabis industry markets products based on anecdotes and preclinical data. Epidiolex went through the full drug development pipeline. The evidence bar for FDA approval is the same for every molecule, regardless of source.
What the researchers found
Cannabidiol (20 mg/kg/day) reduced convulsive seizure frequency by 39% compared to 13% with placebo in children with Dravet syndrome. 5% of CBD patients became seizure-free during the trial; none in the placebo group did. This is the definitive RCT that led to FDA approval of Epidiolex.
Why it matters
This NEJM trial provided the gold-standard evidence the FDA needed to approve Epidiolex — the first cannabis-derived drug ever approved in the United States. It completed the evidence chain from Charlotte Figi's case report through open-label trials to definitive proof.
The numbers in context
- 120 patients randomized (CBD: 61, placebo: 59)
- CBD dose: 20 mg/kg/day oral solution for 14 weeks
- Seizure reduction: 39% (CBD) vs 13% (placebo)
- Adjusted median difference: -22.8 percentage points (95% CI: -41.1 to -5.4; p=0.01)
- 5% seizure-free on CBD vs 0% on placebo
- 43% of CBD group had ≥50% seizure reduction vs 27% on placebo
How the study worked
Multicenter, randomized, double-blind, placebo-controlled trial. 14-week treatment period. Cannabidiol oral solution (Epidiolex) at 20 mg/kg/day or placebo. Primary endpoint: change in convulsive seizure frequency vs baseline.
Who was studied
120 children and young adults (2-18 years) with Dravet syndrome and drug-resistant seizures, multicenter
What this study cannot tell us
Industry-funded (GW Pharmaceuticals). 14-week duration only. Side effects included somnolence, diarrhea, decreased appetite, and abnormal liver function tests. High dropout rate in CBD group partially due to adverse events.
How to read the evidence
Strong: multicenter, double-blind, placebo-controlled RCT published in NEJM. Industry-funded but well-designed and independently replicated.
When this study was published
Published 2017. Epidiolex approved June 2018. Subsequent trials confirmed efficacy in Lennox-Gastaut syndrome and tuberous sclerosis complex.
The bigger picture
This trial completed a remarkable journey: from a forgotten 1980 Brazilian case study, through Charlotte Figi's desperate experiment, to a gold-standard RCT in the world's most prestigious medical journal. FDA approval of Epidiolex in 2018 forced the DEA to reschedule CBD and created a legal paradox: the same molecule was Schedule V as a drug and Schedule I as a plant extract.
Funding
GW Pharmaceuticals
Conflicts of interest
Stephen Wright is an employee of GW Pharmaceuticals. Multiple authors received consulting fees or research support from GW.
Questions still open
- Does CBD work for other epilepsy types beyond Dravet and Lennox-Gastaut?
- Are whole-plant CBD extracts more effective than purified CBD (as Maa & Figi argued)?
- What are the long-term effects of CBD treatment in developing children?
Common questions
Did CBD cure Dravet syndrome?
Is Epidiolex the same as CBD oil from a dispensary?
What were the side effects?
Read the original research
Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome
New England Journal of Medicine, 376(21), 2011-2020
The New England Journal of Medicine is the most prestigious medical journal in the world.
Citation
Devinsky, Orrin; Cross, J Helen; Laux, Linda; Marsh, Eric; Miller, Ian; Nabbout, Rima; Scheffer, Ingrid E; Thiele, Elizabeth A; Wright, Stephen. (2017). Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. New England Journal of Medicine, 376(21), 2011-2020. https://doi.org/10.1056/NEJMoa1611618