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The May issue of The Rx Consultant focused on cannabidiol (CBD) and included a brief summary of drug interactions. We’d like to provide some additional information on potential interactions with CBD.

CBD inhibits the drug-metabolizing enzyme CYP2C19, and may increase serum levels of CYP2C19 substrates like proton pump inhibitors, diazepam, clobazam, and certain antidepressants. Some in vitro and animal studies have suggested that CBD is also an inhibitor of CYP2C9 (which metabolizes warfarin), albeit to a lesser extent. A larger dose of CBD may be required to inhibit CYP2C9 compared with CYP2C19. While there are no human studies confirming an interaction with 2C9 substrates, a 2018 case report describes a patient who was taking warfarin after a mitral valve replacement and started on CBD for the management of treatment-resistant epilepsy. Over about 17 months, his CBD dose was increased from 5 to 35 mg/kg per day and his INR increased with the dose. After about 12 months, his warfarin dose had been lowered from 7.5 mg/day to an average of 5.36 mg/day. There were no bleeding complications.

Because CBD may increase serum levels (and possibly side effects) of CYP2C9 substrates (including the NSAIDs diclofenac, ibuprofen, meloxicam and celecoxib; amitriptyline; warfarin; glipizide; and losartan), cautioned is advised with combined use of CBD and CYP2C9 substrates. Individuals with a genetic variant of the 2C19 or 2C9 enzyme are poor metabolizers of the respective substrates and may be more susceptible to CBD-drug interactions. In patients taking warfarin, INR monitoring has been suggested during initiation of CBD and when CBD doses are increased.

Grayson L, et al. Epilepsy Behav Case Rep. 2018; 9: 10–11.

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