The Trial That Made CBD a Medicine: From Desperate Parents to FDA Approval
Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial.
Devinsky's clinical program produced the evidence that turned CBD from an anecdote into an FDA-approved drug. The open-label trial (214 patients, 36.5% seizure reduction) paved the way for the NEJM RCT (120 Dravet patients, 38.9% vs 13.3% placebo, p=0.01) and Epidiolex approval in June 2018.
Before this trial, parents were fleeing across state lines. Families with children suffering from Dravet syndrome — a rare, catastrophic epilepsy that kills 15-20% of those it afflicts — were relocating to Colorado, a state where they could legally access cannabis oil. Some were dosing their seizing toddlers with homemade extracts. Some were breaking federal law. All were desperate.
In 2013, CNN's Sanjay Gupta told the story of Charlotte Figi, a Colorado girl with Dravet syndrome whose seizures dropped from 300 per week to less than one per month after her parents began giving her a CBD-rich cannabis extract. The segment was watched by millions. Families flooded Colorado. States began passing "CBD-only" laws. Charlotte's Web — the cannabis strain developed for her — became a household name.
The science was trailing the desperation. There were no randomized clinical trials. No placebo controls. No FDA-approved CBD product. Just parent reports and a tidal wave of hope.
Orrin Devinsky, director of the NYU Comprehensive Epilepsy Center, set out to produce the evidence that the families needed and the regulators required. The result was the clinical program that turned CBD from an anecdote into a medicine.
The Disease
The Open-Label Trial (2016)
Devinsky's program began with an open-label expanded access trial — the largest clinical study of CBD for epilepsy at that time.
36.5%
median reduction in monthly motor seizure frequency over 12 weeks in 137 patients with treatment-resistant epilepsy (including Dravet and Lennox-Gastaut syndromes) who received add-on CBD at 2-5 mg/kg/day titrated up to 25-50 mg/kg/day. Baseline median seizure frequency was 30 per month; at 12 weeks it dropped to 15.8. This was the first large-scale clinical evidence that CBD reduces seizures.
These were patients who had failed multiple anti-epileptic drugs. A 36.5% reduction in a treatment-resistant population is clinically significant — many conventional drugs fail to achieve any meaningful reduction in these patients.
Devinsky et al. (2016), Lancet Neurol 15:270-278
The trial enrolled 214 patients aged 1-30 across 11 US epilepsy centers. It was open-label — everyone knew they were getting CBD — which meant the placebo effect couldn't be ruled out. But the results were encouraging enough to justify what mattered next: a proper randomized controlled trial.
The NEJM Trial (2017)
The study that changed everything was published in the New England Journal of Medicine on May 25, 2017 — the most prestigious medical journal in the world.
The results:
The p-value was 0.01. In a patient population where nothing else had worked, CBD cut convulsive seizures by nearly 40%. The placebo group showed essentially no change — confirming that the effect was real, not wishful thinking.
From Trial to Approval
On June 25, 2018, the FDA approved Epidiolex — purified CBD oral solution — for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome in patients two years of age and older. It was the first cannabis-derived drug ever approved by the FDA. Three months later, the DEA placed it in Schedule V — the least restrictive federal drug schedule.
What the Trial Proved — and What It Didn't
Myth vs. Reality
This trial proved that cannabis oil cures epilepsy.
This trial proved that pharmaceutical-grade purified CBD, at specific doses (20 mg/kg/day), significantly reduces convulsive seizure frequency in Dravet syndrome when added to existing anti-epileptic drugs. It is not a cure — most patients still had seizures, and only 5% achieved seizure freedom. It used purified CBD (Epidiolex), not cannabis oil — no THC, no other cannabinoids, no terpenes. The results cannot be directly extrapolated to dispensary CBD products, which vary in purity, dosage, and formulation.
The Evidence
Devinsky et al. (2017): 38.9% median reduction in convulsive seizures vs 13.3% placebo (p=0.01). 5% seizure-free in CBD group vs 0% placebo. Epidiolex is ≥98% pure CBD.
Devinsky et al. (2017), NEJM 376:2011-2020
Several important nuances:
It used pure CBD, not whole-plant cannabis. Epidiolex is pharmaceutical-grade cannabidiol — no THC, no terpenes, no minor cannabinoids. This is significant for the entourage effect debate: pure CBD works for epilepsy without any "entourage." Whatever makes CBD anticonvulsant, it doesn't require other cannabis compounds.
The doses are high. 20 mg/kg/day for a 30 kg child is 600 mg of CBD daily. Typical over-the-counter CBD products contain 10-50 mg per serving. The clinical doses that produced seizure reduction are an order of magnitude higher than what most consumers take.
Adverse events were real. Somnolence, decreased appetite, diarrhea, and elevated liver enzymes (especially in patients also taking valproate) occurred at clinically significant rates. CBD is not a supplement without side effects — at therapeutic doses, it's a drug with a drug's risk profile.
It doesn't generalize to all epilepsy. The trial studied Dravet syndrome specifically. Subsequent trials confirmed efficacy in Lennox-Gastaut syndrome. Extrapolating to all forms of epilepsy — or to other conditions entirely — is not supported by this data.
Devinsky: The Right Scientist at the Right Time
Orrin Devinsky was uniquely positioned to run this program. A Harvard Medical School graduate mentored by Norman Geschwind, he had spent decades building the NYU Comprehensive Epilepsy Center into one of the premier programs in the country. He founded Finding A Cure for Epilepsy and Seizures (FACES) and co-founded epilepsy.com.
Devinsky understood the desperation of epilepsy families. He also understood that desperation wasn't evidence. When families began moving to Colorado for CBD oil, he recognized that the movement would either be validated by rigorous science or collapse under the weight of uncontrolled anecdotes.
He chose to produce the science. GW Pharmaceuticals provided the pharmaceutical-grade CBD (Epidiolex) and funding. The Epilepsy Foundation and FACES provided infrastructure. Eleven epilepsy centers across the United States enrolled patients. The result was the clinical evidence that turned a folk remedy into an FDA-approved drug.
Frequently Asked Questions
Cite this study
Devinsky, Orrin; Marsh, Eric; Friedman, Daniel; Thiele, Elizabeth; Laux, Linda; Sullivan, Joseph; Miller, Ian; Flamini, Robert; Wilfong, Angus; Filloux, Francis; Wong, Matthew; Tilton, Nicole; Bruno, Patricia; Bluvstein, Judith; Hedlund, Julie; Kamens, Rebecca; Maclean, Jane; Nangia, Srishti; Singhal, Nilika Shah; Wilson, Carey A; Patel, Anup; Cilio, Maria Roberta. (2016). Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial.. The Lancet. Neurology, 15(3), 270-8. https://doi.org/10.1016/S1474-4422(15)00379-8