Blood cannabinoid molar metabolite ratios are superior to blood THC as an indicator of recent cannabis smoking

Abstract

Introduction Cannabis use is a growing concern in transportation and workplace incidents. Because Δ9-tetrahydrocannabinol is detectable after acute psychoactive effects have resolved, it has limitations as an indicator of recent usage or potential impairment. Methods In an observational study of driving and psychomotor performance, we measured whole blood Δ9-tetrahydrocannabinol plus its metabolites 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol by liquid chromatography with tandem mass spectrometry at baseline and 30 min after starting a 15-minute interval of smoking cannabis in 24 occasional and 32 daily cannabis smokers. We calculated two blood cannabinoid molar metabolite ratios: 1) [Δ9-tetrahydrocannabinol] to [11-nor-9-carboxy-Δ9-tetrahydrocannabinol] and 2) ([Δ9-tetrahydrocannabinol] + [11-hydroxy-Δ9-tetrahydrocannabinol]) to [11-nor-9-carboxy-Δ9-tetrahydrocannabinol]. We compared these to blood [Δ9-tetrahydrocannabinol] alone as indicators of recent cannabis smoking. Results Median Δ9-tetrahydrocannabinol concentrations increased from 0 (<limit of detection 0.2 µg/L) at baseline to 5.6 µg/L post-smoking in occasional users. Among daily users, these were 2.7 µg/L at baseline and 21.3 µg/L post-smoking. Median molar metabolite ratio 1 increased from 0 at baseline to 0.62 post-smoking in occasional users and from 0.08 at baseline to 0.44 post-smoking in daily users. The median molar metabolite ratio 2 increased from 0 to 0.76 in occasional users and from 0.12 to 0.54 among daily users. A molar metabolite ratio 1 cut-point of 0.18 yielded 98% specificity, 93% sensitivity, and 96% accuracy for identifying recent cannabis smoking. A molar metabolite ratio 2 cut-point of 0.27 yielded 98% specificity, 91% sensitivity, and 95% accuracy. The receiver operating characteristic curves for molar metabolite ratio 1 and molar metabolite ratio 2 were not statistically different (P > 0.38). By comparison, a cut-point for Δ9-tetrahydrocannabinol of 5.3 µg/L yielded 88% specificity, 73% sensitivity, and 80% accuracy. Conclusions In occasional and daily users, the blood cannabinoid molar metabolite ratios were superior to whole blood Δ9-tetrahydrocannabinol as indicators of recent cannabis smoking. We recommend measurement and reporting of Δ9-tetrahydrocannabinol, 11-hydroxy-Δ9-tetrahydrocannabinol, and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol, and their molar metabolite ratios in forensic and safety investigations.