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

Clin Toxicol (Phila). 2023 May;61(5):355-362. doi: 10.1080/15563650.2023.2214697.

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.

PMID:37293900 | DOI:10.1080/15563650.2023.2214697