CBD works for seizures whether or not patients also take clobazam | Research

The takeaway

A meta-analysis of four trials found CBD reduced seizures in both Dravet and Lennox-Gastaut syndrome regardless of whether patients were also taking the benzodiazepine clobazam.

Epileptologists, neurologists managing anti-epileptic drug combinations, and epilepsy researchers.

CBD effective with clobazam (RR 1.85) and without it (RR 1.80)

What the researchers found

Across four RCTs with 714 participants, CBD was associated with significantly higher seizure response rates compared to placebo both in patients taking clobazam (52.9% vs 27.8%, RR=1.85) and those not taking it (29.1% vs 15.7%, RR=1.80). The effect sizes were similar regardless of clobazam status.

Why it matters

A key debate in epilepsy medicine was whether CBD works on its own or only because it boosts clobazam blood levels through a drug interaction. This analysis suggests CBD has independent anti-seizure efficacy.

The numbers in context

714 participants (429 CBD, 285 placebo); CLB-On: 52.9% vs 27.8% response (RR=1.85, p<0.001); CLB-Off: 29.1% vs 15.7% response (RR=1.80, p=0.015).

How the study worked

Meta-analysis of four randomized, placebo-controlled trials in Dravet and Lennox-Gastaut syndrome, stratified by concomitant clobazam use. Risk ratios estimated using inverse variance method.

What this study cannot tell us

Patients were not randomized to clobazam status (post-hoc subgroup analysis); limited sample sizes in subgroups; all trials used pharmaceutical-grade CBD (Epidiolex).

How to read the evidence

Strong: meta-analysis of four RCTs, though clobazam subgroup analysis was post-hoc.

When this study was published

Published 2020.

The bigger picture

This finding strengthens the case that CBD is a genuine anti-seizure medication, not just a drug interaction booster. It supports broader use of CBD in epilepsy patients regardless of their existing medication regimen.

Questions still open

Does CBD interact with other anti-epileptic drugs in ways that affect efficacy? Should dosing be adjusted based on concomitant medications?

Common questions

Does CBD only work because it interacts with clobazam?

No. This meta-analysis found CBD significantly reduced seizures both in patients taking clobazam (RR 1.85) and those not taking it (RR 1.80), suggesting independent efficacy.

Were response rates different with and without clobazam?

Overall response rates were higher in the clobazam group (52.9% vs 29.1% for CBD), but the relative benefit of CBD over placebo was similar regardless of clobazam status.

Read the original research

Cannabidiol efficacy and clobazam status: A systematic review and meta-analysis.

Epilepsia, 61(6), 1090-1098

View on PubMed ↗Publisher’s paper ↗

Citation

Lattanzi, Simona; Trinka, Eugen; Striano, Pasquale; Zaccara, Gaetano; Del Giovane, Cinzia; Nardone, Raffaele; Silvestrini, Mauro; Brigo, Francesco. (2020). Cannabidiol efficacy and clobazam status: A systematic review and meta-analysis.. Epilepsia, 61(6), 1090-1098. https://doi.org/10.1111/epi.16546