Clinical trial simulations suggest CBD's reduction of seizures in Lennox-Gastaut syndrome could be explained by its drug interaction with clobazam, which raises levels of clobazam's active metabolite 2- to 7-fold.
Neurologists, epilepsy researchers, and families using CBD for seizures.
CBD raises clobazam's active metabolite 2-7 fold
What the researchers found
Simulations showed that the observed seizure reduction from CBD could be replicated by assuming: (1) patients on clobazam had a 2- to 7-fold increase in norclobazam (active metabolite) exposure, and (2) patients not on clobazam had seizure reduction and variability similar to placebo. This suggests CBD's apparent anti-seizure effect may be primarily a drug interaction rather than a direct pharmacological effect.
Why it matters
If CBD's benefit is primarily through boosting clobazam, simply increasing clobazam doses might achieve the same effect at lower cost, though with potentially more side effects.
The numbers in context
CBD dose: 20 mg/kg/day. Norclobazam exposure increase: 2- to 7-fold. Simulated patients on 10 or 20 mg clobazam.
How the study worked
Clinical trial simulations modeling the effect of 20 mg/kg/day CBD on drop-seizure frequency in Lennox-Gastaut syndrome, assuming known CBD-clobazam interaction parameters.
What this study cannot tell us
Simulation study, not empirical trial. Assumptions may not fully reflect clinical reality. Does not account for all possible mechanisms of CBD action.
How to read the evidence
Simulation study based on known pharmacokinetic data, providing a plausible hypothesis but not proof.
When this study was published
2020 simulation study.
The bigger picture
This challenges the narrative that CBD has independent anti-seizure properties and has implications for the FDA registration of Epidiolex and for patients and families investing in CBD treatment.
Questions still open
- If the benefit is from drug interaction, should clobazam doses be increased instead? Does CBD have any direct anti-seizure effects independent of drug interactions?
Common questions
Does CBD directly stop seizures?
How does CBD interact with clobazam?
Read the original research
Clinical trial simulations of the interaction between cannabidiol and clobazam and effect on drop-seizure frequency.
British journal of clinical pharmacology, 86(2), 380-385
Citation
Bergmann, Kirsten Riber; Broekhuizen, Karen; Groeneveld, Geert Jan. (2020). Clinical trial simulations of the interaction between cannabidiol and clobazam and effect on drop-seizure frequency.. British journal of clinical pharmacology, 86(2), 380-385. https://doi.org/10.1111/bcp.14158
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