CBD Plus Clobazam Achieved 48% Seizure Response Rate in Severe German Epilepsy Patients | Research

The takeaway

In 126 German patients with LGS or DS receiving CBD with clobazam, 47.5% achieved 50%+ seizure reduction at 3 months, with 63% showing tonic-clonic seizure response and 70% remaining on treatment at 1 year.

epileptologists, pharmacologists, epilepsy treatment teams managing CBD-clobazam combinations

What the researchers found

50%+ seizure reduction in total seizures: 47.5% at 3 months, 45.5% at 12 months. For generalized tonic-clonic seizures: 63.0% at 3 months, 56.9% at 12 months. Seizure days decreased from 30 to 15 per month (p<0.001). CGI-C improvement: 66%. Behavioral improvement: 67%. Retention: 89.7% (3 mo), 80.7% (6 mo), 69.8% (12 mo). Main AEs: sedation (23.8%), diarrhea (10.3%).

Why it matters

CBD is approved in the EU specifically for use with clobazam for LGS and DS. This study provides real-world evidence for this specific combination, which showed numerically higher response rates than the broader population (RTHC-07737), likely due to the known pharmacokinetic interaction between CBD and clobazam.

The numbers in context

126 patients (102 LGS, 24 DS). Mean age: 23.2 years. Prior ASMs: median 6. Target CBD: 11.1 mg/kg/day. CLB: 0.14 mg/kg/day. 50%+ response: 47.5% (3 mo), 45.5% (12 mo). GTCS response: 63.0% (3 mo), 56.9% (12 mo). Seizure days: 30 to 15/month. Retention: 69.8% at 12 mo. Sedation: 23.8%.

How the study worked

Retrospective multicenter chart review of 126 patients (102 LGS, 24 DS) from 6 German epilepsy centers receiving adjunctive CBD with concomitant clobazam for up to 12 months.

What this study cannot tell us

Retrospective chart review. No comparator group without clobazam. Selection bias. CBD-clobazam interaction makes it difficult to attribute benefit to CBD alone. Higher sedation may reflect the drug interaction.

How to read the evidence

Multicenter real-world data on the specifically approved CBD-clobazam combination with sustained outcomes supports strong evidence.

When this study was published

German multicenter data up to 12 months of treatment.

The bigger picture

The CBD-clobazam combination appears to enhance seizure control compared to CBD with other medications, consistent with the known pharmacokinetic interaction where CBD increases clobazam's active metabolite levels. The trade-off is higher sedation rates.

Questions still open

How much of the benefit is from CBD vs. the CBD-clobazam pharmacokinetic interaction?
Should clobazam doses be reduced when adding CBD to minimize sedation?

Common questions

Is CBD better with clobazam?

Response rates were numerically higher with the CBD-clobazam combination (48%) than in the broader CBD population (43%), consistent with a known pharmacokinetic interaction that increases clobazam's active metabolite.

What are the main side effects of CBD + clobazam?

Sedation was the most common (23.8%), likely amplified by the drug interaction between CBD and clobazam. Diarrhea (10.3%) and behavioral changes (7.1%) were also reported.

Read the original research

Real-world experience of cannabidiol in conjunction with clobazam for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome: Results from a retrospective multicentre chart review in Germany.

Epilepsy & behavior : E&B, 166, 110302

View on PubMed ↗Publisher’s paper ↗

Citation

Strzelczyk, Adam; Schubert-Bast, Susanne; von Podewils, Felix; Knake, Susanne; Mayer, Thomas; Klotz, Kerstin Alexandra; Buhleier, Elisa; Herold, Luise; Immisch, Ilka; Kurlemann, Gerhard; Rosenow, Felix. (2025). Real-world experience of cannabidiol in conjunction with clobazam for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome: Results from a retrospective multicentre chart review in Germany.. Epilepsy & behavior : E&B, 166, 110302. https://doi.org/10.1016/j.yebeh.2025.110302