Increased cortisol exposure alters 11-COOH-THC disposition without affecting THC pharmacokinetics in premenopausal, healthy women

Increased cortisol exposure alters 11-COOH-THC disposition without affecting THC pharmacokinetics in premenopausal, healthy women | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL British Journal of Clinical Pharmacology This is a preprint and has not been peer reviewed. Data may be preliminary. 12 May 2026 V1 Latest version Share on Increased cortisol exposure alters 11-COOH-THC disposition without affecting THC pharmacokinetics in premenopausal, healthy women Authors : Aurora Authement K [email protected] , John Amory K [email protected] , Katya Rubinow B [email protected] , and Nina Isoherranen 0000-0002-9548-3126 [email protected] Authors Info & Affiliations https://doi.org/10.22541/authorea.15003186/v1 13 views 7 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Aim/Background: Cannabis use during pregnancy is common, yet (–)-Δ 9-tetrahydrocannabinol (THC) disposition during gestation remains poorly defined. Cortisol concentrations increase during pregnancy, which may cause increased metabolic clearance of THC. However, direct evaluation of the effects of increased cortisol concentrations on THC pharmacokinetics in pregnant individuals is not feasible. To address this gap, we tested whether increasing cortisol exposure via hydrocortisone dosing alters THC disposition in premenopausal women. Methods: Healthy, premenopausal women (n=13) were admitted for two 24-hour pharmacokinetic sampling days: a control day reflecting endogenous cortisol exposure and a treatment day following 7 days of oral hydrocortisone administration (30 mg total daily dose) designed to recapitulate physiological cortisol plasma concentrations during pregnancy. On both days, participants received 2.5 mg dronabinol, a synthetic formulation of THC, po. Plasma and urine samples were collected over 24 hours and THC and its circulating metabolites quantified. Noncompartmental analysis was conducted and pharmacodynamic effects were assessed. Results: Hydrocortisone treatment increased cortisol AUC by approximately 2-fold to concentrations comparable to late pregnancy. Despite this increase, THC and 11-hydroxy-THC pharmacokinetics and pharmacodynamics were unchanged. In contrast, the terminal half-life of 11-nor-9-carboxy-THC increased, and the AUC of 11-nor-9-carboxy-THC-glucuronide decreased following cortisol treatment, while 11-nor-9-carboxy-THC AUC was unchanged. These data suggest increased enterohepatic recycling and hepatic transport of 11-nor-9-carboxy-THC-glucuronide after cortisol treatment. Conclusion: A two-fold increase in cortisol AUC had no effect on THC clearance and CYP2C9 activity but altered the disposition of THC metabolites. This suggests that increased cortisol concentrations during pregnancy do not alter CYP2C9 activity. Supplementary Material File (authement_et_al_supplemental_2026.docx) authement_et_al_supplemental_2026 Download 341.18 KB Information & Authors Information Version history V1 Version 1 12 May 2026 Collection British Journal of Clinical Pharmacology Authors Affiliations Aurora Authement K [email protected] University of Washington School of Pharmacy, Seattle, United States, 98195 View all articles by this author John Amory K [email protected] University of Washington School of Pharmacy, Seattle, United States, 98195 View all articles by this author Katya Rubinow B [email protected] University of Washington School of Pharmacy, Seattle, United States, 98195 View all articles by this author Nina Isoherranen 0000-0002-9548-3126 [email protected] University of Washington School of Pharmacy, Seattle, United States, 98195 View all articles by this author Metrics & Citations Metrics Article Usage 13 views 7 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Aurora Authement K, John Amory K, Katya Rubinow B, et al. Increased cortisol exposure alters 11-COOH-THC disposition without affecting THC pharmacokinetics in premenopausal, healthy women. Authorea . 12 May 2026. DOI: https://doi.org/10.22541/authorea.15003186/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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