CBD helped adults with drug-resistant epilepsy regardless of whether they had approved diagnoses | Research

The takeaway

In a real-world study of 91 adults with drug-resistant epilepsy, CBD showed similar response rates (about 31-36%) whether used for approved indications or off-label, with co-prescribed clobazam strongly predicting response in off-label patients.

People interested in CBD treatment for epilepsy, particularly beyond the currently approved diagnoses.

35.6% response rate in off-label epilepsy patients

What the researchers found

No significant difference in responder rates (greater than 50% seizure reduction) between authorized-indication patients (31.3%) and off-label patients (35.6%, p=0.85). One-year retention rates were also similar (75.0% vs. 74.6%). Among off-label patients, clobazam co-prescription strongly predicted response (71.4% of responders vs. 28.9% of non-responders took clobazam, p=0.002).

Why it matters

Pharmaceutical CBD is currently approved only for three specific epilepsy syndromes. This real-world data suggests it may benefit a broader population of adults with drug-resistant epilepsy, particularly those already taking clobazam.

The numbers in context

91 patients included. 35.2% in authorized group. Responder rates: 31.3% authorized vs. 35.6% off-label (p=0.85). 1-year retention: 75% vs. 74.6% (p=0.97). Clobazam in off-label responders: 71.4% vs. 28.9% in non-responders (p=0.002). Median follow-up: 24 months.

How the study worked

Retrospective study at the epilepsy unit of Pitie Salpetriere Hospital in Paris. Included patients initiating pharmaceutical CBD and followed for at least 1 year. Patients divided into authorized (LGS, Dravet, TSC) and off-label groups. Median follow-up: 24 months.

What this study cannot tell us

Retrospective, single-center design with no randomization or placebo control. Relatively small sample. The strong clobazam association may reflect a pharmacokinetic interaction (CBD inhibits clobazam metabolism) rather than true synergy. No blinding.

How to read the evidence

Real-world retrospective study from a single tertiary center. Consistent results but limited by lack of randomization, small sample, and potential confounding by clobazam interaction.

When this study was published

Published in 2024 with median 24-month follow-up data.

The bigger picture

As real-world evidence accumulates, the question of whether CBD should be approved for broader epilepsy populations gains traction. This study from a major French epilepsy center adds to evidence that the current approved indications may be too narrow.

Questions still open

Is the clobazam-CBD interaction a true pharmacological synergy, or does CBD simply raise clobazam levels? Would a randomized controlled trial in off-label patients confirm these observational findings? Which off-label epilepsy types respond best to CBD?

Common questions

Is CBD only approved for certain types of epilepsy?

Yes. Pharmaceutical CBD (Epidiolex) is currently approved for Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. This study suggests it may also help adults with other forms of drug-resistant epilepsy.

Why does clobazam matter?

Among off-label patients who responded to CBD, 71% were also taking clobazam, compared to only 29% of non-responders. This strong association may reflect a pharmacokinetic interaction where CBD increases clobazam levels in the body.

Read the original research

Cannabidiol Treatment for Adult Patients with Drug-Resistant Epilepsies: A Real-World Study in a Tertiary Center.

Brain and behavior, 14(11), e70122

View on PubMed ↗Publisher’s paper ↗

Citation

Calonge, Quentin; Besnard, Aurore; Bailly, Laurent; Damiano, Maria; Pichit, Phintip; Dupont, Sophie; Gourfinkel-An, Isabelle; Navarro, Vincent. (2024). Cannabidiol Treatment for Adult Patients with Drug-Resistant Epilepsies: A Real-World Study in a Tertiary Center.. Brain and behavior, 14(11), e70122. https://doi.org/10.1002/brb3.70122