Assessment of urine drug screen utility at autopsy to predict laboratory postmortem blood toxicology.

When faced with increasing drug-related deaths and decline in practicing forensic pathologists, the need to quickly identify toxicology-related deaths is evident in order to appropriately triage cases and expedite turnaround times. Lateral flow immunoassays conducted pre-autopsy offer quick urine drug screen (UDS) results in minutes and are used to inform the need for autopsy. Over 1000 medicolegal cases were reviewed to compare UDS results to laboratory enzyme-linked immunosorbent assay (ELISA) blood results to evaluate how well autopsy UDS predicted laboratory findings. Mass spectral analysis was performed on ELISA-positive specimens and these data were used to investigate UDS false-negative (FN) results when possible. Five different UDS devices (STAT One Step Drug of Abuse dip card and cassette, Premiere Biotech multi-drug and fentanyl dip cards and ATTEST 6-acetylmorphine (6-AM) dip card) were tested encompassing 11 drug classes: 6-AM, amphetamine/methamphetamine, benzodiazepines, benzoylecgonine, fentanyl, methadone, opioids, phencyclidine, and delta-9-tetrahydrocannabinol. Sensitivity, specificity, efficiency, and positive and negative predictive values >80% indicated that UDS was useful for predicting cases involving benzoylecgonine, methadone, methamphetamine, and phencyclidine. UDS was unreliable in predicting amphetamine, benzodiazepines, fentanyl, and opiates-related cases due to a high percentage of FN (up to 11.2%, 8.0%, 12.4%, and 5.5%, respectively) when compared to ELISA blood results. For the later analytes, sensitivities were as low as 57.5%, 60.0%, 72.2%, and 66.7%, respectively. Overall results support that UDS cannot replace laboratory testing. Because UDS is subject to false-positive and FN results users must understand the limitations of using UDS for triage or decision-making purposes.

Kratom safety and toxicology in the public health context: research needs to better inform regulation.

Although kratom use has been part of life for centuries in Southeast Asia, the availability and use of kratom in the United States (US) increased substantially since the early 2000s when there was little information on kratom pharmacology, use patterns, and effects, all critical to guiding regulation and policy. Here we provide a synthesis of research with several hundred English-language papers published in the past 5 years drawing from basic research, epidemiological and surveillance data, and recent clinical research. This review of available literature aims to provide an integrated update regarding our current understanding of kratom's benefits, risks, pharmacology, and epidemiology, which may inform United States-based kratom regulation. Recent surveillance indicates there are likely several million past-year kratom consumers, though estimates vary widely. Even without precise prevalence data, kratom use is no longer a niche, with millions of United States adults using it for myriad reasons. Despite its botanical origins in the coffee tree family and its polypharmacy, kratom is popularly characterized as an opioid with presumed opioid-system-based risks for addiction or overdose. Neuropharmacology, toxicology, and epidemiology studies show that kratom is more accurately characterized as a substance with diverse and complex pharmacology. Taken together the work reviewed here provides a foundation for future scientific studies, as well as a guide for ongoing efforts to regulate kratom. This work also informs much-needed federal oversight, including by the United States Food and Drug Administration. We conclude with recommendations for kratom regulation and research priorities needed to address current policy and knowledge gaps around this increasingly used botanical product.

LC-MS/MS quantification of Δ8-THC, Δ9-THC, THCV ISOMERS and their main metabolites in human plasma.

BACKGROUND: In recent years, potential therapeutic applications of several different cannabinoids, such as Δ9-tetrahydrocannabinol (Δ9-THC), its isomer Δ8-THC and Δ9-tetrahydrocannabivarin (Δ9-THCV), have been investigated. Nevertheless, to establish dose-effect relationship and to gain knowledge of their pharmacokinetics and metabolism, sensitive and specific analytical assays are needed to measure these compounds in patients. For this reason, we developed and validated an online extraction high-performance liquid chromatography- tandem mass spectrometry (LC/LC-MS/MS) method for the simultaneous quantification of 13 cannabinoids and metabolites including the Δ8 and Δ9 isomers of THC, THCV and those of their major metabolites in human plasma. METHODS: Plasma was fortified with cannabinoids at varying concentrations within the working range of the respective compound and 200 µL were extracted using a simple one-step protein precipitation procedure. The extracts were analyzed using online trapping LC/LC-atmospheric pressure chemical ionization (APCI)-MS/MS running in the positive multiple reaction monitoring (MRM) mode. RESULTS: The lower limit of quantification ranged from 0.5 to 2.5 ng/mL and the upper limit of quantification was 400 ng/mL for all analytes. Inter-day analytical accuracy and imprecision ranged from 82.9 to 109% and 4.3 to 20.3% (coefficient of variance), respectively. Of 534 plasma samples following controlled oral administration of Δ8-THCV, 236 were positive for Δ8-THCV (median; interquartile ranges: 3.5 ng/mL; 1.8 - 11.9 ng/mL), 383 for the major metabolite (-)-11-nor-9-carboxy-Δ8-tetrahydrocannabivarin (Δ8-THCV-COOH) (95.4 ng/mL; 20.7 - 328 ng/mL), 260 for (-)-11-nor-9-carboxy-Δ9-tetrahydrocannabivarin (Δ9-THCV-COOH) (5.8 ng/mL; 2.5 - 16.1 ng/mL), 157 for (-)-11-hydroxy-Δ8-tetrahydrocannabivarin (11-OH-Δ8-THCV) (1.7 ng/mL; 1.0 - 3.7 ng/mL), 49 for Δ8-THC-COOH (1.7 ng/mL; 1.4 - 2.3 ng/mL) and 42 for Δ9-THCV (1.3 ng/mL; 0.8 - 1.6 ng/mL). CONCLUSIONS: We developed and validated the first LC/LC-MS/MS assay for the specific quantification of Δ8-THC, Δ9-THC and THCV isomers and their respective metabolites in human plasma. Δ8-THCV-COOH, 11-hydroxy-Δ8-THCV and Δ9-THCV-COOH were the major Δ8-THCV metabolites in human plasma after oral administration of 98.6% pure Δ8-THCV.

Reliability of roadside oral fluid testing devices for ∆9 -tetrahydrocannabinol (∆9 -THC) detection.

Driving under the influence of cannabis (DUIC) is increasing worldwide, and cannabis is the most prevalent drug after alcohol in impaired driving cases, emphasizing the need for a reliable traffic enforcement strategy. ∆9 -tetrahydrocannabinol (THC) detection in oral fluid has great potential for identifying recent cannabis use; however, additional data are needed on the sensitivities, specificities, and efficiencies of different oral fluid devices for detecting cannabinoids at the roadside by police during routine traffic safety enforcement efforts. At the roadside, 8945 oral fluid THC screening tests were performed with four devices: AquilaScan®, Dräger DrugTest®, WipeAlyser Reader®, and Druglizer®. A total of 530 samples screened positive for THC (5.9%) and were analyzed by liquid chromatography-tandem mass spectrometry at multiple cutoff concentrations (2 ng/mL, 10 ng/mL, and manufacturers' recommended device cutoffs) to investigate device performance. Results varied substantially, with sensitivities of 0%-96.8%, specificities of 89.8%-98.5%, and efficiencies of 84.3%-97.8%. The Dräger DrugTest® outperformed the other devices with a 96.8% sensitivity, 97.1% specificity, and 97.0% efficiency at a 5-ng/mL LC-MS/MS confirmation cutoff. The WipeAlyser Reader® had good performance with a 91.4% sensitivity, 97.2% specificity, and 96.4% efficiency. AquilaScan® and Druglizer® had unacceptable performance for cannabinoid detection, highlighted by sensitivity <13%. The choice of roadside oral fluid testing device must offer good analytical performance for cannabinoids because of its high prevalence of use and impact on road safety.

Exposure to Synthetic Psychoactive Substances: A Potential Cause for Increased Human Hepatotoxicity Markers.

BACKGROUND: Approximately 30 million people worldwide consume new psychoactive substances (NPS), creating a serious public health issue due to their toxicity and potency. Drug-induced liver injury is the leading cause of liver disease, responsible for 4% of global deaths each year. CONTENT: A systematic literature search revealed 64 case reports, in vitro and in vivo studies on NPS hepatotoxicity. Maximum elevated concentrations of aspartate aminotransferase (136 to 15 632 U/L), alanine transaminase (121.5 to 9162 U/L), total bilirubin (0.7 to 702 mg/dL; 0.04 to 39.03 mmol/L), direct (0.2-15.1 mg/dL; 0.01-0.84 mmol/L) and indirect (5.3 mg/dL; 0.29 mmol/L) bilirubin, alkaline phosphatase (79-260 U/L), and gamma-glutamyltransferase (260 U/L) were observed as biochemical markers of liver damage, with acute and fulminant liver failure the major toxic effects described in the NPS case reports. In vitro laboratory studies and subsequent in vivo NPS exposure studies on rats and mice provide data on potential mechanisms of toxicity. Oxidative stress, plasma membrane stability, and cellular energy changes led to apoptosis and cell death. Experimental studies of human liver microsome incubation with synthetic NPS, with and without specific cytochrome P450 inhibitors, highlighted specific enzyme inhibitions and potential drug-drug interactions leading to hepatotoxicity. SUMMARY: Mild to severe hepatotoxic effects following synthetic NPS exposure were described in case reports. In diagnosing the etiology of liver damage, synthetic NPS exposure should be considered as part of the differential diagnosis. Identification of NPS toxicity is important for educating patients on the dangers of NPS consumption and to suggest promising treatments for observed hepatotoxicity.

Recommendations for effective collaboration and capacity building in epidemiological studies on the effect of alcohol and drug use on traffic safety in low- and middle-income countries.

OBJECTIVE: Alcohol or drug impairment is a major risk factor for road traffic crashes, and studies on this issue are essential to provide evidence-based data for policymakers. In low- and middle-income countries (LMICs), such studies are often conducted in partnership with one or more organizations in high-income countries (HICs). The aim of this article is to provide recommendations for improving project planning and decision-making processes in epidemiological studies on alcohol, drug and traffic safety in LMICs involving HICs. METHODS: We searched Pubmed, Google Scholar, and Google Search for articles and reports in English about lessons learned when conducting collaborative research in LMIC as well as papers presenting recommendations for effective research collaboration with partners in LMICs. RESULTS: Based on the search results, we selected 200 papers for full text examination. Few were related to studies on the effect of alcohol or drug use on road traffic safety. However, several conclusions and recommendations from other studies were found to be relevant. We combined the findings with our own experience in a narrative review. We also present a checklist for risk and quality assessment. CONCLUSIONS: Many papers presented similar recommendations, which included the importance of addressing local needs, ensuring adequate resources, local project ownership and leadership, establishing strong partnerships among all involved stakeholders, promoting shared decision-making and planning, and implementing strategies to translate research findings into policy, practice, and publications. It is also important to avoid HIC bias, which prioritizes the interests or perspectives of HICs over those of LMICs.

Metabolite markers for three synthetic tryptamines N-ethyl-N-propyltryptamine, 4-hydroxy-N-ethyl-N-propyltryptamine, and 5-methoxy-N-ethyl-N-propyltryptamine.

N-Ethyl-N-propyltryptamine (EPT), 4-hydroxy-N-ethyl-N-propyltryptamine (4-OH-EPT), and 5-methoxy-N-ethyl-N-propyltryptamine (5-MeO-EPT) are new psychoactive substances classified as tryptamines, sold online. Many tryptamines metabolize rapidly, and identifying the appropriate metabolites to reveal intake is essential. While the metabolism of 4-OH-EPT and 5-MeO-EPT are not previously described, EPT is known to form metabolites by indole ring hydroxylation among others. Based on general knowledge of metabolic patterns, 5-MeO-EPT is also expected to form ring hydroxylated EPT (5-OH-EPT). In the present study, the aim was to characterize the major metabolites of EPT, 4-OH-EPT, and 5-MeO-EPT, to provide markers for substance identification in forensic casework. The tryptamines were incubated with pooled human liver microsomes at 37°C for up to 4 h. The generated metabolites were separated and detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry analysis. The major in vitro EPT metabolites were formed by hydroxylation, N-dealkylation, and carbonylation. In comparison, 4-OH-EPT metabolism was dominated by double bond formation, N-dealkylation, hydroxylation, and carbonylation in vitro and hydroxylation or carbonylation combined with double bond loss, carbonylation, N-dealkylation, and hydroxylation in vivo. 5-MeO-EPT was metabolized by O-demethylation, hydroxylation, and N-dealkylation in vitro. The usefulness of the characterized metabolites in forensic casework was demonstrated by identification of unique metabolites for 4-OH-EPT in a human postmortem blood sample with suspected EPT or 4-OH-EPT intoxication.

Human Mitragynine and 7-Hydroxymitragynine Pharmacokinetics after Single and Multiple Daily Doses of Oral Encapsulated Dried Kratom Leaf Powder.

Kratom leaves, consumed by millions worldwide as tea or ground leaf powder, contain multiple alkaloids, with mitragynine being the most abundant and responsible for most effects. Mitragynine is a partial µ-opioid receptor agonist and competitive antagonist at κ- and δ-opioid receptors; however, unlike morphine, it does not activate the ß-arrestin-2 respiratory depression pathway. Due to few human mitragynine data, the largest randomized, between-subject, double-blind, placebo-controlled, dose-escalation study of 500-4000 mg dried kratom leaf powder (6.65-53.2 mg mitragynine) was conducted. LC-MS/MS mitragynine and 7-hydroxymitragynine plasma concentrations were obtained after single and 15 daily doses. Mitragynine and 7-hydroxymitragynine Cmax increased dose proportionally, and AUC was slightly more than dose proportional. The median mitragynine Tmax was 1.0-1.3 h after single and 1.0-1.7 h after multiple doses; for 7-hydroxymitragynine Tmax, it was 1.2-1.8 h and 1.3-2.0 h. Steady-state mitragynine concentrations were reached in 8-9 days and 7-hydroxymitragynine within 7 days. The highest mean mitragynine T1/2 was 43.4 h after one and 67.9 h after multiple doses, and, for 7-hydroxymitragynine, it was 4.7 and 24.7 h. The mean 7-hydroxy-mitragynine/mitragynine concentration ratios were 0.20-0.31 after a single dose and decreased (0.15-0.21) after multiple doses. These mitragynine and 7-hydroxymitragynine data provide guidance for future clinical kratom dosing studies and an interpretation of clinical and forensic mitragynine and 7-hydroxymitragynine concentrations.

Metabolic Stability and Metabolite Identification of N-Ethyl Pentedrone Using Rat, Mouse and Human Liver Microsomes.

New Psychoactive Substances (NPSs) are defined as a group of substances produced from molecular modifications of traditional drugs. These molecules represent a public health problem since information about their metabolites and toxicity is poorly understood. N-ethyl pentedrone (NEP) is an NPS that was identified in the illicit market for the first time in the mid-2010s, with four intoxication cases later described in the literature. This study aims to evaluate the metabolic stability of NEP as well as to identify its metabolites using three liver microsomes models. To investigate metabolic stability, NEP was incubated with rat (RLM), mouse (MLM) and human (HLM) liver microsomes and its concentration over time evaluated by liquid chromatography-mass spectrometry. For metabolite identification, the same procedure was employed, but the samples were analyzed by liquid chromatography-high resolution mass spectrometry. Different metabolism profiles were observed depending on the model employed and kinetic parameters were determined. The in vitro NEP elimination half-lives (t1/2) were 12.1, 187 and 770 min for the rat, mouse and human models, respectively. Additionally, in vitro intrinsic clearances (Cl int, in vitro) were 229 for rat, 14.8 for mouse, and 3.6 µL/min/mg in the human model, and in vivo intrinsic clearances (Cl int, in vivo) 128, 58.3, and 3.7 mL/min/kg, respectively. The HLM model had the lowest rate of metabolism when compared to RLM and MLM. Also, twelve NEP metabolites were identified from all models, but at different rates of production.

Tolerability of High-Dose Oral Δ9-THC: Implications for Human Laboratory Study Design.

Background: Δ9-tetrahydrocannabinol (THC), the primary intoxicating compound in cannabis, has been tested extensively in controlled administration human studies. Some studies require a high THC dose that may induce adverse events (AEs), such as those testing novel treatments for cannabinoid overdose. Although there are ethical concerns related to administering high THC doses, there is no systematic analysis on studies utilizing these doses. In this review, we examine studies that administered oral THC doses ≥30 mg ("high-dose THC"), focusing on reported tolerability, subjective effects, and pharmacokinetics (PK), with the objective to inform the design of future studies. Methods: A comprehensive PubMed search was performed to identify studies meeting pre-specified criteria. Results: Our search identified 27 publications from 17 high-dose oral THC laboratory studies, with single doses up to 90 mg and multiple doses up to 210 mg per day. The maximum plasma THC concentration (Cmax) appeared to increase in a dose-proportional manner over this dose range. All high-dose THC studies enrolled participants with previous cannabis experience, although current use ranged from nonusers to regular cannabis users. High-dose THC was generally well tolerated with transient mild to moderate AE, including nausea and vomiting, anxiety, paranoia, and sedation. There were occasional participant withdrawals due to AEs, but there were no serious AE. Participants with frequent cannabis use tolerated high-dose THC best. Conclusion: Although based on limited data, THC was generally adequately tolerated with single oral doses of at least 50 mg in a controlled laboratory setting in healthy participants with past cannabis experience.

Cannabis use and neurocognitive performance at 13-14 Years-Old: Optimizing assessment with hair toxicology in the Adolescent brain cognitive development (ABCD) study.

OBJECTIVE: Cannabis is widely used, including in early adolescence, with prevalence rates varying by measurement method (e.g., toxicology vs. self-report). Critical neurocognitive development occurs throughout adolescence. Given conflicting prior brain-behavior results in cannabis research, improved measurement of cannabis use in younger adolescents is needed. METHODS: Data from the Adolescent Brain Cognitive Development (ABCD) Study Year 4 follow-up (participant age: 13-14 years-old) included hair samples assessed by LC-MS/MS and GC-MS/MS, quantifying THCCOOH (THC metabolite), THC, and cannabidiol concentrations, and the NIH Toolbox Cognitive Battery. Youth whose hair was positive for cannabinoids or reported past-year cannabis use were included in a Cannabis Use (CU) group (n = 123) and matched with non-using Controls on sociodemographics (n = 123). Standard and nested ANCOVAs assessed group status predicting cognitive performance, controlling for family relationships. Follow-up correlations assessed cannabinoid hair concentration, self-reported cannabis use, and neurocognition. RESULTS: CU scored lower on Picture Memory (p = .03) than Controls. Within the CU group, THCCOOH negatively correlated with Picture Vocabulary (r = -0.20, p = .03) and Flanker Inhibitory Control and Attention (r = -0.19, p = .04), and past-year cannabis use was negatively associated with List Sorting Working Memory (r = -0.33, p = .0002) and Picture Sequence Memory (r = -0.19, p = .04) performances. CONCLUSIONS: Youth who had used cannabis showed lower scores on an episodic memory task, and more cannabis use was linked to poorer performances on verbal, inhibitory, working memory, and episodic memory tasks. Combining hair toxicology with self-report revealed more brain-behavior relationships than self-report data alone. These youth will be followed to determine long-term substance use and neurocognition trajectories.

Circulating Endocannabinoids and N-Acylethanolamines in Individuals with Cannabis Use Disorder-Preliminary Findings.

BACKGROUND: Endocannabinoids and related N-acylethanolamines (NAEs) are bioactive lipids with important physiological functions and putative roles in mental health and addictions. Although chronic cannabis use is associated with endocannabinoid system changes, the status of circulating endocannabinoids and related NAEs in people with cannabis use disorder (CUD) is uncertain. METHODS: Eleven individuals with CUD and 54 healthy non-cannabis using control participants (HC) provided plasma for measurement by high-performance liquid chromatography-mass spectrometry of endocannabinoids (2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)) and related NAE fatty acids (N-docosahexaenoylethanolamine (DHEA) and N-oleoylethanolamine (OEA)). Participants were genotyped for the functional gene variant of FAAH (rs324420, C385A) which may affect concentrations of AEA as well as other NAEs (OEA, DHEA). RESULTS: In overnight abstinent CUD, AEA, OEA and DHEA concentrations were significantly higher (31-40%; p < 0.05) and concentrations of the endocannabinoid 2-AG were marginally elevated (55%, p = 0.13) relative to HC. There were no significant correlations between endocannabinoids/NAE concentrations and cannabis analytes, self-reported cannabis use frequency or withdrawal symptoms. DHEA concentration was inversely related with marijuana craving (r = -0.86; p = 0.001). Genotype had no significant effect on plasma endocannabinoids/NAE concentrations. CONCLUSIONS: Our preliminary findings, requiring replication, might suggest that activity of the endocannabinoid system is elevated in chronic cannabis users. It is unclear whether this elevation is a compensatory response or a predating state. Studies examining endocannabinoids and NAEs during prolonged abstinence as well as the potential role of DHEA in craving are warranted.

Time- and temperature-dependent postmortem ∆9-tetrahydrocannabinol concentration changes in rabbits following controlled inhaled cannabis administration.

ostmortem redistribution (PMR), a well-known phenomenon in forensic toxicology, can result in substantial changes in drug concentrations after death, depending on the chemical characteristics of the drug, blood collection site, storage conditions of the body and postmortem interval (PMI). Limited PMR data are available for ∆9-tetrahydrocannabinol (THC), the primary psychoactive component in Cannabis sativa. PMR was evaluated after controlled cannabis inhalation via a smoking machine and exposure chamber in New Zealand white rabbits. Necropsies were performed on five control rabbits immediately after euthanasia, whereas 27 others were stored at room temperature (21°C) or refrigerated conditions (4°C) until necropsy at 2, 6, 16, 24 or 36 h after death. THC and its Phase I and glucuronidated Phase II metabolites were quantified in blood, vitreous humor, urine, bile and tissues by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Under refrigerated temperature, heart blood THC concentrations significantly increased at PMI 2 h in rabbits, whereas peripheral blood THC concentrations showed a significant increase at PMI 16 h. Central:peripheral blood and liver:peripheral blood ratios for THC ranged from 0.13 to 4.1 and 0.28 to 8.9, respectively. Lung revealed the highest THC concentrations, while brain and liver exhibited the most stable THC concentrations over time. This report contributes much needed data to our understanding of postmortem THC behavior and can aid toxicologists in the interpretation of THC concentrations in medicolegal death investigations.

Evaluation of Field Sobriety Tests for Identifying Drivers Under the Influence of Cannabis: A Randomized Clinical Trial.

Importance: With increasing medicinal and recreational cannabis legalization, there is a public health need for effective and unbiased evaluations for determining whether a driver is impaired due to Δ9-tetrahydrocannabinol (THC) exposure. Field sobriety tests (FSTs) are a key component of the gold standard law enforcement officer-based evaluations, yet controlled studies are inconclusive regarding their efficacy in detecting whether a person is under the influence of THC. Objective: To examine the classification accuracy of FSTs with respect to cannabis exposure and driving impairment (as determined via a driving simulation). Design, Setting, and Participants: This double-blind, placebo-controlled parallel randomized clinical trial was conducted from February 2017 to June 2019 at the Center for Medicinal Cannabis Research, University of California, San Diego. Participants were aged 21 to 55 years and had used cannabis in the past month. Data were analyzed from August 2021 to April 2023. Intervention: Participants were randomized 1:1:1 to placebo (0.02% THC), 5.9% THC cannabis, or 13.4% THC cannabis smoked ad libitum. Main Outcome and Measures: The primary end point was law enforcement officer determination of FST impairment at 4 time points after smoking. Additional measures included officer estimation as to whether participants were in the THC or placebo group as well as driving simulator data. Officers did not observe driving performance. Results: The study included 184 participants (117 [63.6%] male; mean [SD] age, 30 [8.3] years) who had used cannabis a mean (SD) of 16.7 (9.8) days in the past 30 days; 121 received THC and 63, placebo. Officers classified 98 participants (81.0%) in the THC group and 31 (49.2%) in the placebo group as FST impaired (difference, 31.8 percentage points; 95% CI, 16.4-47.2 percentage points; P < .001) at 70 minutes after smoking. The THC group performed significantly worse than the placebo group on 8 of 27 individual FST components (29.6%) and all FST summary scores. However, the placebo group did not complete a median of 8 (IQR, 5-11) FST components as instructed. Of 128 participants classified as FST impaired, officers suspected 127 (99.2%) as having received THC. Driving simulator performance was significantly associated with results of select FSTs (eg, ≥2 clues on One Leg Stand was associated with impairment on the simulator: odds ratio, 3.09; 95% CI, 1.63-5.88; P < .001). Conclusions and Relevance: This randomized clinical trial found that when administered by highly trained officers, FSTs differentiated between individuals receiving THC vs placebo and driving abilities were associated with results of some FSTs. However, the high rate at which the participants receiving placebo failed to adequately perform FSTs and the high frequency that poor FST performance was suspected to be due to THC-related impairment suggest that FSTs, absent other indicators, may be insufficient to denote THC-specific impairment in drivers. Trial Registration: ClinicalTrials.gov Identifier: NCT02849587.

Driving Under the Influence of Cannabis: Impact of Combining Toxicology Testing with Field Sobriety Tests.

BACKGROUND: Cannabis is increasingly used both medically and recreationally. With widespread use, there is growing concern about how to identify cannabis-impaired drivers. METHODS: A placebo-controlled randomized double-blinded protocol was conducted to study the effects of cannabis on driving performance. One hundred ninety-one participants were randomized to smoke ad libitum a cannabis cigarette containing placebo or delta-9-tetrahydrocannabinol (THC) (5.9% or 13.4%). Blood, oral fluid (OF), and breath samples were collected along with longitudinal driving performance on a simulator (standard deviation of lateral position [SDLP] and car following [coherence]) over a 5-hour period. Law enforcement officers performed field sobriety tests (FSTs) to determine if participants were impaired. RESULTS: There was no relationship between THC concentrations measured in blood, OF, or breath and SDLP or coherence at any of the timepoints studied (P > 0.05). FSTs were significant (P < 0.05) for classifying participants into the THC group vs the placebo group up to 188 minutes after smoking. Seventy-one minutes after smoking, FSTs classified 81% of the participants who received active drug as being impaired. However, 49% of participants who smoked placebo (controls) were also deemed impaired at this same timepoint. Combining a 2 ng/mL THC cutoff in OF with positive findings on FSTs reduced the number of controls classified as impaired to zero, 86 minutes after smoking the placebo. CONCLUSIONS: Requiring a positive toxicology result in addition to the FST observations substantially improved the classification accuracy regarding possible driving under the influence of THC by decreasing the percentage of controls classified as impaired.

Prenatal tobacco and cannabis co-exposure and offspring obesity development from birth to mid-childhood.

BACKGROUND: Although the association between prenatal tobacco exposure and child obesity risk is well-established, less is known about co-exposure to tobacco and cannabis. OBJECTIVE: Determine the relation between prenatal substance co-exposure and obesity risk. METHODS: In a diverse sample of pregnant women, we examined the association between prenatal substance exposure (tobacco-only and co-exposure) and child BMI (kg/m2 ) trajectories from birth to mid-childhood (n = 262), overweight/obese status based on BMI percentiles from toddlerhood (24 months) to mid-childhood (9-12 years), and adiposity outcomes at mid-childhood (fat mass [kg], fat mass [%] and fat free mass [kg]; n = 128). Given that the major goal of this study was to examine the associations between prenatal substance exposure and child outcomes, we oversampled pregnant women for substance use (with tobacco as the primary focus). RESULTS: Multilevel models demonstrated that children in both exposure groups had a steeper increase in BMI trajectory from birth to mid-childhood and among co-exposed children, girls had a steeper increase than boys. Odds ratio of having obesity by mid-childhood was 12 times higher among those co-exposed than non-exposed. Co-exposure led to significantly greater fat mass and fat mass % compared with no exposure, but exposure to only tobacco was no different than no exposure. CONCLUSIONS: Results highlight potentiating effects of cannabis exposure in the context of maternal tobacco use in pregnancy on obesity risk and the importance of multi-method assessments of obesity.

Concordance between substance use self-report and hair analysis in community-based adolescents.

Background: Accurate drug use identification through subjective self-report and toxicological biosample (hair) analysis are necessary to determine substance use sequelae in youth. Yet consistency between self-reported substance use and robust, toxicological analysis in a large sample of youth is understudied.Objectives: We aim to assess concordance between self-reported substance use and hair toxicological analysis in community-based adolescents.Methods: Hair results by LC-MS/MS and GC-MS/MS and self-reported past-year substance use from an Adolescent Brain Cognitive Development (ABCD) Study subsample (N = 1,390; ages 9-13; 48% female) were compared. The participants were selected for hair selection through two methods: high scores on a substance risk algorithm selected 93%; 7% were low-risk, randomly selected participants. Kappa coefficients the examined concordance between self-report and hair results.Results: 10% of youth self-reported any past-year substance use (e.g. alcohol, cannabis, nicotine, and opiates), while a mostly non-overlapping 10% had hair results indicating recent substance use (cannabis, alcohol, non-prescription amphetamines, cocaine, nicotine, opiates, and fentanyl). In randomly selected low-risk cases, 7% were confirmed positive in hair. Combining methods, 19% of the sample self-reported substance use and/or had a positive hair sample. Kappa coefficient of concordance between self-report and hair results was low (kappa = 0.07; p = .007).Conclusions: Hair toxicology identified substance use in high-risk and low-risk ABCD cohort subsamples. Given low concordance between hair results and self-report, reliance on either method alone would incorrectly categorize 9% as non-users. Multiple methods for characterizing substance use history in youth improves accuracy. Larger representative samples are needed to assess the prevalence of substance use in youth.