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Desrosiers N.A.,Clinical Pharmacology and Therapeutic Research Branch | Desrosiers N.A.,University of Maryland, Baltimore | Barnes A.J.,Clinical Pharmacology and Therapeutic Research Branch | Hartman R.L.,Clinical Pharmacology and Therapeutic Research Branch | And 6 more authors.
Analytical and Bioanalytical Chemistry | Year: 2013

Oral fluid (OF) offers a noninvasive sample collection for drug testing. However, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) in OF has not been adequately characterized in comparison to plasma. We administered oral low-dose (1.0 mg/kg) and high-dose (1.6 mg/kg) MDMA to 26 participants and collected simultaneous OF and plasma specimens for up to 143 h after dosing. We compared OF/plasma (OF/P) ratios, time of initial detection (tfirst), maximal concentrations (Cmax), time of peak concentrations (tmax), time of last detection (tlast), clearance, and 3,4-methylenedioxyamphetamine (MDA)-to- MDMA ratios over time. For OF MDMA and MDA, Cmax was higher, tlast was later, and clearance was slower compared to plasma. For OF MDA only, tfirst was later compared to plasma. Median (range) OF/P ratios were 5.6 (0.1-52.3) for MDMA and 3.7 (0.7-24.3) for MDA. OF and plasma concentrations were weakly but significantly correlated (MDMA: R2=0.438, MDA: R2=0.197, p<0.0001). Median OF/P ratios were significantly higher following high dose administration: MDMA low=5.2 (0.1-40.4), high=6.0 (0.4-52.3, p<0.05); MDA low=3.3 (0.7-17.1), high=4.1 (0.9-24.3, p<0.001). There was a large intersubject variation in OF/P ratios. The MDA/MDMA ratios in plasma were higher than those in OF (p<0.001), and the MDA/MDMA ratios significantly increased over time in OF and plasma. The MDMA and MDA concentrations were higher in OF than in plasma. OF and plasma concentrations were correlated, but large inter-subject variability precludes the estimation of plasma concentrations from OF. © Springer-Verlag Berlin Heidelberg 2012.


Desrosiers N.A.,Clinical Pharmacology and Therapeutic Research Branch | Desrosiers N.A.,University of Maryland, Baltimore | Ramaekers J.G.,Maastricht University | Chauchard E.,Clinical Pharmacology and Therapeutic Research Branch | And 4 more authors.
Journal of Analytical Toxicology | Year: 2015

Δ9-Tetrahydrocannabinol (THC), the primary psychoactive constituent in cannabis, impairs psychomotor performance, cognition and driving ability; thus, driving under the influence of cannabis is a public safety concern. We documented cannabis' psychomotor, neurocognitive, subjective and physiological effects in occasional and frequent smokers to investigate potential differences between these smokers. Fourteen frequent (≥4x/week) and 11 occasional (<2x/week) cannabis smokers entered a secure research unit ~19 h prior to smoking one 6.8% THC cigarette. Cognitive and psychomotor performance was evaluated with the critical tracking (CTT), divided attention (DAT), n-back (working memory) and Balloon Analog Risk (BART) (risk-taking) tasks at 21.75, 1.5, 3.5, 5.5 and 22.5 h after starting smoking. GLM (General Linear Model) repeated measures ANOVA was utilized to compare scores. Occasional smokers had significantly more difficulty compensating for CTT tracking error compared with frequent smokers 1.5 h after smoking. Divided attention performance declined significantly especially in occasional smokers, with session × group effects for tracking error, hits, false alarms and reaction time. Cannabis smoking did not elicit session × group effects on the n-back or BART. Controlled cannabis smoking impaired psychomotor function, more so in occasional smokers, suggesting some tolerance to psychomotor impairment in frequent users. These data have implications for cannabis-associated impairment in driving under the influence of cannabis cases. © Published by Oxford University Press 2015.


PubMed | University of Nantes, Clinical Pharmacology and Therapeutic Research Branch, University of Maryland, Baltimore, Maastricht University and University of Maryland Baltimore County
Type: Clinical Trial | Journal: Journal of analytical toxicology | Year: 2015

9-Tetrahydrocannabinol (THC), the primary psychoactive constituent in cannabis, impairs psychomotor performance, cognition and driving ability; thus, driving under the influence of cannabis is a public safety concern. We documented cannabis psychomotor, neurocognitive, subjective and physiological effects in occasional and frequent smokers to investigate potential differences between these smokers. Fourteen frequent (4x/week) and 11 occasional (<2x/week) cannabis smokers entered a secure research unit 19 h prior to smoking one 6.8% THC cigarette. Cognitive and psychomotor performance was evaluated with the critical tracking (CTT), divided attention (DAT), n-back (working memory) and Balloon Analog Risk (BART) (risk-taking) tasks at -1.75, 1.5, 3.5, 5.5 and 22.5 h after starting smoking. GLM (General Linear Model) repeated measures ANOVA was utilized to compare scores. Occasional smokers had significantly more difficulty compensating for CTT tracking error compared with frequent smokers 1.5 h after smoking. Divided attention performance declined significantly especially in occasional smokers, with session group effects for tracking error, hits, false alarms and reaction time. Cannabis smoking did not elicit session group effects on the n-back or BART. Controlled cannabis smoking impaired psychomotor function, more so in occasional smokers, suggesting some tolerance to psychomotor impairment in frequent users. These data have implications for cannabis-associated impairment in driving under the influence of cannabis cases.


Desrosiers N.A.,Clinical Pharmacology and Therapeutic Research Branch | Desrosiers N.A.,University of Maryland, Baltimore | Himes S.K.,Clinical Pharmacology and Therapeutic Research Branch | Himes S.K.,University of Maryland, Baltimore | And 4 more authors.
Clinical Chemistry | Year: 2014

BACKGROUND: δ9-Tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) have been reported in blood from frequent cannabis smokers for an extended time during abstinence. We compared THC, 11-OHTHC, THCCOOH, cannabidiol, cannabinol, THCglucuronide, and 11-nor-9-carboxy-THC-glucuronide (THCCOO-glucuronide) blood and plasma disposition in frequent and occasional cannabis smokers. METHODS: Frequent and occasional smokers resided on a closed research unit and smoked one 6.8%THCcannabis cigarette ad libitum. Bloodandplasma cannabinoids were quantified on admission (approximately 19 h before), 1 h before, and up to 15 times (0.5-30 h) after smoking. RESULTS: Cannabinoid blood and plasma concentrations were significantly higher in frequent smokers compared with occasional smokers at most time points for THC and 11-OH-THC and at all time points for THCCOOH and THCCOO-glucuronide. Cannabidiol, cannabinol, and THC-glucuronide were not significantly different at any time point. Overall blood and plasma cannabinoid concentrations were significantly higher in frequent smokers for THC, 11-OH-THC, THCCOOH, and THCCOO-glucuronide, with and without accounting for baseline concentrations. For blood THC μ5 μg/L, median (range) time of last detection was 3.5 h (1.1->30 h) in frequent smokers and 1.0 h (0-2.1 h) in 11 occasional smokers; 2 individuals had no samples with THC >5 μg/L. CONCLUSIONS: Cannabis smoking history plays a major role in cannabinoid detection. These differences may impact clinical and impaired driving drug detection. The presence of cannabidiol, cannabinol, or THCglucuronide indicates recent use, but their absence does not exclude it. © 2014 American Association for Clinical Chemistry.

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