CBD and epilepsy: what Epidyolex proves, and its limits
Epidyolex, authorised since 19 September 2019, is the only cannabidiol medicine authorised in Europe. Its use is limited to three rare, severe epilepsies, always on top of another antiepileptic drug, at 10 to 25 mg per kilo per day with liver monitoring. No over-the-counter CBD product carries an epilepsy indication or comes near that dose.
Key takeaways
- Epidyolex is prescribed from age 2 in Lennox-Gastaut and Dravet syndromes, together with clobazam, and in tuberous sclerosis complex.
- The pivotal trials recorded a seizure reduction 20 to 25 points larger than on placebo.
- A 20 kg child takes 200 to 400 mg of cannabidiol a day, whereas EFSA sets 2 mg for a 70 kg adult in food supplements.
- In 12% of treated patients, liver enzymes climb above three times normal; with valproate and clobazam the rate reaches 23%.
- Any shop CBD product claiming an effect on epilepsy would legally count as a medicine by presentation.
Epidyolex: one medicine, three indications
Epidyolex is an oral solution of purified cannabidiol at 100 mg per millilitre. The European Medicines Agency page shows it has been authorised in the EU since 19 September 2019 as an adjunctive therapy, given in addition to an existing treatment. The authorisation covers:
- seizures in Lennox-Gastaut syndrome and Dravet syndrome, combined with clobazam;
- seizures linked to tuberous sclerosis complex, a rare genetic disease;
- patients from the age of 2.
All three are rare, severe and usually drug-resistant epilepsies; epilepsy in general falls outside the indication. The French public medicines database places Epidyolex on List I. Only neurology and paediatric neurology specialists and departments may prescribe it, and it is reimbursed at 65%.
The Haute Autorité de santé (HAS), France's health technology body, has assessed it twice. Its opinion of 13 May 2020 rated the clinical benefit as important and the added benefit as minor (level IV) in Lennox-Gastaut and Dravet syndromes. For tuberous sclerosis, the opinion of 1 December 2021 rated the benefit as moderate in drug-resistant epilepsy, with no added benefit over existing options (level V), and as insufficient in other cases. The HAS also warned of dosing errors, since the dose is expressed in milligrams while the syringes are graduated in millilitres.
The pivotal trials, in figures
The indications rest on three randomised placebo-controlled trials run by GW Pharmaceuticals as part of its GWPCARE programme.
| Trial | Patients | Dose | Result on cannabidiol | On placebo |
|---|---|---|---|---|
| Dravet, NEJM 2017 | 120 children and young adults | 20 mg/kg/day | Convulsive seizures: 12.4 → 5.9 a month | 14.9 → 14.1 a month |
| Lennox-Gastaut, NEJM 2018 | 225 patients aged 2 to 55 | 10 or 20 mg/kg/day | Drop seizures: −37.2% (10 mg) and −41.9% (20 mg) | −17.2% |
| Tuberous sclerosis, JAMA Neurology 2021 | 224 patients aged 1 to 57 | 25 or 50 mg/kg/day | Seizures: −48.6% (25 mg) | −26.5% |
In Dravet syndrome, seizures at least halved in 43% of treated patients and in 27% on placebo. That difference was not statistically significant, whereas the primary endpoint, seizure frequency, was. In Lennox-Gastaut syndrome, both doses did better than placebo on drop seizures. In tuberous sclerosis, 50 mg brought no gain over 25 mg and nearly doubled the rate of diarrhoea (56% against 31%).
For patients with no other option, these results count. They remain modest, as the placebo group improves too and the net gap is about 20 points. No trial tested cannabidiol on its own, without another antiepileptic drug.
Doses on a different scale from consumer use
The summary of product characteristics describes the treatment schedule. It begins at 2.5 mg per kilo twice a day, that is 5 mg/kg/day, and rises to 10 mg/kg/day after a week. The ceiling is 20 mg/kg/day in Lennox-Gastaut and Dravet syndromes and 25 mg/kg/day in tuberous sclerosis.
Converted to milligrams, a 20 kg child takes 200 to 400 mg a day, and a 70 kg adult at 20 mg/kg/day takes 1,400 mg. For food supplements, EFSA sets a provisional safe level of 2 mg a day for a 70 kg adult. Our article on daily CBD intake explains that value.
The ratio runs from 100 to 700. Trial doses are given in a medical setting with regular blood tests, and no trial conclusion can be applied to an oil sold in a shop.
Documented side effects and interactions
According to the summary of product characteristics, the most frequent side effects are sleepiness (23% of patients), reduced appetite (21%), diarrhoea (20%), fever (16%), vomiting (12%) and fatigue (10%).
Doctors watch the liver most closely. In controlled trials, transaminases (liver enzymes) rose above three times normal in 12% of patients on cannabidiol and in less than 1% on placebo. The other drugs taken change that risk:
| Other treatment | Transaminases above 3 times normal |
|---|---|
| Valproate and clobazam | 23% |
| Valproate alone | 19% |
| Clobazam alone | 3% |
| Neither | 3% |
Dose matters as well: 15% at 20 or 25 mg/kg/day, against 3% at 10 mg/kg/day. Transaminases and bilirubin must be checked at one, three and six months.
Cannabidiol also alters the blood levels of other drugs. With clobazam, the active metabolite rises three- to fourfold, probably because cannabidiol inhibits the CYP2C19 enzyme. Sleepiness then affects 43% of patients, compared with 14% without clobazam. Our articles on CBD and liver enzymes and on the grapefruit effect cover these mechanisms. If you take medication, talk to your doctor or pharmacist before using any CBD product.
Why a shop CBD product has nothing to do with it
A medicine comes with a marketing authorisation, a clinical file, pharmacovigilance and a prescription; a consumer CBD product has none of them. Under article L5111-1 of France's Public Health Code, any substance "presented as having curative or preventive properties" with regard to human diseases is a medicine. A product presented as acting on epilepsy would therefore meet that definition.
ANSM, the French medicines agency, published an alert on this exact issue, updated in March 2025. It reports products sold with claims targeting epilepsy and names three risks. CBD may be toxic to the liver, it may raise the levels of antiepileptic drugs, and nothing guarantees either the real amount of CBD or the absence of other compounds. The agency asks patients never to change their treatment without medical advice.
Medical cannabis is accessed through a separate scheme, described in our update on medical cannabis in France. Our review of CBD clinical studies sorts the evidence from the other published cannabidiol trials.
Frequently asked questions
No. Epidyolex is a purified, precisely dosed pharmaceutical cannabidiol, authorised for three indications and prescribed with blood tests. A consumer oil has no authorisation and no indication, and it comes nowhere near the doses used in trials.
No. Stopping or changing an antiepileptic drug without medical advice exposes you to a serious risk of seizures. Even Epidyolex is given on top of the existing treatment and never replaces it.
The trials used 10 or 20 mg per kilo per day in Lennox-Gastaut and Dravet syndromes, and 25 or 50 mg in tuberous sclerosis. A 20 kg child therefore received several hundred milligrams a day.
Epidyolex alone is reimbursed, at 65%, and only within its indications. Consumer CBD products are not medicines and are not reimbursed.
No. Epidyolex is a purified cannabidiol medicine holding a standard marketing authorisation. Medical cannabis runs under a separate scheme with other products.
Written by the Phytogrammes team
Each journal article draws on cited primary sources: ANSM, EFSA, EUR-Lex and peer-reviewed publications. Product profiles are distinguished from documented laboratory results. Our approach.
Article published on . CBD is not a medicine.