Cannabidiol's impact on drug-metabolization.

Importance: Products containing cannabidiol(CBD) are easily accessible. CBD is reported to inhibit the drug-metabolizing proteins(DMP) Cytochrome P450(CYP)3A4/5, CYP2C9, CYP2B6, CYP2D6, CYP2E1, CYP1A2, CYP2C19, carboxylesterase 1(CES1), uridine 5'diphospho-glucoronosyltransferase(UGT)1A9, UGT2B7, P-glycoprotein(P-gp) and Breast Cancer Resistance Protein(BCRP). The relevance of CBD-drug interactions is largely unknown. Aim of the study was to identify drugs, potentially interacting with orally ingested CBD, to assess whether CBD-drug interactions have been reported, and if substrates of DMP are frequently prescribed drugs.

Observations: Identified were 403 drugs as substrates of DMP. CBD-drug interactions were reported for 53/403 substrates in humans (n = 25), in vivo (n = 13) or in vitro (n = 15). In 31/53 substrates, CBD induced an increase, in 1/53 a decrease, in 4/53 no change in the substrate level. For 5/53 substrates, the results were controversial, and in 12/53 no substrate levels were reported. Among the 30 most frequently prescribed drugs in Germany were 67% substrates of DMP and among the 50 most frequently prescribed drugs in the USA 68%.

Relevance And Conclusions: There is an urgent need for pharmacologic studies on CBD-drug interactions. Patients should be educated on the potential risk and awareness should be increased among physicians. Regulatory authorities should become aware of the problem and start an initiative on an international level to increase the safety of CBD.