Urinary excretion profiles of 11-nor-9-carboxy-Δ⁹- tetrahydrocannabinol and 11-hydroxy-Δ⁹-THC: Cannabinoid metabolites to creatinine ratio study IV

The objective of this study was to compare urinary excretion patterns of two cannabinoid metabolites in subjects with a history of chronic marijuana use. The first metabolite analyzed was nor-9-carboxy-Δ⁹- tetrahydrocannabinol (Δ⁹-THC-COOH), the major urinary cannabinoid metabolite that is pharmacologically inactive. The second metabolite 11-OH-Δ⁹-THC is an active cannabinoid metabolite and is not routinely measured. Urine specimens were collected from four subjects on 12-20 occasions ≥96 h apart in an uncontrolled clinical setting. Creatinine was analyzed in each urine specimen by the colorimetric modified Jaffé reaction on a SYVA 30R biochemical analyzer. All urine specimens analyzed for 11-OH-Δ⁹-THC had screened positive for cannabinoids with the EMIT II Plus cannabinoids assay (cut-off 50 ng/mL) on a SYVA 30R analyzer and submitted for Δ⁹-THC-COOH confirmation by GC-MS (cut-off concentration 15 ng/mL). Eleven-OH-Δ⁹-THC was measured by GC-MS with a cut-off concentration of 3 ng/mL. Both GC-MS methods for cannabinoid metabolites used deuterated internal standards for quantitative analysis. The mean (range) of urinary Δ⁹-THC-COOH concentration was 1153 ng/mL (78.7-2634) with a cut-off of 15 ng/mL. The mean (range) of Δ⁹-THC-COOH/creatinine ratios (ng/mL Δ⁹-THC- COOH/mmol/L creatinine) was 84.1 (8.1-122.1). The mean (range) urinary of 11-OH-Δ⁹-THC concentration was 387.6 ng/mL (11.9-783) with a cut-off of 3 ng/mL, and the mean (range) of 11-OH-Δ⁹-THC/ creatinine ratio (ng/mL 11-OH-Δ⁹-THC/mmol/L creatinine) was 29.7 (1.2-40.7). Of the 63 urine specimens submitted for Δ⁹- THC-COOH confirmation by GC-MS, 59/63 urine specimens (94%) were positive for Δ⁹ -THC-COOH and 51/63 (81%) were positive for 11-OH-Δ⁹-THC. Overall, the concentrations of 11-OH-Δ⁹-THC in urine specimens collected ≥96 h apart were lower than Δ⁹-THC-COOH concentrations in 50/51 of the urine specimens in this population. Further urinary cannabinoid excretion studies are needed to assess whether 11-OH-Δ⁹-THC analyses have a role when assessing previous marijuana or hashish use in chronic users whose urine specimens remain positive for Δ⁹-THC-COOH for an extended period of time after last drug use.