Cannabis-drug interactions: Implications for medicinal cannabis use

Medicinal cannabis (MC) products are typically derived from the plant Cannabis sativa. Hence, patients using MC are taking an entourage of constituents including major cannabinoids delta-9-tetrahydrocannabinol (△9THC), cannabidiol (CBD), and cannabinol as well as other cannabinoids and non-cannabinoid phytochemicals. In addition to △9THC and CBD, which are known to affect the drug-metabolizing P450 enzymes, many of these other constituents have been reported to have pharmacologic activity as well as activity on these and other drug-metabolizing enzyme systems. The study of drug-drug interactions with MC must include consideration of all of these constituents. Unlike pharmaceuticals that undergo United States (US) Food and Drug Administration approval system, other than △9THC and CBD, the constituents of MC are not standardized from product to product or even within the same product over time. Therefore, it is possible that there are drug-drug interactions that change between refills and/or over time. It is well established that MC use may result in pharmacokinetic and/or pharmacodynamic drug-drug interactions. However, there is much uncertainty for the clinician treating patients with MC products regarding potential for clinically significant interactions with other pharmaceutical agents used by those patients. This chapter describes: (1) the effects of various constituents of MC on drug-metabolizing enzyme systems; (2) formulation and route of administration variables that can influence cannabinoid concentrations and ratio of drug to active metabolite, which may affect the likelihood of a drug–drug interaction; and (3) drug-drug interactions that have been reported clinically in peer-reviewed literature. This is a dynamic field that will likely undergo much change in the near future.