Prescription CBD Shows Promise for Rare Epilepsies Beyond Its Approved Uses | Research

The takeaway

A systematic review of 57 studies found that prescription CBD (Epidiolex) reduced seizures across 37 different rare epilepsy types, with some patients becoming seizure-free — extending evidence beyond its three approved conditions.

Epilepsy patients and caregivers (especially rare/treatment-resistant types), neurologists, and anyone following CBD medical research.

What the researchers found

CBD reduced seizure frequency in at least one patient across 47 of 57 studies, spanning 37 different developmental and epileptic encephalopathies (DEEs) and treatment-resistant epilepsies (TREs). Twenty-two studies reported at least one patient seizure-free for 48+ days. Most common adverse effects were gastrointestinal.

Why it matters

Epidiolex is only approved for three specific epilepsies, but many patients with other rare seizure disorders lack effective treatment options. This review suggests CBD may help a broader range of epilepsy patients than currently indicated.

The numbers in context

57 studies included, 37 DEE/TRE types, 971 patients total. Most common: focal/multifocal-onset epilepsy (401 patients), Angelman syndrome (188). Seizure reduction in 47/57 studies. 22 studies reported seizure freedom ≥48 days. AEs: diarrhea 17-50%, decreased appetite 7-45%, vomiting 5-86%.

How the study worked

Systematic literature review per PRISMA guidelines searching Embase, PubMed, and Cochrane through March 2024. Evaluated studies reporting CBD effectiveness and tolerability in DEEs/TREs beyond Lennox-Gastaut, Dravet, and tuberous sclerosis (the approved indications). 57 studies included, covering 971 patients.

What this study cannot tell us

Most studies (33/57) were case reports or small case series — the lowest evidence tier. Heterogeneous study designs and outcome definitions. No placebo-controlled data for most conditions. Publication bias likely favors positive results.

How to read the evidence

Systematic review with 57 studies and 971 patients, but most individual studies are case reports/small series — suggestive but not definitive.

When this study was published

Published in 2026, providing the most comprehensive review to date of CBD's broader epilepsy applications.

The bigger picture

With over 37 rare epilepsy types showing potential benefit, this review supports clinical investigation of CBD across the broader spectrum of treatment-resistant epilepsies. For families dealing with rare epilepsies, this offers hope that approved treatment options may eventually expand.

Questions still open

Which specific epilepsy types are most likely to benefit from CBD? Should clinical trials prioritize certain rare epilepsies? Can the gastrointestinal side effects be mitigated?

Common questions

Does CBD work for epilepsies beyond Lennox-Gastaut, Dravet, and TSC?

This review found evidence of seizure reduction across 37 additional rare epilepsy types, with some patients becoming completely seizure-free. However, most evidence comes from small studies, and larger trials are needed.

What are the side effects of prescription CBD for epilepsy?

The most common side effects were gastrointestinal: diarrhea (17-50% of patients), decreased appetite (7-45%), and vomiting (5-86%). These were generally described as mild to moderate in severity.

Read the original research

A systematic review of highly purified cannabidiol in developmental and epileptic encephalopathies and complex treatment-resistant epilepsies: Changes in seizure frequency and adverse events.

Epilepsy research, 220, 107731

View on PubMed ↗Publisher’s paper ↗

Citation

Coppola, Antonietta; Moore-Ramdin, Lisa; Navetta, Marco; Samanta, Debopam. (2026). A systematic review of highly purified cannabidiol in developmental and epileptic encephalopathies and complex treatment-resistant epilepsies: Changes in seizure frequency and adverse events.. Epilepsy research, 220, 107731. https://doi.org/10.1016/j.eplepsyres.2026.107731