The Impact of Pregnancy and Associated Hormones on the Pharmacokinetics of Δ-tetrahydrocannabinol

Overview

Journal Expert Opin Drug Metab Toxicol

Publisher Informa Healthcare

Specialties Endocrinology
Pharmacology
Toxicology

Date 2024 Jan 23

PMID 38258511

Authors

Aurora K Authement

Nina Isoherranen

Affiliations

Soon will be listed here.

Abstract

Introduction: (-)-Δ-tetrahydrocannabinol (THC) is the main psychoactive component of cannabis. Cannabis is the most widely used drug of abuse by pregnant individuals, but its maternal-fetal safety is still unclear. The changes in THC disposition during pregnancy may affect THC safety and pharmacology.

Areas Covered: This review summarizes the current literature on THC metabolism and pharmacokinetics in humans. It provides an analysis of how hormonal changes during pregnancy may alter the expression of cannabinoid metabolizing enzymes and THC and its metabolite pharmacokinetics. THC is predominately (>70%) cleared by hepatic metabolism to its psychoactive active metabolite, 11-OH-THC by cytochrome P450 (CYP) 2C9 and to other metabolites (<30%) by CYP3A4. Other physiological processes that change during pregnancy and may alter cannabinoid disposition are also reviewed.

Expert Opinion: THC and its metabolites disposition likely change during pregnancy. Hepatic CYP2C9 and CYP3A4 are induced in pregnant individuals and by pregnancy hormones. This induction of CYP2C9 and CYP3A4 is predicted to lead to altered THC and 11-OH-THC disposition and pharmacodynamic effects. More studies of THC metabolism and induction of the enzymes metabolizing cannabinoids are necessary to improve the prediction of THC pharmacokinetics in pregnant individuals.

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