Cannabinoids and drug metabolizing enzymes: potential for drug-drug interactions and implications for drug safety and efficacy

Expert Rev Clin Pharmacol. 2022 Dec;15(12):1443-1460. doi: 10.1080/17512433.2022.2148655. Epub 2022 Dec 1.

Abstract

Introduction: Cannabis is an increasingly popular recreational and medicinal drug in the USA. While cannabis is still a Schedule 1 drug federally, many states have lifted the ban on its use. With its increased usage, there is an increased possibility for potential drug-drug interactions (DDI) that may occur with concomitant use of cannabis and pharmaceuticals.

Area covered: This review focuses on the current knowledge of cannabis induced DDI, with a focus on pharmacokinetic DDI arising from enzyme inhibition or induction. Phase I and phase II drug metabolizing enzymes, specifically cytochrome P450s, carboxylesterases, and uridine-5'-diphosphoglucuronosyltransferases, have historically been the focus of research in this field, with much of the current knowledge of the potential for cannabis to induce DDI within these families of enzymes coming from in vitro enzyme inhibition studies. Together with a limited number of in vivo clinical studies and in silico investigations, current research suggests that cannabis exhibits the potential to induce DDI under certain circumstances.

Expert opinion: Based upon the current literature, there is a strong potential for cannabis-induced DDI among major drug-metabolizing enzymes.

Keywords: CBD; Cannabis; THC; UDP glucuronosyltransferase; cannabinoids; cytochrome P450; drug-drug interactions; pharmacokinetics.

Publication types

  • Review

MeSH terms

  • Cannabinoid Receptor Agonists
  • Cannabinoids* / adverse effects
  • Cannabis* / adverse effects
  • Cytochrome P-450 Enzyme System
  • Drug Interactions
  • Hallucinogens*
  • Humans

Substances

  • Cannabinoids
  • Cytochrome P-450 Enzyme System
  • Cannabinoid Receptor Agonists
  • Hallucinogens