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

Although Cannabidiol (CBD) has recently been approved for use in some neurological diseases, the pharmacology of CBD is not fully understood. Experimental reports suggest CBD inhibits a large number of enzymes, generating the possibility of multiple interactions. The aim is to describe the main known interactions, evidence, and actual risk in clinical practice. Existing indexed publications and product monographs were reviewed. The authors cataloged and classified the information based on the severity of the interaction, type (Pharmacokinetic vs. Pharmacodynamic), and level of evidence. 1,289 drug-drug interactions were identified (634 pharmacokinetic and 655 pharmacodynamic interactions). There were a total of 19 major interactions (colchicine, levomethadyl acetate, Mipomersen, propoxyphene, brexanolone, buprenorphine, esketamine, fezolinetant, ketamine, leflunomide, levoketoconazole, lomitapide, morphine, pexidartinib, pralsetinib, relugolix, sodium oxybate, teriflunomide, venetoclax), 393 moderate interactions, 49 minor interactions, and 828 of unknown significance. Drugs that should be avoided in the presence of cannabidiol, those that should be monitored, and those interactions that, while frequently mentioned, do not present sufficient evidence to recommend therapeutic changes are identified. The information highlights the need for caution. While many interactions have been postulated, only a small group warrants consideration in clinical practice. For the remaining drugs, special caution is needed. The long history of human use of the cannabis plant is often confused with the limited timeframe for scientific study of its isolated derivatives. The available information allows us to identify drugs with potential Drug-Drug Interactions of varying severity. This information can be used to improve treatment safety.