FDA Issues Warning About 'Gas Station Heroin'.

The highly addictive dietary supplement mimics opioid effects.

Long-access heroin self-administration induces region specific reduction of grey matter volume and microglia reactivity in the rat.

In opioid use disorder (OUD) patients, a decrease in brain grey matter volume (GMV) has been reported. It is unclear whether this is the consequence of prolonged exposure to opioids or is a predisposing causal factor in OUD development. To investigate this, we conducted a structural MRI longitudinal study in NIH Heterogeneous Stock rats exposed to heroin self-administration and age-matched naïve controls housed in the same controlled environment. Structural MRI scans were acquired before (MRI1) and after (MRI2) a prolonged period of long access heroin self-administration resulting in escalation of drug intake. Heroin intake resulted in reduced GMV in various cortical and sub-cortical brain regions. In drug-naïve controls no difference was found between MRI1 and MRI2. Notably, the degree of GMV reduction in the medial prefrontal cortex (mPFC) and the insula positively correlated with the amount of heroin consumed and the escalation of heroin use. In a preliminary gene expression analysis, we identified a number of transcripts linked to immune response and neuroinflammation. This prompted us to hypothesize a link between changes in microglia homeostasis and loss of GMV. For this reason, we analyzed the number and morphology of microglial cells in the mPFC and insula. The number of neurons and their morphology was also evaluated. The primary motor cortex, where no GMV change was observed, was used as negative control. We found no differences in the number of neurons and microglia cells following heroin. However, in the same regions where reduced GMV was detected, we observed a shift towards a rounder shape and size reduction in microglia, suggestive of their homeostatic change towards a reactive state. Altogether these findings suggest that escalation of heroin intake correlates with loss of GMV in specific brain regions and that this phenomenon is linked to changes in microglial morphology.

High Interest in Injectable Opioid Agonist Treatment With Hydromorphone Among Urban Syringe Service Program Participants.

BACKGROUND: Injectable opioid agonist treatment with hydromorphone (iOAT-H) is effective for persons who inject drugs (PWID) with opioid use disorder (OUD) but remains unavailable in the United States. Our objective was to determine interest in iOAT-H among syringe services program (SSP) participants. METHODS: We recruited PWID with OUD from SSPs in New York City. Interest in iOAT-H was assessed on a 4-point scale. We compared participants who were and were not interested in iOAT-H regarding sociodemographic characteristics and self-reported variables (past 30 days): heroin use, public injection practices, and participation in illegal activity other than drug possession. Participants reported their preferred OUD treatment and reasons for these preferences. RESULTS: Of 108 participants, most were male (69%), Hispanic (68%), and median age was 42 years. The median number of prior OUD treatment episodes was 6 (interquartile range: 2-12). Most (65%) were interested in iOAT-H. Interested participants (vs not interested) reported, over the prior 30 days, greater heroin use days (mean, 26.4 vs 22.3), injecting in public more times (median, 15 vs 6), and a higher percentage having participated in illegal activity (40% vs 16%). Preferences for OUD treatment were: iOAT-H (43%), methadone (39%), and buprenorphine (9%). Participants who preferred iOAT-H to conventional OUD treatments reported preferring injection as a route of administration and that available OUD treatments helped them insufficiently. CONCLUSIONS: SSP participants with OUD reported high interest in iOAT-H. Participants had attempted conventional treatments but still used heroin almost daily. We identified PWID at risk for opioid-related harms who potentially could benefit from iOAT-H.

Brain-derived neurotrophic factor serum levels as a candidate biomarker for withdrawal in crack heroin dependence.

BACKGROUND: Crack heroin is a novel opiate derivative with highly addictive properties and unfamiliar health consequences. It causes a variety of brain dysfunctions that are mediated by neurochemical alterations and abnormal neuroplasticity. Brain-derived neurotrophic factor (BDNF) is a widely recognized biological marker implicated in the neuropathology of substance use during substance use disorder and withdrawal. Its involvement can significantly contribute to the severity of withdrawal symptoms. Hence, this study aimed to evaluate BDNF levels in crack heroin users before and after withdrawal. METHODS: In this cross-sectional study, 148 male participants were recruited and divided into two groups: persons with crack heroin use disorder (n = 74) and the controls (n = 74). The BDNF serum levels were measured in both crack heroin users and control groups upon hospitalization and again after twenty-one days of withdrawal using the enzyme-linked immunosorbent assay. RESULTS: The results demonstrated that BDNF levels in persons with crack heroin use disorder upon admission were significantly lower than the levels observed upon discharge and in the control group (p < 0.05). Additionally, a significant difference in BDNF levels was found between persons with crack heroin use disorder at admission and discharge (p = 0.038). Furthermore, BDNF levels showed an inverse correlation with the daily dose of substance use (r= -0.420, p = 0.03) and the duration of crack heroin use (r= -0.235, p = 0.001). CONCLUSIONS: A progressive increment in BDNF levels during early detoxification is associated with the daily amount of substance use and the duration of substance use. Our findings suggest that changes in BDNF serum levels during crack heroin use disorder and withdrawal could serve as potential biomarkers for assessing the intensity of withdrawal symptoms and substance use-related behaviors.

Correlates of Stimulant Use among People Who Use Heroin Undergoing Treatment in Out-Patient Facilities in France, 2010-2020.

Background: Polydrug use has been implicated in driving a "fourth wave" of the overdose crisis in North America, specifically through concurrent use of stimulants and opioids, especially fentanyl. In France, however, heroin has historically been and remains the easiest-to-access opioid, accounting for most drug treatment demand. Whether similar polydrug use is increasing in Western Europe remains understudied, despite severe health implications and potential inadequate public health responses.Methods: We take advantage of a nation-wide dataset containing information on all patients serviced in treatment centers in France from 2010 to 2020. We conduct Poisson regression to determine the main predictors of stimulant use among people who use heroin (PWUH) and opioids (PWUO) generally.Results: Heroin remains the primary opioid within drug treatment in France. A decreasing number of out-patients seeking treatment for heroin use has been accompanied by an increasing trend of stimulant use over time, most commonly with powder cocaine. Our results suggest a significant increase of crack cocaine use among the most vulnerable PWUH. Concurrent use of stimulants among PWUH was positively associated with use of alcohol, cannabis, unprescribed psychotropics and hallucinogens, and negatively with tobacco. Similar results were found for all in-treatment PWUO.Conclusions: Our results uncover heterogeneity in the profiles of PWUH that should be fully acknowledged to ensure better efficiency in substance use clinical practices and policy, while simultaneously drawing attention to trends in concurrent opioid-stimulant use outside North America. We advocate for an extension of the generalized risk framework and its implementation in prevention programs.

Characterizing prescription opioid, heroin, and fentanyl initiation trajectories: A qualitative study.

We understand the current crisis of overdose deaths to be driven by widespread opioid use, characterized by distinct 'waves' of drug use. The first wave was driven by prescription opioids, the second by heroin, and the third by illicit, non-pharmaceutical fentanyl and fentanyl analogues (henceforth, fentanyl). The purpose of this study is to describe opioid initiation within each of the three waves from the perspective of people who use illicit opioids, with a focus on emerging pathways into fentanyl use. The authors recruited sixty people reporting past-30-day illicit opioid use in Dayton, Ohio. Participants completed a brief survey and a semi-structured in-depth qualitative interview, conducted from March to November 2020 with a total of 13 in-person and 47 virtual interviews. The qualitative interviews were transcribed in their entirety and analyzed thematically using NVivo 12. We noted supply-side changes as influencing trajectories in all three waves. However, we also noted differences in the experiences of prescription opioid and heroin initiation, with these trajectories influenced by pharmacological effects, pain management, curiosity, intergenerational use, pricing, and peers. In comparison, most participants were unaware that they were initiating fentanyl, and many reported overdosing with their first use of fentanyl. We identified a trajectory into fentanyl with limited to no prior heroin use among a few participants. The increased risk of overdose with initiation into fentanyl use further emphasizes the need for an expansion of naloxone distribution and the implementation of more comprehensive measures, such as overdose prevention centers, drug testing, and a safer supply. Further research on the dynamics of the ongoing overdose death crisis in the era of fentanyl and the 4th wave of the overdose crisis is critical in developing responsive prevention and intervention strategies.

Cold nociception as a measure of hyperalgesia during spontaneous heroin withdrawal in mice.

Opioids are powerful analgesic drugs that are used clinically to treat pain. However, chronic opioid use causes compensatory neuroadaptations that result in greater pain sensitivity during withdrawal, known as opioid withdrawal-induced hyperalgesia (OWIH). Cold nociception tests are commonly used in humans, but preclinical studies often use mechanical and heat stimuli to measure OWIH. Thus, further characterization of cold nociception stimuli is needed in preclinical models. We assessed three cold nociception tests-thermal gradient ring (5-30 °C, 5-50 °C, 15-40 °C, and 25-50 °C), dynamic cold plate (4 °C to -1 °C at -1 °C/min, -1 °C to 4 °C at +1 °C/min), and stable cold plate (10 °C, 6 °C, and 2 °C)-to measure hyperalgesia in a mouse protocol of heroin dependence. On the thermal gradient ring, mice in the heroin withdrawal group preferred warmer temperatures, and the results depended on the ring's temperature range. On the dynamic cold plate, heroin withdrawal increased the number of nociceptive responses, with a temperature ramp from 4 °C to -1 °C yielding the largest response. On the stable cold plate, heroin withdrawal increased the number of nociceptive responses, and a plate temperature of 2 °C yielded the most significant increase in responses. Among the three tests, the stable cold plate elicited the most robust change in behavior between heroin-dependent and nondependent mice and had the highest throughput. To pharmacologically characterize the stable cold plate test, we used µ-opioid and non-opioid receptor-targeting drugs that have been previously shown to reverse OWIH in mechanical and heat nociception assays. The full µ-opioid receptor agonist methadone and µ-opioid receptor partial agonist buprenorphine decreased OWIH, whereas the preferential µ-opioid receptor antagonist naltrexone increased OWIH. Two N-methyl-d-aspartate receptor antagonists (ketamine, MK-801), a corticotropin-releasing factor 1 receptor antagonist (R121919), a ß2-adrenergic receptor antagonist (butoxamine), an α2-adrenergic receptor agonist (lofexidine), and a 5-hydroxytryptamine-3 receptor antagonist (ondansetron) had no effect on OWIH. These data demonstrate that the stable cold plate at 2 °C yields a robust, reliable, and concise measure of OWIH that is sensitive to opioid agonists.

Blood Oxygenation and Heart Rate Changes After Diamorphine Intravenous Injection During Opioid Agonist Treatment for Outpatients With Heroin Dependence.

OBJECTIVES: More than 60 million people use opioids each year, and many countries have declared an opioid overdose crisis. Heroin, one of the most commonly used opioids, has depressant effects on autonomic functioning; however, few studies have been able to examine the effects of heroin or its pharmaceutically prepared equivalent, diamorphine, in human clinical populations. The present study examined heart rate and oxygen saturation in the minutes immediately after acute diamorphine administration in outpatients with heroin dependence. METHODS: The sample was a subset of participants (N = 36) in the German Project of Heroin Assisted Treatment of Opiate Dependent Patients Trial in Bonn, Germany. Patients were given 3 daily doses of intravenous diamorphine. Doses were determined on an individual basis by study physicians. Pulse oximetry was recorded at baseline and at 30-second intervals from 0 to 450 seconds after diamorphine administration. RESULTS: Heart rate was significantly higher than baseline at 30 seconds after diamorphine administration and significantly lower than baseline at 270 seconds onward. Oxygen saturation was significantly lower than baseline at 60 seconds onward. CONCLUSIONS: Results are consistent with other studies in which depressant effects of opioids were observed. Our findings suggest that even therapeutic doses of diamorphine may have rapid and significant-predominantly depressant-effects on oxygenation and heart rate in populations that frequently use opioids. Monitoring of potential adverse opioid effects would be beneficial even in populations presumed to have developed physiological tolerance.

Metabolic and functional substrates of impulsive decision-making in individuals with heroin addiction after prolonged methadone maintenance treatment.

Elevated impulsivity has been frequently reported in individuals with opioid addiction receiving methadone maintenance therapy (MMT), but the underlying neural mechanisms and cognitive subprocesses are not fully understood. We acquired functional magnetic resonance imaging (fMRI) data from 37 subjects with heroin addiction receiving long-term MMT and 33 healthy controls who performed a probabilistic reversal learning task, and measured their resting-state brain glucose using fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET). Subjects receiving MMT exhibited significantly elevated self-reported impulsivity, and computational modeling revealed a marked impulsive decision bias manifested as switching more frequently without available evidence. Moreover, this impulsive decision bias was associated with the dose and duration of methadone use, irrelevant to the duration of heroin use. During the task, the switch-related hypoactivation in the left rostral middle frontal gyrus was correlated with the impulsive decision bias while the function of reward sensitivity was intact in subjects receiving MMT. Using prior brain-wide receptor density data, we found that the highest variance of regional metabolic abnormalities was explained by the spatial distribution of µ-opioid receptors among 10 types of neurotransmitter receptors. Heightened impulsivity in individuals receiving prolonged MMT is manifested as atypical choice bias and noise in decision-making processes, which is further driven by deficits in top-down cognitive control, other than reward sensitivity. Our findings uncover multifaceted mechanisms underlying elevated impulsivity in subjects receiving MMT, which might provide insights for developing complementary therapies to improve retention during MMT.

Incidence of rhabdomyolysis occurrence in psychoactive substances intoxication: a systematic review and meta-analysis.

Rhabdomyolysis is a potentially life-threatening condition induced by diverse mechanisms including drugs and toxins. We aimed to investigate the incidence of rhabdomyolysis occurrence in intoxicated patients with psychoactive substances. In this review, three databases (PubMed, Scopus, Web of Science) and search engine (Google Scholar) were searched by various keywords. After the screening of retrieved documents, related data of included studies were extracted and analyzed with weighted mean difference (WMD) in random effect model. The highest incidence of rhabdomyolysis was observed in intoxication with heroin (57.2 [95% CI 22.6-91.8]), amphetamines (30.5 [95% CI 22.6-38.5]), and cocaine (26.6 [95% CI 11.1-42.1]). The pooled effect size for blood urea nitrogen (WMD = 8.78, p = 0.002), creatinine (WMD = 0.44, p < 0.001), and creatinine phosphokinase (WMD = 2590.9, p < 0.001) was high in patients with rhabdomyolysis compared to patients without rhabdomyolysis. Our results showed a high incidence of rhabdomyolysis induced by psychoactive substance intoxication in ICU patients when compared to total wards. Also, the incidence of rhabdomyolysis occurrence was high in ICU patients with heroin and amphetamine intoxication. Therefore, clinicians should anticipate this complication, monitor for rhabdomyolysis, and institute appropriate treatment protocols early in the patient's clinical course.

Toxic leukoencephalopathy versus delayed post-hypoxic leukoencephalopathy after oral morphine sulphate overdose.

Toxic leukoencephalopathy (TLE) is a rare pathology caused by various substances including opioids (notably heroin), immunosuppressants, chemotherapy agents, cocaine, alcohol and carbon monoxide. However, although heroin is metabolised by the body into morphine, there is a striking paucity in cases of primary oral morphine-induced TLE, especially in the adult population. We present the case of a man in his 40s admitted to hospital in respiratory depression with a Glasgow Coma Scale (GCS) score of 6 after taking an overdose of oral morphine sulphate. Following a complete recovery to baseline, he was then readmitted with an acute deterioration in his neurobehavioural condition. Initial investigations returned normal but MRI showed changes characteristic for TLE.In cases of opioid toxicity such as ours, TLE is difficult to differentiate from delayed post-hypoxic leukoencephalopathy, due to their similar clinical presentation, disease progression and radiological manifestation. We explore how clinicians can approach this diagnostic uncertainty.

Xylazine effects on opioid-induced brain hypoxia.

RATIONALE: Xylazine has emerged in recent years as an adulterant in an increasing number of opioid-positive overdose deaths in the United States. Although its exact role in opioid-induced overdose deaths is largely unknown, xylazine is known to depress vital functions and cause hypotension, bradycardia, hypothermia, and respiratory depression. OBJECTIVES: In this study, we examined the brain-specific hypothermic and hypoxic effects of xylazine and its mixtures with fentanyl and heroin in freely moving rats. RESULTS: In the temperature experiment, we found that intravenous xylazine at low, human-relevant doses (0.33, 1.0, 3.0 mg/kg) dose-dependently decreases locomotor activity and induces modest but prolonged brain and body hypothermia. In the electrochemical experiment, we found that xylazine at the same doses dose-dependently decreases nucleus accumbens oxygenation. In contrast to relatively weak and prolonged decreases induced by xylazine, intravenous fentanyl (20 µg/kg) and heroin (600 µg/kg) induce stronger biphasic brain oxygen responses, with the initial rapid and strong decrease, resulting from respiratory depression, followed by a slower, more prolonged increase reflecting a post-hypoxic compensatory phase, with fentanyl acting much quicker than heroin. The xylazine-fentanyl mixture eliminated the hyperoxic phase of oxygen response and prolonged brain hypoxia, suggesting xylazine-induced attenuation of the brain's compensatory mechanisms to counteract brain hypoxia. The xylazine-heroin mixture strongly potentiated the initial oxygen decrease, and the pattern lacked the hyperoxic portion of the biphasic oxygen response, suggesting more robust and prolonged brain hypoxia. CONCLUSIONS: These findings suggest that xylazine exacerbates the life-threatening effects of opioids, proposing worsened brain hypoxia as the mechanism contributing to xylazine-positive opioid-overdose deaths.

Transcriptional signatures of heroin intake and relapse throughout the brain reward circuitry in male mice.

Opioid use disorder (OUD) looms as one of the most severe medical crises facing society. More effective therapeutics will require a deeper understanding of molecular changes supporting drug-taking and relapse. Here, we develop a brain reward circuit-wide atlas of opioid-induced transcriptional regulation by combining RNA sequencing (RNA-seq) and heroin self-administration in male mice modeling multiple OUD-relevant conditions: acute heroin exposure, chronic heroin intake, context-induced drug-seeking following abstinence, and relapse. Bioinformatics analysis of this rich dataset identified numerous patterns of transcriptional regulation, with both region-specific and pan-circuit biological domains affected by heroin. Integration of RNA-seq data with OUD-relevant behavioral outcomes uncovered region-specific molecular changes and biological processes that predispose to OUD vulnerability. Comparisons with human OUD RNA-seq and genome-wide association study data revealed convergent molecular abnormalities and gene candidates with high therapeutic potential. These studies outline molecular reprogramming underlying OUD and provide a foundational resource for future investigations into mechanisms and treatment strategies.

Heroin and its metabolites: relevance to heroin use disorder.

Heroin is an opioid agonist commonly abused for its rewarding effects. Since its synthesis at the end of the nineteenth century, its popularity as a recreational drug has ebbed and flowed. In the last three decades, heroin use has increased again, and yet the pharmacology of heroin is still poorly understood. After entering the body, heroin is rapidly deacetylated to 6-monoacetylmorphine (6-MAM), which is then deacetylated to morphine. Thus, drug addiction literature has long settled on the notion that heroin is little more than a pro-drug. In contrast to these former views, we will argue for a more complex interplay among heroin and its active metabolites: 6-MAM, morphine, and morphine-6-glucuronide (M6G). In particular, we propose that the complex temporal pattern of heroin effects results from the sequential, only partially overlapping, actions not only of 6-MAM, morphine, and M6G, but also of heroin per se, which, therefore, should not be seen as a mere brain-delivery system for its active metabolites. We will first review the literature concerning the pharmacokinetics and pharmacodynamics of heroin and its metabolites, then examine their neural and behavioral effects, and finally discuss the possible implications of these data for a better understanding of opioid reward and heroin addiction. By so doing we hope to highlight research topics to be investigated by future clinical and pre-clinical studies.

Interest in treatment with injectable diacetylmorphine among people who use opioids in Baltimore City, Maryland (USA).

INTRODUCTION: Treatment for opioid use disorder (OUD) with diacetylmorphine is an evidence-based form of drug treatment, but it is not available in the United States (US). Better understanding acceptability of treatment with injectable diacetylmorphine among people who use opioids (PWUO) in the US may expedite future initiatives designed to engage persons in this form of treatment should it become available. The purpose of this research is to examine factors associated with interest in treatment with injectable diacetylmorphine among a sample of PWUO in the US. METHODS: Data are from a cross-sectional study of PWUO in Baltimore City, Maryland. Participants were given a brief description of treatment with injectable diacetylmorphine and then asked to rate their level of interest. We used Poisson regression with robust variance to assess factors associated with interest in treatment with injectable diacetylmorphine. RESULTS: The average age of participants was 48 years, 41% were women, and most (76%) identified as non-Hispanic, Black. The most commonly used substances were non-injection heroin (76%), opioid pain relievers (73%), and non-injection crack/cocaine (73%). Two-thirds of participants (68%) indicated interest in treatment with injectable diacetylmorphine. Factors significantly associated with interest in injectable diacetylmorphine treatment included: having at least a high school education (adjusted prevalence ratio [aPR]: 1.23; 95% confidence interval [CI]: 1.04-1.45), not having health insurance (aPR: 1.23; 95% CI: 1.06-1.44), having ever overdosed (aPR: 1.20; 95% CI: 1.01-1.42), and past utilization of medications for opioid use disorder (aPR: 1.22; 95% CI: 1.01-1.47). Recent non-injection cocaine use was inversely associated with interest in treatment with injectable diacetylmorphine (aPR 0.80; 95% CI: 0.68-0.94). CONCLUSION: The majority of participants reported interest in treatment with injectable diacetylmorphine. Given worsening trends in the addiction and overdose crisis in the US, treatment with injectable diacetylmorphine should be considered as another evidence-based option for treating OUD.KEY MESSAGESInterest in treatment with injectable diacetylmorphine was high among a sample of people who use opioids in the United States.Factors associated with increased interest in treatment with injectable diacetylmorphine included having at least a high school education, having ever overdosed, and not having health insurance.Past utilization of medications for opioid use disorder was associated with interest in treatment with injectable diacetylmorphine.

Heroin- and Fentanyl-Induced Respiratory Depression in a Rat Plethysmography Model: Potency, Tolerance, and Sex Differences.

The opioid overdose death toll in the United States is an ongoing public health crisis. We characterized the magnitude and duration of respiratory depression, the leading cause of death in opioid overdose cases, induced by heroin or fentanyl and the development of tolerance in male and female rats. We used whole-body plethysmography to first establish dose-response curves by recording breathing for 60 minutes post-intravenous opioid injection. We then tested the development of respiratory tolerance to acute heroin or fentanyl over several weeks and to chronic fentanyl with acute fentanyl or heroin challenge. Heroin and fentanyl each provoked dose-dependent respiratory depression. Heroin caused prolonged (45-60 minute) respiratory depression in female and male rats, characterized by decreased frequency, tidal volume, and minute ventilation and increased inspiratory time and apneic pause. Fentanyl produced similar changes with a shorter duration (10-15 minutes). High-dose heroin or fentanyl produced robust respiratory depression that was slightly more severe in females and, when given intermittently (acute doses 2 to 3 weeks apart), did not lead to tolerance. In contrast, chronic fentanyl delivered with an osmotic minipump resulted in tolerance to acute fentanyl and heroin, characterized by a shorter duration of respiratory depression. This effect persisted during withdrawal in males only. Our model and experimental design will allow for investigation of the neurobiology of opioid-induced respiratory depression and for testing potential therapeutics to reverse respiratory depression or stimulate breathing. SIGNIFICANCE STATEMENT: Fentanyl was more potent and had shorter duration in producing respiratory depression than heroin in both sexes, whereas female rats were more sensitive than males to heroin-induced respiratory depression. Tolerance/cross-tolerance develops in chronic fentanyl administration but is minimized with long interadministration intervals.

Trends in heroin use and injection drug use among high school students in five urban school districts in the US (2005-2017).

Background. We describe the prevalence of and changes in heroin use and injection drug use (IDU) among high school students in five large, urban school districts in the US (2005-2017); nearly three-fourths of the students were Black and/or Hispanic/Latino.Methods. Data are from the Centers for Disease Control and Prevention's "Youth Risk Behavior Survey" program, which includes biennial surveys in urban school districts. We pooled data across districts and survey years, and then generated weighted prevalence estimates (and 95% CIs) for any lifetime heroin use and IDU. Joinpoint regression modeling was used to estimate changes in prevalence over the study period.Results. Biennial prevalence estimates (2005-2017) for heroin use and IDU were above 1.8% for all seven timepoints. In 2017, prevalence of heroin use and IDU were 2.9% and 2.5%, respectively. Both heroin use and IDU were higher among boys than girls. There were statistically significant increases in heroin use and IDU among girls from 2005-2009, whereas changes over time were stable among boys.Conclusions. High school students in large, urban school districts may have higher rates of heroin use and IDU than US high school students in general, and there is little evidence of increases since 2009. This study suggests that adolescence may be a critical period for initiation of heroin use among adolescents in large urban school districts, the majority of whom are Black and/or Latino.Supplemental data for this article is available online at https://doi.org/10.1080/15332640.2021.1992327 .

Heroin Use Is Associated With Vascular Inflammation in Human Immunodeficiency Virus.

BACKGROUND: Heroin use may work synergistically with human immunodeficiency virus (HIV) infection to cause greater immune dysregulation than either factor alone. Unraveling how this affects end-organ disease is key as it may play a role in the excess mortality seen in people with HIV (PWH) who use heroin despite access to care and antiretroviral therapy. METHODS: This is a prospectively enrolled, cross-sectional study of adults with and without HIV who use and do not use heroin using (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to compare tissue-specific inflammation including aortic (target-to-background ratio [TBR]), splenic, and bone marrow (standardized uptake value [SUV]). RESULTS: A total of 120 participants were enrolled. The unadjusted mean difference in aortic TBR was 0.43 between HIV-positive [HIV+] heroin+ and HIV+ heroin-negative [heroin-] (P = .02); however, among HIV-, aortic TBR was similar regardless of heroin-use status. Further, HIV-by-heroin-use status interaction was significant (P = .02), indicating that the relationship between heroin use and higher aortic TBR depended on HIV status. On the other hand, both HIV (1.54 vs 1.68; P = .04, unadjusted estimated means for HIV+ vs HIV-) and heroin use were associated with lower bone marrow SUV, although the effect of heroin depended on sex (heroin-use-by-sex interaction, P = .03). HIV-by-heroin-use interaction was not significant for splenic or bone marrow SUV. CONCLUSIONS: Aortic inflammation was greatest in PWH who use heroin, but paradoxically, bone marrow activity was the least in this group, suggesting complex and possibly divergent pathophysiology within these different end organs.

A qualitative exploration of unintentional versus intentional exposure to fentanyl among people who use drugs in Austin, TX.

BACKGROUND: The prevalence of deaths involving synthetic opioids has historically been lower in Texas than most U.S. states but more than quadrupled from January 2020 to January 2022. This paper explores the emergence of fentanyl in a drug supply where black tar heroin predominates, a factor considered protective against fentanyl adulteration, through the perspectives of people who use drugs (PWUD). OBJECTIVES: We describe experiences of unintentional exposure to fentanyl, illustrate how some people identify fentanyl in their supply, and present harm reduction strategies that PWUD use to avoid overdose. METHODS: Thirty rapid assessment interviews were conducted in July 2021 at 2 mobile outreach sites of a harm reduction organization in Austin, Texas. The brief semistructured interviews were designed to assess participant fentanyl exposure experiences. RESULTS: Participants were clients who reported using heroin or fentanyl in the past week and had lived in Texas for at least 6 months. Seventeen participants identified as male, 10 as female, and 3 as nonbinary. Half identified as white; other participants were Latinx (6), black (2), American Indian (1), and mixed race (6). Two-thirds were unhoused or in transitional housing. The drug supply in Texas has evolved; most participants reported that the heroin and other drugs they obtained contain fentanyl. Participants detected differences by observing changes in the physical characteristics of the drug, experiencing unexpected effects, and using fentanyl test strips. Many had been unintentionally exposed to fentanyl and expressed concerns about fentanyl's presence. The presence of fentanyl had negative unintended consequences for participants, including adverse effects and developing a dependence on opioids. CONCLUSION: PWUD in Austin, Texas, report increasing prevalence of unintentional fentanyl exposure, despite the predominance of black tar heroin. Pharmacists can provide crucial supplies and education to safeguard the health of this vulnerable population.