Free and glucuronide urine cannabinoids after controlled smoked, vaporized and oral cannabis administration in frequent and occasional cannabis users

Total urinary 11-nor-9-carboxy-tetrahydrocannabinol (THCCOOH) concentrations are generally reported following cannabis administration. Few data are available for glucuronide and minor cannabinoid metabolite concentrations. All urine specimens from 11 frequent and 9 occasional cannabis users were analyzed for 11 cannabinoids for ∼85 h by liquid chromatography with tandem mass spectrometry following controlled smoked, vaporized or oral 50.6 mg Δ⁹-tetrahydrocannabinol (THC) in a randomized, placebo-controlled, within-subject dosing design. No cannabidiol, cannabinol, cannabigerol, tetrahydrocannabivarin (THCV), THC, 11-OH-THC and Δ⁹-tetrahydrocannabinolic acid were detected in urine. Median THCCOOH-glucuronide maximum concentrations (C_max) following smoked, vaporized and oral routes were 68.0, 26.7 and 360 μg/L for occasional and 378, 248 and 485 μg/L for frequent users, respectively. Median time to specific gravity-normalized C_max (T_max) was 5.1–7.9 h for all routes and all users. Median C_max for THCCOOH, THC-glucuronide and 11-nor-9-carboxy-Δ⁹-THCV (THCVCOOH) were <7.5% of THCCOOH-glucuronide C_max concentrations. Only THC-glucuronide mean T_max differed between routes and groups, and was often present only in occasional users’ first urine void. Multiple THCCOOH-glucuronide and THCCOOH peaks were observed. We also evaluated these urinary data with published models for determining recency of cannabis use. These urinary cannabinoid marker concentrations from occasional and frequent cannabis users following three routes of administration provide a scientific database to assess single urine concentrations in cannabis monitoring programs. New target analytes (CBD, CBN, CBG, THCV and phase II metabolites) were not found in urine. The results are important to officials in drug treatment, workplace and criminal justice drug monitoring programs, as well as policy makers with responsibility for cannabis regulations.