Potential Adverse Drug Events with Tetrahydrocannabinol (THC) Due to Drug-Drug Interactions

Abstract

Tetrahydrocannabinol (THC) is the primary psychoactive ingredient in cannabis. While the safety of THC and cannabis has been extrapolated from millennia of recreational use, medical marijuana programs have increased exposure among medically complex individuals with comorbid conditions and many co-prescribed medications. Thus, THC should be recognized as a pharmacologically complex compound with potential for drug-drug interactions and adverse drug events. This review summarizes potential adverse drug events related to THC when combined with other medications. Metabolic drug-drug interactions are primarily due to THC conversion by CYP3A4 and CYP2C9, which can be impacted by several common medications. Further, CYP2C9 polymorphisms are highly prevalent in certain racial groups (up to 35% in Caucasians) and increase the bioavailability of THC. THC also has broad interactions with drug-metabolizing enzymes and can enhance adverse effects of other medications. Pharmacodynamic interactions include neurological effects, impact on the cardiovascular system, and risk of infection. General clinical recommendations for THC use include starting with low doses and titrating to desired effects. However, many interactions may be unavoidable, dose-limiting, or a barrier to THC-based therapy. Future work and research must establish sufficient data resources to capture medical marijuana use for such studies. Meanwhile, clinicians should balance the potential risks of THC and cannabis and the lack of strong evidence of efficacy in many conditions with patient desires for alternative therapy.

Keywords: THC; adverse drug events; cannabis; drug–drug interactions; medical marijuana; safety; tetrahydrocannabinol.

Figure 1

Potential pharmacokinetic drug–drug interactions involving key metabolism enzymes that convert THC to its metabolites for excretion.

Figure 2

Enzyme targets and example medications that could be affected by THC if co-administered.

Figure 3

Representation of main adverse effects of tetrahydrocannabinol use that can be potentiated by other medications.