Characteristics of women concordant and discordant for urine drug screens for cannabis exposure and self-reported cannabis use during pregnancy.

BACKGROUND: Increasing cannabis use among pregnant people and equivocal evidence linking prenatal cannabis exposure to adverse outcomes in offspring highlights the need to understand its potential impact on pregnancy and child outcomes. Assessing cannabis use during pregnancy remains a major challenge with potential influences of stigma on self-report as well as detection limitations of easily collected biological matrices. OBJECTIVE: This descriptive study examined the concordance between self-reported (SR) cannabis use and urine drug screen (UDS) detection of cannabis exposure during the first trimester of pregnancy and characterized concordant and discordant groups for sociodemographic factors, modes of use, secondhand exposure to cannabis and tobacco, and alcohol use and cotinine positivity. STUDY DESIGN: The Cannabis Use During Development and Early Life (CUDDEL) Study is an ongoing longitudinal study that recruits pregnant individuals presenting for obstetric care, who report lifetime cannabis use as well as using (n = 289) or not using cannabis (n = 169) during pregnancy. During the first trimester pregnancy visit, SR of cannabis use and a UDS for cannabis, other illicit drugs and nicotine are acquired from eligible participants, of whom 333 as of 05/01/2023 had both. RESULTS: Using available CUDDEL Study data on both SR and UDS (n = 333; age 26.6 ± 4.7; 88.6% Black; 45.4% below federal poverty threshold; 56.5% with paid employment; 89% with high school education; 22% first pregnancy; 12.3 ± 3.6 weeks gestation), we classified pregnant individuals with SR and UDS data into 4 groups based on concordance (k = 0.49 [95% C.I. 0.40-0.58]) between SR cannabis use and UDS cannabis detection during the first trimester: 1) SR+/UDS+ (n = 107); 2) SR-/UDS- (n = 142); 3) SR+/UDS- (n = 44); 4) SR-/UDS+ (n = 40). Those who were SR+/UDS- reported less frequent cannabis use and fewer hours under the influence of cannabis during their pregnancy. Those who were SR-/UDS+ were more likely to have joined the study at a lower gestational age with 62.5% reporting cannabis use during their pregnancy prior to being aware that they were pregnant. Of the 40 SR-/UDS+ women, 14 (i.e., 35%) reported past month secondhand exposure, or blunt usage. In the subset of individuals with SR and UDS available at trimester 2 (N = 160) and 3 (N = 140), concordant groups were mostly stable and > 50% of those in the discordant groups became concordant by the second trimester. Classifying individuals as exposed or not exposed who were SR+ and/or UDS+ resulted in minor changes in group status based on self-report at screening. CONCLUSION: Overall, there was moderate concordance between SR and UDS for cannabis use/exposure during pregnancy. Instances of SR+/UDS- discordancy may partially be attributable to lower levels of use that are not detected on UDS. SR-/UDS+ discordancy may arise from recent use prior to knowledge of pregnancy, extreme secondhand exposure, deception, and challenges with completing questionnaires. Acquiring both self-report and biological detection of cannabis use/exposure allows for the examination of convergent evidence. Classifying those who are SR+ and/or UDS+ as individuals who used cannabis during their first trimester after being aware of their pregnancy resulted in only a minor change in exposure status; thus, relying on self-report screening, at least in this population and within this sociocultural context likely provides an adequate approximation of cannabis use during pregnancy.

Secondhand marijuana exposure in a convenience sample of young children in New York City.

BACKGROUND: Biomarkers of exposure to marijuana smoke can be detected in the urine of children with exposure to secondhand marijuana smoke, but the prevalence is unclear. METHODS: We studied children between the ages of 0 to 3 years who were coming in for well-child visits or hospitalized on the inpatient general pediatric unit between 2017 and 2018 at Kravis Children's Hospital at Mount Sinai. Parents completed an anonymous survey, and urine samples were analyzed for cotinine and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (COOH-THC), a metabolite of Δ9-tetrahydrocannabinol. RESULTS: Fifty-three children had urine samples available for analysis. COOH-THC was detectable in 20.8% of the samples analyzed and urinary cotinine was detectable in 90.2%. High levels of tobacco exposure (defined as cotinine ≥2.0 ng/ml) were significantly associated with COOH-THC detection (p < 0.01). We found that 34.8% of children who lived in attached housing where smoking was allowed within the property had detectable COOH-THC compared to 13.0% of children who lived in housing where smoking was not allowed at all. CONCLUSIONS: This study adds to the growing evidence that children are being exposed to marijuana smoke, even in places where recreational marijuana use is illegal. It is critical that more research be done on the impact of marijuana smoke exposure on children's health and development. IMPACT: We found that 20.8% of the 53 children recruited from Mount Sinai Hospital had detectable marijuana metabolites in their urine. Children with household tobacco smoke exposure and children who lived in attached housing where smoking was allowed on the premises were more likely to have detectable marijuana smoke metabolites. This study adds to the growing evidence that children are being exposed to marijuana smoke, even in places where marijuana remains illegal by state law. As states consider marijuana legalization, it is critical that the potential adverse health effects from marijuana exposure in children be taken into account.

Cannabis legalisation and testing for cannabis use in safety- and risk-sensitive environments.

The legalisation of cannabis by the High Court of South Africa, which was confirmed by the Constitutional Court, imposes challenges to occupational medical practitioners acting as medical review officers in compliance testing and fit-for-service medical examinations. The lipophilic character of the psychoactive component of cannabis, delta-9-tetrahydrocannabinol (Δ9-THC), and its prolonged elimination half-life, create challenges for the ethically and scientifically correct management of the legal use of cannabis in risk-sensitive environments. Important issues to consider in testing for cannabis use are: the stance of 'zero tolerance'; screening and confirmation cut-off concentrations; and the bio-matrices used for testing. Constitutional rights relate to privacy, freedom, autonomy, freedom of religion and the equal enjoyment of rights and privileges, which must be balanced against the health and safety of others.

Inclusion of Cannabis Users in Alcohol Research Samples: Screening In, Screening Out, and Implications.

BACKGROUND: Alcohol and cannabis are frequently co-used, as 20-50% of those who drink alcohol report co-using cannabis. This study is based on the argument that alcohol researchers should enroll cannabis users in human laboratory studies of alcohol use disorder (AUD) to strengthen generalizability. This study examines how heavy drinking cannabis users differ from non-cannabis using heavy drinkers. METHODS: In a community sample of non-treatment-seeking heavy drinkers (n = 551, 35% female), cannabis users were identified through: (a) self-reported cannabis use in the past 6 months and (b) positive urine toxicology test for tetrahydrocannabinol (THC). Cannabis users, identified as described previously, were compared with non-cannabis users on demographic and clinical characteristics. RESULTS: Those who endorsed cannabis use in the past 6 months reported more binge drinking days. Participants who tested positive for THC had higher Alcohol Use Disorder Identification Test scores and more binge drinking days. Younger age and being a tobacco smoker were associated with an increased likelihood of cannabis use in the past 6 months, whereas male gender and being a tobacco use were associated with a greater likelihood of testing positive for THC. Individuals with cannabis use disorder (CUD) endorsed more depression and anxiety and had higher AUD symptom counts than cannabis users without CUD. CONCLUSIONS: The inclusion of cannabis users in AUD samples allows for increased clinical severity. Excluding cannabis users from AUD studies may limit representativeness and expend unnecessary study resources. Lastly, tobacco use may explain a large portion of the effects of cannabis use on sample characteristics. SHORT SUMMARY: Alcohol and cannabis are frequently co-used substances. In a sample of non-treatment-seeking heavy drinkers (n = 551, 35% female), cannabis users reported higher alcohol use and higher likelihood of tobacco use than non-cannabis users. Including cannabis users in alcohol research studies will improve representativeness and likely increase clinical severity.

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

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://clinicaltrials.gov/ct2/show/NCT03276221?term=Randi+Schuster&rank=1.

Interest of adjusting urine cannabinoids to creatinine level to monitor cannabis cessation therapy in heavy smokers with psychiatric disorders.

Up to 25% of hospitalized patients in a psychiatric department exhibit troubles linked to cannabis use. Weaning patients with psychiatric disorders off drugs of abuse requires specific care to improve their clinical outcome. The present study aims to develop a predictive model of urinary excretion of creatinine-normalized cannabinoids (UCNC ) and to determine UCNC thresholds corresponding to the widely used cut-offs of 20 ng/mL and 50 ng/mL for cannabinoids. One hundred thirty-two patients with 452 urine samples were included between 2013 and 2017. Urinary cannabinoids and UCNC elimination curves were computed for each patient. Using a mono-exponential mixed effect model with 88 samples from 26 subjects exhibiting at least 3 decreasing UCNC in a row, the average calculated elimination rate constant was 0.0108 ± 0.0026 h-1 , corresponding to a mean elimination half-life of 64 ± 12 hours. The use of UCNC is of particular interest because of a high inter- and intra-individual variability of urinary creatinine concentration (from 0.06 to 3.81 mg/mL). Moreover, UCNC allows for the detection of diluted or concentrated urine specimens that may lead to false positive (FP) or false negative (FN) results. Receiver operator characteristic (ROC) curves were used to assess UCNC thresholds of 32.4 and 124.7 ng/mg that provide a strong discrimination between positive and negative samples for cannabinoids cut-offs of 20 and 50 ng/mL respectively. The developed model and the defined UCNC thresholds allowed for the accurate prediction of the time needed to reach a negative UCNC result that could be used by clinicians to optimize clinical care.

Cannabis Use Based on Urine Drug Screens in Pregnancy and Its Association With Infant Birth Weight.

OBJECTIVES: This study aims to clarify any association between infant birth weight and cannabis use in pregnancy based on urine drug screens. METHODS: A retrospective medical record review of singleton births from August 2013 through December 2014 with available urine drug screens (UDS) at initiation of prenatal care and delivery was conducted at a large tertiary academic referral center. Patients who used drugs other than cannabis were excluded. RESULTS: The prevalence of cannabis use in pregnancies not complicated by use of other drugs as evidenced by tetrahydrocannabinol in the urine of 2173 patients was 22.6%. Infants born to mothers who tested positive for only tetrahydrocannabinol in urine at both presentation for prenatal care and delivery were of lower median birth weight compared with those who tested negative [2925 g (IQR 2522-3265) vs 3235 g (IQR 2900-3591), P = <0.001]. There was no clinically relevant difference in gestational age at birth [39.0 weeks (IQR 37.1-40.0) vs 39.3 weeks (IQR 38.3-40.0), P = 0.012] between those positive for tetrahydrocannabinol (THC) and those who tested negative. Concomitant tobacco use during pregnancy was not noted to impact infant birth weight using the analysis of covariance. Higher perinatal mortality was observed among those who used cannabis with an adjusted odds ratio of 4.2 (95% CI, 1.53-11.49). CONCLUSIONS: Cannabis use is negatively correlated with fetal birth weight (up to 450 g less) in patients who tested positive for THC when compared with those who did not as documented in the urine drug screens. On the basis of these findings, additional patient education and cessation interventions should be explored with regard to cannabis use in pregnancy.

Correlation of creatinine- and specific gravity-normalized free and glucuronidated urine cannabinoid concentrations following smoked, vaporized, and oral cannabis in frequent and occasional cannabis users.

Variability in urine dilution complicates urine cannabinoid test interpretation. Normalizing urine cannabinoid concentrations to specific gravity (SG) or creatinine was proposed to account for donors' hydration states. In this study, all urine voids were individually collected from eight frequent and eight occasional cannabis users for up to 85 hours after each received on separate occasions 50.6 mg Δ9-tetrahydrocannabinol (THC) by smoking, vaporization, and oral ingestion in a randomized, within-subject, double-blind, double-dummy, placebo-controlled protocol. Each urine void was analyzed for 11 cannabinoids and phase I and II metabolites by liquid chromatography-tandem mass spectrometry (LC-MS/MS), SG, and creatinine. Normalized urine concentrations were log10 transformed to create normal distributions, and Pearson correlation coefficients determined the degree of association between the two normalization methods. Repeated-measures linear regression determined if the degree of association differed by frequent or occasional cannabis use, or route of administration after adjusting for gender and time since dosing. Of 1880 urine samples examined, only 11-nor-9-carboxy-THC (THCCOOH), THCCOOH-glucuronide, THC-glucuronide, and 11-nor-9-carboxy-Δ9-tetrahydrocannabivarin (THCVCOOH) were greater than the method's limits of quantification (LOQs). Associations between SG- and creatinine-normalized concentrations exceeded 0.90. Repeated-measures regression analysis found small but statistically significant differences in the degree of association between normalization methods for THCCOOH and THCCOOH-glucuronide in frequent vs occasional smokers, and in THCVCOOH and THC-glucuronide by route of administration. For the first time, SG- and creatinine-normalized urine cannabinoid concentrations were evaluated in frequent and occasional cannabis users and following oral, smoked, and inhaled cannabis. Both normalization methods reduced variability, improving the interpretation of urine cannabinoid concentrations and methods were strongly correlated.

Marijuana and Tobacco Coexposure in Hospitalized Children.

BACKGROUND: The impact of secondhand marijuana smoke exposure on children is unknown. New methods allow for the detection of marijuana smoke exposure in children. METHODS: We studied children who were hospitalized in Colorado and had a parent participating in a smoking cessation study; all children had urine samples remaining from the original study as well as consent for future research. Parents completed a survey and urine samples were analyzed for cotinine and marijuana metabolites, including 11-hydroxy-Δ9-tetrahydrocannabinol (COOH-THC), by using liquid chromatography-tandem mass spectrometry. RESULTS: The median age of the children was 6.0 years (range 0-17 years); 57% were boys. Half (55%) were white, 12% were African American, and 33% were of another race; 39% identified as Hispanic. Approximately 46% had detectable COOH-THC, and 11% had detectable THC. Of those with detectable THC, 3 were teenagers, and 6 were <8 years of age. There were no significant differences in urinary COOH-THC concentrations by age, sex, race and/or ethnicity, or socioeconomic status. Children with positive results for COOH-THC were more likely to have parents who use marijuana daily, smoke marijuana versus other forms of use, use daily in the home, and smoke marijuana in another room if the children are around compared with smoking outside. CONCLUSIONS: Approximately half of the children who qualified for our study had biological evidence of exposure to marijuana. Researchers in studies such as this provide valuable data on secondhand exposure to children from parents using tobacco and marijuana and can inform public health policies to reduce harm.

Determination of cannabinoids in oral fluid and urine of "light cannabis" consumers: a pilot study.

Background In those countries where cannabis use is still illegal, some manufacturers started producing and selling "light cannabis": dried flowering tops containing the psychoactive principle Δ-9-tetrahydrocannabinol (THC) at concentrations lower than 0.2% together with variable concentration of cannabidiol (CBD). We here report a pilot study on the determination of cannabinoids in the oral fluid and urine of six individuals after smoking 1 g of "light cannabis". Methods On site screening for oral fluid samples was performed, as a laboratory immunoassay test for urine samples. A validated gas chromatography-mass spectrometry (GC-MS) method was then applied to quantify THC and CBD, independently from results of screening tests. Results On site screening for oral fluid samples, with a THC cut-off of 25 ng/mL gave negative results for all the individuals at different times after smoking. Similarly, negative results for urine samples screening from all the individuals were obtained. Confirmation analyses showed that oral fluid THC was in the concentration range from 2.5 to 21.5 ng/mL in the first 30 min after smoking and then values slowly decreased. CBD values were usually one order of magnitude higher than those of THC. THC-COOH, the principal urinary THC metabolite, presented the maximum urinary value of 1.8 ng/mL, while urinary CBD had a value of 15.1 ng/mL. Conclusions Consumers of a single 1 g dose of "light cannabis" did not result as positive in urine screening, assessing recent consumption, so that confirmation would not be required. Conversely, they might result as positive to oral fluid testing with some on-site kits, with THC cut-off lower than 25 ng/mL, at least in the first hour after smoking and hence confirmation analysis can be then required. No conclusions can be drawn of eventual chronic users.

Cannabinoid concentrations in blood and urine after smoking cannabidiol joints.

In Switzerland, the sale of cannabis with tetrahydrocannabinol (THC) content less than 1% has recently been legalized. As a consequence, cannabis with low THC and high cannabidiol (CBD) values up to approximately 25% is legally available on the market. In this study, we investigated cannabinoid blood and urine concentrations of a naive user and of a modeled chronic user after smoking a single CBD joint. Chronic use was modeled as smoking 2 joints per day for 10 days. Joints contained 200mg of cannabis with THC concentrations of 0.94% and 0.8% and CBD concentrations of 23.5% and 17% in the naive-smoker and chronic-smoker experiment, respectively. After smoking, blood and urine samples were collected for 4 and 20h after smoking start, respectively. THC blood concentrations reached 2.7 and 4.5ng/mL in the naive and chronic user, respectively. In both cases, the blood THC concentration is significantly above the Swiss road traffic threshold of 1.5ng/mL. Consequently, the user was legally unfit to drive directly after smoking. CBD blood concentrations of 45.7 and 82.6ng/mL were reached for the naive and chronic user, respectively. During the 10-day smoking period, blood and urine samples were regularly collected. No accumulation of any cannabinoid was found in the blood during this time. Urinary 11-nor-9-carboxy-THC concentrations seemed to increase during the 10-day period, which is important in abstinence testing.

Prevalence and associated birth outcomes of co-use of Cannabis and tobacco cigarettes during pregnancy.

Use of Cannabis and use of tobacco overlap, and co-use of Cannabis and tobacco has increased over the past decade among adults. The current study aims to document the prevalence and correlates of co-use of Cannabis and tobacco cigarettes among adult pregnant women utilizing secondary data from a larger study that compared and validated screeners for illicit and prescription drug use during pregnancy. Pregnant women (N = 500; 71% African American; 65% never married, average age of 28 years) were recruited from two urban University obstetric clinics between January and December 2017. Participants self-reported demographic, Cannabis, and tobacco cigarette use characteristics, and provided urine and hair samples for drug testing. Within two weeks after due date, research staff reviewed participants' electronic medical records to collect birth outcome data. Results showed that 9.0% reported co-use of Cannabis and tobacco, 12.1% reported Cannabis only use, 7.8% reported tobacco cigarette only use, and 71.1% reported no Cannabis or tobacco cigarette use in the past month. The birth outcomes to emerge as significant correlates of co-use of Cannabis and tobacco cigarettes were small head circumference, and the occurrence of birth defects, with the co-use group having the highest odds of a small head circumference [aOR: 5.7 (1.1-28.9)] and birth defects [aOR: 3.1 (1.2-8.3)] compared with other use groups. The Cannabis only group had 12 times higher odds of a stillbirth or miscarriage (aOR = 12.1). Screening and interventions to address concurrent Cannabis and tobacco use during pregnancy are needed, particularly among subpopulations with higher co-use rates. It is imperative to further explore and highlight the possible health implications of maternal co-use given the high prevalence rates found in this study sample.

Optimization of recombinant ß-glucuronidase hydrolysis and quantification of eight urinary cannabinoids and metabolites by liquid chromatography tandem mass spectrometry.

Prolonged urinary cannabinoid excretion in chronic frequent cannabis users confounds identification of recent cannabis intake that may be important in treatment, workplace, clinical, and forensic testing programs. In addition, differentiation of synthetic Δ9-tetrahydrocannabinol (THC) intake from cannabis plant products might be an important interpretive issue. THC, 11-hydroxy-THC (11-OH-THC) and 11-nor-9-carboxy-THC (THCCOOH) urine concentrations were evaluated during previous controlled cannabis administration studies following tandem alkaline/E. coli ß-glucuronidase hydrolysis. We optimized recombinant ß-glucuronidase enzymatic urinary hydrolysis before simultaneous liquid chromatography tandem mass spectrometry (LC-MS/MS) quantification of THC, 11-OH-THC, THCCOOH, cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), tetrahydrocannabivarin (THCV) and 11-nor-9-carboxy-THCV (THCVCOOH) in urine. Enzyme amount, incubation time and temperature, buffer molarity and pH were optimized using pooled urine samples collected during a National Institute on Drug Abuse, Institutional Review Board-approved clinical study. Optimized cannabinoid hydrolysis with recombinant ß-glucuronidase was achieved with 2000 IU enzyme, 2 M pH 6.8 sodium phosphate buffer, and 0.2 mL urine at 37°C for 16 h. The LC-MS/MS quantification method for hydrolyzed urinary cannabinoids was validated per the Scientific Working Group on Toxicology guidelines. Linear ranges were 1-250 µg/L for THC and CBG, 2-250 µg/L for 11-OH-THC, CBD, CBN, THCV and THCVCOOH, and 1-500 µg/L for THCCOOH. Inter-batch analytical bias was 92.4-112.4%, imprecision 4.4-9.3% CV (n = 25), extraction efficiency 44.3-97.1% and matrix effect -29.6 to 1.8% (n = 10). The method was utilized to analyze urine specimens collected during our controlled smoked, vaporized, and edible cannabis administration study to improve interpretation of urine cannabinoid test results.

Incremental validity of estimated cannabis grams as a predictor of problems and cannabinoid biomarkers: Evidence from a clinical trial.

BACKGROUND: Quantifying cannabis use is complex due to a lack of a standardized packaging system that contains specified amounts of constituents. A laboratory procedure has been developed for estimating physical quantity of cannabis use by utilizing a surrogate substance to represent cannabis, and weighing the amount of the surrogate to determine typical use in grams. METHOD: This secondary analysis utilized data from a multi-site, randomized, controlled pharmacological trial for adult cannabis use disorder (N=300), sponsored by the National Drug Abuse Treatment Clinical Trials Network, to test the incremental validity of this procedure. In conjunction with the Timeline Followback, this physical scale-based procedure was used to determine whether average grams per cannabis administration predicted urine cannabinoid levels (11-nor-9-carboxy-Δ9-tetrahydrocannabinol) and problems due to use, after accounting for self-reported number of days used (in the past 30 days) and number of administrations per day in a 12-week clinical trial for cannabis use disorder. RESULTS: Likelihood ratio tests suggest that model fit was significantly improved when grams per administration and relevant interactions were included in the model predicting urine cannabinoid level (X2=98.3; p<0.05) and in the model predicting problems due to cannabis use (X2=6.4; p<0.05), relative to a model that contained only simpler measures of quantity and frequency. CONCLUSIONS: This study provides support for the use of a scale-based method for quantifying cannabis use in grams. This methodology may be useful when precise quantification is necessary (e.g., measuring reduction in use in a clinical trial).

Changes in marijuana use symptoms and emotional functioning over 28-days of monitored abstinence in adolescent marijuana users.

RATIONALE: Advancing marijuana prevention and intervention efforts are important given the decreasing perception of harm among adolescents and increasing marijuana legalization. OBJECTIVES: This study evaluates how a monitored abstinence protocol may contribute to emotional functioning and changes in marijuana problems that can enhance successful outcomes for non-treatment-seeking adolescent marijuana users. METHODS: Adolescent marijuana users (n = 26) and demographically matched controls (n = 30) completed 28 days of monitored abstinence confirmed by biweekly urine toxicology. Participants were given measures of emotional functioning, marijuana use symptoms, and reward sensitivity during monitored abstinence. RESULTS: All participants (n = 56) completed the protocol, and 69% of marijuana users (n = 18 of 26) were confirmed abstinent for 28 days, with all users showing decreasing marijuana use. Reductions in subsyndromal depression, positive marijuana use expectancies, and poor sleep quality were observed by the end of the monitored abstinence period (n = 26, p values < .05). Marijuana users also reported more attentional impulsivity and less responsiveness to reward stimuli during the second week of abstinence compared to controls. Later age of onset of regular marijuana use and more cumulative lifetime use were associated with a greater degree of emotional change and increased recognition of the negative effects of marijuana use. CONCLUSIONS: Monitored abstinence programs may be beneficial in reducing marijuana use, subsyndromal emotional distress symptoms, and changing beliefs about marijuana use. Future prevention and intervention efforts may consider targeting reward sensitivity and impulsivity, in addition to marijuana use, expectancies, and emotional functioning.

Detecting biomarkers of secondhand marijuana smoke in young children.

BACKGROUND: The impact of secondhand marijuana smoke exposure on children is unknown. New methods allow detection of secondhand marijuana smoke in children. METHODS: We studied children ages 1 mo to 2 y hospitalized with bronchiolitis in Colorado from 2013 to 2015. Parents completed a survey, and urine samples were analyzed for cotinine using LC/MS/MS (limits of detection 0.03 ng/ml) and marijuana metabolites including COOH-THC (limits of detection 0.015 ng/ml). RESULTS: A total of 43 subjects had urine samples available for analysis. Most (77%) of the subjects were male, and 52% were less than 1 y of age. COOH-THC was detectable in 16% of the samples analyzed (THC+); the range in COOH-THC concentration was 0.03-1.5 ng/ml. Two subjects had levels >1 ng/ml. Exposure did not differ by gender or age. Non-white children had more exposure than white children (44 vs. 9%; P < 0.05). 56% of children with cotinine >2.0 ng/ml were THC+, compared with 7% of those with lower cotinine (P < 0.01). CONCLUSION: Metabolites of marijuana smoke can be detected in children; in this cohort, 16% were exposed. Detectable COOH-THC is more common in children with tobacco smoke exposure. More research is needed to assess the health impacts of marijuana smoke exposure on children and inform public health policy.

Comparison of Cannabinoid Concentrations in Plasma, Oral Fluid and Urine in Occasional Cannabis Smokers After Smoking Cannabis Cigarette.

PURPOSE: A randomized cross-over, double blind placebo controlled study of smoked cannabis was carried out on occasional cannabis smokers. The objective of this research was to describe the pharmacokinetic parameters of THC and its metabolites in plasma, oral fluid and urine, from samples obtained simultaneously to provide estimations of THC and metabolites concentrations after smoking a cannabis cigarette. METHODS: Blood, oral fluid and urine samples were collected until up to 72 h after smoking the cannabis cigarette (4% of delta-9-tetrathydrocannabinol (THC)). THC, 11-OH-THC and THC-COOH were analyzed by gas-chromatography-mass spectrometry. Pharmacokinetic parameters were estimated from these data. RESULTS: Eighteen male healthy adults participated in the study. In total, 560 plasma, 288 oral fluid and 448 urine samples were quantified for cannabinoids. Plasma, oral fluid and urine pharmacokinetic parameters were calculated. A wide range of median THC Cmax (1.6-160.0 µg/L and 55.4-123120.0 µg/L in plasma and oral fluid, respectively), 11-OH-THC Cmax (0-11.1 µg/L in plasma) and THC-COOH Cmax (1.0-56.3 µg/L in plasma) was observed. When expressed as a percentage of the total available THC dose, and corrected for molar equivalents, mean percentage of total THC dose excreted was 1.9 +/-2.5 % with range of 0.2-7.5%. This high inter-individual variability was also observed on other calculated pharmacokinetic parameters. CONCLUSION: Prediction of plasma THC concentration from THC oral fluid concentration or from THC-COOH urinary concentrations is not feasible due to the large variations observed. The results from this study support the assumption that a positive oral fluid THC result or a positive urine fluid result are indicative of a recent cannabis exposure. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Simultaneous quantification of 11 cannabinoids and metabolites in human urine by liquid chromatography tandem mass spectrometry using WAX-S tips.

A comprehensive cannabinoid urine quantification method may improve clinical and forensic result interpretation and is necessary to support our clinical research. A liquid chromatography tandem mass spectrometry quantification method for ∆(9)-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), ∆(9)-tetrahydrocannabinolic acid (THCAA), cannabinol (CBN), cannabidiol (CBD), cannabigerol (CBG), ∆(9)-tetrahydrocannabivarin (THCV), 11-nor-9-carboxy-THCV (THCVCOOH), THC-glucuronide (THC-gluc), and THCCOOH-glucuronide (THCCOOH-gluc) in urine was developed and validated according to the Scientific Working Group on Toxicology guidelines. Sample preparation consisted of disposable pipette extraction (WAX-S) of 200 µL urine. Separation was achieved on a Kinetex C18 column using gradient elution with flow rate 0.5 mL/min, mobile phase A (10 mM ammonium acetate in water), and mobile phase B (15 % methanol in acetonitrile). Total run time was 14 min. Analytes were monitored in both positive and negative ionization modes by scheduled multiple reaction monitoring. Linear ranges were 0.5-100 µg/L for THC and THCCOOH; 0.5-50 µg/L for 11-OH-THC, CBD, CBN, THCAA, and THC-gluc; 1-100 µg/L for CBG, THCV, and THCVCOOH; and 5-500 µg/L for THCCOOH-gluc (R (2) > 0.99). Analytical biases were 88.3-113.7 %, imprecisions 3.3-14.3 %, extraction efficiencies 42.4-81.5 %, and matrix effect -10 to 32.5 %. We developed and validated a comprehensive, simple, and rapid LC-MS/MS cannabinoid urine method for quantification of 11 cannabinoids and metabolites. This method is being used in a controlled cannabis administration study, investigating urine cannabinoid markers documenting recent cannabis use, chronic frequent smoking, or route of drug administration and potentially improving urine cannabinoid result interpretation.