Significant Drug-Drug Interactions With Cannabidiol and Antiepileptics

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Clobazam had been previously identified as an AED with a significant interaction with CBD.
Clobazam had been previously identified as an AED with a significant interaction with CBD.

HOUSTON – Several antiepileptic drugs (AEDs), including clobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine have significant drug-drug interactions with cannabidiol (CBD), according to results from an open-label extension study presented at the 2016 American Epilepsy Society Annual Meeting.

CBD is compound isolated from the marijuana plant that, in its purest form, contains no tetrahydrocannabinol (THC), the psychoactive compound responsible for the “high” associated with marijuana use. Like many other medications, CBD is metabolized in the liver by cytochrome P-450 enzymes, sometimes resulting in drug-drug interactions. These interactions may be significant in patients with epilepsy who may be taking several concomitant AEDs to control seizures.

In this study, Tyler E. Gaston, MD, of the University of Alabama, and colleagues examined baseline serum AED levels to identify drug-drug interactions between CBD and 19 AEDS during an open-label safety study in 81 patients (39 adults, 42 children) with refractory epilepsy.

As doses of CBD were increased, the researchers noted an increase in serum levels of topiramate (P <.01), rufinamide (P <.01), and desmethylclobazam (P <.01), and a decrease in levels of clobazam (P <.01) in both adult and pediatric patients. In adult patients, a significant increase in serum levels of zonisamide (P =.02) and eslicarbazepine (P =.04) was observed with increasing CBD dose. No other drug interactions among the 19 AEDs were noted.

The results emphasize the importance of monitoring serum AED levels in patients receiving CBD, as drug-drug interactions may be correlated with adverse events and lab abnormalities, the authors concluded.

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Reference

Gaston T, Liu Y, Cutter G, Bebin E, Szaflarski J. Drug interactions between pharmaceutical grade cannabidiol (CBD) oil and commonly used anti-epileptic drugs (AEDs). Presented at: 2016 American Epilepsy Society Annual Meeting; December 2-6, 2016; Houston, TX. Abstract 2.208. 

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