Plasma and urine profiles of tetrahydrocannabinol metabolites after cannabis smoking

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Since 2004, cannabis has been prohibited by the World Anti-Doping Agency for all sports competitions. In the years since then, about half of all positive doping cases in Switzerland have been related to cannabis consumption. In doping urine analysis, the target analyte is 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH), the cutoff being 15 ng/mL. However, the wide urinary detection window of the long-term metabolite of Δ9-tetrahydrocannabinol (THC) does not allow a conclusion to be drawn regarding the time of consumption or the impact on the physical performance. The purpose of the present study on light cannabis smokers was to evaluate target analytes with shorter urinary excretion times. Twelve male volunteers smoked a cannabis cigarette standardized to 70 mg THC per cigarette. Plasma and urine were collected up to 8 h and 11 days, respectively. Total THC, 11-hydroxy-Δ9-tetrahydrocannabinol (THC-OH), and THC-COOH were determined after hydrolysis followed by solid-phase extraction and gas chromatography/mass spectrometry. The limits of quantitation were 0.1–1.0 ng/mL. Eight puffs delivered a mean THC dose of 45 mg. Plasma levels of total THC, THC-OH, and THC-COOH were measured in the ranges 0.2–59.1, 0.1–3.9, and 0.4–16.4 ng/mL, respectively. Peak concentrations were observed at 5, 5–20, and 20–180 min. Urine levels were measured in the ranges 0.1–1.3, 0.1–14.4, and 0.5–38.2 ng/mL, peaking at 2, 2, and 6–24 h, respectively. The times of the last detectable levels were 2–8, 6–96, and 48–120 h. Besides high to very high THC-COOH levels (245 ± 1,111 ng/mL), THC (3 ± 8 ng/mL) and THC-OH (51 ± 246 ng/mL) were found in 65 and 98% of cannabis-positive athletes' urine samples, respectively. In conclusion, in addition to THC-COOH, the pharmacologically active THC and THC-OH should be used as target analytes for doping urine analysis.