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

Joshua D Brown

doi:10.3390/jcm9040919

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.

Highlights

Cannabis (Cannabis sativa; “marijuana”) is the most commonly used illicit substance worldwide, but there is increasing interest and opportunity in employing cannabis and cannabinoids for medical purposes [1,2,3]
A number of components in cannabis influence, or are influenced by, drug-metabolizing enzymes (DMEs) and drug transporters which can alter the disposition of co-administered medications, i.e., pharmacokinetic drug–drug interactions (DDIs) [8,9,10,11,12,13,14,15,16,17]
Anecdotal evidence suggests that medical cannabis is a benign product with the potential to treat a myriad of conditions with few side effects

Summary

Introduction

Cannabis (Cannabis sativa; “marijuana”) is the most commonly used illicit substance worldwide, but there is increasing interest and opportunity in employing cannabis and cannabinoids for medical purposes [1,2,3]. Legislation implemented in 33 U.S states has increased the overall number of cannabis users [1], it has introduced a population of more medically complex individuals with serious chronic diseases who are exposed to these biologically and pharmacologically active phytochemicals. The belief that cannabis is a benign medicinal plant is extrapolated from younger individuals’ recreational use, but not established for chronic use by an increasingly medically complex and older user base [4,5]. Cannabis has significant pharmacodynamic effects, e.g., sedation and cognitive impairment, which can be potentiated with concomitant medications with similar effects or biological targets (e.g., opioids or benzodiazepines) [18,19]. The current lack of clinical evidence related to ADEs with cannabis use creates serious patient safety concerns due to the expanding use of cannabis. Existing knowledge of cannabis-related ADEs is limited to theoretical and clinically untested hypotheses

Results

Discussion

Conclusion