Accuracy and replicability of identifying eyelid tremor as an indicator of recent cannabis smoking.

INTRODUCTION: Cannabis intoxication may increase the risk of motor vehicle crashes. However, reliable methods of assessing cannabis intoxication are limited. The presence of eyelid tremors is among the signs of cannabis use identified under the Drug Evaluation and Classification Program of the International Association of Chiefs of Police. Our objectives were to assess the accuracy and replicability of identifying eyelid tremor as an indicator of recent cannabis smoking using a blinded, controlled study design. METHODS: Adult subjects (N = 103) were recruited into three groups based on their cannabis use history: daily, occasional, and no current cannabis use. Participants' closed eyelids were video recorded for 30 seconds by infrared videography goggles before and at a mean ± standard deviation time of 71.4 ± 4.6 minutes after the onset of a 15-minute interval of ad libitum cannabis flower smoking or vaping. Three observers with expertise in neuro-ophthalmology and medical toxicology were trained on exemplar videos of eyelids to reach a consensus on how to grade eyelid tremor. Without knowledge of subjects' cannabis use history or time point (pre- or post-smoking), observers reviewed each video for eyelid tremor graded as absent, slight, moderate, or severe. During subsequent data analysis, this score was further dichotomized as a consensus score of absent (absent/slight) or present (moderate/severe). RESULTS: Kappa and intraclass correlation coefficient statistics demonstrated moderate agreement among the coders, which ranged from 0.44-0.45 and 0.58-0.61, respectively. There was no significant association between recent cannabis use and the observers' consensus assessment that eyelid tremor was present, and cannabis users were less likely to have tremors (odds ratio: 0.75; 95 percent confidence interval: 0.25, 2.40). The assessment of eyelid tremor as an indicator of recent cannabis smoking had a sensitivity of 0.86, specificity of 0.18, and accuracy of 0.64. DISCUSSION: Eyelid tremor has fair sensitivity but poor specificity and accuracy for identification of recent cannabis use. Inter-rater reliability for assessment of eyelid tremor was moderate for the presence and degree of tremor. The weak association between recent cannabis use and eyelid tremor does not support its utility in identifying recent cannabis use. LIMITATIONS: Videos were recorded at only one time point after cannabis use. Adherence to abstinence could not be strictly supervised. Due to regulatory restrictions, we were unable to control the cannabis product used or administer a fixed Δ9-tetrahydrocannabinol dose. Participants were predominately non-Hispanic and White. CONCLUSIONS: In a cohort of participants with a range of cannabis use histories, acute cannabis smoking was not associated with the presence of eyelid tremor, regardless of cannabis use history, at 70 minutes post-smoking. Additional research is needed to identify the presence of eyelid tremor accurately, determine the relationship between cannabis dose and timeline in relation to last cannabis use to eyelid tremor, and determine how it should be, if at all, utilized for cannabis Drug Recognition Evaluator examinations.

Effects of acute cannabis inhalation on reaction time, decision-making, and memory using a tablet-based application.

BACKGROUND: Acute cannabis use has been demonstrated to slow reaction time and affect decision-making and short-term memory. These effects may have utility in identifying impairment associated with recent use. However, these effects have not been widely investigated among individuals with a pattern of daily use, who may have acquired tolerance. The purpose of this study was to examine the impact of tolerance to cannabis on the acute effects as measured by reaction time, decision-making (gap acceptance), and short-term memory. METHODS: Participants (ages 25-45) completed a tablet-based (iPad) test battery before and approximately 60 min after smoking cannabis flower. The change in performance from before to after cannabis use was compared across three groups of cannabis users: (1) occasional use (n = 23); (2) daily use (n = 31); or (3) no current use (n = 32). Participants in the occasional and daily use group self-administered ad libitum, by smoking or vaping, self-supplied cannabis flower with a high concentration of total THC (15-30%). RESULTS: The occasional use group exhibited decrements in reaction time (slowed) and short-term memory (replicated fewer shapes) from before to after cannabis use, as compared to the no-use group. In the gap acceptance task, daily use participants took more time to complete the task post-smoking cannabis as compared to those with no use or occasional use; however, the level of accuracy did not significantly change. CONCLUSIONS: The findings are consistent with acquired tolerance to certain acute psychomotor effects with daily cannabis use. The finding from the gap acceptance task which showed a decline in speed but not accuracy may indicate a prioritization of accuracy over response time. Cognitive and psychomotor assessments may have utility for identifying impairment associated with recent cannabis use.

Health Effects of High-Concentration Cannabis Products: Scoping Review and Evidence Map.

Background. The concentration of pharmacologically active tetrahydrocannabinol (THC) in cannabis products has been increasing over the past decade. Concerns about potential harmful health effects of using these increasingly higher-concentration products have led some states to consider regulation of cannabis product THC concentration. We conducted a scoping review of health effects of high-concentration cannabis products to inform policy on whether the THC concentrations of cannabis product should be regulated or limited. Objectives. We conducted a scoping review to (1) identify and describe human studies that explore the relationship of high-concentration cannabis products with any health outcomes in the literature and (2) create an interactive evidence map of the included studies to facilitate further analyses. Search Methods. An experienced medical information specialist designed a comprehensive search strategy of 7 electronic databases. Selection Criteria. We included human studies of any epidemiological design with no restrictions by age, sex, health status, country, or outcome measured that reported THC concentration or included a known high-concentration cannabis product. Data Collection and Analysis. We imported search results into Distiller SR, and trained coders conducted artificial intelligence‒assisted screening. We developed, piloted, and revised data abstraction forms. One person performed data abstraction, and a senior reviewer verified a subset. We provide a tabular description of study characteristics, including exposures and outcomes measured, for each included study. We interrogated the evidence map published in Tableau to answer specific questions and provide the results as text and visual displays. Main Results. We included 452 studies in the scoping review and evidence map. There was incomplete reporting of exposure characteristics including THC concentration, duration and frequency of use, and products used. The evidence map shows considerable heterogeneity among studies in exposures, outcomes, and populations studied. A limited number of reports provided data that would facilitate further quantitative synthesis of the results across studies. Conclusions. This scoping review and evidence map support strong conclusions concerning the utility of the literature for characterizing risks and benefits of the current cannabis marketplace and the research approaches followed in the studies identified. Relevance of the studies to today's products is limited. Public Health Implications. High-quality evidence to address the policy question of whether the THC concentration of cannabis products should be regulated is scarce. The publicly available interactive evidence map is a timely resource for other entities concerned with burgeoning access to high-concentration cannabis. (Am J Public Health. 2023;113(12):1332-1342. https://doi.org/10.2105/AJPH.2023.307414).

2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care

In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, ß-adrenergic receptor antagonists (also known as ß-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.

2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, ß-adrenergic receptor antagonists (also known as ß-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.

Impact of Recreational Cannabis Legalization on Opioid Prescribing and Opioid-Related Hospital Visits in Colorado: an Observational Study.

BACKGROUND: Cannabis may be a substitute for opioids but previous studies have found conflicting results when using data from more recent years. Most studies have examined the relationship using state-level data, missing important sub-state variation in cannabis access. OBJECTIVE: To examine cannabis legalization on opioid use at the county level, using Colorado as a case study. Colorado allowed recreational cannabis stores in January 2014. Local communities could decide whether to allow dispensaries, creating variation in the level of exposure to cannabis outlets. DESIGN: Observational, quasi-experimental design exploiting county-level variation in allowance of recreational dispensaries. SUBJECTS: Colorado residents MEASURES: We use licensing information from the Colorado Department of Revenue to measure county-level exposure to cannabis outlets. We use the state's Prescription Drug Monitoring Program (2013-2018) to construct opioid-prescribing measures of number of 30-day fills and total morphine equivalents, both per county resident per quarter. We construct outcomes of opioid-related inpatient visits (2011-2018) and emergency department visits (2013-2018) with Colorado Hospital Association data. We use linear models in a differences-in-differences framework that accounts for the varying exposure to medical and recreational cannabis over time. There are 2048 county-quarter observations used in the analysis. RESULTS: We find mixed evidence of cannabis exposure on opioid-related outcomes at the county level. We find increasing exposure to recreational cannabis is associated with a statistically significant decrease in number of 30-day fills (coefficient: -117.6, p-value<0.01) and inpatient visits (coefficient: -0.8, p-value: 0.03), but not total MME nor ED visits. Counties with no medical exposure prior to recreational legalization experience greater reductions in the number of 30-day fills and MME than counties with prior medical exposure (p=0.02 for both). CONCLUSIONS: Our mixed findings suggest that further increases in cannabis beyond medical access may not always reduce opioid prescribing or opioid-related hospital visits at a population level.

Blood cannabinoid molar metabolite ratios are superior to blood THC as an indicator of recent cannabis smoking.

INTRODUCTION: Cannabis use is a growing concern in transportation and workplace incidents. Because Δ9-tetrahydrocannabinol is detectable after acute psychoactive effects have resolved, it has limitations as an indicator of recent usage or potential impairment. METHODS: In an observational study of driving and psychomotor performance, we measured whole blood Δ9-tetrahydrocannabinol plus its metabolites 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol by liquid chromatography with tandem mass spectrometry at baseline and 30 min after starting a 15-minute interval of smoking cannabis in 24 occasional and 32 daily cannabis smokers. We calculated two blood cannabinoid molar metabolite ratios: 1) [Δ9-tetrahydrocannabinol] to [11-nor-9-carboxy-Δ9-tetrahydrocannabinol] and 2) ([Δ9-tetrahydrocannabinol] + [11-hydroxy-Δ9-tetrahydrocannabinol]) to [11-nor-9-carboxy-Δ9-tetrahydrocannabinol]. We compared these to blood [Δ9-tetrahydrocannabinol] alone as indicators of recent cannabis smoking. RESULTS: Median Δ9-tetrahydrocannabinol concentrations increased from 0 ( 0.38). By comparison, a cut-point for Δ9-tetrahydrocannabinol of 5.3 µg/L yielded 88% specificity, 73% sensitivity, and 80% accuracy. CONCLUSIONS: In occasional and daily users, the blood cannabinoid molar metabolite ratios were superior to whole blood Δ9-tetrahydrocannabinol as indicators of recent cannabis smoking. We recommend measurement and reporting of Δ9-tetrahydrocannabinol, 11-hydroxy-Δ9-tetrahydrocannabinol, and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol, and their molar metabolite ratios in forensic and safety investigations.

The minor cannabinoid cannabigerol (CBG) is a highly specific blood biomarker of recent cannabis smoking.

INTRODUCTION: The determination of recent cannabis use is of forensic interest in the investigation of automotive crashes, workplace incidents and other mishaps. Because Δ9-tetrahydrocannabinol may persist in blood after psychoactive effects of intoxication resolve, particularly in regular users, short-lived minor cannabinoids such as cannabigerol have merited examination as adjunct indicators of recent cannabis inhalation. METHODS: As part of an observational cohort study, whole blood cannabinoids including cannabigerol were measured in whole blood by liquid chromatography with tandem mass spectrometry at baseline, and 30 minutes after initiation of a 15-minute supervised interval of ad libitum cannabis smoking in occasional (1-2 days/week over the past 30 days) (n = 24) and daily cannabis smokers (n = 32). Per protocol, subjects self-reported abstention from inhaling cannabis (>8 h) or ingesting cannabis (>12 h) prior to baseline measurement. RESULTS: At baseline, none of the occasional users had detectable cannabigerol (limit of detection = 0.2 µg/L), whereas cannabigerol was detectable post-smoking in 7 of 24 (29%). Among daily cannabis users, 2 of 32 (6%) had detectable cannabigerol at baseline, increasing to 21 of 32 (66%) post-smoking. The odds ratio for recent cannabis smoking associated with a detectable cannabigerol was 27 (95% confidence interval: 6.6, 110.3). In this mixed cohort of occasional and daily cannabis users, receiver operator characteristic curve analysis indicated that whole blood cannabigerol concentration of ≥ 0.2 µg/L had 96% specificity, 50% sensitivity, and 73% accuracy for identifying a 15-minute interval of ad libitum cannabis smoking initiated 30 minutes earlier. Post smoking blood Δ9-tetrahydrocannabinol (median = 5.6 µg/L in occasional users, 21.3 µg/L in daily users) was significantly correlated with post-smoking cannabigerol (P < 0.0001). CONCLUSION: Whole blood cannabigerol may have forensic utility as a highly specific albeit insensitive biomarker of recent cannabis smoking.

Comparison of Two-Bag Versus Three-Bag N-Acetylcysteine Regimens for Pediatric Acetaminophen Toxicity.

BACKGROUND: Acetaminophen overdose is a leading cause of liver failure, and a leading cause of pediatric poisoning requiring hospital admission. The antidote, N-acetylcysteine (NAC), is traditionally administered as a three-bag intravenous infusion. Despite its efficacy, NAC is associated with high incidence of nonallergic anaphylactoid reactions (NAARs). Adult evidence demonstrates that alternative dosing regimens decrease NAARs and medication errors (MEs). OBJECTIVES: To compare NAARs and MEs associated with two- versus three-bag NAC for acetaminophen overdose in a pediatric population. METHODS: This is a retrospective observational cohort study comparing pediatric patients who received three- versus two-bag NAC for acetaminophen toxicity. The primary outcome was incidence of NAARs. Secondary outcomes were rates of MEs and relevant hospital outcomes (length of stay [LOS], intensive care unit (ICU) admission, liver transplant, death). RESULTS: Two hundred forty-three patients met inclusion criteria (median age of 15 years): 150 (62%) three-bag NAC and 93 (38%) two-bag NAC. There was no difference in overall NAARs (p = 0.54). Fewer cutaneous NAARs were observed in the two-bag group, three-bag: 15 (10%), two-bag: 2 (2%), p = 0.02. MEs were significantly decreased with the two-bag regimen, three-bag: 59 (39%), two-bag: 21 (23%), p = 0.01. No statistical differences were observed in LOS, ICU admissions, transplant, or death. CONCLUSION AND RELEVANCE: A significant decrease in cutaneous NAARs and MEs was observed in pediatric patients by combining the first two bags of the traditional three-bag NAC regimen. In pediatric populations, a two-bag NAC regimen for acetaminophen overdose may improve medication tolerance and safety.

Adolescent US Poison Center Exposure Calls During the COVID-19 Pandemic.

PURPOSE: The objective of this study was to evaluate trends and characteristics in adolescent poison center (PC) exposure calls before and during the COVID-19 pandemic. METHODS: A retrospective review of PC calls for adolescents aged 13-17 years from January 1, 2018 through June 30, 2021. RESULTS: During the pandemic, US PCs had a higher proportion of adolescent exposure calls managed in a healthcare facility (71.9% vs. 67.4%) and hospital admissions (27.2% vs. 25.7%) than prior to the pandemic. There was a higher proportion with suicide intent (55.8% vs. 48.8%), moderate/major clinical effects (22.8% vs. 20.1%), and deaths (0.07% vs. 0.05%). Monthly calls significantly increased from 30 calls/month to 204 calls/month (p < .001). The slope of hospital admissions significantly increased (0.19% per month, p < .001) during the pandemic. DISCUSSION: During the COVID-19 pandemic, US PCs observed an increase in adolescent suicidal intent exposure calls with more severe outcomes, hospitalizations, and deaths.

Significance of temperature in antimuscarinic toxicity: a case-control study.

INTRODUCTION: Antimuscarinic toxicity can result in temperature dysregulation, but the clinical significance of this is unclear. The objective of this study was to compare peak temperatures between antimuscarinic patients with and without severe clinical outcomes. METHODS: This was a case-control analysis at two large, urban, academic medical centers from January 1, 2016, through December 31, 2021. We compared peak temperature (Tmax) amongst antimuscarinic patients who experienced severe outcomes with those who did not. Severe outcome was defined as seizure, ventricular dysrhythmia, hypotension, or intubation. RESULTS: Fifty-six patients met inclusion criteria of which 23 developed severe outcomes: 16 seizures, 9 cases with hypotension, 5 intubations, and 2 ventricular dysrhythmias. Tmax amongst all patients ranged from 36.4-39.2 °C. There were no fatalities. There was no difference in Tmax in the emergency department or throughout hospitalization between groups, and Tmax was not predictive for the development of severe outcomes. DISCUSSION: Maximum temperatures did not differ between patients with and without severe outcomes in the setting of antimuscarinic toxicity, and temperature was poorly predictive of outcomes. Our findings suggest that mild temperature dysregulation in antimuscarinic toxicity is not a key prognostic indicator for severe outcome. Further study is needed to assess implication of severe hyperthermia.

Impact of cannabis legalization on healthcare utilization for psychosis and schizophrenia in Colorado.

BACKGROUND: Emergency department (ED) visits involving psychosis and schizophrenia have increased at a rate exceeding population growth in the United States over the past decade. Research shows a strong dose-response relationship between chronic use of high-potency cannabis and odds of developing symptoms of psychosis. The aim of this study was to evaluate the impact of cannabis legalization on psychosis and schizophrenia-related ED visits in Colorado. METHODS: Using administrative data from Colorado Hospital Association (CHA) on county-level quarterly ED visits between January 1, 2013, and December 31, 2018, we applied a difference-in-difference analysis to examine how new exposure to recreational cannabis dispensaries after 2014 differentially influenced the rate of ED visits for psychosis and schizophrenia, comparing counties with no prior medical cannabis dispensary exposure to counties with low or high medical dispensary exposure. RESULTS: As recreational dispensaries per 10,000 residents increased, there was no significant association with the rate of schizophrenia ED visits per capita (incidence rate ratio or IRR: 0.95, 95% CI [0.69, 1.30]) while the rate of psychosis visits increased 24% (IRR: 1.24, 95% CI [1.02, 1.49]). Counties with no previous medical dispensaries experienced larger increases in schizophrenia ED visits than counties already exposed to a low level of medical dispensaries, but this effect was not significant. Counties with low baseline medical exposure had lower increases in rates of psychosis visits than counties with high baseline medical exposure (IRR 0.83, 95% CI [0.69, 0.99]). CONCLUSIONS: There was a positive association between the number of cannabis dispensaries and rates of psychosis ED visits across all counties in Colorado. Although it is unclear whether it is access to products, or the types of products that may be driving this association, our findings suggest there is a potential impact on the mental health of the local population that is observed after cannabis legalization.

Management and Associated Toxicokinetics of Massive Valproic Acid Ingestion with High Flow Continuous Venovenous Hemodiafiltration.

INTRODUCTION: Valproic acid (VPA) toxicity commonly results in a self-limited state of CNS depression that is managed with supportive care and levocarnitine. In massive overdose, patients can develop toxic encephalopathy, shock, multisystem organ failure, and death. We present a case with relevant toxicokinetics of a patient presenting with a profoundly elevated VPA concentration resulting in survival, treated with supportive care including high-dose continuous venovenous hemodiafiltration (CVVHDF). CASE REPORT: A 17-year-old female presented to an emergency department after being found unresponsive at home with concern for massive VPA ingestion. She arrived obtunded and hypotensive with initial VPA concentration of 2226 mg/L, estimated 9 h post-ingestion. Her early hospital course was marked by hypotension requiring multiple vasopressors, and her workup was notable for multiple severe metabolic derangements. High-dose CVVHDF was initiated upon transfer to a tertiary children's hospital with the aim to enhance VPA removal and normalize metabolic derangements. At that time, her VPA concentration was 1071 mg/L. Apparent half-life of VPA improved modestly with extracorporeal treatment, but her metabolic derangements and hemodynamic instability corrected rapidly. Her clinical course was complicated by necrotizing pancreatitis, pancytopenia requiring transfusions of multiple cell lines, coma, and seizures. She ultimately recovered with normal neurological function.

Cannabis legalization and cannabis-involved pregnancy hospitalizations in Colorado.

The primary objective of this study was to evaluate the association between presence of recreational cannabis dispensaries and prevalence of cannabis-involved pregnancy hospitalizations in Colorado. This was a retrospective cohort study of pregnancy-related hospitalizations co-coded with cannabis diagnosis codes in the Colorado Hospital Association from January 1, 2011, through December 31, 2018 (recreational cannabis began January 1, 2014). Our primary outcome was cannabis-involved pregnancy hospitalizations per 10 k live births per county. The primary exposure measure was county variation in the number of recreational dispensaries. We controlled for counties' baseline exposure to medical cannabis dispensaries and used Poisson regression to evaluate the association between exposure to recreational cannabis and hospitalizations. During the study period, cannabis-involved pregnancy hospitalizations increased from 429 to 1210. Mean hospitalizations per county (1.7 to 4.7) and per 10 k live births (13.2 to 55.7) increased. Overall, increasing recreational dispensaries were associated with increases in hospitalizations (1.02, CI: 1.00,1.04). When comparing counties with different densities of baseline medical cannabis market, low and high exposure counties had fewer hospitalizations than those counties with no exposure (low: IRR 0.97, CI: 0.96-0.99; high: 0.98, CI: 0.96-0.99). In Colorado, there was more than a two-fold increase in cannabis-involved pregnancy hospitalizations between 2011 and 2018. Counties with no baseline exposure to medical cannabis had a greater increase than other counties, suggesting the recreational market may influence cannabis use among pregnant individuals.

Comparison of hospital claims and poison center data to evaluate health impact of opioids, cannabis and synthetic cannabinoids.

INTRODUCTION: Over the past 10 years, opioids and cannabis have garnered significant attention due to misuse and legalization trends. Different datasets and surveillance mechanisms can lead to different conclusions the due to a variety of factors. The primary objective of this study was to compare and describe trends of opioid, cannabis, and synthetic cannabinoid-related healthcare encounters and poison center (PC) cases in Colorado, a state that has legalized cannabis. METHODS: This was a retrospective study comparing hospital claims data (Colorado Hospital Association (CHA)) and poison center cases to describe opioid, cannabis and synthetic cannabinoid-related healthcare encounters and exposures in Colorado from 2013 to 2017 using related genetic codes and International Statistical Classification of Disease codes. RESULTS: Both datasets observed increases in cannabis related encounters and exposures after recreational cannabis legalization in 2014. CHA reported an increase for cannabis-related ER visits from 14,109 in 2013 to 18,118 in 2017 while PC noted a 74.4% increase in cannabis-related cases (125 to 218). CHA inpatient visits associated with cannabis also increased (8311 in 2013 to 14,659 in 2017). On the other hand, Opioid-related exposures to the PC fell (1092 in 2013 to 971 in 2017) while both Opioid-related ER visits (8580 in 2013 to 12,928 in 2017) and inpatient visits in CHA increased (9084 in 2013 to 13,205). CONCLUSIONS: This study demonstrates the differences in surveillance methodology for concurrent drug abuse epidemics using hospital claims and PC data. Both systems provide incomplete reports, but in combination can provide a more complete picture.

Simultaneous Quantification of 17 Cannabinoids by LC-MS-MS in Human Plasma.

In recent years, the surge in use of tetrahydrocannabinol (THC) and cannabidiol (CBD) has increased the need for sensitive and specific analytical assays to measure the said compounds in patients, to establish dose-effect relationships and to gain knowledge of their pharmacokinetics and metabolism. We developed and validated an online extraction high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) method for simultaneous quantification of 17 cannabinoids and metabolites including THC and its metabolites, CBD and its metabolites and other minor cannabinoids in human plasma. CBD-glucuronide (CBD-gluc) standard was produced in-house by isolation of CBD-gluc from urine of patients using pure CBD oil. For calibration standards and quality control samples, human plasma was spiked with cannabinoids at varying concentrations within the working range of the respective compound and 200 µL of the plasma was extracted using a simple one-step protein precipitation procedure. The extracts were analyzed using online trapping LC/LC-atmospheric pressure chemical ionization-MS-MS running in the positive multiple reaction monitoring mode. The lower limit of quantification ranged from 0.78 to 7.8 ng/mL, and the upper limits of quantification were between 100 and 2,000 ng/mL. Inter-day analytical accuracy and imprecision ranged from 90.4% to 111% and from 3.1% to 17.4%, respectively. The analysis of plasma samples collected during clinical studies showed that (3R-trans)-cannabidiol-7-oic acid (7-CBD-COOH) was the major human metabolite with 5960% (59.6-fold) of CBD followed by 7-hydroxy-CBD (177%), CBD-gluc (157%) and 6α-hydroxy-CBD (39.8%); 6ß-hydroxy-CBD was not detected in any of the samples. In the present study, we developed and validated a robust LC-MS-MS assay for the simultaneous quantification of cannabinoids and their metabolites, which has been used to measure >5,000 samples in clinical studies. Moreover, we were able to quantify CBD-gluc and showed that 7-CBD-COOH, 7-hydroxy-CBD and CBD-gluc are the major CBD metabolites in human plasma.