Cannabidiol May Impact Antiepileptic Drug Levels in Refractory Epilepsy
Cannabidiol is being studied as a potential treatment for severe refractory epilepsy syndromes.
The addition of cannabidiol (CBD) to treatment for refractory epilepsy is associated with significant changes in the serum levels of several antiepileptic drugs (AEDs), abnormalities in liver function tests, and sedation, according to results published in Epilepsia.
Unlike tetrahydrocannabinol, cannabidiol reportedly lacks psychoactive effects and may be a treatmentoption for severe, refractory epilepsy.
There is limited data on the interaction between CBD and AEDs; however, it appear to modulate several cytochrome P450 (CYP) enzymes. Animal studies have linked CBD with potentiation and reduction in various AEDs thought to be secondary to its effects on CYP.
In the current study, Tyler E. Gaston, MD, of the University of Alabama at Birmingham Epilepsy Center, and colleagues, sought to identify interactions between CBD and commonly used AEDs. Data were obtained from the University of Alabama at Birmingham CBD open-label compassionate-use study that sought to investigate the addition of CBD to treatment regimens in treatment-resistant epilepsy.
Participants in the study included individuals with epilepsy that was resistant to 4 or more AEDs at adequate and stable doses for 1 month prior.
Enrolled participants (42 children [mean age, 10.4] and 39 adults [mean age, 29.1]) were initiated on 5 mg/kg/d of CBD and doses were increased by 5 mg/kg/d every 2 weeks up to 50 mg/kg/d. Doses were adjusted based on tolerability, response, or worsening seizures. Baseline serum AED levels were obtained. Patients were evaluated via a neurological examination, laboratory testing, and a seizure diary every 2 weeks. Overall, increasing doses of CBD were tied to decreased serum levels of clobazam and increased serum levels of topiramate, rufinamide, and N-desmethylclobazam (P <.01 for all). In adult participants, increasing doses of CBD were tied to increased serum levels of eslicarbazepine (P =.04) and zonisamide (P =.02). CBD did not seem to have an impact on serum levels of valproate, levetiracetam, phenobarbital, clonazepam, phenytoin, carbamazepine, lamotrigine, oxcarbazepine, ethosuximide, vigabatrin, ezogabine, pregabalin, perampanel, and lacosamide.
Further, participants taking concomitant valproate were found to have significantly higher AST (P =.002) and ALT (P =.023) levels. Valproate was discontinued in 4 children and 1 adult with normalization of liver function tests, according to the investigators.
Finally, higher N-desmethylclobazam levels were linked to sedation (P =.02), resulting in a decrease but not discontinuation of clobazam.
“Because CBD continues to be studied as a potential anticonvulsant, clinicians and researchers alike should be aware of significant changes in serum levels of clobazam/desmethylclobazam, eslicarbazepine, rufinamide, topiramate, and zonisamide,” the investigators wrote. They also highlighted the need for close monitoring of liver function in patients on concomitant CBD and valproate.
Disclosures: Drs Gaston, Bebin, Butter, Liu, and Szaflarski report receiving a salary from the State of Alabama under “Carly's Law.” Drs Bebin and Szaflarski report receiving fees from Greenwich Biosciences, Inc.
Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP. Interactions between cannabidiol and commonly used antiepileptic drugs [published online August 6, 2017]. Epilepsia. doi: 10.1111/epi.13852