Urinary Cannabinoid Disposition in Occasional and Frequent Smokers: Is THC-Glucuronide in Sequential Urine Samples a Marker of Recent Use in Frequent Smokers?

Abstract

There is extended urinary excretion of Δ(9)-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) in abstinent frequent cannabis smokers. We characterized THC, 11-OH-THC, THCCOOH, cannabidiol, cannabinol, THC-glucuronide, and THCCOOH-glucuronide disposition in urine of frequent and occasional cannabis smokers, and we propose a model to predict recent cannabis smoking. Frequent and occasional smokers resided on a closed research unit and smoked one 6.8% THC cannabis cigarette ad libitum. Urinary cannabinoids were quantified in each void by liquid chromatography-tandem mass spectrometry within 24 h of collection. No urine samples had measureable THC, 11-OH-THC, cannabidiol, or cannabinol. THCCOOH, THC-glucuronide, and THCCOOH-glucuronide were measurable in all frequent smokers' urine and 60%, 100%, and 100% of occasional smokers' urine samples, respectively. Pre- and postdose maximal concentrations (non- and creatinine normalized) and probability of being positive were significantly higher in frequent smokers' samples. THC-glucuronide concentrations peaked 0.6-7.4 h after smoking; THCCOOH and THCCOOH-glucuronide concentrations were highly variable. At the newly adopted THCCOOH 175-μg/L World Anti-Doping Agency decision limit, only 50% of frequent smokers were positive 0-6 h postdose; no occasional smokers' samples were positive. An absolute %difference of ≥50% between 2 consecutive THC-glucuronide-positive samples with a creatinine-normalized concentration of ≥2 μg/g in the first sample predicted cannabis smoking with efficiencies of 93.1% in frequent and 76.9% in occasional smokers within 6 h of first sample collection. These controlled urinary cannabinoid data provide a possible means of identifying recent cannabis intake in cannabis smokers' urine within a short collection time frame after smoking.