Urinary 11-nor-9-carboxy-tetrahydrocannabinol elimination in adolescent and young adult cannabis users during one month of sustained and biochemically-verified abstinence

Randi Melissa Schuster, Kevin Potter, Ryan Vandrey, Maya Hareli, Jodi Gilman, David Schoenfeld, A Eden Evins, Randi Melissa Schuster, Kevin Potter, Ryan Vandrey, Maya Hareli, Jodi Gilman, David Schoenfeld, A Eden Evins

Abstract

Background: Despite adolescents and young adults being the most frequent users of cannabis, all information on cannabis drug testing interpretation is based on data from adults.

Aims: This study aimed to define the time course of urinary 11-nor-9-carboxy-tetrahydrocannabinol (THCCOOH) excretion among 70 adolescent and young adult cannabis users during 1 month of biochemically-verified cannabis abstinence.

Methods: Urine specimens were collected at non-abstinent baseline and after 2, 3, 8, 15, 21 and 28 days of abstinence. Specimens were tested for THCCOOH with a 'rapid' immunoassay drug test and a confirmatory assay using liquid chromatography-tandem mass spectrometry, with a 5 ng/mL limit of quantitation. Elimination rate was tested using a population pharmacokinetics model.

Results/outcomes: Participants had an average of 26 days of abstinence (SD = 6). Initial creatinine-adjusted THCCOOH concentration (CN-THCCOOH) was 148 ng/mg (SD = 157). Half-life was 2 days (SD = 5), with a 10-day window of detection (estimated range: 4-80 days). At the final timepoint and among those with > 25 days of abstinence (n = 62), 40% (n = 25) had THCCOOH concentrations > 5 ng/mL (i.e. detectable on confirmatory assay) and 19% (n = 12) were 'positive' per federal drug testing guidelines (i.e. values greater than 50 ng/mL on the screening immunoassay and 15 ng/mL on the confirmatory assay). More frequent past month cannabis use was associated with higher baseline CN-THCCOOH concentrations, but not with rate of elimination. Nested five-fold cross-validation suggested high model reliability and predictive validity.

Conclusions/interpretation: Findings underscore that, as with adults, detectable cannabinoid metabolites do not necessarily indicate recent use in adolescents and young adults. Algorithms that account for THCCOOH levels, assessed longitudinally and time between specimen collections are best equipped to confirm abstinence.

Clinical trial registration: NCT03276221; https://ichgcp.net/clinical-trials-registry/NCT03276221?term=Randi+Schuster&rank=1.

Keywords: Cannabis; THCCOOH; abstinence; adolescents; marijuana; pharmacokinetics; young adults.

Figures

Figure 1.
Figure 1.
Large Intersubject Variability in Starting THCCOOH Levels and Rates of Decay Change in CN-THCCOOH (left panel) and the log of CN-THCCOOH (right panel) over days since last cannabis exposure for 4 representative subjects. Filled points refer to two subjects with low starting concentrations of CN-THCCOOH, while empty points refer to two subjects with high starting concentrations of CN-THCCOOH. The triangular symbols refer to two subjects with rapid elimination rates, while the square and diamond symbols refer to two subjects with slow elimination rates.
Figure 2.
Figure 2.
Raw and Estimated Change in CN-THCCOOH Levels Across 30 Days of Cannabis Abstinence Change in CN-THCCOOH (left panel) and the log of CN-THCCOOH (right panel) over days since last cannabis exposure. Gray points represent the observations for individual participants. Triangles (in right panel) represent values that fell below the limit of quantitation (LOQ; approximated by the dashed line) and were estimated via imputation. Diamonds connected by a line represent mean CN-THCCOOH concentration per day for values above the LOQ, which yielded a variable and potentially biased estimate of the rate of decay during abstinence due to missing data. The solid black line depicts the estimated decline in CN-THCCOOH in the population based on the pharmacokinetic model, which controls for individual differences in CN-THCCOOH levels and missing data.

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