Literature Review

Cannabidiol Changes Serum Levels of Antiepileptic Drugs

The treatment also is associated with abnormal liver function test results in patients taking concomitant valproate.


The pharmaceutical formulation of cannabidiol (CBD) is associated with significant changes in serum levels of clobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine, according to research published online ahead of print August 6 in Epilepsia. Furthermore, patients taking CBD and valproate may have abnormal liver function test results.

“A perception exists that since CBD is plant-based, it is natural and safe; and while this may be mostly true, our study shows that CBD, just like other antiepileptic drugs [AEDs], has interactions with other seizure drugs that patients and providers need to be aware of,” said Tyler Gaston, MD, Assistant Professor of Neurology at the University of Alabama at Birmingham.

Tyler Gaston, MD

Patients in a Compassionate-Use Study

Few data about CBD’s interactions with AEDs are available. To gain more information, Dr. Gaston and colleagues examined 42 children and 39 adults in the University of Alabama’s open-label compassionate-use study of CBD as an add-on therapy for treatment-resistant epilepsy. At baseline, the investigators obtained participants’ serum AED levels. Participants initiated treatment with 5 mg/kg/day of CBD along with their other AEDs. Every two weeks, participants underwent a physical examination and laboratory testing. The investigators obtained serum AED levels and increased the dose of CBD by 5 mg/kg/day to a maximum of 50 mg/kg/day. AED doses were adjusted if a clinical symptom or laboratory result was related to a potential interaction.

Dr. Gaston and colleagues used a mixed linear model to determine whether the plasma levels of each AED changed significantly with increasing CBD dose.

Many Serum Levels Remained in Therapeutic Range

The mean age of pediatric participants was 10, and 20 of the children were female. The mean age of adults was 29, and 20 of the adult participants were female. The mean number of concomitant AEDs at enrollment for all participants was three.

The investigators noted increases in serum levels of topiramate, rufinamide, and N-desmethylclobazam (ie, the active metabolite of clobazam) and a decrease in serum levels of clobazam with increasing CBD dose. They also observed increases in serum levels of zonisamide and eslicarbazepine with increasing CBD dose in adults. All mean level changes were within the accepted therapeutic range, except for those in clobazam and N-desmethylclobazam. Sedation was more frequent with higher N-desmethylclobazam levels in adults. Levels of aspartate aminotransferase and alanine aminotransferase were significantly higher in participants taking concomitant valproate.

One of the study’s limitations was that the sample sizes of patients taking each AED were small, which may have masked potential interactions with CBD, according to the researchers. In addition, the naturalistic study design resulted in significant noise in the data for which the researchers could not completely account in their analyses. Nevertheless, “this study emphasizes the importance of monitoring serum AED levels and liver function tests during treatment with CBD,” said Dr. Gaston.

Erik Greb

Suggested Reading

Gaston TE, Bebin EM, Cutter GR, et al. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017 Aug 6 [Epub ahead of print].

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