Could a drug-drug interaction explain the effectiveness of cannabidiol on severe forms of epilepsy?

Cannabidiol has been big news in the epilepsy community over the last year. We have previously posted about the medication becoming available on the NHS for patients with certain syndromes and types of epilepsy. At present, researchers are unsure as to why cannabidiol has the positive effect that it does. 

However, research reported in the British Journal of Clinical Pharmacology (28 October 2019) that it could be a drug-drug interaction between cannabidiol and anti-epilepstic drug (AED) Clobazam that results in a reduction in the frequency of seizures in patients with Lennox-Gastaut syndrome. 

Through clinical trial simulations, the team investigated the effects of 20mg of cannabidiol on the tonic seizure frequency of patients who had been diagnosed with Lennox-Gastaut syndrome. During this simulation, patients were also taking between 10-20mg of clobazam, a common AED for people with Lennox-Gastaut. 

The researchers simulated the GWPCARE3 trial using population-pharmacokinetic models, the same ones that were employed by the US Food and Drug Administration to approve the use of cannabidiol as an AED. 

The findings from the research indicated that there was a drug-drug interaction between cannabidiol and clobazam that resulted in a six-fold increase in N-desmethylclobazam exposure. It’s this interaction that the researchers believe resulted in a significant reduction in the frequency of drop-seizures. These results were recorded in patients who were given 20mg of both clobazam and cannabidiol simultaneously. 

Geert Jan Groeneveld, chief scientific and medical officer at the Centre for Human Drug Research in Leiden, the Netherlands, said: “The effects of cannabidiol on seizure frequency in Lennox-Gastaut patients could be explained entirely through estimated elevations of blood levels of clobazam, which might mean that cannabidiol in itself may not have any, or at best limited, anti-epileptic effects.”

In effect, this would mean that cannabidiol would be acting to enhance the effects of clobazam. Of course, more research may yet be needed to confirm this theory, but it could have potential impact on the development of an entirely new treatment option. It may also unlock the key to understanding more about cannabidiol medications and how they can prove effective in people with severe epilepsy.

For more information on cannabis-based medications and how they are being used to treat epilepsy, please call us on 01706 373075 or email admin@nationalepilepsytraining.co.uk.