Illicit Heroin Research Articles

Characterization of the Source of Heroin by Ultra-High-Performance Liquid Chromatography with Tandem Mass Spectrometry (UPLC-MS/MS) and Principal Component Analysis (PCA)

The sources of seized heroin can provide information on its manufacture and distribution. Using ultra-high-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS), 15 neutral/acidic characteristic target substances in illicit heroin products were determined. The analysis of these samples was completed by combining mathematical and statistical analysis. In all, 38 heroin samples from different cities were characterized by combining case information, relevant subgroups, and principal component analysis (PCA) results. The samples were initially classified using principal component analysis (PCA). The Pearson distance was used to calculate the correlation between samples in each group separately, and r > 0.98 was selected as the threshold value to screen out 11 groups with strong correlations. It was surmised from the case information that the origin or processing methods of heroin seized from different cities may differ. This study applies correlation analysis to relate the seized heroin from different cases to the same upline or network, providing insight for the investigation.

The effect of combat deployments on veteran opioid abuse.

Grim national statistics about the U.S. opioid crisis are increasingly well known to the American public. Far less well known is that U.S. servicemembers are at ground zero of the epidemic, with veterans facing an overdose death rate of up to twice that of civilians. Exploiting a quasi-experiment in overseas deployment assignment, this study estimates the causal impact of combat exposure among the deployed in the Global War on Terrorism on opioid abuse. We find that exposure to war theater substantially increased the risk of prescription painkiller abuse and illicit heroin use among active duty servicemen. The magnitudes of our estimates imply lower-bound combat exposure-induced healthcare costs of $1.04 billion per year for prescription painkiller abuse and $470 million per year for heroin use.

Comparing the effects of decreasing prescription opioid shipments and the release of an abuse deterrent OxyContin formulation on opioid overdose fatalities in WV: an interrupted time series study

IntroductionThe 2010 release of an abuse deterrent formulation (ADF) of OxyContin, a brand name prescription opioid, has been cited as a major driver for the reduction in prescription drug misuse and the associated increasing illicit opioid use and overdose rates. However, studies of this topic often do not account for changes in supplies of other prescription opioids that were widely prescribed before and after the ADF OxyContin release, including generic oxycodone formulations and hydrocodone. We therefore sought to compare the impact of the ADF OxyContin release to that of decreasing prescription opioid supplies in West Virginia (WV).MethodsOpioid tablet shipment and overdose data were extracted from The Washington Post ARCOS (2006–2014) and the WV Forensic Drug Database (2005–2020), respectively. Locally estimated scatterplot smoothing (LOESS) was used to estimate the point when shipments of prescription opioids to WV began decreasing, measured via dosage units and morphine milligram equivalents (MMEs). Interrupted time series analysis (ITSA) was used to compare the impact LOESS-identified prescription supply changes and the ADF OxyContin release had on prescription (oxycodone and hydrocodone) and illicit (heroin, fentanyl, and fentanyl analogues) opioid overdose deaths in WV. Model fit was compared using Akaike Information Criteria (AIC).ResultsThe majority of opioid tablets shipped to WV from 2006 to 2014 were generic oxycodone or hydrocodone, not OxyContin. After accounting for a 6-month lag from ITSA models using the LOESS-identified change in prescription opioid shipments measured via dosage units (2011 Q3) resulted in the lowest AIC for both prescription (AIC = -188.6) and illicit opioid-involved overdoses (AIC = -189.4), indicating this intervention start date resulted in the preferred model. The second lowest AIC was for models using the ADF OxyContin release as an intervention start date.DiscussionWe found that illicit opioid overdoses in WV began increasing closer to when prescription opioid shipments to the state began decreasing, not when the ADF OxyContin release occurred. Similarly, the majority of opioid tablets shipped to the state for 2006–2014 were generic oxycodone or hydrocodone. This may indicate that diminishing prescription supplies had a larger impact on opioid overdose patterns than the ADF OxyContin release in WV.

'You Can Die With Me But I Won't Let You Live With Me', Exploring Social Influences on the Continuation of Heroin Use in Men Who Use Heroin.

Heroin is a substance with a unique social profile in that it is commonly used by individuals alone but there is a paucity of qualitative research exploring how social influences impact the continuation of heroin use, particularly when people are trying to stop using heroin. This study explored social determinants which influence the continuation of heroin use in males in UK community treatment who use illicit heroin alongside opioid replacement therapy. Participants were self-selecting from an initial purposively recruited sample. Using Janis (1972) 8 symptoms of Groupthink as an a priori framework for analysis, the study method utilised qualitative interviews with fourteen males. The discussions were digitally-recorded, transcribed verbatim, and analysed thematically. Contrasting with the evidence base, the sample included people who transitioned from recreational drug use to dependent heroin use without experiencing trauma of any kind. Far from becoming socially isolated when actively using heroin, interviews identified a shift in social networks from networks built on shared moments to networks underpinned by transactional exchange. Components of Groupthink were identified when participants described belonging to heroin using networks and continued to use heroin whilst trying to abstain though individual accountability was central to the decision to continue to use heroin. The conflict between the individual goal of abstinence and the group goal of continuation suggests that social network interventions could be more successful if delivered to cohorts of people who buy heroin together.

Deep learning-assisted multicolor fluorescent probes for image and spectral dual-modal identification of illicit drugs

llicit drug detection is an important part of drug problem management, and existing detection strategies suffer from inefficiency and narrow scope of application, which cannot fully meet the needs of practical work. Here, a multi-color fluorescent carbon dots was synthesized in one step and used as probes for the fluorescence sensing detection of three habitual illicit drugs, heroin, ketamine and methamphetamine. The fluorescence response results were recorded in the form of image fixation and spectral detection, which contained the subtle fingerprint information of these illicit drugs. Further, a multi-modal detector based on multi-task deep learning was constructed to achieve qualitative and semi-quantitative illicit drug detection, with accuracies of 98.4 % and 84.4 % for image and 99.9 % and 99.6 % for spectral, respectively, and a broad detection range from 1 ng/mL to 1 mg/mL. The process showed that deep learning significantly enhanced the detection sensitivity and range of fluorescent probes, and the dual-modal image-spectrum recognition met the practical needs of illicit drug on-site fast detection and accurate analysis, providing a new technical solution for illicit drug detection.

In silico characterization of ligand-receptor interactions for U-47700, N,N-didesmethyl-U-47700, U-50488 at mu- and kappa-opioid receptors.

The increasing misuse of novel synthetic opioids (NSOs) represents a serious public health concern. In this regard, U-47700 (trans-3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide) and related "U-compounds" emerged on recreational drug markets as synthetic substitutes for illicit heroin and constituents of counterfeit pain medications. While the pharmacology of U-compounds has been investigated using in vitro and in vivo methods, there is still a lack of understanding about the details of ligand-receptor interactions at the molecular level. To this end, we have developed a molecular modeling protocol based on docking and molecular dynamics simulations to assess the nature of ligand-receptor interactions for U-47700, N,N-didesmethyl U-47700, and U-50488 at the mu-opioid receptor (MOR) and kappa-opioid receptor (KOR). The evaluation of ligand-receptor and ligand-receptor-membrane interaction energies enabled the identification of subtle conformational shifts in the receptors induced by ligand binding. Interestingly, the removal of two key methyl groups from U-47700, to form N,N-didesmethyl U-47700, caused a loss of hydrogen bond contact with tryptophan (Trp)229, which may underlie the lower interaction energy and reduced MOR affinity for the compound. Taken together, our results are consistent with the reported biological findings for U-compounds and provide a molecular basis for the MOR selectivity of U-47700 and KOR selectivity of U-50488.

Festivals following the easing of COVID-19 restrictions: Prevalence of new psychoactive substances and illicit drugs

The market for illicit drugs and new psychoactive substances (NPS) has grown significantly and people attending festivals have been identified as being at high risk (high extent and frequency of substance use). Traditional public health surveillance data sources have limitations (high costs, long implementation times, and ethical issues) and wastewater-based epidemiology (WBE) can cost-effectively support surveillance efforts. Influent wastewater samples were analyzed for NPS and illicit drug consumption collected during New Year period (from 29-Dec-2021 to 4-Jan-2022) and a summer Festival (from 29-June-2022 to 12-July-2022) in a large city in Spain. Samples were analyzed for phenethylamines, cathinones, opioids, benzodiazepines, plant-based NPS, dissociatives, and the illicit drugs methamphetamine, MDA, MDMA, ketamine, heroin, cocaine, and pseudoephedrine by liquid chromatography mass spectrometry. High consumption rates of specific NPS and established illicit drugs were identified at the peak of each event. Furthermore, a dynamic change in NPS use (presence and absence of substances) was detected over a period of six months. Eleven NPS, including synthetic cathinones, benzodiazepines, plant-based NPS and dissociatives, and seven illicit drugs were found across both the New Year and summer Festival. Statistically significant differences (p < 0.05) were seen for 3-MMC (New Year vs summer Festival), eutylone (New Year vs summer Festival), cocaine (summer Festival vs normal week and summer Festival vs New Year), MDMA (New Year vs normal week and summer Festival vs normal week), heroin (summer Festival vs New Year) and pseudoephedrine (summer Festival vs New Year). This WBE study assessed the prevalence of NPS and illicit drugs at festivals following the reduction of the COVID-19 pandemic restrictions highlighting the high use of specific substances at the peak of each event. This approach identified in a cost-effective and timely manner without any ethical issues the most used drugs and changes in use patterns and, thus, can complement public health information.

Using wastewater-based epidemiology to evaluate the relative scale of use of opioids

Wastewater analysis (WWA) has been used as a tool to monitor population drug use, both pharmaceutical and illicit, for over 15 years. Policymakers, law enforcement and treatment services may use WWA-derived data to seek an objective understanding of the extent of drug use in specific areas. Therefore, wastewater data should best be reported in a meaningful form to allow those that are not experts in the field to compare the scale within and between drug classes. Excreted drug loads quantified in wastewater describe the mass of drug present in the sewer. Normalisation for wastewater flow and population is standard practice and critical for comparing drug loads between different catchments and indicates a transition to an epidemiological approach (wastewater-based epidemiology (WBE)). A further consideration is necessary to accurately compare the measured level of one drug to another. The standard dose of a drug taken to elicit a therapeutic effect will vary, with some compounds requiring microgram amounts, while others are administered in the gram range. When WBE data is expressed with units representing excreted or consumed loads without considering dose amounts, the scale of drug use when comparing multiple compounds becomes distorted. To demonstrate the utility and significance of including known excretion rates, potency and typical dose amounts into back-calculations of the measured drug load, this paper compares the levels of 5 prescribed (codeine, morphine, oxycodone, fentanyl and methadone) and 1 illicit (heroin) opioid from South Australian wastewater. The data is presented at each stage of the back-calculation starting with the total mass load measured, to consumed amounts factoring in excretion rates and finally the number of doses the load equates to. This is the first paper to describe the levels of 6 opioids measured in wastewater over a 4-year period in South Australia that demonstrate the relative scale of use.

Associations of alternative cannabis product use and poly-use with subsequent illicit drug use initiation during adolescence.

Specific cannabis products may differentially increase risk of initiating non-cannabis illicit drug use during adolescence. To determine whether ever- and poly-use of smoked, vaporized, edible, concentrate, or blunt cannabis products are associated with subsequent initiation of non-cannabis illicit drug use. High school students from Los Angeles completed in-classroom surveys. The analytic sample (N = 2163; 53.9% female; 43.5% Hispanic/Latino;baselineM age = 17.1years) included students who reported never using illicit drugs at baseline (spring, 11th grade) and provided data at follow-up (fall and spring, 12th grade). Logistic regression models assessed associations between use of smoked, vaporized, edible, concentrate, and blunt cannabis at baseline (yes/no for each product) and any non-cannabis illicit drug use initiation-including cocaine, methamphetamine, psychedelics, ecstasy, heroin, prescription opioids, or benzodiazepines-at follow-up. Among those who never usednon-cannabis illicit drugs at baseline, ever cannabis use varied by cannabis product (smoked = 25.8%, edible = 17.5%, vaporized = 8.4%, concentrates = 3.9%, and blunts = 18.2%) and patterns of use (single product use = 8.2% and poly-productuse = 21.8%). After adjustment for baseline covariates, odds of illicit drug use at follow-up were largest for baseline ever users of concentrates (aOR [95% CI] = 5.74[3.16-10.43]), followed by vaporized (aOR [95% CI] = 3.11 [2.41-4.01]), edibles (aOR [95% CI] = 3.43 [2.32-5.08]), blunts (aOR [95% CI] = 2.66[1.60-4.41]), and smoked (aOR [95% CI] = 2.57 [1.64-4.02]) cannabis. Ever use of a single product (aOR [95% CI] = 2.34 [1.26-4.34]) or 2 + products (aOR [95% CI] = 3.82 [2.73-5.35]) were also associated with greater odds of illicit drug initiation. For each of five different cannabis products, cannabis use was associated with greater odds of subsequent illicit drug use initiation, especially for cannabis concentrate and poly-product use.

Les enjeux de la cardiologie de demain : le livre blanc du CNP cardiovasculaire

Psychoactive drugs, including illicit drugs, are associated with an increased rate of cardiovascular events. The prevalence and outcome of patients using these drugs at the time of admission to an intensive cardiac care unit is unknown.To assess the prevalence of psychoactive drugs detected in consecutive patients hospitalized in an intensive cardiac care unit for an acute cardiovascular event.This is a nationwide prospective multicentre study, involving 39 centres throughout France, including all consecutive patients hospitalized in an intensive cardiac care unit within 2 weeks. Psychoactive drug use will be assessed systematically by urine drug assay within 2 hours of intensive cardiac care unit admission, to detect illicit (cannabinoids, cocaine, amphetamines, ecstasy, heroin and other opioids) and non-illicit (barbiturates, benzodiazepines, tricyclic antidepressants, methadone and buprenorphine) psychoactive drugs. Smoking will be investigated systematically by exhaled carbon monoxide measurement, and alcohol consumption using a standardized questionnaire. In-hospital major adverse events, including death, resuscitated cardiac arrest and cardiogenic shock, will be recorded. After discharge, all-cause death and major adverse cardiovascular events will be recorded systematically and adjudicated at 12 months of follow-up.The primary outcome will be the prevalence of psychoactive drugs detected by systematic screening among all patients hospitalized in an intensive cardiac care unit. The in-hospital major adverse events will be analysed according to the presence or absence of detected psychoactive drugs. Subgroup analysis stratified by initial clinical presentation and type of psychoactive drug will be performed.This is the first prospective multicentre study to assess the prevalence of psychoactive drugs detected by systematic screening in consecutive patients hospitalized for acute cardiovascular events.

Prevalence of psychoactive drug use in patients hospitalized for acute cardiac events: Rationale and design of the ADDICT-ICCU trial, from the Emergency and Acute Cardiovascular Care Working Group and the National College of Cardiologists in Training of the French Society of Cardiology

Psychoactive drugs, including illicit drugs, are associated with an increased rate of cardiovascular events. The prevalence and outcome of patients using these drugs at the time of admission to an intensive cardiac care unit is unknown. To assess the prevalence of psychoactive drugs detected in consecutive patients hospitalized in an intensive cardiac care unit for an acute cardiovascular event. This is a nationwide prospective multicentre study, involving 39 centres throughout France, including all consecutive patients hospitalized in an intensive cardiac care unit within 2weeks. Psychoactive drug use will be assessed systematically by urine drug assay within 2hours of intensive cardiac care unit admission, to detect illicit (cannabinoids, cocaine, amphetamines, ecstasy, heroin and other opioids) and non-illicit (barbiturates, benzodiazepines, tricyclic antidepressants, methadone and buprenorphine) psychoactive drugs. Smoking will be investigated systematically by exhaled carbon monoxide measurement, and alcohol consumption using a standardized questionnaire. In-hospital major adverse events, including death, resuscitated cardiac arrest and cardiogenic shock, will be recorded. After discharge, all-cause death and major adverse cardiovascular events will be recorded systematically and adjudicated at 12months of follow-up. The primary outcome will be the prevalence of psychoactive drugs detected by systematic screening among all patients hospitalized in an intensive cardiac care unit. The in-hospital major adverse events will be analysed according to the presence or absence of detected psychoactive drugs. Subgroup analysis stratified by initial clinical presentation and type of psychoactive drug will be performed. This is the first prospective multicentre study to assess the prevalence of psychoactive drugs detected by systematic screening in consecutive patients hospitalized for acute cardiovascular events.

Toxicity of heroin laced with synthetic opioid β-U10 and etizolam

Illicit heroin can be substituted or adulterated with New Psychoactive Substances (NPS) including highly potent fentanyl-type substances or other opioid-like compounds to counteract low-purity supply. The addition of unknown NPS to the heroin supply poses an additional risk of overdose and death. In 2020, the Emerging Drug Network of Australia VIC (EDNAV) study was funded to monitor drug related harm in individuals attending emergency departments (ED) at major hospitals within Victoria. In September 2020, a previously unreported NPS, β-U10 (2-napthyl-U-47700), was detected in discarded drug paraphernalia samples collected during a pilot study of an early warning system for illicit drug use in Melbourne, Australia. Subsequently, blood samples of EDNAV project individuals with positive heroin detections were analysed for β-U10, in addition to NPS and traditional illicit drugs. After liquid-liquid extraction, blood samples underwent extensive toxicological analysis via targeted liquid-chromatography tandem mass spectrometry (LC-MS/MS) and untargeted screening via high-resolution quadrupole time-of-flight mass spectrometry (LC-QTOF). Confirmation of β-U10 concentrations were measured via LC-MS/MS using certified reference material. In total, seven cases were found to contain synthetic opioid β-U10. Six samples were collected in October 2020, with the remaining case detected more than a year later in December 2021. Measured β-U10 concentrations ranged from 0.01 to 22 ng/mL (median 3 ng/mL). All cases also contained methylamphetamine and etizolam. Morphine was detected in all cases along with 6-acetylmorphine in three of these cases. Other drugs included diphenhydramine, diazepam, doxylamine, gamma-hydroxybutyrate, MDMA, methadone, and mitragynine. The average age was 37 and ranged from 20 to 52 years of age. All individuals presented to ED with varying levels of sedation (Glascow Coma Scale 3–14, median 9) and recovered with supportive care (median stay 6.8 hours). Two cases showed a positive response to naloxone. The Poisons Severity Score for one case was 3, with 4 cases assessed as level 2. The pharmacological activity of β-U10 is largely unknown. β-U10 was first published by the Upjohn Company in the 1970's and is a structural analogue of the widely reported NPS U-47700, which has approximately seven times greater affinity to the μ-opioid receptor than morphine (Cheney. Journal of Medicinal Chemistry 1985;28:1853–1864). U-47700 has been utilised recreationally for its sedative properties in addition to positive effect on mood. The co-ingestion of other sedatives and respiratory depressants, including opioids and the NPS benzodiazepine etizolam in each of these reported cases precludes definitive conclusions regarding the clinical effect of β-U10. Additional studies that examined heroin supply at the time found the addition of β-U10 was associated with a decrease in heroin purity. The detection of β-U10 in one case 12 months following the previous detection may indicate the drug re-supply of the adulterated mixture in Australia. The detection of β-U10 has also informed toxicological investigations into heroin-related deaths that occurred during the same time-period. The consumption of adulterated illicit substances by unsuspecting individuals with unknown compounds such as β-U10, particularly in conjunction with other opioids and CNS depressants such as etizolam, is an alarming trend and poses a significant public health risk.

Monitoring of changes in illicit drugs, alcohol, and nicotine consumption during Ramadan via wastewater analysis.

Illicit drug use is a global problem imposing social, economic, and health burdens on society. Wastewater-based epidemiology is an approach based on calculating the consumption of substances in the target population by analyzing the concentrations of human metabolic excretion products of licit and illicit substances in wastewater. This study estimated the changes in illicit drugs (cocaine, amphetamine, methamphetamine, ecstasy (3,4-Methylenedioxymethamphetamine), heroin, and marijuana (THC)), alcohol, and nicotine consumption in Adana Province during Ramadan compared to normal periods using wastewater-based epidemiology. An overall decrease was observed during the Ramadan Period, most strongly for ecstasy (29%) followed by heroin (19%). For cocaine, the variation was the slightest (8.6%). The differences were statistically significant for ecstasy, heroin, nicotine, and alcohol but not for cocaine, amphetamine, methamphetamine, and marijuana. This study is the first to show changes in the use of illicit drugs, alcohol, and nicotine under the influence of religious beliefs. In addition, there is limited data about illicit drugs, alcohol and nicotine abusers/users in Ramadan. This study provides information on the literature on this subject.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s11356-022-22016-w.

Nasal administration of diacetylmorphine improved the adherence in a patient receiving heroin-assisted treatment

BackgroundTraditional heroin-assisted treatment in Switzerland consists of oral and injectable diacetylmorphine (pharmaceutical heroin) administration. To date, no suitable treatment option is available for patients who crave rapid onset (“rush”) but are either unable to inject or primarily sniff or inhale illicit heroin. We present a patient who successfully switched to intranasal heroin-assisted treatment following several unsuccessful treatment attempts.Case presentationA 29-year-old male with severe opioid use disorder, injection substance use, and concomitant cocaine use, previously prescribed slow-release oral morphine, was started on intravenous diacetylmorphine. Due to complications and harms associated with intravenous injections, nasal diacetylmorphine was prescribed. With this novel route of administration, the patient who had previously been unable to adhere to other OAT options remained in treatment. Health outcomes improved by reduction of injection-related harms, increased adherence to the heroin-assisted treatment regimen, and increased collaboration with the therapeutic staff.ConclusionsNasal heroin-assisted treatment can be a feasible therapeutic option for individuals with severe opioid use disorder who crave the fast onset of effect of diacetylmorphine but are unable to inject intravenously.

Development and Characterization of Fluorescent Chemical Tools to Study Human Carboxylesterase 2 (CES2)

The two major human carboxylesterases (CESs), CES1 and CES2 play a key role in the hydrolysis of xenobiotic esters including aspirin, methylphenidate (Ritalin), and the illicit narcotics cocaine and heroin. CES‐mediated metabolism of ester containing drugs can result in their activation or deactivation and enhance clearance. Despite the established role of CESs in drug metabolism, few techniques exist to study their activity in live cells. Fluorescent chemical tools have been developed to be able to expand the methods used to study CES activity, however, many existing fluorescent chemical tools are not sufficiently characterized to be able to confidently study CES activity in live cells. This is particularly true for CES2 where substrate specificity can overlap with other cellular esterases. To address this issue, we report the design and synthesis of new fluorescent chemical tools to study CES2. We subsequently evaluated their specificity for CES2 over CES1 in vitro and in live cells using small molecule inhibitors and shRNA. Overall, our studies resulted in a full characterization of fluorescent chemical tools for studying human CESs and will lead to improved methods for studying the role of CESs in human health and drug metabolism.

What lessons from Europe's experience could be applied in the United States in response to the opioid addiction and overdose crisis?

What lessons from Europe's experience could be applied in the United States in response to the opioid addiction and overdose crisis?

Heroin and fentanyl overdose deaths among cases age 50+ in the National Poison Data System, 2015–2020

Context Illicit opioid use and heroin treatment admissions among individuals age 50+ have increased. Little research has, however, examined correlates of illicit opioid overdose deaths in this age group before or during the COVID-19 pandemic or the healthcare services used in these cases. Methods The sample included illicit opioid (heroin, fentanyl, or other synthetic, nonpharmaceutical opioids) poisoning cases age 50+ (N = 5576) in the National Poison Data System (NPDS), 2015–2020. Using descriptive statistics and logistic regression models, we report changes in overdose death rates during the study period and associations of death with healthcare service use, naloxone administration, and clinical and demographic characteristics. Results The 6-year average overdose death rate from illicit opioids among those age 50+ was 2.9%, increasing from 1.4% in 2015 to 4.0% in 2019 and 3.6% in 2020. Logistic regression results showed that exposure year was not a significant factor in the odds of overdose death; however, odds were significantly higher among cases that were not managed at any healthcare facility (HCF) (adjusted odds ratio [AOR] = 4.60, 95% confidence interval [CI] = 3.19–6.63) and lower among those who received naloxone therapy (AOR = 0.64, 95% CI = 0.45–0.92). The odds of death were also higher among cases involving exposure at own or another’s home and co-use of prescription opioids, alcohol, and other illicit drugs. Conclusions Although the NPDS did not show increases in illicit opioid overdose death rates among cases age 50+ in 2020 compared to 2019, overdose deaths were greater among cases that were not managed at HCF and did not receive naloxone therapy. Many appear to have died before they received any intervention to prevent death. Improved access to healthcare services and social support and access to naloxone therapy for older adults with opioid use problems are needed.

Non‐opioid veterinary sedative xylazine implicated in OD deaths

Xylazine, a veterinary drug for sedation, is not approved by the Food and Drug Administration (FDA) for humans. A central nervous system depressant, it has been used as a toxic adulterant in illicit fentanyl and heroin, and it may increase the risk of fatal overdose. It's not an opioid, so naloxone won't reverse its effects. Now, several states are reporting the presence of xylazine in drug overdose deaths.

Compulsivity and impulsivity in opioid dependence

ObjectiveChronic exposure to illicit opioid drugs can cause serious health and social problems. However, less is known about the differential effect of various opioid treatments, such as methadone and buprenorphine, on neurocognitive domains such as compulsivity and impulsivity, despite their relevance to the treatment of opioid dependence. MethodsA total of 186 participants were recruited with a cross-sectional design: i) illicit heroin users (n = 27), ii) former heroin users stabilized on methadone MMT (n = 48), iii) a buprenorphine maintenance treatment (BMT) group (n = 18), iv) an abstinent (ABS) group with a history of opioid dependence who were previously stabilized on MMT or BMT (n = 29) and v) healthy controls (HC) (n = 64). We used the Intra-Extra Dimensional Shift (IED) and Cambridge Gambling Task (CGT) paradigms for measuring compulsivity and impulsivity constructs respectively. ResultsHeightened compulsivity persisted in the heroin, buprenorphine and abstinent groups. Heroin, methadone and buprenorphine groups exhibited impaired behavioral responses to feedback, consisting of increased deliberation time and poorer risk adjustment. Higher compulsivity measures were negatively associated with opioid dose which may reflect sedation effects. ConclusionsOur results suggest that compulsivity and impulsivity are core neurocognitive dimensions for opioid dependence which differ in their presentation according to the stage of treatment. Participants taking higher morphine equivalent doses performed better in compulsivity measures. These findings have implications for the treatment of opioid dependence and longitudinal studies are warranted.

A Data-Driven Mathematical Model of the Heroin and Fentanyl Epidemic in Tennessee.

Opioid addiction represents a major national health issue spanning decades. In recent years, prescription opioid use disorder has increasingly led to heroin and fentanyl use, with subsequent increases in mortality rates due to overdose. In this paper, we present a mechanistic, epidemic model for prescription opioid addiction and illicit heroin or fentanyl addiction which aims to better understand and predict the dynamics between these two stages of opioid use disorder. Our model aims to be both parsimonious and robust: as a system of five differential equations it is appropriate for use in theory advancement and yet it remains powerful enough to capture state-level data from Tennessee for the period 2013-2018. A key finding from our data-driven analysis is that, in the face of changing policy around prescription opioids, heroin and fentanyl are now the driving force behind the Tennessee opioid epidemic. Model projections suggest that both addictions and overdoses related to heroin and fentanyl will continue to increase in the next few years (2020-2022), even as addiction to prescription drugs continues to fall. Finally, management strategy analysis suggests that in the changing face of the epidemic, the most successful approach will target availability of treatment with subsequent monitoring of stably recovered individuals to see that they do not relapse, coincident with direct efforts to decrease opioid overdose fatalities (e.g., further availability of Naloxone).