Phase I and II Cannabinoid Disposition in Blood and Plasma of Occasional and Frequent Smokers Following Controlled Smoked Cannabis

Abstract

Abstract BACKGROUND Δ9-Tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) have been reported in blood from frequent cannabis smokers for an extended time during abstinence. We compared THC, 11-OH-THC, THCCOOH, cannabidiol, cannabinol, THC-glucuronide, and 11-nor-9-carboxy-THC-glucuronide (THCCOO-glucuronide) blood and plasma disposition in frequent and occasional cannabis smokers. METHODS Frequent and occasional smokers resided on a closed research unit and smoked one 6.8% THC cannabis cigarette ad libitum. Blood and plasma cannabinoids were quantified on admission (approximately 19 h before), 1 h before, and up to 15 times (0.5–30 h) after smoking. RESULTS Cannabinoid blood and plasma concentrations were significantly higher in frequent smokers compared with occasional smokers at most time points for THC and 11-OH-THC and at all time points for THCCOOH and THCCOO-glucuronide. Cannabidiol, cannabinol, and THC-glucuronide were not significantly different at any time point. Overall blood and plasma cannabinoid concentrations were significantly higher in frequent smokers for THC, 11-OH-THC, THCCOOH, and THCCOO-glucuronide, with and without accounting for baseline concentrations. For blood THC >5 μg/L, median (range) time of last detection was 3.5 h (1.1–>30 h) in frequent smokers and 1.0 h (0–2.1 h) in 11 occasional smokers; 2 individuals had no samples with THC >5 μg/L. CONCLUSIONS Cannabis smoking history plays a major role in cannabinoid detection. These differences may impact clinical and impaired driving drug detection. The presence of cannabidiol, cannabinol, or THC-glucuronide indicates recent use, but their absence does not exclude it.