Epidiolex is the only cannabis-derived medicine the FDA has approved to treat epilepsy. It is a purified oral solution of cannabidiol (CBD). The FDA approved it in June 2018 for Dravet syndrome and Lennox-Gastaut syndrome in patients age 2 and older. A 2020 approval added tuberous sclerosis complex. Whole-plant cannabis and retail CBD oils are not FDA approved for seizures.
What the trials found
The Dravet syndrome trial enrolled 120 patients. CBD at 20 mg/kg per day lowered median monthly convulsive seizures from 12.4 to 5.9. The placebo group went from 14.9 to 14.1. Results appeared in the New England Journal of Medicine in 2017.
The Lennox-Gastaut trials enrolled 171 patients in one study and 225 in another. Median drop in drop seizures was 43.9 percent at 20 mg/kg per day and 37.2 percent at 10 mg/kg per day. Placebo produced a 17.2 percent drop. No trial showed seizure freedom for most patients. A small number of patients became seizure free.
Dose and side effects
The Epidiolex label starts patients at 2.5 mg/kg twice daily. The target dose is 10 mg/kg per day. The maximum is 20 mg/kg per day, or 10 mg/kg twice daily.
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- Common side effects: sleepiness, sedation, decreased appetite, diarrhea, fatigue.
- Liver enzyme rises (ALT and AST) occur in some patients. The label calls for blood tests before treatment and during titration.
- CBD raises levels of clobazam's active metabolite, norclobazam. This can increase sedation.
- Valproate plus CBD raises the risk of liver injury and low platelet counts.
Medical cannabis vs. Epidiolex
Many state medical cannabis programs list epilepsy as a qualifying condition. Products sold under those programs contain THC, CBD, or both. THC and CBD ratios vary by product and batch. Evidence for THC as a seizure treatment is limited and mixed. Human randomized trial data cover purified CBD, not smoked flower or full-spectrum oils.
Dose matters. Trial doses of 10 to 20 mg/kg per day are far above the doses printed on most retail CBD labels. A 30 kg child at 20 mg/kg per day takes 600 mg daily.
Regulation and claims
The DEA placed Epidiolex in Schedule V in September 2018. Cannabis remains Schedule I at the federal level. The FDA has sent warning letters to companies that market CBD products as epilepsy treatments.
Questions for a neurologist
- Does this patient have a syndrome with trial data, such as Dravet or Lennox-Gastaut?
- What is the current seizure count per month, by type?
- Which current drugs interact with CBD, such as clobazam or valproate?
- When are liver enzyme tests needed?
- Is a state-licensed product under consideration, and what is its measured CBD and THC content?
Bottom line
Purified CBD has placebo-controlled trial data in three rare epilepsy syndromes and FDA approval for those uses. Whole-plant medical cannabis does not have that evidence base, and product content varies. Patients should not change seizure medicines without a neurologist.