Incorporation of methamphetamine and amphetamine in human hair following controlled oral methamphetamine administration

Background: Although hair testing is well established for the assessment of past drug exposure, uncer-tainties persist about mechanisms of drug incorporation into hair and interpretation of results. The aim of this study was to administer methamphetamine (MAMP) under controlled conditions as a model drug to investigate drug incorporation into human hair. Material and methods: Seven volunteers with a history of stimulant use received 4 7 10 mg (low) doses of sustained release S-(+)-MAMP HCl within 1 week, with weekly head hair samples collected by shaving. 3 weeks later, 4 of them received 4 7 20 mg (high) doses. After extensive isopropanol/phosphate buffer washing of the hair, MAMP and its metabolite amphetamine (AMP) concentrations were determined in all weekly hair samples by LC\u2013MS\u2013MS in selected reaction monitoring mode with the undeca- and deca-deuterated drugs, respectively, as internal standards (LLOQ, 0.005 ng mg 121). Results: MAMP Tmaxoccurred from 1 to 2 weeks after both doses, with Cmaxranging from 0.6 to 3.5 ng mg 121 after the low and 1.2 to 5.3 ng mg 121 after the high MAMP doses. AMP Cmaxin hair was 0.1\u20130.3 ng mg 121 and 0.2\u20130.5 ng mg 121 , respectively, for low and high doses. Highly dose-related concentrations within subjects, but large variability between subjects were observed. MAMP concentrations were above the 0.2 ng mg 121 cut-off for at least 2 weeks following administration of both low and high doses. The overall AMP/MAMP ratio ranged from 0.07 to 0.37 with a mean value of 0.15 \ub1 0.07, and a median of 0.13. The percentage of MAMP and AMP removed with the washing procedure decreased with time after administration. A strong correlation was found between area under the curve of MAMP (r2 = 0.90, p = 0.00) and AMP (r2 = 0.94, p = 0.00) concentrations calculated for the 3-week period following administration and the total melanin concentration in hair. Significant correlations were observed also between Cmaxand melanin. Conclusions: This study demonstrated that despite large inter-individual differences, the incorporation of MAMP and AMP into hair is dose-related with much of the observed scatter of MAMP and AMP concentrations explained by melanin concentration in hai

Smoked cannabis' psychomotor and neurocognitive effects in occasional and frequent smokers

International audienceΔ9-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

Psychomotor performance, subjective and physiological effects and whole Blood '9 -Tetrahydrocannabinol Concentrations in Heavy, Chronic Cannabis Smokers Following Acute Smoked Cannabis

Delta(9)-tetrahydrocannabinol (THC) is the illicit drug most frequently observed in accident and driving under the influence of drugs investigations. Whole blood is often the only available specimen collected during such investigations, yet few studies have examined relationships between cannabis effects and whole blood concentrations following cannabis smoking. Nine male and one female heavy, chronic cannabis smokers resided on a closed research unit and smoked ad libitum one 6.8 THC cannabis cigarette. THC, 11-hydroxy-THC and 11-nor-9-carboxy-THC were quantified in whole blood and plasma. Assessments were performed before and up to 6 h after smoking, including subjective [visual analog scales (VAS) and Likert scales], physiological (heart rate, blood pressure and respirations) and psychomotor (critical-tracking and divided-attention tasks) measures. THC significantly increased VAS responses and heart rate, with concentration-effect curves demonstrating counter-clockwise hysteresis. No significant differences were observed for critical-tracking or divided-attention task performance in this cohort of heavy, chronic cannabis smokers. The cannabis influence factor was not suitable for quantifying psychomotor impairment following cannabis consumption and was not precise enough to determine recent cannabis use with accuracy. These data inform our understanding of impairment and subjective effects following acute smoked cannabis and interpretation of whole blood cannabinoid concentrations in forensic investigations

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

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 Delta9 -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 s were THC-positive at admission (median 4.2 microg/L). THC concentrations significantly decreased 24 h after admission, but were still >/=2 microg/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 microg/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

Psychomotor function in chronic daily Cannabis smokers during sustained abstinence

Background: The present study assessed psychomotor function in chronic, daily cannabis smokers during 3 weeks continuously monitored abstinence on a secure research unit. We hypothesized that psychomotor performance would improve during abstinence of chronic, daily cannabis smokers. Methodology/Principal Findings: Performance on the critical tracking (CTT) and divided attention (DAT) tasks was assessed in 19 male chronic, daily cannabis smokers at baseline and after 8, 14-16 and 21-23 days of continuously monitored abstinence. Psychomotor performance was compared to a control group of non-intoxicated occasional drug users. Critical frequency (lambda(c)) of the CTT and tracking error and control losses of the DAT were the primary outcome measures. Results showed that chronic cannabis smokers' performance on the CTT (p Conclusions/Significance: Sustained cannabis abstinence moderately improved critical tracking and divided attention performance in chronic, daily cannabis smokers, but impairment was still observable compared to controls after 3 weeks of abstinence. Between group differences, however, need to be interpreted with caution as chronic smokers and controls were not matched for education, social economic status, life style and race