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Marilyn A Huestis - One of the best experts on this subject based on the ideXlab platform.
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plasma cannabinoid pharmacokinetics after controlled Smoking and ad libitum Cannabis Smoking in chronic frequent users
Journal of Analytical Toxicology, 2015Co-Authors: Dayong Lee, Garry Milman, Allan J Barnes, Mateus M Bergamaschi, Regina Helena Costa Queiroz, Ryan Vandrey, Marilyn A HuestisAbstract:More Americans are dependent on Cannabis than any other illicit drug. The main analytes for Cannabis testing include the primary psychoactive constituent, Δ(9)-tetrahydrocannabinol (THC), equipotent 11-hydroxy-THC (11-OH-THC) and inactive 11-nor-9-carboxy-THC (THCCOOH). Eleven adult chronic frequent Cannabis smokers resided on a closed research unit with unlimited access to 5.9% THC Cannabis cigarettes from 12:00 to 23:00 during two ad libitum Smoking phases, followed by a 5-day abstinence period in seven participants. A single cigarette was smoked under controlled topography on the last day of the Smoking and abstinence phases. Plasma cannabinoids were quantified by two-dimensional gas chromatography-mass spectrometry. Median plasma maximum concentrations (Cmax) were 28.3 (THC), 3.9 (11-OH-THC) and 47.0 μg/L (THCCOOH) 0.5 h after controlled single Cannabis Smoking. Median Cmax 0.2-0.5 h after ad libitum Smoking was higher for all analytes: 83.5 (THC), 14.2 (11-OH-THC) and 155 μg/L (THCCOOH). All 11 participants' plasma samples were THC and THCCOOH-positive, 58.3% had THC ≥5 μg/L and 79.2% were 11-OH-THC-positive 8.1-14 h after last Cannabis Smoking. Cannabinoid detection rates in seven participants 106-112 h (4-5 days) after last Smoking were 92.9 (THC), 35.7 (11-OH-THC) and 100% (THCCOOH), with limits of quantification of 0.5 μg/L for THC and THCCOOH, and 1.0 μg/L for 11-OH-THC. These data greatly expand prior research findings on cannabinoid excretion profiles in chronic frequent Cannabis smokers during ad libitum Smoking. Smoking multiple Cannabis cigarettes led to higher Cmax and AUC compared with Smoking a single cigarette. The chronic frequent Cannabis smokers exhibited extended detection windows for plasma cannabinoids, reflecting a large cannabinoid body burden.
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oral fluid cannabinoids in chronic frequent Cannabis smokers during ad libitum Cannabis Smoking
Drug Testing and Analysis, 2015Co-Authors: Dayong Lee, Allan J Barnes, Ryan Vandrey, Damodara R Mendu, Jeannie Murray, Marilyn A HuestisAbstract:Oral fluid (OF) offers a simple, non-invasive, directly observable sample collection for clinical and forensic drug testing. Given that chronic Cannabis smokers often engage in drug administration multiple times daily, evaluating OF cannabinoid pharmacokinetics during ad libitum Smoking is important for practical development of analytical methods and informed interpretation of test results. Eleven Cannabis smokers resided in a closed research unit for 51 days, and underwent four, 5-day oral delta-9-tetrahydrocannabinol (THC) treatments. Each medication period was separated by 9 days of ad libitum Cannabis Smoking from 12:00 to 23:00 h daily. Ten OF samples were collected from 9:00-22:00 h on each of the last ad libitum Smoking days (Study Days 4, 18, 32, and 46). As the number of Cannabis cigarettes smoked increased over the study days, OF THC, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH) also increased with a significant effect of time since last Smoking (Δtime; range, 0.0-17.4 h) and ≥88% detection rates; concentrations on Day 4 were significantly lower than those on Days 32 and 46 but not Day 18. Within 30 min of Smoking, median THC, CBN, and THCCOOH concentrations were 689 µg/L, 116 µg/L, and 147 ng/L, respectively, decreasing to 19.4 µg/L, 2.4 µg/L, and 87.6 ng/L after 10 h. Cannabidiol and 11-hydroxy-THC showed overall lower detection rates of 29 and 8.6%, respectively. Cannabinoid disposition in OF was highly influenced by Δtime and composition of smoked Cannabis. Furthermore, cannabinoid OF concentrations increased over ad libitum Smoking days, in parallel with increased Cannabis self-administration, possibly reflecting development of increased Cannabis tolerance. Copyright © 2014 John Wiley & Sons, Ltd. Language: en
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simultaneous quantification of δ9 tetrahydrocannabinol 11 nor 9 carboxy tetrahydrocannabinol cannabidiol and cannabinol in oral fluid by microflow liquid chromatography high resolution mass spectrometry
Journal of Chromatography A, 2013Co-Authors: Marta Concheiro, Dayong Lee, Elena Lendoiro, Marilyn A HuestisAbstract:Δ(9)-Tetrahydrocannabinol (THC) is the primary target in oral fluid (OF) for detecting Cannabis intake. However, additional biomarkers are needed to solve interpretation issues, such as the possibility of passive inhalation by identifying 11-nor-9-carboxy-THC (THCCOOH), and determining recent Cannabis Smoking by identifying cannabidiol (CBD) and/or cannabinol (CBN). We developed and comprehensively validated a microflow liquid chromatography (LC)-high resolution mass spectrometry method for simultaneous quantification of THC, THCCOOH, CBD and CBN in OF collected with the Oral-Eze(®) and Quantisal™ devices. One milliliter OF-buffer solution (0.25mL OF and 0.5mL of Oral-Eze buffer, 1:3 dilution, or 0.75mL Quantisal buffer, 1:4 dilution) had proteins precipitated, and the supernatant subjected to CEREX™ Polycrom™ THC solid-phase extraction (SPE). Microflow LC reverse-phase separation was achieved with a gradient mobile phase of 10mM ammonium acetate pH 6 and acetonitrile over 10min. We employed a Q Exactive high resolution mass spectrometer, with compounds identified and quantified by targeted-MSMS experiments. The assay was linear 0.5-50ng/mL for THC, CBD and CBN, and 15-500pg/mL for THCCOOH. Intra- and inter-day and total imprecision were <10.8%CV and bias 86.5-104.9%. Extraction efficiency was 52.4-109.2%, process efficiency 12.2-88.9% and matrix effect ranged from -86 to -6.9%. All analytes were stable for 24h at 5°C on the autosampler. The method was applied to authentic OF specimens collected with Quantisal and Oral-Eze devices. This method provides a rapid simultaneous quantification of THCCOOH and THC, CBD, CBN, with good selectivity and sensitivity, providing the opportunity to improve interpretation of cannabinoid OF results by eliminating the possibility of passive inhalation and providing markers of recent Cannabis Smoking.
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can oral fluid cannabinoid testing monitor medication compliance and or Cannabis Smoking during oral thc and oromucosal sativex administration
Drug and Alcohol Dependence, 2013Co-Authors: Dayong Lee, Robert S. Goodwin, Erin L Karschner, Garry Milman, Allan J Barnes, Marilyn A HuestisAbstract:a b s t r a c t Objectives: We characterize cannabinoid disposition in oral fluid (OF) after dronabinol, synthetic oral � 9 - tetrahydrocannabinol (THC), and Sativex, a Cannabis-extract oromucosal spray, and evaluate whether smoked Cannabis relapse or Sativex compliance can be identified with OF cannabinoid monitoring. Methods: 5 and 15 mg synthetic oral THC, low (5.4 mg THC, 5.0 mg cannabidiol (CBD)) and high (16.2 mg THC, 15.0 mg CBD) dose Sativex, and placebo were administered in random order (n = 14). Oral fluid specimens were collected for 10.5 h after dosing and analyzed for THC, CBD, cannabinol (CBN), and 11- nor-9-carboxy-THC (THCCOOH). Results: After oral THC, OF THC concentrations decreased over time from baseline, reflecting residual THC excretion from previously self-administered smoked Cannabis. CBD and CBN also were rarely detected. After Sativex, THC, CBD and CBN increased greatly, peaking at 0.25-1 h. Median CBD/THC and CBN/THC ratios were 0.82-1.34 and 0.04-0.06, respectively, reflecting cannabinoids' composition in Sativex. THC- COOH/THC ratios within 4.5 h post Sativex were ≤1.6 pg/ng, always lower than after oral THC and placebo. THCCOOH/THC ratios increased throughout each dosing session. Conclusions: Lack of measurable THC, CBD and CBN in OF following oral THC, and high OF CBD/THC ratios after Sativex distinguish oral and sublingual drug delivery routes from Cannabis Smoking. Low THCCOOH/THC ratios suggest recent Sativex and smoked Cannabis exposure. These data indicate that OF cannabinoid monitoring can document compliance with Sativex pharmacotherapy, and identify relapse to smoked Cannabis during oral THC medication but not Sativex treatment, unless samples were collected shortly after Smoking. Published by Elsevier Ireland Ltd.
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Cannabis effects on driving skills
Clinical Chemistry, 2013Co-Authors: Rebecca L. Hartman, Marilyn A HuestisAbstract:BACKGROUND: Cannabis is the most prevalent illicit drug identified in impaired drivers. The effects of Cannabis on driving continue to be debated, making prosecution and legislation difficult. Historically, delays in sample collection, evaluating the inactive Δ(9)-tetrahydrocannabinol (THC) metabolite 11-nor-9-carboxy-THC, and polydrug use have complicated epidemiologic evaluations of driver impairment after Cannabis use.\n\nCONTENT: We review and evaluate the current literature on Cannabis' effects on driving, highlighting the epidemiologic and experimental data. Epidemiologic data show that the risk of involvement in a motor vehicle accident (MVA) increases approximately 2-fold after Cannabis Smoking. The adjusted risk of driver culpability also increases substantially, particularly with increased blood THC concentrations. Studies that have used urine as the biological matrix have not shown an association between Cannabis and crash risk. Experimental data show that drivers attempt to compensate by driving more slowly after Smoking Cannabis, but control deteriorates with increasing task complexity. Cannabis Smoking increases lane weaving and impaired cognitive function. Critical-tracking tests, reaction times, divided-attention tasks, and lane-position variability all show Cannabis-induced impairment. Despite purported tolerance in frequent smokers, complex tasks still show impairment. Combining Cannabis with alcohol enhances impairment, especially lane weaving.\n\nSUMMARY: Differences in study designs frequently account for inconsistencies in results between studies. Participant-selection bias and confounding factors attenuate ostensible Cannabis effects, but the association with MVA often retains significance. Evidence suggests recent Smoking and/or blood THC concentrations 2-5 ng/mL are associated with substantial driving impairment, particularly in occasional smokers. Future Cannabis-and-driving research should emphasize challenging tasks, such as divided attention, and include occasional and chronic daily Cannabis smokers.
Dayong Lee - One of the best experts on this subject based on the ideXlab platform.
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plasma cannabinoid pharmacokinetics after controlled Smoking and ad libitum Cannabis Smoking in chronic frequent users
Journal of Analytical Toxicology, 2015Co-Authors: Dayong Lee, Garry Milman, Allan J Barnes, Mateus M Bergamaschi, Regina Helena Costa Queiroz, Ryan Vandrey, Marilyn A HuestisAbstract:More Americans are dependent on Cannabis than any other illicit drug. The main analytes for Cannabis testing include the primary psychoactive constituent, Δ(9)-tetrahydrocannabinol (THC), equipotent 11-hydroxy-THC (11-OH-THC) and inactive 11-nor-9-carboxy-THC (THCCOOH). Eleven adult chronic frequent Cannabis smokers resided on a closed research unit with unlimited access to 5.9% THC Cannabis cigarettes from 12:00 to 23:00 during two ad libitum Smoking phases, followed by a 5-day abstinence period in seven participants. A single cigarette was smoked under controlled topography on the last day of the Smoking and abstinence phases. Plasma cannabinoids were quantified by two-dimensional gas chromatography-mass spectrometry. Median plasma maximum concentrations (Cmax) were 28.3 (THC), 3.9 (11-OH-THC) and 47.0 μg/L (THCCOOH) 0.5 h after controlled single Cannabis Smoking. Median Cmax 0.2-0.5 h after ad libitum Smoking was higher for all analytes: 83.5 (THC), 14.2 (11-OH-THC) and 155 μg/L (THCCOOH). All 11 participants' plasma samples were THC and THCCOOH-positive, 58.3% had THC ≥5 μg/L and 79.2% were 11-OH-THC-positive 8.1-14 h after last Cannabis Smoking. Cannabinoid detection rates in seven participants 106-112 h (4-5 days) after last Smoking were 92.9 (THC), 35.7 (11-OH-THC) and 100% (THCCOOH), with limits of quantification of 0.5 μg/L for THC and THCCOOH, and 1.0 μg/L for 11-OH-THC. These data greatly expand prior research findings on cannabinoid excretion profiles in chronic frequent Cannabis smokers during ad libitum Smoking. Smoking multiple Cannabis cigarettes led to higher Cmax and AUC compared with Smoking a single cigarette. The chronic frequent Cannabis smokers exhibited extended detection windows for plasma cannabinoids, reflecting a large cannabinoid body burden.
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oral fluid cannabinoids in chronic frequent Cannabis smokers during ad libitum Cannabis Smoking
Drug Testing and Analysis, 2015Co-Authors: Dayong Lee, Allan J Barnes, Ryan Vandrey, Damodara R Mendu, Jeannie Murray, Marilyn A HuestisAbstract:Oral fluid (OF) offers a simple, non-invasive, directly observable sample collection for clinical and forensic drug testing. Given that chronic Cannabis smokers often engage in drug administration multiple times daily, evaluating OF cannabinoid pharmacokinetics during ad libitum Smoking is important for practical development of analytical methods and informed interpretation of test results. Eleven Cannabis smokers resided in a closed research unit for 51 days, and underwent four, 5-day oral delta-9-tetrahydrocannabinol (THC) treatments. Each medication period was separated by 9 days of ad libitum Cannabis Smoking from 12:00 to 23:00 h daily. Ten OF samples were collected from 9:00-22:00 h on each of the last ad libitum Smoking days (Study Days 4, 18, 32, and 46). As the number of Cannabis cigarettes smoked increased over the study days, OF THC, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH) also increased with a significant effect of time since last Smoking (Δtime; range, 0.0-17.4 h) and ≥88% detection rates; concentrations on Day 4 were significantly lower than those on Days 32 and 46 but not Day 18. Within 30 min of Smoking, median THC, CBN, and THCCOOH concentrations were 689 µg/L, 116 µg/L, and 147 ng/L, respectively, decreasing to 19.4 µg/L, 2.4 µg/L, and 87.6 ng/L after 10 h. Cannabidiol and 11-hydroxy-THC showed overall lower detection rates of 29 and 8.6%, respectively. Cannabinoid disposition in OF was highly influenced by Δtime and composition of smoked Cannabis. Furthermore, cannabinoid OF concentrations increased over ad libitum Smoking days, in parallel with increased Cannabis self-administration, possibly reflecting development of increased Cannabis tolerance. Copyright © 2014 John Wiley & Sons, Ltd. Language: en
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cannabinoid disposition in oral fluid after controlled Cannabis Smoking in frequent and occasional smokers
Drug Testing and Analysis, 2014Co-Authors: Dayong Lee, Nathalie A Desrosiers, Damodara R Mendu, Matthew N Newmeyer, Allan J BarnesAbstract:Oral fluid (OF) is an increasingly popular alternative matrix for drug testing, with cannabinoids being the most commonly identified illicit drug. Quantification of multiple OF cannabinoids and understanding differences in OF cannabinoid pharmacokinetics between frequent and occasional smokers improve test interpretation. The new Oral-Eze® OF collection device has an elution buffer that stabilizes analytes and improves drug recovery from the collection pad; however, its performance has not been independently evaluated. After controlled Smoking of a 6.8% Δ(9) -tetrahydrocannabinol (THC) Cannabis cigarette by frequent and occasional smokers, OF was collected with the Oral-Eze device for up to 30 h. Samples were analyzed for multiple cannabinoids by a validated 2D-GC-MS method. Frequent smokers had significantly greater OF THCCOOH concentrations than occasional smokers at all times, and showed positive results for a significantly longer time. We evaluated multiple cannabinoid cut-offs; the shortest last detection times were observed when THC ≥1μg/L was combined with CBD or CBN ≥1μg/L. With these cut-offs, last detection times(1-13.5 h) were not significantly different between groups, demonstrating suitability for short-term cannabinoid detection independent of Smoking history. Cut-offs utilizing THC alone or combined with THCCOOH showed significantly different last detection times between groups. The widest detection windows were observed with THC ≥1 or 2μg/L or THCCOOH ≥20ng/L. Our data illustrate the effectiveness of the Oral-Eze® device for OF collection, the impact of self-administered smoked Cannabis history on OF cannabinoid results, and the ability to improve interpretation and tailor OF cannabinoid cut-offs to fulfill the detection window needs of a given program. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. Language: en
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simultaneous quantification of δ9 tetrahydrocannabinol 11 nor 9 carboxy tetrahydrocannabinol cannabidiol and cannabinol in oral fluid by microflow liquid chromatography high resolution mass spectrometry
Journal of Chromatography A, 2013Co-Authors: Marta Concheiro, Dayong Lee, Elena Lendoiro, Marilyn A HuestisAbstract:Δ(9)-Tetrahydrocannabinol (THC) is the primary target in oral fluid (OF) for detecting Cannabis intake. However, additional biomarkers are needed to solve interpretation issues, such as the possibility of passive inhalation by identifying 11-nor-9-carboxy-THC (THCCOOH), and determining recent Cannabis Smoking by identifying cannabidiol (CBD) and/or cannabinol (CBN). We developed and comprehensively validated a microflow liquid chromatography (LC)-high resolution mass spectrometry method for simultaneous quantification of THC, THCCOOH, CBD and CBN in OF collected with the Oral-Eze(®) and Quantisal™ devices. One milliliter OF-buffer solution (0.25mL OF and 0.5mL of Oral-Eze buffer, 1:3 dilution, or 0.75mL Quantisal buffer, 1:4 dilution) had proteins precipitated, and the supernatant subjected to CEREX™ Polycrom™ THC solid-phase extraction (SPE). Microflow LC reverse-phase separation was achieved with a gradient mobile phase of 10mM ammonium acetate pH 6 and acetonitrile over 10min. We employed a Q Exactive high resolution mass spectrometer, with compounds identified and quantified by targeted-MSMS experiments. The assay was linear 0.5-50ng/mL for THC, CBD and CBN, and 15-500pg/mL for THCCOOH. Intra- and inter-day and total imprecision were <10.8%CV and bias 86.5-104.9%. Extraction efficiency was 52.4-109.2%, process efficiency 12.2-88.9% and matrix effect ranged from -86 to -6.9%. All analytes were stable for 24h at 5°C on the autosampler. The method was applied to authentic OF specimens collected with Quantisal and Oral-Eze devices. This method provides a rapid simultaneous quantification of THCCOOH and THC, CBD, CBN, with good selectivity and sensitivity, providing the opportunity to improve interpretation of cannabinoid OF results by eliminating the possibility of passive inhalation and providing markers of recent Cannabis Smoking.
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can oral fluid cannabinoid testing monitor medication compliance and or Cannabis Smoking during oral thc and oromucosal sativex administration
Drug and Alcohol Dependence, 2013Co-Authors: Dayong Lee, Robert S. Goodwin, Erin L Karschner, Garry Milman, Allan J Barnes, Marilyn A HuestisAbstract:a b s t r a c t Objectives: We characterize cannabinoid disposition in oral fluid (OF) after dronabinol, synthetic oral � 9 - tetrahydrocannabinol (THC), and Sativex, a Cannabis-extract oromucosal spray, and evaluate whether smoked Cannabis relapse or Sativex compliance can be identified with OF cannabinoid monitoring. Methods: 5 and 15 mg synthetic oral THC, low (5.4 mg THC, 5.0 mg cannabidiol (CBD)) and high (16.2 mg THC, 15.0 mg CBD) dose Sativex, and placebo were administered in random order (n = 14). Oral fluid specimens were collected for 10.5 h after dosing and analyzed for THC, CBD, cannabinol (CBN), and 11- nor-9-carboxy-THC (THCCOOH). Results: After oral THC, OF THC concentrations decreased over time from baseline, reflecting residual THC excretion from previously self-administered smoked Cannabis. CBD and CBN also were rarely detected. After Sativex, THC, CBD and CBN increased greatly, peaking at 0.25-1 h. Median CBD/THC and CBN/THC ratios were 0.82-1.34 and 0.04-0.06, respectively, reflecting cannabinoids' composition in Sativex. THC- COOH/THC ratios within 4.5 h post Sativex were ≤1.6 pg/ng, always lower than after oral THC and placebo. THCCOOH/THC ratios increased throughout each dosing session. Conclusions: Lack of measurable THC, CBD and CBN in OF following oral THC, and high OF CBD/THC ratios after Sativex distinguish oral and sublingual drug delivery routes from Cannabis Smoking. Low THCCOOH/THC ratios suggest recent Sativex and smoked Cannabis exposure. These data indicate that OF cannabinoid monitoring can document compliance with Sativex pharmacotherapy, and identify relapse to smoked Cannabis during oral THC medication but not Sativex treatment, unless samples were collected shortly after Smoking. Published by Elsevier Ireland Ltd.
James C Anthony - One of the best experts on this subject based on the ideXlab platform.
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estimated probability of becoming a case of drug dependence in relation to duration of drug taking experience a functional analysis approach
International Journal of Methods in Psychiatric Research, 2017Co-Authors: Olga A Vsevolozhskaya, James C AnthonyAbstract:Measured as elapsed time from first use to dependence syndrome onset, the estimated “induction interval” for cocaine is thought to be short relative to the Cannabis interval, but little is known about risk of becoming dependent during first months after onset of use. Virtually all published estimates for this facet of drug dependence epidemiology are from life histories elicited years after first use. To improve estimation, we turn to new month-wise data from nationally representative samples of newly incident drug users identified via probability sampling and confidential computer-assisted self-interviews for the United States National Surveys on Drug Use and Health, 2004–2013. Standardized modules assessed first and most recent use, and dependence syndromes, for each drug subtype. A four-parameter Hill function depicts the drug dependence transition for subgroups defined by units of elapsed time from first to most recent use, with an expectation of greater cocaine dependence transitions for cocaine versus Cannabis. This study's novel estimates for cocaine users one month after first use show 2–4% with cocaine dependence; 12–17% are dependent when use has persisted. Corresponding Cannabis estimates are 0–1% after one month, but 10–23% when use persists. Duration or persistence of Cannabis Smoking beyond an initial interval of a few months of use seems to be a signal of noteworthy risk for, or co-occurrence of, rapid-onset Cannabis dependence, not too distant from cocaine estimates, when we sort newly incident users into subgroups defined by elapsed time from first to most recent use. Copyright © 2016 John Wiley & Sons, Ltd.
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Cannabis Smoking cardiometabolic health and cardiovascular disease united states nhanes 2005 2010
Drug and Alcohol Dependence, 2015Co-Authors: Omayma Alshaarawy, James C AnthonyAbstract:methods usedwere BBT (1/32 articles) and transvaginal ultrasound (1/32 articles). Conclusions: There is a lack of consistency in methodology used to determine menstrual phase. We recommend combining several methods to improve accuracy of phase identification, minimize costs and burden, and reduce selection bias and confounding. The adoption of these recommendations will yield a decrease in misclassification bias and facilitate cross-study comparisons. Financial support: P50-DA033942, P50-DA016511, P50DA033945, K24DA038240, and K12HD055887.
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Cannabis Smoking clusters within secondary schools results from the united states monitoring the future study 1976 2013
Drug and Alcohol Dependence, 2015Co-Authors: Maria A Parker, James C AnthonyAbstract:whether school-level risk factors were associated with student marijuana use, after accounting for individual-level covariates. Methods: Multilevel modeling was used to analyze data from 27,874 high school students participating in the 2013 Maryland Safe and Supportive Schools Climate Survey. Individual-level factors included gender, age, race/ethnicity, alcohol use, tobacco use, fighting, and perceptions of school safety and support. School-level factors included alcohol use prevalence, tobacco use prevalence, urbanicity, suspensions, racial composition, fighting prevalence, student/teacher ratio, proportion receiving special education services and free/reduced price meals, and student mobility rate. Results: 21% of youth reported marijuana use. Variance was greater at the classroom level ( = 0.15, SD=0.39) vs. the school level ( = 0.02, SD=0.13). Students at schools with a higher proportion of racial/ethnic minorities (AOR=1.01, 95% CI: 1.00, 1.01), mobility rate (AOR=1.02, 95% CI: 1.00, 1.04), and alcohol use prevalence (AOR=1.03, 95% CI: 1.01, 1.04) were slightly more likely to report marijuana use. Individual-level factors were more strongly associated with marijuana use than school-level factors, including older age, Black race/ethnicity, alcohol use, tobacco use, and fighting. Conclusions: Marijuana use is common among high school students, despite differences in school-level factors. Given the continued loosening of marijuana policies, it is likely that adolescent marijuana use will increase. Schools may need to reconsider approaches to drug use prevention education. Financial support: Thisworkwas supported by theU.S. Department of Education’s Safe and Supportive Schools Initiative and a NIDA T32 Training Grant (3T32DA007292-21).
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Cannabis Smoking and diabetes mellitus results from meta analysis with eight independent replication samples
Epidemiology, 2015Co-Authors: Omayma Alshaarawy, James C AnthonyAbstract:Background In preclinical animal studies, evidence links Cannabis with hyperphagia, obesity, and insulin resistance. Epidemiologic data, however, suggest an inverse Cannabis Smoking-diabetes mellitus association. Here, we offer epidemiologic estimates from eight independent replications from (1) the National Health and Nutrition Examination Surveys, and (2) the National Surveys on Drug Use and Health (2005-2012). Methods For each national survey participant, computer-assisted self-interviews assess Cannabis Smoking and physician-diagnosed diabetes mellitus; the National Health and Nutrition Examination Surveys provide additional biomarker values and a composite diabetes diagnosis. Regression analyses produce estimates of Cannabis Smoking-diabetes associations. Meta-analyses summarize the replication estimates. Results Recently active Cannabis Smoking and diabetes mellitus are inversely associated. The meta-analytic summary odds ratio is 0.7 (95% confidence interval = 0.6, 0.8). Conclusions Current evidence is too weak for causal inference, but there now is a more stable evidence base for new lines of clinical translational research on a possibly protective (or spurious) Cannabis Smoking-diabetes mellitus association suggested in prior research.
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Cannabis Smoking and serum c reactive protein a quantile regressions approach based on nhanes 2005 2010
Drug and Alcohol Dependence, 2015Co-Authors: Omayma Alshaarawy, James C AnthonyAbstract:Background Pre-clinical studies link cannabinoid-1 receptor activation to inflammation and atherosclerotic effects; anti-inflammation and immunosuppression seem to be mediated by cannabinoid-2 receptor activation. In this epidemiological study, we aim to present estimates on suspected Cannabis-attributable immunomodulation as manifest in serum C-reactive protein (CRP) levels as non-specific inflammatory markers with interpretable clinical values. With strength of data from recent large nationally representative community sample surveys, the research approach illustrates value of a quantile regressions approach in lieu of the commonly used but relatively arbitrary cutpoints for CRP values. Methods The study population encompasses 20-59 year old participants from the National Health and Nutrition Examination Surveys, 2005-2010 (n=1115 recently active Cannabis smokers and 8041 non-smokers, identified via confidential Audio Computer Assisted Self-Interviews). Age, sex, race, education, income-poverty ratio, alcohol consumption, and tobacco Smoking also were measured, together with body mass index (BMI), which actually might be on a mediational path. Quantile regressions, with bootstrapping for variance estimation, made it possible to hold these covariates constant while estimating Cannabis-CRP associations. Results Evidence suggesting possible Cannabis-attributable immunomodulation emerges at CRP levels below the median (p Conclusions Extending pre-clinical research on Cannabis-attributable immunomodulation, this study's CRP evidence points toward possible anti-inflammatory effects of Cannabis Smoking. More definitive evidence can be derived by combining pre-clinical research, studies of patients, and epidemiological research approaches.
Luis Ribeiro - One of the best experts on this subject based on the ideXlab platform.
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marijuana and the lung hysteria or cause for concern
Breathe, 2018Co-Authors: Luis RibeiroAbstract:Increasing Cannabis use and legalisation highlights the paucity of data we have on the safety of Cannabis Smoking for respiratory health. Unfortunately, concurrent use of tobacco among marijuana smokers makes it difficult to untangle individual effect of marijuana Smoking. Chronic Cannabis only Smoking has been shown in large cohort studies to reduce forced expiratory volume in 1 s/forced vital capacity via increasing forced vital capacity in chronic use contrary to the picture seen in tobacco Smoking. The cause of this is unclear and there are various proposed mechanisms including respiratory muscle training secondary to method of inhalation and acute anti-inflammatory effect and bronchodilation of Cannabis on the airways. While Cannabis smoke has been shown to increase symptoms of chronic bronchitis, it has not been definitively shown to be associated with shortness of breath or irreversible airway changes. The evidence surrounding the development of lung cancer is less clear; however, preliminary evidence does not suggest association. Bullous lung disease associated with marijuana use has long been observed in clinical practice but published evidence is limited to a total of 57 published cases and only one cross-sectional study looking at radiological changes among chronic users which did not report any increase in macroscopic emphysema. More studies are required to elucidate these missing points to further guide risk stratification, clinical diagnosis and management. Key points Cannabis Smoking has increased and is likely to increase further with relaxation of legalisation and medicinal use of cannabinoids. Chronic marijuana Smoking often produces symptoms similar to those of chronic tobacco Smoking such as cough, sputum production, shortness of breath and wheeze. Cessation of marijuana Smoking is associated with a reduction in respiratory symptoms and no increased risk of chronic bronchitis. Spirometry changes seen in chronic marijuana smokers appear to differ from those in chronic tobacco smokers. In chronic marijuana smokers there is an increase in FVC as opposed to a definite decrease in FEV1. Multiple case series have demonstrated peripheral bullae in marijuana smokers, but no observational studies have elucidated the risk. There is currently no clear association between Cannabis Smoking and lung cancer, although the research is currently limited. Educational aims To update readers on legalisation of recreational and medicinal Cannabis. To summarise the evidence base surrounding the respiratory effects of inhaled marijuana use. To provide clinicians with an understanding of the main differences between Cannabis and tobacco to be able to apply this to patient education. To highlight common respiratory problems among Cannabis users and the need for recreational drug history taking.
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s127 effect of Cannabis Smoking on the development of bullous lung disease a structured literature review
Thorax, 2016Co-Authors: Luis Ribeiro, Philip W IndAbstract:Background With increasing Cannabis use, physicians need to know more about its respiratory effects. However, there are few long term studies of Cannabis Smoking, mostly due to legality issues and the confounding effects of tobacco. Aims We reviewed the effect of chronic Cannabis use on bullous lung disease. Methods 18 out of 69 English-language publications, prior to April 2016, from MEDLINE, Scopus, and Web of Science databases, which reported bullous lung disease in Cannabis users, were examined. Case reports and case series were included. Results The only cross-sectional study reported an increase in the rates of macroscopic emphysema in tobacco only (17 of 92) and tobacco + Cannabis smokers (15 of 91), but not in Cannabis only smokers (1 of 75) compared to non-smokers.1 The remaining case series and case reports described a total of 56 marijuana smokers presenting with bullous lung disease, often with pneumothorax and predominantly upper lobe involvement (Table 1). Concurrent tobacco Smoking was present in all but 3 cases. The majority of cases reported heavy Cannabis use, though direct comparison was difficult due to variation in usage measurements. All 4 case series that measured lung function reported normal findings. Conclusions While the clinical association of Cannabis Smoking and peripheral lung bullae is well recognised (and consequently often not reported) there is scant documentation in the literature correlating marijuana Smoking with bullous lung disease. Reference Aldington S, et al . Effect of Cannabis on pulmonary structure, function and symptoms. Thorax . 2007; 62 (12):1058–63.
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p147 effect of Cannabis Smoking on respiratory symptoms and lung function a structured literature review
Thorax, 2016Co-Authors: Luis Ribeiro, Philip W IndAbstract:Background With increasing Cannabis use, physicians need to know more about its respiratory effects. However, there are few long term studies of Cannabis Smoking, due to legality issues and confounding effects of tobacco. Aims We reviewed effect of chronic Cannabis use on respiratory symptoms and lung function, particularly FEV1, FVC and FEV1/FVC ratio. Methods 19 out of 256 English-language publications, prior to June 2015, from MEDLINE, Scopus, and Web of Science databases, reporting lung function in chronic Cannabis users, were examined. Results 11 cross-sectional studies and 8 observational cohort studies were included. All 9 studies (n = 11,848) examining respiratory symptoms reported an increase with Cannabis Smoking (odds ratio up to 3.0). 2 studies (n = 1,336) reported that quitting Cannabis with/without tobacco reduced chronic bronchitis symptoms to those of never Cannabis smokers. 8 studies (n = 9,939) reported no significant changes in FEV1/FVC; 6 (n = 3,722) found a significant decrease (0.5%−1.9%) in chronic marijuana only smokers compared to controls. While most reports omitted absolute FVC results, 3 large studies (n = 13,858) demonstrated increased FVC with marijuana Smoking. 4 studies (n = 13, 674) found dose-related reductions in FEV1/FVC. 7 studies associated chronic Cannabis Smoking with other evidence of airflow obstruction [increased airway resistance in 3; (0.03 to 0.38 cm H 2 O/L/s), reduced specific airway conductance in 4; (0.007 to 0.07 mL/s/cm H 2 O/L)]. The larger studies (n = 13,858) suggested increased FVC may cause reduced FEV1/FVC chronically. 1 This contrasts with airflow obstruction in tobacco Smoking. Anti-inflammatory or acute bronchodilator effects of Cannabis, on top of chronic effects, may partly explain these results. Conclusions Cannabis, like tobacco, Smoking causes chronic bronchitis but increased FVC is more consistently found than reduced FEV1. No studies in marijuana smokers have found a linear decline in FEV1 with time. More work is needed to explain the differing effects on lung function and to examine effects on small airways, imaging and histology. Reference Hancox RJ, et al . Effect of Cannabis Smoking on lung function: a population-based cohort study. Eur Respir J 2010; 35 :42–7.
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Respiratory effects of Cannabis Smoking: A literature review
European Respiratory Journal, 2016Co-Authors: Luis RibeiroAbstract:Background: With increasing Cannabis use, physicians need to know more about its respiratory effects. However, there are few long term studies of Cannabis Smoking, mostly due to legality issues and the confounding effects of tobacco. Aims: We reviewed the effect of chronic Cannabis use on lung function, particularly FEV1, FVC and FEV1/FVC ratio. Methods: 19 out of 256 English-language publications, prior to June 2015, from MEDLINE, Scopus, and Web of Science databases, which reported lung function in chronic Cannabis users, were examined. Results: 8 studies reported no significant changes in FEV1/FVC ratio, while 6 found a significant decrease (0.5%-1.9%) in chronic marijuana only smokers compared to controls. While most reports omitted absolute FVC results, 3 large studies demonstrated increased FVC with marijuana Smoking. 4 studies found a dose-related reduction in FEV1/FVC. All 8 studies examining respiratory symptoms reported an increase with Cannabis Smoking (odds ratio up to 3.0). The larger studies suggested that increased FVC may cause the reduced FEV1/FVC with chronic marijuana use (Hancox, et al. ERJ 2010;35:42-7). This contrasts starkly with airflow obstruction in tobacco Smoking. Also, FEV1 appears to have a non-linear relationship with Cannabis Smoking: increasing up to 7 joint-years, but declining afterwards (Pletcher, et al. JAMA 2012;307:173-81). Acute bronchodilator effects of Cannabis, on top of chronic effects, may partly explain these results. Conclusions: Cannabis, like tobacco, Smoking causes chronic bronchitis but more work is needed to explain the different effects on lung function and address issues such as effects on small airways, imaging and histology.
Allan J Barnes - One of the best experts on this subject based on the ideXlab platform.
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plasma cannabinoid pharmacokinetics after controlled Smoking and ad libitum Cannabis Smoking in chronic frequent users
Journal of Analytical Toxicology, 2015Co-Authors: Dayong Lee, Garry Milman, Allan J Barnes, Mateus M Bergamaschi, Regina Helena Costa Queiroz, Ryan Vandrey, Marilyn A HuestisAbstract:More Americans are dependent on Cannabis than any other illicit drug. The main analytes for Cannabis testing include the primary psychoactive constituent, Δ(9)-tetrahydrocannabinol (THC), equipotent 11-hydroxy-THC (11-OH-THC) and inactive 11-nor-9-carboxy-THC (THCCOOH). Eleven adult chronic frequent Cannabis smokers resided on a closed research unit with unlimited access to 5.9% THC Cannabis cigarettes from 12:00 to 23:00 during two ad libitum Smoking phases, followed by a 5-day abstinence period in seven participants. A single cigarette was smoked under controlled topography on the last day of the Smoking and abstinence phases. Plasma cannabinoids were quantified by two-dimensional gas chromatography-mass spectrometry. Median plasma maximum concentrations (Cmax) were 28.3 (THC), 3.9 (11-OH-THC) and 47.0 μg/L (THCCOOH) 0.5 h after controlled single Cannabis Smoking. Median Cmax 0.2-0.5 h after ad libitum Smoking was higher for all analytes: 83.5 (THC), 14.2 (11-OH-THC) and 155 μg/L (THCCOOH). All 11 participants' plasma samples were THC and THCCOOH-positive, 58.3% had THC ≥5 μg/L and 79.2% were 11-OH-THC-positive 8.1-14 h after last Cannabis Smoking. Cannabinoid detection rates in seven participants 106-112 h (4-5 days) after last Smoking were 92.9 (THC), 35.7 (11-OH-THC) and 100% (THCCOOH), with limits of quantification of 0.5 μg/L for THC and THCCOOH, and 1.0 μg/L for 11-OH-THC. These data greatly expand prior research findings on cannabinoid excretion profiles in chronic frequent Cannabis smokers during ad libitum Smoking. Smoking multiple Cannabis cigarettes led to higher Cmax and AUC compared with Smoking a single cigarette. The chronic frequent Cannabis smokers exhibited extended detection windows for plasma cannabinoids, reflecting a large cannabinoid body burden.
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oral fluid cannabinoids in chronic frequent Cannabis smokers during ad libitum Cannabis Smoking
Drug Testing and Analysis, 2015Co-Authors: Dayong Lee, Allan J Barnes, Ryan Vandrey, Damodara R Mendu, Jeannie Murray, Marilyn A HuestisAbstract:Oral fluid (OF) offers a simple, non-invasive, directly observable sample collection for clinical and forensic drug testing. Given that chronic Cannabis smokers often engage in drug administration multiple times daily, evaluating OF cannabinoid pharmacokinetics during ad libitum Smoking is important for practical development of analytical methods and informed interpretation of test results. Eleven Cannabis smokers resided in a closed research unit for 51 days, and underwent four, 5-day oral delta-9-tetrahydrocannabinol (THC) treatments. Each medication period was separated by 9 days of ad libitum Cannabis Smoking from 12:00 to 23:00 h daily. Ten OF samples were collected from 9:00-22:00 h on each of the last ad libitum Smoking days (Study Days 4, 18, 32, and 46). As the number of Cannabis cigarettes smoked increased over the study days, OF THC, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH) also increased with a significant effect of time since last Smoking (Δtime; range, 0.0-17.4 h) and ≥88% detection rates; concentrations on Day 4 were significantly lower than those on Days 32 and 46 but not Day 18. Within 30 min of Smoking, median THC, CBN, and THCCOOH concentrations were 689 µg/L, 116 µg/L, and 147 ng/L, respectively, decreasing to 19.4 µg/L, 2.4 µg/L, and 87.6 ng/L after 10 h. Cannabidiol and 11-hydroxy-THC showed overall lower detection rates of 29 and 8.6%, respectively. Cannabinoid disposition in OF was highly influenced by Δtime and composition of smoked Cannabis. Furthermore, cannabinoid OF concentrations increased over ad libitum Smoking days, in parallel with increased Cannabis self-administration, possibly reflecting development of increased Cannabis tolerance. Copyright © 2014 John Wiley & Sons, Ltd. Language: en
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cannabinoid disposition in oral fluid after controlled Cannabis Smoking in frequent and occasional smokers
Drug Testing and Analysis, 2014Co-Authors: Dayong Lee, Nathalie A Desrosiers, Damodara R Mendu, Matthew N Newmeyer, Allan J BarnesAbstract:Oral fluid (OF) is an increasingly popular alternative matrix for drug testing, with cannabinoids being the most commonly identified illicit drug. Quantification of multiple OF cannabinoids and understanding differences in OF cannabinoid pharmacokinetics between frequent and occasional smokers improve test interpretation. The new Oral-Eze® OF collection device has an elution buffer that stabilizes analytes and improves drug recovery from the collection pad; however, its performance has not been independently evaluated. After controlled Smoking of a 6.8% Δ(9) -tetrahydrocannabinol (THC) Cannabis cigarette by frequent and occasional smokers, OF was collected with the Oral-Eze device for up to 30 h. Samples were analyzed for multiple cannabinoids by a validated 2D-GC-MS method. Frequent smokers had significantly greater OF THCCOOH concentrations than occasional smokers at all times, and showed positive results for a significantly longer time. We evaluated multiple cannabinoid cut-offs; the shortest last detection times were observed when THC ≥1μg/L was combined with CBD or CBN ≥1μg/L. With these cut-offs, last detection times(1-13.5 h) were not significantly different between groups, demonstrating suitability for short-term cannabinoid detection independent of Smoking history. Cut-offs utilizing THC alone or combined with THCCOOH showed significantly different last detection times between groups. The widest detection windows were observed with THC ≥1 or 2μg/L or THCCOOH ≥20ng/L. Our data illustrate the effectiveness of the Oral-Eze® device for OF collection, the impact of self-administered smoked Cannabis history on OF cannabinoid results, and the ability to improve interpretation and tailor OF cannabinoid cut-offs to fulfill the detection window needs of a given program. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. Language: en
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can oral fluid cannabinoid testing monitor medication compliance and or Cannabis Smoking during oral thc and oromucosal sativex administration
Drug and Alcohol Dependence, 2013Co-Authors: Dayong Lee, Robert S. Goodwin, Erin L Karschner, Garry Milman, Allan J Barnes, Marilyn A HuestisAbstract:a b s t r a c t Objectives: We characterize cannabinoid disposition in oral fluid (OF) after dronabinol, synthetic oral � 9 - tetrahydrocannabinol (THC), and Sativex, a Cannabis-extract oromucosal spray, and evaluate whether smoked Cannabis relapse or Sativex compliance can be identified with OF cannabinoid monitoring. Methods: 5 and 15 mg synthetic oral THC, low (5.4 mg THC, 5.0 mg cannabidiol (CBD)) and high (16.2 mg THC, 15.0 mg CBD) dose Sativex, and placebo were administered in random order (n = 14). Oral fluid specimens were collected for 10.5 h after dosing and analyzed for THC, CBD, cannabinol (CBN), and 11- nor-9-carboxy-THC (THCCOOH). Results: After oral THC, OF THC concentrations decreased over time from baseline, reflecting residual THC excretion from previously self-administered smoked Cannabis. CBD and CBN also were rarely detected. After Sativex, THC, CBD and CBN increased greatly, peaking at 0.25-1 h. Median CBD/THC and CBN/THC ratios were 0.82-1.34 and 0.04-0.06, respectively, reflecting cannabinoids' composition in Sativex. THC- COOH/THC ratios within 4.5 h post Sativex were ≤1.6 pg/ng, always lower than after oral THC and placebo. THCCOOH/THC ratios increased throughout each dosing session. Conclusions: Lack of measurable THC, CBD and CBN in OF following oral THC, and high OF CBD/THC ratios after Sativex distinguish oral and sublingual drug delivery routes from Cannabis Smoking. Low THCCOOH/THC ratios suggest recent Sativex and smoked Cannabis exposure. These data indicate that OF cannabinoid monitoring can document compliance with Sativex pharmacotherapy, and identify relapse to smoked Cannabis during oral THC medication but not Sativex treatment, unless samples were collected shortly after Smoking. Published by Elsevier Ireland Ltd.
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cannabinoid stability in authentic oral fluid after controlled Cannabis Smoking
Clinical Chemistry, 2012Co-Authors: Dayong Lee, Garry Milman, Allan J Barnes, David A Gorelick, David M Schwope, Marilyn A HuestisAbstract:BACKGROUND: Defining cannabinoid stability in authentic oral fluid (OF) is critically important for result interpretation. There are few published OF stability data, and of those available, all employed fortified synthetic OF solutions or elution buffers; none included authentic OF following controlled Cannabis Smoking. METHODS: An expectorated OF pool and a pool of OF collected with Quantisal™ devices were prepared for each of 10 participants. Δ9-Tetrahydrocannabinol (THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD), and cannabinol (CBN) stability in each of 10 authentic expectorated and Quantisal-collected OF pools were determined after storage at 4 °C for 1 and 4 weeks and at −20 °C for 4 and 24 weeks. Results within ±20% of baseline concentrations analyzed within 24 h of collection were considered stable. RESULTS: All Quantisal OF cannabinoid concentrations were stable for 1 week at 4 °C. After 4 weeks at 4 °C, as well as 4 and 24 weeks at −20 °C, THC was stable in 90%, 80%, and 80% and THCCOOH in 89%, 40%, and 50% of Quantisal samples, respectively. Cannabinoids in expectorated OF were less stable than in Quantisal samples when refrigerated or frozen. After 4 weeks at 4 and −20 °C, CBD and CBN were stable in 33%–100% of Quantisal and expectorated samples; by 24 weeks at −20 °C, CBD and CBN were stable in ≤44%. CONCLUSIONS: Cannabinoid OF stability varied by analyte, collection method, and storage duration and temperature, and across participants. OF collection with a device containing an elution/stabilization buffer, sample storage at 4 °C, and analysis within 4 weeks is preferred to maximize result accuracy.
