Prescription CBD Without Clobazam Reduced Seizures in 30% of Lennox-Gastaut Patients at 12 Months | Research

The takeaway

In a real-world European study, plant-derived CBD (Epidyolex) used without the commonly co-prescribed drug clobazam achieved a 50%+ seizure reduction in 30% of Lennox-Gastaut patients and 13% of Dravet patients at 12 months, with good retention and tolerability.

Epilepsy patients and families, neurologists prescribing CBD, anyone interested in medical cannabis for seizures.

30% of LGS patients achieved 50%+ seizure reduction with CBD alone at 12 months

What the researchers found

Among 107 patients (92 LGS, 15 DS) receiving CBD without clobazam for at least 3 months, median seizure frequency change ranged from -6.2% to -20.9% for LGS and 0% to -16.7% for DS over 3-month intervals. At 12 months, 30% of LGS and 13% of DS patients achieved 50%+ seizure reduction. Retention on CBD without clobazam was 63% at 12 months. Adverse events occurred in 31%, mostly somnolence, seizure, diarrhea, and decreased appetite.

Why it matters

Most clinical trials of CBD for epilepsy included clobazam, raising questions about whether CBD works independently. This real-world study provides evidence that CBD without clobazam still provides meaningful seizure reduction for some patients with severe epilepsy syndromes.

The numbers in context

107 patients (92 LGS, 15 DS). Mean CBD dose: 13.54 mg/kg/day (LGS), 11.56 mg/kg/day (DS). 50%+ seizure reduction at 12 months: 30% LGS, 13% DS. 12-month retention: 63%. Adverse events: 31%. Four patients had elevated liver enzymes.

How the study worked

Retrospective chart review of patients aged 2+ with LGS or DS enrolled in a European Early Access Program for plant-derived CBD (Epidyolex). Data covered 3 months before through 12 months after CBD initiation. Only patients not taking clobazam were included.

What this study cannot tell us

No placebo control or randomization. Retrospective chart review with potential for incomplete documentation. Small DS subgroup (n = 15). Open-label design introduces expectation bias. Mean CBD dose was below the upper end of the approved dose range.

How to read the evidence

Real-world chart review from a structured access program, providing practical effectiveness data but lacking placebo control.

When this study was published

Published 2023, data from European Early Access Program.

The bigger picture

CBD has been approved for LGS and DS primarily based on trials where many patients also took clobazam. Because clobazam and CBD interact (CBD raises clobazam levels), there has been debate about how much of the benefit comes from CBD alone. This study, while uncontrolled, helps fill that gap.

Questions still open

Would higher CBD doses without clobazam produce better seizure control?
Why is the response rate lower in Dravet syndrome than Lennox-Gastaut when CBD is used without clobazam?

Common questions

Does CBD work for seizures without clobazam?

This study suggests it can. About 30% of Lennox-Gastaut patients achieved meaningful seizure reduction with CBD alone at 12 months, and 63% stayed on it for a full year.

What side effects were seen?

Adverse events occurred in 31% of patients, most commonly somnolence, seizure recurrence, diarrhea, and decreased appetite. Four patients had elevated liver enzymes.

Read the original research

Retrospective chart review study of use of cannabidiol (CBD) independent of concomitant clobazam use in patients with Lennox-Gastaut syndrome or Dravet syndrome.

Seizure, 110, 78-85

View on PubMed ↗Publisher’s paper ↗

Citation

Nabbout, Rima; Arzimanoglou, Alexis; Auvin, Stéphane; Berquin, Patrick; Desurkar, Archana; Fuller, Douglas; Nortvedt, Charlotte; Pulitano, Patrizia; Rosati, Anna; Soto, Victor; Villanueva, Vicente; Cross, J Helen. (2023). Retrospective chart review study of use of cannabidiol (CBD) independent of concomitant clobazam use in patients with Lennox-Gastaut syndrome or Dravet syndrome.. Seizure, 110, 78-85. https://doi.org/10.1016/j.seizure.2023.05.003