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 similar to 85 h by liquid chromatography with tandem mass spectrometry following controlled smoked, vaporized or oral 50.6 mg Delta(9)-tetrahydrocannabinol (THC) in a randomized, placebo-controlled, within-subject dosing design. No cannabidiol, cannabinol, cannabigerol, tetrahydrocannabivarin (THCV), THC, 11-OH-THC and Delta(9)-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 mu g/L for occasional and 378, 248 and 485 mu g/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-Delta(9)-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.