The Pharmacokinetic and Pharmacodynamic Drug-drug Interaction Potential of Cannabidiol.

Keller G.; Aimar J. · Drug metabolism and bioanalysis · 2026

**Background & Methods** This is a systematic review examining the pharmacokinetic and pharmacodynamic drug-drug interactions (DDIs) of cannabidiol (CBD). The authors reviewed indexed publications and product monographs to catalog and classify identified interactions based on severity, type, and level of evidence. **Key Findings** - A total of 1,289 potential drug-drug interactions were identified: 634 pharmacokinetic interactions and 655 pharmacodynamic interactions, with 19 major interactions requiring avoidance (including colchicine, morphine, buprenorphine, ketamine, venetoclax, and others). - Of all identified interactions, 393 were classified as moderate severity, 49 as minor, and 828 of unknown significance, indicating that while many interactions have been postulated, only a small subset warrants clinical consideration. - CBD inhibits multiple enzymes, generating substantial interaction potential; however, current evidence supports therapeutic intervention changes for only the major interaction category, while the remaining drugs require individual clinical assessment and monitoring. **Dosage & Administration** Not reported. **Safety & Adverse Effects** Not reported. **Evidence Quality** This review is limited by its reliance on experimental reports and existing literature without conducting original clinical trials. The authors acknowledge that many postulated interactions lack sufficient evidence to recommend therapeutic changes. A critical limitation is the confusion between the long historical use of cannabis plant material and the limited scientific timeframe for studying isolated CBD derivatives, which may inflate reported interaction numbers. The categorization of 828 interactions as "unknown significance" highlights substantial gaps in the current evidence base. The study does not differentiate between in vitro enzyme inhibition data and clinically meaningful interactions, which may overestimate real-world risk. As a narrative review rather than a meta-analysis, the methodology lacks systematic quality assessment of included studies. The authors appropriately emphasize the need for caution while noting that clinical practice should focus on the well-documented major interactions rather than all 1,289 identified associations.

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