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Laws concerning the growing, selling and consuming of cannabis and its related products have been changing considerably over the last few years. The legalization of hemp in 2018 sparked an interest in ∆9-tetrahydrocannabinol (∆9-THC) isomers and analogs that are derived from hemp and sold with minimal oversight. One example is ∆8-tetrahydrocannabinol (∆8-THC). Although less potent than ∆9-THC, ∆8-THC is gaining popularity and can easily be found where cannabis-related products are sold. The Forensic Toxicology Laboratory at the University of Florida routinely tested decedents for 11-nor-∆9-tetrahydrocannabinol-9-carboxylic acid (∆9-THC-acid), the primary metabolite of ∆9-THC. Urine samples from ∼900 decedents were received by the laboratory between mid-November 2021 and mid-March 2022 and subjected to CEDIA™ immunoassay testing. Subsequent confirmation of 194 presumptive positive samples was performed by gas chromatography--mass spectrometry. A peak eluting immediately after ∆9-THC-acid was identified as 11-nor-∆8-tetrahydrocannabinol-9-carboxylic acid (∆8-THC-acid), a metabolite of ∆8-THC, in 26 of those samples (13%). Six of the samples were positive for ∆8-THC-acid only. Other toxicological findings were consistent with poly-drug use including fentanyl/fentanyl analogs, ethanol, cocaine and methamphetamine. There has been an emergence of ∆8-THC use as indicated by the presence of ∆8-THC-acid in 26 of 194 presumptive positive cases during a four-month period. The majority of individuals were White males with a history of drug and/or alcohol use. ∆9-THC-acid, as well as other drugs, was often present. Given the psychoactive potential and availability of ∆8-THC, monitoring ∆8-THC-acid in decedents is important to characterize the risk and prevalence of ∆8-THC use.

BACKGROUND: Fentanyl-related deaths continue to increase in the United States; however, most national studies focus on fatal overdose. More research, including data on nonfatal overdose, is needed. OBJECTIVE: We examined trends in characteristics of fatal and nonfatal fentanyl-related poisonings (“exposures”) in the US. METHODS: National Poison Control data were examined to estimate trends in characteristics of reported exposures between 2015 and 2021 (N = 15,391; 38.7% female). We also delineated correlates of experiencing a major adverse effect or death. RESULTS: The proportion of exposures increased among all age groups between ages 13 and 39 (ps < .05) with the largest increase among those age 13–19 (a 127.8% increase). With respect to reasons for use, the proportion of cases involving fentanyl “abuse” increased by 63.8% (p < .001). The proportion involving fentanyl inhalation increased 427.6% from 5.7% to 29.9% and injection increased from 6.7% to 9.6%, a 42.3% increase (ps < .01). The proportion also increased for co-use of methamphetamine (by 669.0%), cocaine (by 374.0%), and heroin (by 159.5%). The proportion of major adverse effects increased from 15.5% to 39.6% (p < .001). In the multivariable model, “abuse”, suspected suicide attempts, and use via inhalation were risk factors for experiencing a major effect or death, and misuse, ingestion, dermal use, and co-use of methamphetamine were associated with lower risk. CONCLUSION: Poison Control data suggest that characteristics of individuals exposed to fentanyl continue to shift, with use via inhalation increasing and medical outcomes of nonfatal poisonings becoming more severe. These results complement mortality data and inform prevention and harm reduction efforts.

Increased prevalence of illicitly manufactured fentanyl and fentanyl analogs has contributed substantially to overdose deaths in the United States (1-3). On October 26, 2015, CDC issued a Health Advisory regarding rapid increases in deaths involving fentanyl. This CDC Health Advisory has been updated twice to address increases in fentanyl and fentanyl analog overdoses and their co-occurrence with nonopioids (4). Deaths involving carfentanil, an analog reportedly 10,000 times more potent than morphine and 100 times more potent than fentanyl, were first reported in Florida, Michigan, and Ohio in 2016 and described in an August 2016 CDC Health Advisory (1,5). Carfentanil is used to rapidly immobilize large animals in veterinary medicine and has no U.S. approved therapeutic use in humans. Carfentanil's street price per dose is likely lower than that of heroin. During 2016 and 2017, an outbreak of carfentanil-involved fatal overdoses in Florida emerged, and the Medical Examiner jurisdiction serving Sarasota, Manatee, and DeSoto counties (the Sarasota area) was the outbreak epicenter. This report describes toxicology profiles, sociodemographic information, and geographic distributions of carfentanil-involved fatal overdoses (carfentanil deaths) in the Sarasota area compared with those in the rest of Florida (i.e., all Florida counties excluding Sarasota area) from January 2016 to December 2017. The Sarasota area accounted for 19.0% of 1,181 statewide carfentanil deaths that occurred during this time and experienced a peak in carfentanil deaths preceding the larger Florida outbreak. The report of a single carfentanil death from August to December 2017 (compared with 73 reported deaths during the same period in 2016) appeared to mark the end of the outbreak in the area. The threat of such rapid, intense fatal overdose outbreaks highlights the need for accelerated reporting, reliable data sharing systems, and novel proactive surveillance to support targeted prevention and response efforts by public health and safety organizations (6).

The opioid epidemic continues to evolve in the USA, with fentanyl the most prevalent synthetic opioid in fatal drug overdoses. Following the scheduling of fentanyl’s core structure in 2018, there was a notable decline in the prevalence of fentanyl analogs in decedents; however, fluorofentanyl began being reported in casework in the winter of 2020. Fluorofentanyl has three positional isomers (para-fluorofentanyl (p-FF), ortho-fluorofentanyl (o-FF) and meta-fluorofentanyl (m-FF)), with the most predominant isomer that has recently emerged in the USA being p-FF. The goal of this study was to identify p-FF in postmortem cases between October 2020 and April 2021. Urine and blood were extracted using UCT Clean Screen® extraction columns and then screened using an Agilent 1290 Infinity liquid chromatograph (LC) coupled to an Agilent 6545 accurate mass time-of-flight mass spectrometer (TOF-MS) and quantified using an Agilent 6890N GC system coupled with an Agilent 5973 MS. The limit of quantitation (LOQ) for fentanyl, acetyl fentanyl, butyryl fentanyl, p-FF, o-FF and m-FF was 2.5 ng/mL. The screening method could not differentiate the three positional isomers of fluorofentanyl. Suspected overdose cases (n = 370) received from October 2020 through April 2021 from four Medical Examiner Districts in the state of Florida were analyzed for the presence of fluorofentanyl. The LC–QTOF-MS screen yielded 27 decedents positive for fluorofentanyl, with a majority being Caucasian (93%) and male (70%) with ages ranging from 27 to 63 years. Analysis of the blood and urine by GC–MS yielded 14 decedents positive for p-FF, nine of which were positive in the blood. The blood concentrations (n = 9) for p-FF ranged from

Purpose of Review Effective responses to the US opioid overdose epidemic rely on accurate and timely drug overdose mortality data, which are generated from medicolegal death investigations (MDI) and certifications of overdose deaths. We identify nuances of MDI and certification of overdose deaths that can influence drug overdose mortality surveillance, as well as recent research, recommendations, and epidemiological tools for improved identification and quantification of specific drug involvement in overdose mortality. Recent Findings Death certificates are the foundation of drug overdose mortality surveillance. Accordingly, counts and rates of specific drug involvement in overdose deaths are only as accurate as the drug listed on death certificates. Variation in systematic approaches or jurisdictional office policy in drug overdose death certification can lead to bias in mortality rate calculations. Recent research has examined statistical adjustments to improve underreported opioid involvement in overdose deaths. New cause-of-death natural language text analysis tools improve quantification of specific opioid overdose mortality rates. Enhanced opioid overdose surveillance, which combines death certificate data with other MDI-generated data, has the potential to improve understanding of factors and circumstances of opioid overdose mortality. Summary The opioid overdose crisis has brought into focus some of the limitations of US MDI systems for drug overdose surveillance and has given rise to a sense of urgency regarding the pressing need for improvements in our MDI data for public health action and research. Epidemiologists can stimulate positive changes in MDI data quality by demonstrating the critical role of data in guiding public health and safety decisions and addressing the challenges of accurate and timely overdose mortality measures with stakeholders. Education, training, and resources specific to drug overdose surveillance and analysis will be essential as the nation’s overdose crisis continues to evolve.

In 2013, the Centers for Disease Control and Prevention released a warning regarding a new recreational drug, acetyl fentanyl. Acetyl fentanyl is a μ-opioid receptor agonist, and its pharmacological effects include euphoria, altered mood, miosis and central nervous system depression. The objective of this report was to develop a sensitive and specific method for the quantitation of acetyl fentanyl by gas chromatography-mass spectrometry in postmortem casework. Acetyl fentanyl was isolated from biological matrices using solid-phase extraction and acetyl fentanyl-13C6 was employed as an internal standard. The method was validated utilizing the Scientific Working Group for Forensic Toxicology's published method validation parameters, and the biological matrices used for analysis were postmortem blood and urine. In addition to the quantitation of acetyl fentanyl, a demographic study of cases obtained from the Rhode Island Office of State Medical Examiners and the University of Florida Health Pathology Laboratories-Forensic Toxicology Laboratory was performed to examine potential risk factors for acetyl fentanyl use. The results from this study found that the blood concentrations in these individuals ranged from 17 to 945 ng/mL. This suggests acetyl fentanyl is less potent than its prototype drug, fentanyl and requires an increased dose to achieve its desired effects. The demographic analysis indicated white males aged 21-40 years and individuals with a previous history of drug use have the highest risk for acetyl fentanyl abuse.

This chapter illustrates the practical application of drug testing in field studies of drug abuse as conducted by the first author over the past decade. Issues addressed are the rationale for drug testing and the choice of test(s), techniques and difficulties of implementing drug testing in various field situations, interpretation of drug test results, and the contributions of drug testing vs. self-reports to arriving at study conclusions. The experiences indicate that biological testing for drugs of abuse can make a significant contribution to improve behavioral drug-abuse research. Biological testing is far from perfect. More needs to be learned about both hair analysis and saliva analysis including such issues as appropriate cutoff concentrations, conditions influencing sensitivity and specificity, dose/assay relationships and the interpretation of quantitative results, and the effects of external contamination, possible deposition by sweat, cosmetic treatments, and hair pigmentation and structure on analytical results.

A recently proposed model for the incorporation of xenobiotics of forensic interest into the human skeleton suggests nerve agent metabolites may incorporate into bone at relatively elevated concentrations based on their unique chemical properties. To test the hypothesis that nerve agent metabolites interact with bone, methods for the extraction, isolation and semi-quantitative detection of nerve agent metabolites (MPA, EMPA, IMPA, iBuMPA, CMPA and PMPA, corresponding to the nerve agents VX, Russian VX, sarin, cyclosarin and soman, respectively) from osseous tissue were developed using liquid chromatography–mass spectrometry with both quadrupole time-of-flight and triple quadrupole (QqQ) instruments. The optimized methods were validated on the QqQ instrument. Despite high ion suppression, the achieved limits of detection (5–20 pg/g for four analytes; 350 pg/g for the fifth analyte) were lower than many of those published for the same analytes in other biomatrices, including serum and urine. These methods were tested on the skeletal remains of minipigs exposed to the chemical weapon VX in vivo. The VX metabolite was detected in multiple minipig bone samples; to the authors’ knowledge, this is the first time in vivo nerve agent exposure has been detected from bone. Further, detected concentrations and diaphyseal-to-epiphyseal area count ratios reflect animal exposure history. Although the results are limited, they are promising, indicating that nerve agent metabolites may interact with bone as a pharmacokinetic compartment and can be extracted from bone postmortem. Additional studies, assessing the effects of different agents, exposure pathways and taphonomic variables, are needed; however, these results suggest the method may be used with human bone to detect use of chemical weapons from postmortem biomatrices even well after a suspected attack. More general implications for both nerve agent toxicology and skeletal toxicology are also discussed.

Between March 2017 and November 2018, 54 prisoner fatal overdose cases submitted to the University of Florida Forensic Toxicology Laboratory involved synthetic cannabinoids including 5F-ADB, FUB-AMB, 5F-AMB, MDMB-FUBINACA and AB-CHMINACA. Analysis of blood and urine samples was performed at NMS Labs (Horsham, PA) by liquid chromatography/tandem mass spectrometry screening, confirmatory and quantitative methods validated according to Scientific Working Group for Forensic Toxicology guidelines. This work highlights the importance of effective communication between toxicologists and medical examiners/coroners, and the value of public-private partnerships to provide coverage while laboratories work to update instrumentation and validate their own new methods to keep up with the challenges of emerging substances.

In many jurisdictions, public safety and public health entities are working together to enhance the timeliness and accuracy of the analytical characterization and toxicology testing of novel synthetic opioids. The improved sharing and early detection of these analytical data are intended to inform surveillance, interdiction efforts, patient intervention and treatment, all of which are critical to curbing the opioid epidemic. Forensic practitioners working to identify novel synthetic opioids struggle to provide timely results when encountering new or unknown substances, such as the fentanyl analogs. These compounds, which mimic heroin in pharmacologic effect but can be far more potent, are inconsistently present in chemical identification libraries, and are currently largely unavailable as reference materials for analytical comparison. Additionally, federal, state and local governments as well as nongovernmental organizations require potency, toxicity and potential-for-abuse data to evaluate the potential health risks of emerging drug threats. Subsequent scheduling efforts and criminal prosecutions also require these thorough drug characterization studies. Pilot programs have demonstrated that early communication of real-time drug toxicity and analytical data significantly impacts the successful response to emerging opioids. High-quality, real-time, national-level data on chemical composition, toxicological test data, drug toxicity and overdoses, and analysis of seized materials by law enforcement are needed to track drug trends. However, the USA still lacks a national system to coordinate and communicate toxicology, medical and medical examiner and coroner data with the broader medical and law enforcement communities. Opportunities to address these gaps as well as recent advancements collected through interagency efforts and technical workshops in the toxicology and analytical chemistry communities are presented here. Opportunities for partnership, increased communication and expanding best practices to move toward an integrated, holistic analytical response are also explored.

This preliminary study examined the postmortem distribution of pentobarbital in the remains of three domestic dogs (Canis lupus familiaris) after intravenous administration of pentobarbital sodium to determine optimal sampling practices for veterinary forensic casework. It was thought that pentobarbital would be absent in many traditional toxicological samples, such as bile and urine, because of the brief period between administration and death. However, all samples tested via gas chromatography, coupled with a nitrogen–phosphorus detector, contained quantifiable levels of pentobarbital. These initial results suggest that when the Florida Animal Control Association’s recommended method of euthanasia is used in healthy individuals, pentobarbital extensively distributes throughout the body.

Background Novel psychoactive substances (NPS) present continuous and growing challenges for the scientific, medical, and interventional communities as emerging substances on recreational drug markets change national and international drug landscapes. NPS account for an increasing proportion of adverse events, hospitalizations, and deaths due to increasing potency and unanticipated biological effects compared to predecessors. This study evaluated the utility of drug use forums as an early indicator or predictor of impending intoxications with potentially harmful or lethal outcomes prior to their occurrences. Methods Eight NPS were selected for evaluation to assess the relationship between online mentions of drugs and their involvement in toxic exposures or overdoses. Mentions on Reddit drug forum discussions were tallied and toxicology testing results from forensic investigations in the US were assessed. The selected NPS covered several subclasses and a predetermined time range (2013–2020). They included carfentanil, U-47700, eutylone, flualprazolam, N-ethylpentylone, 5F-MDMB-PICA, isotonitazene, and brorphine. Results Seven NPS (excluding 5F-MDMB-PICA) appeared in discussions on Reddit prior to their implication in poisonings or intoxications. Distinct increases and decreases in number of mentions and number of exposures were observed. For most substances (n = 5, 63%), a rise in Reddit mentions was soon followed by a corresponding rise in toxicology positivity. Peak positivity for carfentanil and flualprazolam, however, preceded peak Reddit mentions. Conclusions This study demonstrated the utility of social media sites, such as Reddit, as a predictor for future trends in NPS-related exposures. These results provide confirmation that activity on drug use forums in the virtual world can help predict changes in exposures associated with new or re-emerging NPS in the real world. The results warrant further evaluation as a strategy for inclusion in early warning systems.

Preliminary estimates of U.S. drug overdose deaths exceeded 60,000 in 2016 and were partially driven by a fivefold increase in overdose deaths involving synthetic opioids (excluding methadone), from 3,105 in 2013 to approximately 20,000 in 2016 (1,2). Illicitly manufactured fentanyl, a synthetic opioid 50-100 times more potent than morphine, is primarily responsible for this rapid increase (3,4). In addition, fentanyl analogs such as acetylfentanyl, furanylfentanyl, and carfentanil are being detected increasingly in overdose deaths (5,6) and the illicit opioid drug supply (7). Carfentanil is estimated to be 10,000 times more potent than morphine (8). Estimates of the potency of acetylfentanyl and furanylfentanyl vary but suggest that they are less potent than fentanyl (9). Estimates of relative potency have some uncertainty because illicit fentanyl analog potency has not been evaluated in humans. This report describes opioid overdose deaths during July-December 2016 that tested positive for fentanyl, fentanyl analogs, or U-47700, an illicit synthetic opioid, in 10 states participating in CDC's Enhanced State Opioid Overdose Surveillance (ESOOS) program.* Fentanyl analogs are similar in chemical structure to fentanyl but not routinely detected because specialized toxicology testing is required. Fentanyl was detected in at least half of opioid overdose deaths in seven of 10 states, and 57% of fentanyl-involved deaths also tested positive for other illicit drugs, such as heroin. Fentanyl analogs were present in >10% of opioid overdose deaths in four states, with carfentanil, furanylfentanyl, and acetylfentanyl identified most frequently. Expanded surveillance for opioid overdoses, including testing for fentanyl and fentanyl analogs, assists in tracking the rapidly changing illicit opioid market and informing innovative interventions designed to reduce opioid overdose deaths.

Objective: Effective use of state prescription drug monitoring programs (PDMPs) to track controlled substance prescribing and dispensing may help mitigate the current opioid crisis. Our objective was to examine trends in registration for and use of Florida's PDMP by physicians and pharmacists, from 2013 to 2016. We discuss implications for PDMP uptake and policy. Design: Key measures, such as cumulative number of registrants per license type and monthly utilization intensity, are presented. A time series forecasting approach was used to (1) model the monthly count of new PDMP registrants and users from January 2013 to December 2016 and (2) estimate cumulative registration totals after 1 year. Setting: Florida. Results: As of November 2016, there were 16,498 physicians (representing 31 percent of Drug Enforcement Administration licensees) and 17,241 pharmacists registered with the PDMP, representing 21 and 57 percent of professional licensees, respectively. Of note, the PDMP's designation as a “specialized registry” for electronic medical record “meaningful use” criteria led to a nearly sevenfold increase in physician registrations in a single month. In November 2016, pharmacists displayed a higher past-month PDMP utilization rate (52.2 percent vs 30.1 percent), while physicians displayed a higher past-month PDMP utilization intensity (58.1 vs. 36.1 queries per user). Approximately 25,000 physicians and 31,000 pharmacists must register by the end of 2017 to meet national policy goals. Conclusion: PDMP registration among physicians and pharmacists is limited, and the use of the PDMP among registrants is more limited still. Our findings suggest that Florida will not meet national policy goals for registrants by the end of 2017, although new initiatives may alter this trend. Allowing the PDMP to help prescribers meet other professional needs, such as “meaningful use” or similar efforts, may be effective in increasing PDMP use.

In March and October 2015, the Drug Enforcement Administration (DEA) and CDC issued nationwide alerts identifying fentanyl, particularly illicitly manufactured fentanyl (IMF), as a threat to public health and safety (1,2). IMF is pharmacologically similar to pharmaceutical fentanyl (PF), but is unlawfully produced in clandestine laboratories, obtained via illicit drug markets, and includes fentanyl analogs. Fentanyl is a synthetic opioid 50-100 times more potent than morphine and approved for the management of surgical/postoperative pain, severe chronic pain, and breakthrough cancer pain.* DEA's National Forensic Laboratory Information System (NFLIS) collects drug identification results from drug cases analyzed by federal, state, and local forensic laboratories throughout the United States.(†) In 2014, 80% of fentanyl submissions (i.e., drug products obtained by law enforcement that tested positive for fentanyl) in NFLIS were identified from 10 states, including Florida and Ohio (2), and seven of these 10 states reported sharp increases in fentanyl-related overdose deaths (fentanyl deaths) (3). This report presents findings of increased fentanyl deaths during 2013-2015 from investigations conducted by the University of Florida and the Ohio Department of Public Health, in collaboration with CDC. Analyses examined the association between trends in fentanyl-related law enforcement submissions and fentanyl deaths and describes groups at risk for fentanyl death using medical examiner and coroner reports. The marked increases in fentanyl death in Florida and Ohio during 2013-2015 were closely associated with parallel increases in fentanyl submissions, with the largest impact on persons who use heroin, consistent with reports that IMF is commonly mixed with or sold as heroin (1,4). In Ohio, circumstances associated with fentanyl deaths included a current diagnosed mental health disorder(§) and recent release from an institution such as a jail, rehabilitation facility, or hospital.

The abuse of 'bath salts' has raised concerns because of their adverse effects, which include delirium, violent behavior, and suicide ideation in severe cases. The bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) has been closely linked to these and other adverse effects. The abnormal behavioral pattern produced by acute high-dose MDPV intake suggests possible disruptions of neural communication between brain regions. Therefore, we determined if MDPV exerts disruptive effects on brain functional connectivity, particularly in areas of the prefrontal cortex. Male rats were imaged following administration of a single dose of MDPV (0.3, 1.0, or 3.0 mg/kg) or saline. Resting state brain blood oxygenation level-dependent (BOLD) images were acquired at 4.7 T. To determine the role of dopamine transmission in MDPV-induced changes in functional connectivity, a group of rats received the dopamine D1/D2 receptor antagonist cis-flupenthixol (0.5 mg/kg) 30 min before MDPV. MDPV dose-dependently reduced functional connectivity. Detailed analysis of its effects revealed that connectivity between frontal cortical and striatal areas was reduced. This included connectivity between the prelimbic prefrontal cortex and other areas of the frontal cortex and the insular cortex with hypothalamic, ventral, and dorsal striatal areas. Although the reduced connectivity appeared widespread, connectivity between these regions and somatosensory cortex was not as severely affected. Dopamine receptor blockade did not prevent the MDPV-induced decrease in functional connectivity. The results provide a novel signature of MDPV's in vivo mechanism of action. Reduced brain functional connectivity has been reported in patients suffering from psychosis and has been linked to cognitive dysfunction, audiovisual hallucinations, and negative affective states akin to those reported for MDPV-induced intoxication. The present results suggest that disruption of functional connectivity networks involving frontal cortical and striatal regions could contribute to the adverse effects of MDPV.

Synthetic cathinones are an emerging class of designer drugs, frequently with deceptive labels and a multitude of analogs to circumvent drug control regulations. Research regarding the pharmacological effects and toxicity of these amphetamine derivatives is scarce, heightening the risk to the public health and safety. The composition of synthetic cathinone products continually changes and laboratories began to notice ethylone-positive products in late 2011. This report presents nine postmortem cases in whom ethylone was identified. Ethylone was isolated using solid-phase extraction and detected by gas chromatography-mass spectrometry. Seven of the cases had measurable concentrations of ethylone in blood, ranging from 38 to 2,572 ng/mL; ethylone was detected in the blood sample of one case with a concentration below the assay limit of quantification (25 ng/mL), and one case did not have detectable ethylone in blood. Besides ethylone, all but one case were also positive for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol; seven cases had other drugs quantified in blood, including ethanol, alprazolam, benzoylecgonine, diphenhydramine, morphine and tramadol. In five cases where ethylone was present at blood concentrations >400 ng/mL, no other drugs excluding ethanol, cannabis metabolite and doxylamine (one case) were found. The assay also tested for mephedrone, methylone and three dimethoxyamphetamine analogs; no case was positive for these analytes. The present report documents postmortem blood concentrations of ethylone, a novel synthetic cathinone, along with other concurrently identified substances. The findings provide valuable information for developing analytical assays and evaluating a toxic concentration range of ethylone.

BACKGROUND Since 2013, an unprecedented surge in fentanyl overdose deaths has been caused by heroin laced with illicitly produced fentanyl and/or fentanyl analogs (FAs) sold as heroin. The US Drug Enforcement Agency's National Forensic Laboratory Information System reported a >300% increase in fentanyl encounters from 4697 in 2014 to 14440 in 2015. In 2015, the CDC reported 9580 deaths caused by synthetic opioids, primarily fentanyl, a 72% increase from 2014. The European Monitoring Centre for Drugs and Drug Addiction has also encountered several new FAs in the heroin supply. Counterfeit pharmaceuticals containing mixtures of fentanyl and FAs continue to be a poorly recognized worldwide problem despite the WHO classifying several FAs as a serious threat to public health. CONTENT This review covers the epidemiology of fentanyl abuse and discusses the clinical practice implications of widespread fentanyl abuse. It includes a historical perspective on the illicit FAs that have appeared in the US and European Union and reviews the methods available to identify FAs and emerging technologies useful for identifying previously undescribed analogs. A compilation of structural and mass spectral data on FAs reported thus far is provided. SUMMARY Fentanyl and FAs have evolved into a global public health threat. It is important to understand the analytical, clinical, and regulatory efforts underway to assist communities affected by the current fentanyl epidemic.

The synthetic opioid propoxyphene was a schedule IV controlled substance with multiple reported health risks before the US Food and Drug Administration issued a request for voluntary market withdrawal in November 2010. The purpose of this study is to investigate the characteristics and occurrences of propoxyphene-related deaths in Florida before and after voluntary market removal. Decedent-level toxicology data from Florida's Medical Examiners Commission was used to compare the temporal, polysubstance use, sociodemographic, and geographic profiles associated with propoxyphene-involved deaths for a pre-withdrawal (November 2008-November 2010) and post-withdrawal (December 2010-December 2012) period. Sensitivity analyses using multiple data sources, including Florida's Prescription Drug Monitoring Program and other states' data, were conducted to examine potential reporting bias. Results showed that the number of propoxyphene-involved deaths declined by 84% from 580 deaths to 92 deaths after market withdrawal. The co-occurrence of other prevalent drugs, such as oxycodone (17.2% to 26.1%, p=0.0422) increased significantly in the post-withdrawal study period. A larger proportion of the propoxyphene-related deaths were reported from South Florida after the withdrawal (28.4% to 56.5%, p

Background Urine drug testing is an essential component of treating patients for chronic pain and/or anxiety and is used to monitor compliance during treatment. A common algorithm is to use an immunoassay as a urine drug screen (UDS), followed by mass spectrometry to confirm all presumptive positive samples. Many UDSs, however, have significant limitations, and false-negative test results can be common due to lack of antibody specificity. Methods Urine samples were screened by a benzodiazepine immunoassay followed by confirmatory testing using LC-MS/MS to determine an initial false-negative test rate for the screen. Attempts to improve the false-negative test rate included hydrolysis before screening and optimization of the absorbance cutoff required for a positive result. Results Hydrolysis corrected 41% of false-negative test results in samples containing parent benzodiazepines and/or metabolites but had no effect on samples containing only clonazepam. Of the confirmed false-negative test results, 85% (17 of 20) demonstrated absorbance values between 20 and 100, with 100 being the cutoff for a positive result. Implementing an optimized absorbance cutoff of 20, rather than 100, for a reflexive confirmation testing algorithm decreases the false-negative test rate of detecting benzodiazepine from 47% to 2%. Conclusions Hydrolyzing samples before the benzodiazepine screen provided a modest improvement in the false-negative test rate; however, the screen still missed samples containing clonazepam. Optimization of the absorbance cutoff to reflex samples to LC-MS/MS markedly improved the false-negative test rate for all benzodiazepines.

Objectives. To investigate the effects of precursor chemical regulation aimed at reducing cocaine production on cocaine-related maternal and newborn hospital stays in the United States. Methods. We analyzed monthly counts of maternal and neonatal stays from January 2002 through December 2013 by using a quasi-experimental interrupted time series design. We estimated the preregulation linear trend, postregulation change in linear trend, and abrupt change in level. Results. The number of monthly cocaine-related maternal and neonatal stays decreased by 221 and 128 stays, respectively, following the cocaine precursor regulation change. We also observed a further decline in per-month maternal and neonatal stays of 18 and 8 stays, respectively. Conclusions. A supply-side disruption in the United States cocaine market was associated with reduced hospital stays for 2 vulnerable populations: pregnant women and newborns. Results support findings that federal precursor regulation can positively reduce cocaine availability in the United States.

Florida, the epicenter of the recent prescription drug epidemic in the United States, maintains a statewide drug mortality surveillance system. We evaluated yearly profiles, demographic characteristics, and correlation between drug trends to understand the factors influencing drug-induced mortality.All drug-related deaths reported to the Florida Medical Examiners Commission during 2001-2012 were included (n=92,596). A death was considered "drug-related" if at least one drug was identified in the decedent. Depending on its contribution to death, a drug could be listed as a causative agent or merely present, but not both.Rate of drug-caused deaths was 8.0 per 100,000 population in 2001, increasing to 17.0 in 2010 and then decreasing to 13.9 in 2012. Benzodiazepines had the highest mortality rate in 2010, although10% were solely due these drugs. Opioid-caused mortality rate also peaked in 2010 and started to decline (-28%) in 2010-2012. The heroin-caused mortality rates were negatively correlated with opioids and benzodiazepines (ρ's ≥ -0.670; P≤0.034). Ethanol- and cocaine-mortality rates stabilized to 3.0-3.1 and 2.8-3.0 per 100,000 over 2009-2012, respectively. Amphetamines, zolpidem, and inhalants-caused deaths were on the rise with rates of ≤0.6 per 100,000.Overall declines in benzodiazepine- and opioid-caused deaths in 2011-2012 may have been related to Florida's attempts to regulate prescription drug abuse. This period, however, was also marked by a rise in heroin-caused mortality, which may reflect growing use of heroin as an alternative. Increases in amphetamines, zolpidem, and inhalants-induced mortality are an additional public health concern.

Summary Background Previous attempts to assess the prevalence of drug use in Afghanistan have focused on subgroups that are not generalisable. In the Afghanistan National Urban Drug Use Study, we assessed risk factors and drug use in Afghanistan through self-report questionnaires that we validated with laboratory test confirmation using analysis of hair, urine, and saliva. Methods The study took place between July 13, 2010, to April 25, 2012, in 11 Afghan provinces. 2187 randomly selected households completed a survey, representing 19 025 household members. We completed surveys with the female head of the household about past and current drug use among members of their household. We also obtained hair, urine, and saliva samples from 5236 people in these households and tested them for metabolites of 13 drugs. Findings Of 2170 households with biological samples tested, 247 (11·4%) tested positive for any drug. Overall, opioids were the most prevalent drug in the biological samples (5·6%), although prescription drugs (prescription pain pills, sedatives, and tranquilliser) were the most commonly reported in the past 30 days in the questionnaires (7·6%). Of individuals testing positive for at least one substance, opioids accounted for more than 50% of substance use in women and children, but only a third of substances in men, who predominantly tested positive for cannabinoids. After controlling for age with direct standardisation, individual prevalence of substance use (from laboratory tests) was 7·2% (95% CI 6·1–8·3) in men and 3·1% (2·5–3·7) in women—with a national prevalence of 5·1% (4·4–5·8) and a prevalence of 5·0% (4·1–5·8) in Kabul. Concordance between laboratory test results and self-reports was high. Interpretation These data suggest the female head of household to be a knowledgeable informant for household substance use. They also might provide insight into new avenues for targeted behavioural interventions and prevention messages. Funding US Department of State.

The major psychoactive component of marijuana, Δ(9)-tetrahydrocannabinol (THC), also acts to suppress inflammatory responses. Receptors for THC, CB1, CB2, and GPR55, are differentially expressed on multiple cell types including monocytes and macrophages, which are important modulators of inflammation in vivo and target cells for HIV-1 infection. Use of recreational and medicinal marijuana is increasing, but the consequences of marijuana exposure on HIV-1 infection are unclear. Ex vivo studies were designed to investigate effects on HIV-1 infection in macrophages exposed to THC during or following differentiation. THC treatment of primary human monocytes during differentiation reduced HIV-1 infection of subsequent macrophages by replication competent or single cycle CCR5 using viruses. In contrast, treatment of macrophages with THC immediately prior to or continuously following HIV-1 exposure failed to alter infection. Specific receptor agonists indicated that the THC effect during monocyte differentiation was mediated primarily through CB2. THC reduced the number of p24 positive cells with little to no effect on virus production per infected cell, while quantitation of intracellular viral gag pinpointed the THC effect to an early event in the viral life cycle. Cells treated during differentiation with THC displayed reduced expression of CD14, CD16, and CD163 and donor dependent increases in mRNA expression of selected viral restriction factors, suggesting a fundamental alteration in phenotype. Ultimately, the mechanism of THC suppression of HIV-1 infection was traced to a reduction in cell surface HIV receptor (CD4, CCR5 and CXCR4) expression that diminished entry efficiency.

Background High-risk combinations of controlled medications, such as those involving opioid analgesics, are under increased scrutiny because of their contribution to the opioid epidemic in the United States. Responsible prescribing guidelines indicate that the triple drug combination--opioids, benzodiazepines and skeletal muscle relaxants, especially carisoprodol--should not be concurrently prescribed. Methods This pharmacoepidemiologic study was designed to primarily examine the characteristics of patients receiving this triple combination compared to the group receiving only opioids and benzodiazepines. Results Results show that, while the number of exposed patients has declined since 2012, approximately 17,000 Floridians were prescribed this combination in 2017 alone. Demographically, recipients of these prescriptions were younger, more likely to be female, and geographically-localized. Furthermore, these patients were more frequently associated with a prescriber in the top 1% of opioid and/or benzodiazepine prescribing, have more multiple provider episodes (“doctor shopping”), and receive higher mean daily opioid dosages. Conclusions These findings raise important questions as to how frequently prescribers are checking prescription drug monitoring programs, following US Centers for Disease Control and Prevention opioid prescribing guidelines, and/or handling the clinical challenges associated with pharmaceutical management of patients with complex, painful health conditions.

Background Substance use by youth living with HIV (YLWH) is a concern, given potential interactions with virus-associated immune suppression and adverse effects on risk behaviors, neurocognition, and adherence. Self-report substance use measures provide efficient cost-effective assessments. Analyses describe self-reported substance use among YLWH and examine agreement with toxicology assays. Methods Seventy-eight youth age 18–24 years (87% male, 71% African–American) with behaviorally acquired HIV-1 infection and 55 uninfected youth completed the Alcohol, Smoking, and Substance Involvement Screening Test to assess drug use frequency, including tobacco, marijuana, cocaine, and alcohol, over the prior three months. Elisa-based toxicology assays were used to detect 27 substances in plasma. Chi-square tests compared substance use between YLWH and uninfected youth; Kappa statistics compared agreement between self-report and toxicology. Results YLWH reported marijuana (49%), tobacco (56%), and alcohol (87%) use, with 20%, 28% and 3% reporting daily use of each substance, respectively; other substance use was uncommon. Uninfected youth reported less tobacco use but otherwise similar substance use. All youth who reported daily use of marijuana or tobacco had positive plasma toxicology results, while concordance decreased with less frequent self-reported use. Among youth reporting no substance use, few tested positive (4% YLWH, 2% uninfected youth for cannabis; 8%YLWH for tobacco). Conclusions Youth report high rates of marijuana, tobacco, and alcohol use. Concordance between self-report and toxicology for marijuana and tobacco use, particularly for daily users, supports self-report as a valid indicator of substance use in research studies of youth with or without HIV-1 infection.

Enzyme immunoassays (EIA) are commonly utilized for the evaluation of androgens in biological fluids; however, careful consideration must be given to cross-reactivity with other endogenous sex-steroid hormones. Our purpose was to determine the validity of a commonly-utilized commercially-available dihydrotestosterone (DHT) EIA. Serum samples obtained from older hypogonadal men who participated in a 12-month randomized controlled trial evaluating the effects of testosterone-enanthate (125 mg/week) or vehicle in combination with finasteride (5 mg/day) or placebo were assayed for DHT via EIA and using a validated gold-standard LC–MS/MS approach. Additionally, commercially-available (DHT-free) buffer containing graded testosterone doses was evaluated by DHT immunoassay. DHT concentrations measured via EIA were 79% to >1000% higher than values obtained by LC–MS/MS (p < 0.05), with the largest differences (415–1128%) occuring in groups receiving finasteride. Both LC–MS/MS and EIA indicated that testosterone-enanthate increased serum DHT to a similar magnitude. In contrast, finasteride-induced reductions in DHT were detected by LC–MS/MS, but not EIA (p < 0.05). No significant associations were present for DHT concentrations between measurement techniques. Cross-reactivity of testosterone with the immunoassay ranged from 18% to 99% and DHT concentrations measured by EIA were highly associated with the spiked testosterone concentrations in DHT-free buffer (r = 0.885, p < 0.001). In conclusion, we provide evidence invalidating a commonly-utilized commercially-available DHT immunoassay because significant cross-reactivity exists between testosterone and the EIA and because the changes in DHT observed via EIA were not associated with a validated gold-standard measurement technique. The cross-reactivity of testosterone is particularly concerning because testsoterone is present in 100-fold greater concentrations than is DHT within the circulation.

Deaths involving prescription and illicit opioids are on the rise, which is an issue of increasing concern to health care professionals, policymakers, and the public. However, because medical examiners, coroners, and other practitioners do not use uniform standards and case definitions in classifying such drug-related deaths, the incidence and prevalence data are challenging to analyze and difficult to interpret, and thus form a poor basis for crafting effective responses. To address this situation, the Substance Abuse and Mental Health Services Administration convened a Consensus Panel and charged it with devising uniform standards and case definitions that can assist medical examiners, coroners, public health officials, and others in consistently distinguishing between deaths that were caused by a certain opioids and deaths in which such a drug was detected but was not a major cause of or contributor to the death. The consensus statement presented here incorporates the panel's recommendations in four key areas.

Fentanyl induces pharmacological effects and abuse liability comparable to other prescription opioids and heroin. A surge in fentanyl-related fatalities has been periodically reported throughout the USA. The University of Florida Forensic Toxicology Laboratory observed a significant increase in fentanyl-related deaths starting in mid-2014. The present report evaluated toxicological findings, demographics of the decedents and circumstances of death in the postmortem cases that were submitted to the laboratory for toxicological analysis from July 2014 to January 2015 and that were tested for fentanyl in biological specimens. The cases originated from 6 of the 24 Florida Medical Examiner Districts, with the majority from District 12 (Desoto, Manatee and Sarasota counties). The specimens were analyzed for fentanyl by gas chromatography-mass spectrometry; the limit of detection (LOD) was 0.62 ng/mL and the limit of quantification (LOQ) was 2.5 ng/mL. During the 7-month period, the laboratory tested 143 postmortem cases for fentanyl and 50% had quantifiable fentanyl in postmortem blood. Fentanyl concentrations ranged from 2.5 to 68 ng/mL (n = 66; median: 9.8 ng/mL); six cases were positive for fentanyl >LOD but

Abuse of the psychoactive "designer drug" methylenedioxypyrovalerone (MDPV) has become a serious international public health concern because of the severity of its physical and behavioral toxicities. MDPV is the primary ingredient in so-called "bath salts," labeled as such to avoid criminal prosecution and has only been classified recently as a controlled substance in the United States and some other countries. However, it remains a danger because of illegal sources, including the Internet. MDPV is a synthetic, cathinone-derivative, central nervous system stimulant and is taken to produce a cocaine- or methamphetamine-like high. Administered via oral ingestion, nasal insufflation, smoking, intravenous or intramuscular methods, or the rectum, the intoxication lasts 6 to 8 hours and has high addictive potential. Overdoses are characterized by profound toxicities, causing increased attention by emergency department and law enforcement personnel. Physical manifestations range from tachycardia, hypertension, arrhythmias, hyperthermia, sweating, rhabdomyolysis, and seizures to those as severe as stroke, cerebral edema, cardiorespiratory collapse, myocardial infarction, and death. Behavioral effects include panic attacks, anxiety, agitation, severe paranoia, hallucinations, psychosis, suicidal ideation, self-mutilation, and behavior that is aggressive, violent, and self-destructive. Treatment is principally supportive and focuses on counteracting the sympathetic overstimulation, including sedation with intravenous benzodiazepines, seizure-prevention measures, intravenous fluids, close (eg, intensive care unit) monitoring, and restraints to prevent harm to self or others. Clinical presentation is often complicated by coingestion of other psychoactive substances that may alter the treatment approach. Clinicians need to be especially vigilant in that MDPV is not detected by routine drug screens and overdoses can be life-threatening.

Death certificates are a source of information on deaths caused by specific drugs. However, the completeness of such information has been questioned. This study compared counts in the Florida Medical Examiner Commission's drug related death reporting system (ME) with those from death certificates (DC) for overdose deaths involving selected drugs during 2005-2008 to assess the completeness of death certificate information. DC data indicated 2,401 deaths with benzodiazepines as a cause, 2,182 for cocaine, 2,055 for methadone, and 416 for heroin. The ratios of ME deaths to DC deaths were 1.19 (95% CI 1.13-1.26) for benzodiazepines, 1.38 (95% CI 1.31-1.46) for cocaine, 1.37 (95% CI 1.29-1.44) for methadone, and 0.96 (95% CI 0.83-1.09) for heroin. For each drug, ratios were similar for unintentional (accidental), suicide, and undetermined intent deaths. Ratios varied across the 24 ME districts, but few districts reported significantly fewer deaths in the ME system than in the DC system. Results suggest that surveillance based on death certificate data underestimates specific drug caused deaths as counted by medical examiners in a state with multiple, independent medical examiners. Death certificate data might therefore underestimate drug overdose mortality nationwide.

Drugs, whether illicit, prescription, or over-the-counter, cause or contribute to death in many cases falling under medical examiner or coroner jurisdiction. Thus, toxicological analysis often plays a critical role in the determination of the cause and manner of death. There is significant variability, however, between medicolegal death investigation systems with respect to standards of practice for the performance of “routine” toxicological analysis. Depending on a multitude of variables, including the size of the office, caseload, population base, budget, laboratory testing panel, pathologist philosophy, and personnel availability, routine toxicological analysis may range from no testing at all, to minimalistic urine screening, to complete quantification of all potential toxins identified on screening assays. As physicians, forensic pathologists are trained to search for the correct diagnosis in every case, every time. When establishing protocols and defining routine toxicological analyses, however, the pathologist is often forced to consider the pros of thoroughness and accuracy, versus the cons of cost and diminished timeliness of results. A rational approach to forensic toxicology is offered in an attempt to combine efficiency and frugality with acquisition of essential medicolegal data.

We designed and built a novel, miniature gas chromatograph (mGC) to use exhaled breath to estimate blood ethanol concentrations that may offer GC quality sensitivity and specificity, but with portability, reduced size, and decreased cost. We hypothesized that the mGC would accurately estimate the serum ethanol concentration using exhaled breath. Human subjects (n = 8) were dosed with ethanol employing the Widmark criteria, targeting a blood concentration of 0.08 g/dL. Serum and breath samples were collected concurrently over an hour. Ethanol concentrations in serum were measured using a CLIA-approved laboratory. Ethanol concentrations in conventional breath were assayed using a calibrated mGC or Intoxilyzer 400PA. Data were analyzed using Bland-Altman analysis using serum concentrations as a "gold standard". For the mGC, the regression line (correlation coefficient), bias, and 95% limits of agreement were y = 1.013x - 0.009 (r = 0.91), -0.008 g/dL, and -0.031 to 0.016 g/dL, respectively, for 30 specimens. For the Intoxilyzer 400PA, the regression line (correlation coefficient), bias, and 95% limits of agreement were y = 0.599x + 0.008 (r = 0.86), -0.024 g/dL, and -0.049 to 0.002 g/dL, respectively, for 71 specimens with a large magnitude effect. We concluded that the mGC, using exhaled breath, performed well to estimate the serum ethanol concentrations.

Dear Editor: Urine drug test methods are classified as either screening or confirmatory. Immunoassay-based point-of-care (POC) drug screens offer results within minutes, often allowing physicians to make real-time clinical decisions ⇓. Immunoassay also has important limitations, including limited test menus; inability to distinguish among members of a drug class; inability to differentiate drugs from their metabolites; inability to quantitate compounds; and cross-reactivity with nontargeted compounds. For confirmatory analysis, mass spectrometry in conjunction with liquid or gas chromatography is commonly utilized to supplement immunoassay. This analytical technique, while more expensive and time-consuming than immunoassay, allows highly sensitive and specific identification of analytes by measuring the distinctive mass-to-charge ratios of ions. However, there is a lack of general agreement on the indications for confirmation testing. Another critical consideration is tampered urine samples. To conceal inappropriate drug use, individuals may substitute with drug-free synthetic or authentic urine, or add oxidizing chemicals or other adulterates to the samples that could interference with the test performance ⇓. Such donor behavior sometimes necessitates that toxicology laboratories perform specimen validity tests in addition to drug analysis. Buprenorphine/naloxone is U.S. Food and Drug Administration-approved for the treatment of opioid dependence. It is also used off-label for analgesia, particularly for patients with co-occurring chronic pain and opioid …

The serotonin transporter promoter polymorphism (5-HTTLPR) has been linked to a number of human behavioral traits and disorders. The variants of 5-HTTLPR are commonly reported in three forms, L/L, S/L and S/S, with the latter most often associated with emotional distress and/or behavioral dysfunction. Missing from the research literature are investigations that assess event-level associations between 5-HTTLPR genotype and specific incidents of risk behavior in natural drinking settings. This study reports associations between 5-HTTLPR, alcohol intoxication and intention to drive among young adult patrons exiting on-premise drinking establishments (i.e. bars) at night. Self-report measures, breath alcohol concentration (BrAC) readings and saliva samples for DNA analysis were collected from 477 bar patrons. Analyses were performed on 225 patrons likely to be near their peak intoxication level for the night. Results from a linear regression revealed that the 5-HTTLPR genotype was associated with exiting patron BrAC, after adjusting for random and fixed effects of other variables. An interaction effect involving 5-HTTLPR and bar-sponsored drink specials also had an independent association with BrAC, suggesting that selection of price-discounted alcoholic beverages increased intoxication in patrons with an L allele. In addition, results from logistic regression indicated that patrons with the S/S genotype were three times more likely to intend to drive a motor vehicle (after drinking on the night of study participation) compared with those with the L/L genotype. The 5-HTTLPR genotype may play an important role in the etiology of problems associated with on-premise drinking establishments.

Aim To assess event-level associations between energy drink consumption, alcohol intoxication, and intention to drive a motor vehicle in patrons exiting bars at night. Method Alcohol field study. Data collected in a U.S. college bar district from 802 randomly selected and self-selected patrons. Anonymous interview and survey data were obtained as well as breath alcohol concentration (BrAC) readings. Results Results from logistic regression models revealed that patrons who had consumed alcohol mixed with energy drinks were at a 3-fold increased risk of leaving a bar highly intoxicated (BrAC ≥ 0.08 g/210 L), as well as a 4-fold increased risk of intending to drive upon leaving the bar district, compared to other drinking patrons who did not consume alcoholic beverages mixed with energy drinks. Discussion These event-level associations provide additional evidence that energy drink consumption by young adults at bars is a marker for elevated involvement in nighttime risk-taking behavior. Further field research is needed to develop sound regulatory policy on alcohol/energy drink sales practices of on-premise establishments.

A 41-year-old African-American woman was admitted to an inpatient hospice facility with advanced, inoperable cervical cancer. The patient was experiencing severe pain secondary to extensive local tumor invasion, osseous pelvic metastases, and sacral decubitus ulcers. Her pain was treated with an escalating-dose schedule of morphine sulfate until satisfactory analgesia was achieved with stable doses of a combination of controlled-release morphine sulfate (MSContin®, Purdue Pharma LP) 400 mg orally every 8 h, and immediate-release morphine sulfate (MSIR®, Purdue Pharma LP), 180 mg orally every 4 h, as needed for breakthrough pain (average 2 to 3 doses per day). The patient experienced several episodes of life-threatening vaginal bleeding for which she was hospitalized for red blood cell transfusions and bilateral hypogastric artery embolizations. She spent the final 12 weeks of her life exclusively on the inpatient hospice unit. Approximately 3 weeks before her death, the patient underwent urine specimen collection and analysis of morphine and metabolites. GC-MS analysis revealed the presence of morphine as well as small quantities of hydromorphone. During the past 2 decades, chronic opioid analgesic therapy (COAT) for chronic nonmalignant pain has gained increasing clinical acceptance. An unintended consequence of more liberal opioid prescription practices has been a dramatic increase in the abuse and diversion of these drugs. According the most recent National Survey on Drug Abuse and Health (1), the number of new, past-year abusers of prescription opioids was 2 147 000—more than the number of new abusers of any other single class …

Objective: The authors describe the epidemiology of risk behavior associated with poly-drug use in a college bar district of a large campus community. Participants: A total of 469 bar patrons participated in the study. Methods: The authors used self-report data and biological measures collected from patrons outside bars in July and August of 2007. Results: The mean breath alcohol concentration of the exiting patrons was 0.09. Illicit and prescription drug use on the nights of data collection and in the recent past were significant features of the profile of patron risk behavior. About one-quarter of the patrons using only alcohol reported an intention to drive a vehicle within 60 minutes of leaving an establishment, compared with almost one-half of those using both alcohol and marijuana. Conclusions: A substantial amount of high-risk behavior was generated from the bar district on 4 typical nights. College bar districts should be a priority focus for prevention efforts.

Objective: The study examined associations between bar-sponsored drink specials and alcohol intoxication at the patron level. Method: Data were collected in a college bar district located in a large campus community in the southeastern United States. Random and self-selected samples of patrons were interviewed after exiting college bars at night on four different nights (N = 383). Anonymous interview and questionnaire data were collected as well as breath alcohol concentration (BrAC) readings. Results: Significant gender differences existed in patron drinking practices. Women were more likely to take advantage of drink specials, whereas men reported greater alcohol expenditures, consumed more drinks, and drank for longer periods of time. Gender differences in BrAC were very small and not meaningful. Patrons who did not take advantage of drink specials reported consuming more drinks before bar entry than patrons who did participate in these promotions. Participation in "all-you-can-drink" promotions was significantly associated with higher BrAC readings after adjusting for covariates and random effects attributable to drinking establishment. Other drink specials did not have significant associations with alcohol intoxication. Conclusions: The all-you-can-drink special may be the specific discounting practice with the greatest potential for boosting patron intoxication and thus may need to be a stronger focus of alcohol-control policies aimed at improving the beverage service of drinking establishments. Language: en