Hepatic Enzymes Relevant to the Disposition of (-)-∆9- Tetrahydrocannabinol (THC) and Its Psychoactive Metabolite, 11-OH-THC
Patilea-Vrana, G. I., Anoshchenko, O., & Unadkat, J. D. (2019). Hepatic Enzymes Relevant to the Disposition of (−)-∆ 9-Tetrahydrocannabinol (THC) and Its Psychoactive Metabolite, 11-OH-THC. Drug Metabolism and Disposition, 47(3), 249-256.
Up to 7.5% of pregnant women in the United States use cannabis during their pregnancy. The concentration of THC in cannabis is increasing as is the number of pregnant women who use cannabis. It is critical that the developmental risk of THC and its main active metabolite, 11-OH-THC, be determined. Ethical reasons make it impossible to directly measure exposure to cannabinoids in a developing fetus. However, an understanding of the parameters that metabolize and eliminate THC would allow for a Physiologically Based Pharmacokinetic (PCPK) modeling system that can accurately predict fetal exposure to THC and 11-OH-THC. This paper reports the first set of drug dependent parameters that are necessary to predict maternal-fetal cannabinoid exposure through PBPK modeling. Researchers investigated liver enzymes and confirmed previous studies showing that that CYP2C9 is the major enzyme responsible for the elimination of THC and for the creation of 11-OH-THC. The paper also reports that 11-OH-THC is eliminated primarily by UGT enzymes in the liver. In order to accurately predict maternal-fetal exposure and therefore risk, future studies need to be conducted on placenta, intestine, and lung enzymes. Additionally, 11-OH-THC is one of forty metabolites that form after THC is metabolized. Future studies should also investigate the metabolic pathways of other THC metabolites to accurately assess the risks of maternal-fetal exposure.View This Research