• Dayong Lee, Ryan Vandrey, Damodara R Mendu, Sebastien Anizan, Garry Milman, Jeannie A Murray, Allan J Barnes, and Marilyn A Huestis.
• Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD;
• Clin. Chem. 2013 Dec 1;59(12):1770-9.

BackgroundOral Δ(9)-tetrahydrocannabinol (THC) is effective for attenuating cannabis withdrawal and may benefit treatment of cannabis use disorders. Oral fluid (OF) cannabinoid testing, increasing in forensic and workplace settings, could be valuable for monitoring during cannabis treatment.MethodsEleven cannabis smokers resided on a closed research unit for 51 days and received daily 0, 30, 60, and 120 mg of oral THC in divided doses for 5 days. There was a 5-puff smoked cannabis challenge on the fifth day. Each medication session was separated by 9 days of ad libitum cannabis smoking. OF was collected the evening before and throughout oral THC sessions and analyzed by 2-dimensional GC-MS for THC, cannabidiol (CBD), cannabinol (CBN), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH).ResultsDuring all oral THC administrations, THC OF concentrations decreased to ≤ 78.2, 33.2, and 1.4 μg/L by 24, 48, and 72 h, respectively. CBN also decreased over time, with concentrations 10-fold lower than THC, with none detected beyond 69 h. CBD and 11-OH-THC were rarely detected, only within 19 and 1.6 h after smoking, respectively. THCCOOH OF concentrations were dose dependent and increased over time during 120-mg THC dosing. After cannabis smoking, THC, CBN, and THCCOOH concentrations showed a significant dose effect and decreased significantly over time.ConclusionsOral THC dosing significantly affected OF THCCOOH but minimally contributed to THC OF concentrations; prior ad libitum smoking was the primary source of THC, CBD, and CBN. Higher cannabinoid concentrations following active oral THC administrations vs placebo suggest a compensatory effect of THC tolerance on smoking topography.

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