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Extended plasma cannabinoid excretion in chronic frequent cannabis smokers during sustained abstinence and correlation with psychomotor performance.

ABSTRACT: Cannabis smoking increases motor vehicle accident risk. Empirically defined cannabinoid detection windows are important to drugged driving legislation. Our aims were to establish plasma cannabinoid detection windows in frequent cannabis smokers and to determine if residual cannabinoid concentrations were correlated with psychomotor performance. Twenty-eight male chronic frequent cannabis smokers resided on a secure research unit for up to 33 days with daily blood collection. Plasma specimens were analyzed for ?(9) -tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) by gas chromatography-mass spectrometry. Critical tracking and divided attention tasks were administered at baseline (after overnight stay to ensure lack of acute intoxication) and after 1, 2, and 3 weeks of cannabis abstinence. Twenty-seven of the twenty-eight participants were THC-positive at admission (median 4.2 µg/L). THC concentrations significantly decreased 24 h after admission, but were still ?2 µg/L in 16 of the 28 participants 48 h after admission. THC was detected in 3 of 5 specimens on day 30. The last positive 11-OH-THC specimen was 15 days after admission. THCCOOH was measureable in 4 of 5 participants after 30 days of abstinence. Years of prior cannabis use significantly correlated with THC concentrations on admission, and days 7 and 14. Tracking error, evaluated by the Divided Attention Task, was the only evaluated psychomotor assessment significantly correlated with cannabinoid concentrations at baseline and day 8 (11-OH-THC only). Median THC was 0.3 µg/L in 5 chronic frequent cannabis smokers' plasma samples after 30 days of sustained abstinence. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

SUBMITTER: Karschner EL

PROVIDER: S-EPMC4676741 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Extended plasma cannabinoid excretion in chronic frequent cannabis smokers during sustained abstinence and correlation with psychomotor performance.

Karschner Erin L EL Swortwood Madeleine J MJ Hirvonen Jussi J Goodwin Robert S RS Bosker Wendy M WM Ramaekers Johannes G JG Huestis Marilyn A MA

Drug testing and analysis 20150611 7

Cannabis smoking increases motor vehicle accident risk. Empirically defined cannabinoid detection windows are important to drugged driving legislation. Our aims were to establish plasma cannabinoid detection windows in frequent cannabis smokers and to determine if residual cannabinoid concentrations were correlated with psychomotor performance. Twenty-eight male chronic frequent cannabis smokers resided on a secure research unit for up to 33 days with daily blood collection. Plasma specimens wer ...[more]

PMID: 26097154

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Project description:Background: Recently increased access to cannabis products in the United States has been associated with increased rates of driving after cannabis use. Although numerous studies indicate that cannabis impairs psychomotor and neurocognitive functions that can affect driving ability, the determination of cannabis-impaired driving risk is complicated by the extent to which frequent cannabis users develop tolerance to THC's subjective, cognitive, and psychomotor effects, and by the fact that there is no validated behavioral or biological marker of recent cannabis use or cannabis-related impairment. This study examined the psychomotor impairment-related effects experienced by frequent cannabis users in Colorado after naturalistic consumption of smoked cannabis, both immediately and 1 h postuse. Results were then validated in a smaller replication sample from Washington state. Methods: In the primary Colorado study, participants (n=70) used the DRUID® mobile app, a brief measure of psychomotor and cognitive domains that are sensitive to the effects of cannabis. First, participants used DRUID to establish a sober baseline impairment score. During a second appointment, they used DRUID at three time points: preuse, immediately after acutely using cannabis, and 1 h postuse. In the Washington replication sample, participants (n=39) used DRUID before acute cannabis consumption and then every half hour for 2.5 h. Results: In both studies, peak DRUID impairment effects were seen immediately after cannabis use, with recovery of performance at 1 h postuse. Specifically, significant quadratic effects of time emerged for both studies (Colorado study: (β=-0.935, SE=0.204, p<0.001); Washington study: β=3.0299, SE=1.3085, p<0.01). Domain-specific effects were tested in the larger Colorado study and were observed for reaction time within a complex divided attention task and a postural-stability balance task. Conclusions: These findings demonstrate that psychomotor impairment emerges immediately after acute cannabis use even in regular users, but decreases significantly 1 h postuse. These results underscore the potential utility of the DRUID app for assessing acute cannabis-related psychomotor impairment. Further research is needed to explore whether the DRUID app and/or the specific psychomotor functions it assesses might serve as a tool for measuring cannabis-related driving impairment. Clinical trials registration number for the Colorado Study: NCT03522103.

Project description:Traditionally, smoking has been the predominant method for administering cannabis, but alternative routes of administration have become more prevalent. Additionally, research examining urinary cannabinoid excretion profiles has primarily focused on 11-nor-9-carboxy-∆9-tetrahydrocannabinol (∆9-THC-COOH), a metabolite of ∆9-tetrahydrocannabinol (∆9-THC), as the primary analyte. The aim of the current study was to characterize the urinary excretion profile of ∆9-THC-COOH, ∆9-THC, ∆8-tetrahydrocannabinol (∆8-THC), 11-hydroxy-∆9-tetrahydrocannabinol (11-OH-∆9-THC), ∆9-tetrahydrocannabivarin (THCV), 11-nor-∆9-tetrahydrocannabivarin-9-carboxlic acid (THCV-COOH), cannabidiol (CBD), cannabinol (CBN) and 8,11-dihydroxytetrahydrocannabinol (8,11-diOH-∆9-THC) following controlled administration of both oral and vaporized cannabis. Participants (n = 21, 11 men/10 women) who were infrequent cannabis users ingested cannabis-containing brownies (0, 10 and 25 mg ∆9-THC) and inhaled vaporized cannabis (0, 5 and 20 mg ∆9-THC) across six double-blind outpatient sessions. Urinary concentrations of ∆9-THC analytes were measured at baseline and for 8 h after cannabis administration. Sensitivity, specificity and agreement between the three immunoassays (IAs) for ∆9-THC-COOH (cutoffs of 20, 50 and 100 ng/mL) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) analyses (confirmatory cutoff concentrations of 15 ng/mL) were assessed. Urinary concentrations for ∆9-THC-COOH, ∆9-THC, 11-OH-∆9-THC, THCV, CBN and 8,11-diOH-∆9-THC all peaked at 5-6 h and 4 h following oral and vaporized cannabis administration, respectively. At each active dose, median maximum concentrations (Cmax) for detected analytes were quantitatively higher after oral cannabis administration compared to vaporized. Using current recommended federal workplace drug-testing criteria (screening via IA with a cutoff of ≥50 ng/mL and confirmation via LC-MS-MS at a cutoff of ≥15 ng/mL), urine specimens tested positive for ∆9-THC-COOH in 97.6% of oral sessions and 59.5% of vaporized sessions with active ∆9-THC doses. These data indicate that while ∆9-THC-COOH may serve as the most consistent confirmatory analyte under the current drug-testing guidelines, future work examining 11-OH-∆9-THC under similar parameters could yield an alternative analyte that may be helpful in distinguishing between licit and illicit cannabis products.

Dataset Information

Extended plasma cannabinoid excretion in chronic frequent cannabis smokers during sustained abstinence and correlation with psychomotor performance.

Publications

Extended plasma cannabinoid excretion in chronic frequent cannabis smokers during sustained abstinence and correlation with psychomotor performance.

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