Compound Derived from Marijuana Interacts with Antiepileptic Drugs

The argument against the notion that marijuana and marijuana-derived compounds have medicinal properties is almost immaterial these days. However, due to complicated legal restrictions, it has been difficult to study the pharmacodynamics of cannabis drugs and contraindications with other commonly prescribed therapeutics. In recent years, cannabis compounds have moved from being utilized just to treat chronic pain as evidence for their usefulness in diminishing epileptic seizures has mounted.

Now, a team of investigators from the University of Alabama (UAB) has just published findings that suggest an investigational neurological treatment derived from cannabis, cannabidiol (CBD), may alter the blood levels of commonly used antiepileptic drugs. Data from the new study, published recently in Epilepsia through an article entitled “Interactions between Cannabidiol and Commonly Used Antiepileptic Drugs”, may provide much-needed drug interaction information to clinicians when considering treatments for complex conditions.

“With any new potential seizure medication, it is important to know if drug interactions exist and if there are labs that should be monitored while taking a specific medication,” explained lead study investigator Tyler Gaston, M.D., assistant professor at UAB.

CBD, which is derived from the cannabis plant, is being studied as a potential anticonvulsant, and it has demonstrated effectiveness in animal models of epilepsy and humans. An ongoing open-label study (Expanded Access Program) conducted by investigators at the University of Alabama at Birmingham is testing the potential of CBD as a therapy for children and adults with difficult-to-control epilepsy. Currently, the study includes 39 adults and 42 children, all of whom receive the cannabis compound.

“In 39 adults and 42 children, CBD dose was started at 5 mg/kg/day and increased every 2 weeks by 5 mg/kg/day up to a maximum of 50 mg/kg/day,” the authors wrote. “Serum AED [antiepileptic drugs] levels were obtained at baseline prior to CBD initiation and at most study visits. AED doses were adjusted if it was determined that a clinical symptom or laboratory result was related to a potential interaction. The Mixed Procedure was used to determine if there was a significant change in the serum level of each of the 19 AEDs with increasing CBD dose.”

The UAB team discovered that there were significant changes in levels of the drugs clobazam (and its active metabolite N-desmethylclobazam), topiramate, and rufinamide in both adults and children, and zonisamide and eslicarbazepine in adults only. With the exception of clobazam and desmethylclobazam, the drug levels did not change outside of the normally accepted range. In addition, adult participants in the study taking clobazam reported sedation more frequently.

However, liver function assays showed that participants taking valproate and CBD had higher aspartate transaminase (AST) and alanine transaminase (ALT) levels, compared with participants not taking valproate. Very high ALT and AST indicate abnormal liver function, but significant ALT and AST elevation occurred only in a small number of participants (four children and one adult), and the levels returned to normal after discontinuation of valproate and CBD.

“While the interaction between CBD and clobazam has been established in the literature, there are currently no published human data on CBD’s potential interactions with other seizure medications,” Dr. Gaston noted. “However, given the open-label and naturalistic follow-up design of this study, our findings will need to be confirmed under controlled conditions.”

The findings emphasize the importance of monitoring blood levels of antiepileptic drugs as well as liver function during treatment with CBD. “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, has interactions with other seizure drugs that patients and providers need to be aware of,” Dr. Gaston concluded.