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Sexual health is a key element to the well-being and quality of life of individuals. However, it is rarely incorporated into care delivery for women with an addictive condition. Female with severe dependence to opiate have their medical and social conditions improved by diacetylmorphine treatment. Which allows them to escape situations of high-risk of sexual violence. However, this pharmacotherapy can also induce adverse effects on the sexual sphere. This paper describes the relevance of integrating psycho-socio-sexological counselling into the care provision for the opiate dependence. The counselling should be oriented to respond to the specific relational and sexual issues faced by these female patients and empowering them on their lives and in recovering a better quality of life., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

The highly addictive dietary supplement mimics opioid effects., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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 (MRI 1 ) and after (MRI 2 ) 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 MRI 1 and MRI 2 . 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (Copyright © 2023 American Society of Addiction Medicine.)

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 β 2 -adrenergic receptor antagonist (butoxamine), an α 2 -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., Competing Interests: Conflict of interest The authors report no conflicts of interest related to the content of this work., (Published by Elsevier Inc.)

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., (© 2024. The Author(s).)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: ADF receives royalties for an online chapter on primary care for patients with opioid use disorder from Wolters Kluwer. Other authors report no financial conflicts of interest.

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.

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., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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.

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 ( 18 F-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., Competing Interests: Declaration of Competing Interest The authors report no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (© 2023. Springer Nature Limited.)

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., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

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.

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., (U.S. Government work not protected by U.S. copyright.)

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., (© 2023. The Author(s).)

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., Competing Interests: Potential conflicts of interest . C. O. H. has served as consultant for Theratechnologies and Gilead and has received research grant support from Gilead. N. F. has served as consultant for Gilead. G. A. M. has served as consultant for Gilead, Merck, Theratechnologies, Janssen, and GSK/ViiV and has received research grants from Gilead, Merck, Janssen, and Theratechnologies, including payment for expert testimony from Gilead (no direct relationship with Gilead, deals with lawyer only). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The United States is experiencing a dramatic increase in maternal opioid misuse and, consequently, the number of individuals exposed to opioids in utero. Prenatal opioid exposure has both acute and long-lasting effects on health and wellbeing. Effects on the brain, often identified at school age, manifest as cognitive impairment, attention deficit, and reduced scholastic achievement. The neurobiological basis for these effects is poorly understood. Here, we examine how in utero exposure to heroin affects brain development into early adolescence in a mouse model. Pregnant C57BL/6J mice received escalating doses of heroin twice daily on gestational days 4-18. The brains of offspring were assessed on postnatal day 28 using 9.4 T diffusion MRI of postmortem specimens at 36 μm resolution. Whole-brain volumes and the volumes of 166 bilateral regions were compared between heroin-exposed and control offspring. We identified a reduction in whole-brain volume in heroin-exposed offspring and heroin-associated volume changes in 29 regions after standardizing for whole-brain volume. Regions with bilaterally reduced standardized volumes in heroin-exposed offspring relative to controls include the ectorhinal and insular cortices. Regions with bilaterally increased standardized volumes in heroin-exposed offspring relative to controls include the periaqueductal gray, septal region, striatum, and hypothalamus. Leveraging microscopic resolution diffusion tensor imaging and precise regional parcellation, we generated whole-brain structural MRI diffusion connectomes. Using a dimension reduction approach with multivariate analysis of variance to assess group differences in the connectome, we found that in utero heroin exposure altered structure-based connectivity of the left septal region and the region that acts as a hub for limbic regulatory actions. Consistent with clinical evidence, our findings suggest that prenatal opioid exposure may have effects on brain morphology, connectivity, and, consequently, function that persist into adolescence. This work expands our understanding of the risks associated with opioid misuse during pregnancy and identifies biomarkers that may facilitate diagnosis and treatment., (© 2022 John Wiley & Sons Ltd.)

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., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

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 .

Drug abuse has become a major problem of the modern world where drug-induced kidney injury can be caused by both prescribed drugs for clinical conditions and illegal (illicit) drugs or drugs of abuse. Heroin, cocaine, nicotine and alcohol are the most commonly abused drugs but with the emergence of various synthetic drugs, numerous novel descriptions of their nephrotoxic effects have been described. This review summarizes the key renal manifestations of recreational drugs as reported in case reports and case. A comprehensive review of published case reports and case series in English language of renal toxicity related to recreational drugs/drugs of abuse was conducted using search engines like PubMed/Medline. Publications which reported renal injury with raised creatinine levels, clinically symptomatic patients, those with oliguria and with renal biopsies are chosen. The medical literature on recreational drugs is full of claims of renal complications including different glomerular diseases, acute kidney injury, rhabdomyolysis, interstitial nephritis, and debilitating irreversible conditions like renal infarction and end stage renal disease, even though the pathogenesis of drug- related renal manifestations are not available for all the newer agents. The outcome of this review paper will help multidisciplinary physicians to understand the renal side effects of recreational drugs, their pathophysiology, and most importantly, the clinical presentations of renal dysfunction in relation each drug. Emphasizing these adverse effects will prevent future unfavorable outcomes., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Opioid use disorder (OUD) is a chronic relapsing psychiatric disorder. An unconditioned stimulus (US)-triggers a memory reconsolidation updating procedure (MRUP) that has been developed and demonstrated its effectiveness in decreasing relapse to cocaine and heroin in preclinical models. However, utilizations of abused drugs as the US to initiate MRUP can be problematic. We therefore designed a translational rat study and human study to evaluate the efficacy of a novel methadone-initiated MRUP., Methods: In the rodent study, male rats underwent heroin self-administration training for 10 consecutive days, and were randomly assigned to receive saline or methadone at 10 min, 1 h or 6 h before extinction training after 28-day withdrawal. The primary outcome was operant heroin seeking after reinstatement. In the human experimental study, male OUD patients were randomly assigned to get MRUP at 10 min or 6 h after methadone or methadone alone. The primary outcomes included experimental cue-induced heroin craving change, sustained abstinence and retention in the study at post intervention and the 5 monthly follow-up assessments. The secondary outcomes were changes in physiological responses including experimental cue-induced blood pressure and heart rate., Findings: Methadone exposure but not saline exposure at 10 min or 1 h before extinction decreased heroin-induced reinstatement of heroin seeking after 28-day of withdrawal in rats (F (8,80)  = 8.26, p < 0.001). In the human study, when the MRUP was performed 10 min, but not 6 h after methadone dosing, the MRUP promoted sustained abstinence from heroin throughout 5 monthly follow-up assessments compared to giving methadone alone without MRUP (Hazard Ratio [95%CI] of 0.43 [0.22, 0.83], p = 0.01). The MRUP at 10 min, but not at 6 h after dosing also decreased experimental cue-induced heroin craving and blood pressure increases during the 6-month study duration (group × months × cue types, F (12, 63·3)  = 2.41, p = 0.01)., Interpretation: The approach of MRUP within about 1 to 6 h after a methadone dose potently improved several key outcomes of OUD patients during methadone maintenance treatment, and could be a potentially novel treatment to prevent opioid relapse., Funding: National Natural Science Foundation of China (NO. U1802283, 81761128036, 82001400, 82001404 and 31671143) and Chinese National Programs for Brain Science and Brain-like Intelligence Technology (NO. 2021ZD0200800)., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The coronavirus disease 2019 (COVID-19) has highlighted the scope of heroin dependence and need for evidence-based treatment amongst marginalised people in South Africa. Acute opioid withdrawal management without maintenance therapy carries risks of increased morbidity and mortality. Due to the high costs of methadone, Tshwane's Community Oriented Substance Use Programme (COSUP) used tramadol for opioid withdrawal management during the initial COVID-19 response., Aim: To describe demographics, route of heroin administration and medication-related experiences amongst people accessing tramadol for treatment of opioid withdrawal., Setting: Three community-based COSUP sites in Mamelodi (Tshwane, South Africa)., Methods: A retrospective cross-sectional study was conducted. Data were collected using an interviewer-administered paper-based tool between April and August 2020. Descriptive statistics were used to analyse data., Results: Of the 220 service users initiated onto tramadol, almost half (n = 104, 47%) were not contactable. Fifty-eight (26%) people participated, amongst whom most were male (n = 55, 95%). Participants' median age was 32 years. Most participants injected heroin (n = 36, 62.1%). Most participants experienced at least one side effect (n = 47, 81%) with 37 (64%) experiencing two or more side effects from tramadol. Insomnia occurred most frequently (n = 26, 45%). One person without a history of seizures experienced a seizure. Opioid withdrawal symptoms were experienced by 54 participants (93%) whilst taking tramadol. Over half (n = 38, 66%) reported using less heroin whilst on tramadol., Conclusion: Tramadol reduced heroin use but was associated with withdrawal symptoms and unfavourable side effects. Findings point to the limitations of tramadol as opioid withdrawal management to retain people in care and the importance of access to first-line opioid agonists.Contribution: This research contributes to the limited data around short-acting tramadol for opioid withdrawal management in the African context, with specific focus on the need for increased access to opioid agonists for those who need them, in primary care settings.

Background: There are ongoing concerns regarding pharmaceutical opioid-related harms, including overdose and dependence, with an associated increase in treatment demand. People dependent on pharmaceutical opioids appear to differ in important ways from people who use heroin, yet most opioid agonist treatment research has been conducted in people who use heroin.  OBJECTIVES: To assess the effects of maintenance opioid agonist pharmacotherapy for the treatment of pharmaceutical opioid dependence., Search Methods: We updated our searches of the following databases to January 2022: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, four other databases, and two trial registers. We checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs)., Selection Criteria: We included RCTs with adults and adolescents examining maintenance opioid agonist treatments that made the following two comparisons. 1. Full opioid agonists (methadone, morphine, oxycodone, levo-alpha-acetylmethadol (LAAM), or codeine) versus different full opioid agonists or partial opioid agonists (buprenorphine) for maintenance treatment. 2. Full or partial opioid agonist maintenance versus non-opioid agonist treatments (detoxification, opioid antagonist, or psychological treatment without opioid agonist treatment)., Data Collection and Analysis: We used standard Cochrane methods., Main Results: We identified eight RCTs that met inclusion criteria (709 participants). We found four studies that compared methadone and buprenorphine maintenance treatment, and four studies that compared buprenorphine maintenance to either buprenorphine taper (in addition to psychological treatment) or a non-opioid maintenance treatment comparison. We found low-certainty evidence from three studies of a difference between methadone and buprenorphine in favour of methadone on self-reported opioid use at end of treatment (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.28 to 0.86; 165 participants), and low-certainty evidence from four studies finding a difference in favour of methadone for retention in treatment (RR 1.21, 95% CI 1.02 to 1.43; 379 participants). We found low-certainty evidence from three studies showing no difference between methadone and buprenorphine on substance use measured with urine drug screens at end of treatment (RR 0.81, 95% CI 0.57 to 1.17; 206 participants), and moderate-certainty evidence from one study of no difference in days of self-reported opioid use (mean difference 1.41 days, 95% CI 3.37 lower to 0.55 days higher; 129 participants). There was low-certainty evidence from three studies of no difference between methadone and buprenorphine on adverse events (RR 1.13, 95% CI 0.66 to 1.93; 206 participants). We found low-certainty evidence from four studies favouring maintenance buprenorphine treatment over non-opioid treatments in terms of fewer opioid positive urine drug tests at end of treatment (RR 0.66, 95% CI 0.52 to 0.84; 270 participants), and very low-certainty evidence from four studies finding no difference on self-reported opioid use in the past 30 days at end of treatment (RR 0.63, 95% CI 0.39 to 1.01; 276 participants). There was low-certainty evidence from three studies of no difference in the number of days of unsanctioned opioid use (standardised mean difference (SMD) -0.19, 95% CI -0.47 to 0.09; 205 participants). There was moderate-certainty evidence from four studies favouring buprenorphine maintenance over non-opioid treatments on retention in treatment (RR 3.02, 95% CI 1.73 to 5.27; 333 participants). There was moderate-certainty evidence from three studies of no difference in adverse effects between buprenorphine maintenance and non-opioid treatments (RR 0.50, 95% CI 0.07 to 3.48; 252 participants). The main weaknesses in the quality of the data was the use of open-label study designs, and difference in follow-up rates between treatment arms., Authors' Conclusions: There is  very low- to moderate-certainty evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence. Methadone or buprenorphine did not differ on some outcomes, although on the outcomes of retention and self-reported substance use some results favoured methadone. Maintenance treatment with buprenorphine appears more effective than non-opioid treatments. Due to the overall very low- to moderate-certainty evidence and small sample sizes, there is the possibility that the further research may change these findings., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Heroin-induced toxic leukoencephalopathy (TLE) is an uncommon condition that presents with nonspecific and variable neuropsychiatric findings. It may result in satisfactory recovery or death. Traditionally referred to as "chasing the dragon" syndrome and associated with inhalation of pyrolyzed heroin, recent publications have reported forms of the syndrome associated with noninhaled heroin. We report 2 cases of heroin-induced TLE associated with noninhaled routes of administration and a well-documented history of opioid use disorder. The patient in the first case presented with moderate to severe symptoms. Magnetic resonance imaging of the brain revealed increased T2 and fluid-attenuated inversion recovery signals bilaterally throughout subcortical and periventricular white matter. She survived with significant cognitive issues at discharge from which she adequately recovered by 11-month follow up. The patient in the second case presented with severe symptoms. Magnetic resonance imaging of the brain showed diffuse abnormal increased T2 and fluid-attenuated inversion recovery signals in the white matter of the centrum semiovale and corona radiata. The patient died within 3 weeks of presentation. Both cases illustrate the underrecognition of the form of TLE associated with noninhaled heroin and the difficulties involved in confirming recent heroin use that likely delayed the diagnosis. Further, noninhaled heroin-induced TLE can present with specific signs and symptoms that may help clinicians delineate it from the inhaled form. Given the ongoing opioid epidemic, early and accurate recognition of this condition is of paramount importance., Competing Interests: A.J.R. has received consulting fees from Akili Brain Resource Inc., Compass Inc., Curbstone Consultant LLC., Emmes Corp., Holmusk, Janssen (USA); Liva-Nova, Neurocrine, Otsuka-US, Sunovion; speaking fees from Liva-Nova; and royalties from Guilford Press and the University of Texas Southwestern Medical Center, Dallas, TX (for the Inventory of Depressive Symptoms and its derivatives). He is also named co-inventor on 2 patents: US Patent No. 7,795,033: Methods to Predict the Outcome of Treatment with Antidepressant Medication, Inventors: McMahon F.J., Laje G., Manji H., Rush A.J., Paddock S., Wilson A.S.; and US Patent No. 7,906,283: Methods to Identify Patients at Risk of Developing Adverse Events During Treatment with Antidepressant Medication, Inventors: McMahon F.J., Laje G., Manji H., Rush A.J., Paddock S. The remaining authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Administration of heroin results in the engagement of multiple brain regions and the rewarding and addictive effects are mediated, at least partially, through activation of the mesolimbic dopamine system. However, less is known about dopamine system function following chronic exposure to heroin. Withdrawal from chronic heroin exposure is likely to drive a state of low dopamine in the nucleus accumbens (NAc), as previously observed during withdrawal from other drug classes. Thus, we aimed to investigate alterations in NAc dopamine terminal function following chronic heroin self-administration to identify a mechanism for dopaminergic adaptations. Adult male Long Evans rats were trained to self-administer heroin (0.05 mg/kg/inf, IV) and then placed on a long access (FR1, 6-h, unlimited inf, 0.05 mg/kg/inf) protocol to induce escalation of intake. Following heroin self-administration, rats had decreased basal extracellular levels of dopamine and blunted dopamine response following a heroin challenge (0.1 mg/kg/inf, IV) in the NAc compared to saline controls. FSCV revealed that heroin-exposed rats exhibited reduced stimulated dopamine release during tonic-like, single-pulse stimulations, but increased phasic-like dopamine release during multi-pulse stimulation trains (5 pulses, 5-100 Hz) in addition to an altered dynamic range of release stimulation intensities when compared to controls. Further, we found that presynaptic D3 autoreceptor and kappa-opioid receptor agonist responsivity were increased following heroin self-administration. These results reveal a marked low dopamine state following heroin exposure and suggest the combination of altered dopamine release dynamics may contribute to increased heroin seeking.

Background: Beginning in the 1990s, nonmedical use of prescription opioids (POs) became a major public health crisis. In response to rising rates of opioid dependence and fatal poisonings, measures were instituted to decrease the prescription, diversion, and nonmedical use of POs including prescription drug monitoring programs (PDMPs), pain clinic laws, prescription duration limits, disciplining doctors who prescribed an excessive number of POs, and the advent of abuse deterrent formulations of POs. This paper explores the unintended effects of these policies in the descriptions of why people who use opioids transitioned from PO to injection or heroin/fentanyl use., Methods: We conducted 148 in-depth-interviews with people who use prescription opioids nonmedically, fentanyl or heroin from a rural, urban and suburban area in three states, Connecticut, Kentucky and Wisconsin. Interviews with people who use opioids (PWUO) focused on how they initiated their opioid use and any transitions they made from PO use to heroin, fentanyl or injection drug use., Results: The majority of participants reported initiating use with POs, which they used for medical or nonmedical purposes. They described needing to take more POs or switched to heroin or fentanyl as their tolerance increased. As more policies were passed to limit opioid prescribing, participants noticed that doctors were less likely to prescribe or refill POs. This led to scarcity of POs on the street which accelerated the switch to heroin or fentanyl. These transitions likely increased risk of overdose and HIV/HCV infection., Conclusions: A careful analysis of how and why people say they transitioned from PO to heroin or fentanyl reveals many unintended harms of policy changes to prevent overprescribing and diversion. Results highlight the importance of mitigating harms that resulted from policy changes., (© 2022. The Author(s).)

Background and Aims: This qualitative study aimed to explore how the development of tolerance to both the psychoactive and respiratory depressant effects of heroin on re-exposure are experienced by people who use heroin., Methods: Semi-structured one-to-one interviews were conducted with 20 adults who currently or previously used heroin (for at least 6 months), with any type of administration (injected, smoked) and experience of abstinence (at least 2 weeks) and relapse. Topic guides explored the participants understanding of tolerance, their experience of developing tolerance to heroin and of tolerance following relapse. Interviews were audio-recorded and transcribed. Thematic analysis was used to generate salient themes., Results: The analysis produced three broad themes: lay understanding of tolerance; tolerating tolerance; and rapid tolerance development following relapse. Tolerance was defined as the body adapting to regular drug use, so that the drug no longer produced the same level of effect. Tolerance was experienced as interacting and co-developing with physical dependence and the symptoms of withdrawal. Indeed, several participants did not differentiate between tolerance and dependence. Most participants did not notice tolerance to respiratory depression. Tolerance levels fluctuated-increasing over periods of regular use and reducing when abstinent. Using more drug was the most common response to increasing tolerance to the desired effects. On re-use following abstinence, tolerance was experienced as developing more quickly in the most recent relapse compared to the first. Tolerance was also perceived to return more quickly with each abstinence-relapse cycle., Conclusions: Qualitative accounts of tolerance report that tolerance returns more quickly with each relapse episode. By elucidating the mechanism(s) involved and potentially discovering how they could be switched on prior to relapse occurring we might be able to develop a beneficial harm reduction treatment for people in abstinence that would protect against overdose occurring on subsequent relapse., Competing Interests: The authors have declared that no competing interests exist.

This commentary discusses the novelty of the preclinical opioid choice model published in Heinsbroek et al., Nat Commun, 2021, and the potential influence of altitude on the reported findings. The studies were performed in the Mile High City of Denver, Colorado, where a unique subpopulation of heroin-choosing rats were noted., (© 2022 Wiley Periodicals LLC.)

Background: The prevalence of opioid use disorder during pregnancy is increasing in the United States. However, evidence to guide appropriate dosing of pharmacotherapy for the treatment of opioid use disorder, such as methadone, based on self-reported opioid use during pregnancy is limited., Objective: This study aimed to examine the relationship between self-reported consumption of heroin and methadone dose among pregnant people with opioid use disorder admitted to the hospital for methadone titration., Study Design: This was an analysis of a single-site retrospective cohort of pregnant people admitted for the management of opioid use disorder at an urban, tertiary care center between 2013 and 2020. Patient-reported consumption of heroin was evaluated by clinical staff and described as a self-reported dollar amount of heroin consumed per day. The primary outcome was methadone dose at the time of discharge. The secondary outcome was methadone dose at the time of delivery. Bivariate and linear regression modeling were performed. A priori covariates included in the model were an epoch of admission, Clinical Opioid Withdrawal Scale score at the time of admission, gestational age at admission, and need for readmission because of recurrent opioid use. A sensitivity analysis was performed using propensity score matching. Statistical significance was set at P<.05., Results: Of 100 people admitted during the study period, 53 and 47 individuals met the inclusion criteria for the primary and secondary outcomes, respectively. On bivariate and multivariate linear regression modeling, the self-reported dollar amount of heroin consumed per day was independently associated with the dose of methadone at the time of discharge. For every $10 of heroin consumed, the dosage of methadone increased by 1.3 mg (95% confidence interval, 0.4-2.2). On sensitivity analysis with the use of a propensity score, the self-reported dollar amount of heroin consumed per day was independently associated with the dose of methadone at the time of discharge. There was no significant relationship between self-reported dollar amount of heroin consumed per day and methadone dose at the time of delivery., Conclusion: Self-reported dollar amount of heroin consumed per day was independently associated with the dose of methadone at the time of discharge, but not at the time of delivery. These data can be useful in clinical counseling and management of pregnant people with opioid use disorder admitted for initiation of methadone., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Morphine/heroin may increase oxidative stress in drug-dependent persons. The imbalance between oxidative stress and antioxidant defense mechanisms can accelerate the shortening of telomere length. This article reports two sets of data; comparison of relative telomere length between heroin-dependent patients and healthy control group, as well as, investigation of the effect of morphine on the relative telomere length of human SH-SY5Y cells treated by morphine. Study participants were composed of 163 heroin-dependent patients and 166 unrelated healthy controls. SH-SY5Y cells were treated with (5 μM) morphine hydrochloride and incubated for 40 and 60 days. The relative telomere length was calculated as the T/S (telomere/single-copy gene) ratio using 36B4 as a reference for each sample, using quantitative real-time PCR. The mean (± SE) value of relative telomere length was 4.81 ± 0.21 and 6.38 ± 0.23 in leukocytes of heroin-dependent and control groups, respectively. The telomere length was significantly decreased in heroin-dependent participants (t = 4.97; df = 327; P < 0.0001). The relative telomere length in cells treated with morphine for 60 days was 4.50 ± 0.14 and in untreated cells was 5.75 ± 0.08. The difference was highly significant (t  =  7.68; df = 4; P = 0.002). Our present findings indicate that morphine and dependency on heroin are significantly associated with shorter telomeres. The present findings may help to explain some of the adverse effects of drug dependency on health such as accelerating biologic processes related to aging., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Fentanyl and fentanyl analogs have invaded the street-sourced opioid market in North America which has resulted in an unprecedented number of unintentional opioid overdoses. Existing guidelines to treat opioid use disorder are based on evidence that was developed when heroin was the primary street-sourced opioid and proposed dosages of opioid agonist treatments are increasingly inadequate to address patients with high opioid tolerances., Case Summary: The authors examine one case study of a patient with an extremely high opioid tolerance and review how responsive dose adjustments outside of the recognized maximum doses allowed for meaningful functional outcomes., Discussion: This case demonstrates how patient-centered dose responses with a focus on functional outcomes supersede existing opioids agonist treatment dosing ranges, especially in the context of a patient with a higher than typical opioid tolerance., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 American Society of Addiction Medicine.)

Abstract: The adulteration of drugs of abuse is a well-known practice with alarming public health implications. In fact, the presence of other substances than those declared by the drug dealers may expose the consumers to unexpected adverse effects, even potentially fatal ones depending on the adulterant. Various adulterants are often added during the manufacturing process as cutting agent for deliberate underdosing, such as in case of levamisole for cocaine, or to strengthen the drug ef-fect, as in case of fentanyl for heroin. The authors aimed to elaborate on such unfolding dynamics and concluded that continuous development of effective analytical tools, along with a closely focused evaluation of each case by the medical doctor is essential to clarify the origin of the intoxications, so as to undertake the best therapeutic pathway.

Background: Increases in U.S. older adults' nonprescription opioid and psychostimulant use call for examining their treatment admissions for these substances., Methods: Using admissions age 55 + involving heroin (N = 299,073) from the 2012-2019 Treatment Episode Data Set-Admissions, we examined trends and sociodemographic and clinical characteristics of three groups: (1) heroin-only admissions (i.e., not involving cocaine or methamphetamine), (2) heroin-cocaine admissions, and (3) heroin-methamphetamine admissions. Bivariable and multivariable logistic regression analyses were conducted to examine the research questions., Results: Between 2012 and 2019, the numbers of both heroin-only and heroin-cocaine admissions increased 2.3-fold and heroin-methamphetamine admissions increased seven-fold. First time heroin-methamphetamine admissions increased 18-fold. Heroin-methamphetamine admissions were concentrated in the Western region and heroin-cocaine admissions in the Northeastern region. Multivariable analyses showed a nearly 6 times higher relative risk ratio (RRR; 95% CI=5.24-6.74) for heroin-methamphetamine vs. heroin-only admissions in 2019 compared to 2012. Being non-Hispanic Black, compared to non-Hispanic White, was associated with a RRR of 2.4 (95% CI=2.34-2.46) for heroin-cocaine admissions and a RRR of 0.14 (95% CI=0.12-0.15) for heroin-methamphetamine admissions. Late-onset heroin use, experience of homelessness and other psychiatric problems, and past 30-day arrest episodes were associated with a higher likelihood of heroin-cocaine and heroin-methamphetamine admissions, while injection drug use (IDU) was associated with a higher likelihood of heroin-methamphetamine admissions only., Conclusions: Healthcare providers should assess and monitor psychostimulant, methamphetamine in particular, use among older adults. Those who use heroin and psychostimulants should receive substance use treatment and help to secure stable housing and meet other living needs., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Co-occurring heroin and methamphetamine use is a growing public health problem. This study assessed the characteristics of Medicaid patients admitted to substance use disorder (SUD) treatment programs for heroin and methamphetamine use compared with patients admitted for heroin only., Methods: The study identified patients who entered treatment for heroin and methamphetamine and those admitted for heroin only between 2014 and 2017 from the Oregon Treatment Episode Data Set linked with Medicaid enrollment, and medical and pharmacy claims. We used a cross-sectional design to compare demographics, type of treatment, and substance use characteristics between the two groups. We used logistic regression models to assess differences in the odds of opioid-related and all-cause adverse events., Results: Among the 3802 study sample, 2004 (53%) were admitted for both heroin and methamphetamine use. The heroin and methamphetamine group were more likely to be younger, female, White or American Indian/Alaska Native; and had more comorbidities than patients admitted for heroin only. Patients admitted for heroin and methamphetamine treatment were less likely to receive any medication for opioid use disorder (MOUD) (56% vs 75%, p < 0.001) and received fewer days of MOUD treatment (mean 188 vs. 265 days, p < 0.001) compared to the heroin only group. The heroin and methamphetamine group were more likely to receive buprenorphine (28.1% vs 24.2%) and less likely to receive methadone (39.9% vs 62.5%). The heroin and methamphetamine group began use at a younger age, used and injected more frequently than those admitted for heroin only. Patients treated for heroin and methamphetamine had 17% lower odds of OUD-related adverse events (aOR 0.83; 95% CI 0.70-0.99) and 52% higher odds of all-cause adverse events (aOR 1.52; 95% CI 1.14-2.03) relative to the heroin only group., Conclusion: Patients admitted for both heroin and methamphetamine reported greater addiction severity (more frequent use, earlier onset of use, and injection use), yet less commonly received MOUD compared to those who were admitted for heroin only. These findings indicate substantial missed opportunities for MOUD treatment even among people who successfully engage with the SUD treatment system., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The incidence of chronic heroin use disorder, including overdose deaths, has reached epidemic proportions. Here we summarise and evaluate our knowledge of the relationship between chronic heroin use disorder and the brain through a narrative review. A broad range of areas was considered including causal mechanisms, cognitive and neurological consequences of chronic heroin use and novel neuroscience-based clinical interventions. Chronic heroin use is associated with limited or very limited evidence of impairments in memory, cognitive impulsivity, non-planning impulsivity, compulsivity and decision-making. Additionally, there is some evidence for certain neurological disorders being caused by chronic heroin use, including toxic leukoencephalopathy and neurodegeneration. However, there is insufficient evidence on whether these impairments and disorders recover after abstinence. Whilst there is a high prevalence of comorbid psychiatric disorders, there is no clear evidence that chronic heroin use per se causes depression, bipolar disorder, PTSD and/or psychosis. Despite the growing burden on society from heroin use, knowledge of the long-term effects of chronic heroin use disorder on the brain remains limited. Nevertheless, there is evidence for progress in neuroscience-based interventions being made in two areas: assessment (cognitive assessment and neuroimaging) and interventions (cognitive training/remediation and neuromodulation). Longitudinal studies are needed to unravel addiction and neurotoxic mechanisms and clarify the role of pre-existing psychiatric symptoms and cognitive impairments., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Outbreaks of wound botulism are rare, but clinicians and health departments should maintain suspicion for signs, symptoms, and risk factors of wound botulism among persons who inject drugs in order to initiate treatment quickly. This report describes an outbreak of three wound botulism cases among persons in two adjacent counties who injected drugs. Provisional information about these cases was previously published in the CDC National Botulism Surveillance Summary. All three cases in this outbreak were laboratory-confirmed, including one case with detection of botulinum toxin type A in a wound culture sample taken 43 days after last possible heroin exposure. Findings highlight the delay in diagnosis which led to prolonged hospitalization and the persistence of botulinum toxin in one patient., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Middaugh, Edwards, Chatham-Stephens and Arguello.)

Opioid use disorder (OUD) is a significant health problem, and understanding mechanisms of various aspects of OUD including drug use and withdrawal is important. Preclinical models provide an ideal opportunity to evaluate mechanisms underlying opioid withdrawal. Current models are limited by their reliance upon forced opioid administration, focus on the acute (and not protracted) syndrome, and exclusion of females. In this study, male and female rats self-administered heroin (maintenance dose of 12.5 μg/kg/infusion) and opioid withdrawal after abrupt discontinuation was measured. In Phase 1, acute withdrawal symptoms were rated in male and female rats at 0, 16, 48, and 72 hr after the last self-administration session. Total somatic signs increased until 48 hr (predominantly in females), and heroin intake positively correlated with total somatic signs at the 48 and 72 hr timepoints. Measures of hyperactivity and anxiety-like behavior increased by 16 and 48 hr, respectively. In Phase 2, symptoms were assessed at baseline, acute, and protracted (168 and 312 hr after self-administration) timepoints in a subset of male and female rats from Phase 1. The total number of somatic signs did not differ across timepoints, though females displayed significantly higher body temperature at all timepoints compared with males, indicating sex-specific protracted withdrawal symptomatology. These data provide a thorough characterization of rodent opioid withdrawal symptomatology after self-administration and abrupt discontinuation that serve as a foundation for future studies designed to mimic the human experience, and demonstrate the importance of characterizing acute and protracted withdrawal with sex-specificity in preclinical models of opioid self-administration. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Clinical trials have indicated that a vaccine must be immunogenic in genetically diverse human populations and that immunogenicity and protective efficacy in animal models are two key indices required for the approval of a new vaccine. Additionally, the immune response (immunogenicity) and immunoprotection are dependent on the mouse strain. Therefore, the objective of the present study was to determine the immune response (immunogenicity) and the protective efficacy (behavioral response) in three inbred mouse strains immunized with the M 6 TT vaccine. Female BALB/c, C57Bl/6, and DBA/2 inbred mice were immunized with the M 6 -TT vaccine. A solid-phase antibody-capture ELISA was used to monitor antibody titer responses after each booster dose in vaccinated animals. The study used tail-flick testing to evaluate the antinociceptive effects induced by heroin. Additionally, heroin-induced locomotor activity and place preference were evaluated. The M 6 -TT vaccine was able to generate a specific antibody titer in the three inbred mouse strains evaluated. The antibodies reduced the antinociceptive effect of different doses of heroin. In addition, they decreased the heroin-induced locomotor activity and place preference. These findings suggest that the M 6 -TT vaccine generates a powerful immunogenic response capable of reducing the antinociceptive and reinforcing effects of heroin in different inbred mouse strains, which supports its possible future use in clinical trials in genetically diverse human populations., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Drug addiction is a chronic relapsing disorder, as more than 80% of former drug users relapse within a year after quit attempts have ended. This review examines incubated craving that develops over long periods of weeks to months after addictive drug use ends, when rats are given a small priming exposure to the formerly used drug, and a large amount of drug seeking occurs, reflecting large increases in craving over time. Expanded craving occurs when not only the recently-used drug, but other related or unrelated drugs of abuse elicit drug seeking that leads to relapse behavior, including common drugs like caffeine or nicotine, Thus, expanded craving is an increase in the conditions that elicit relapse, such as, a variety of drugs, and it persists weeks after drug use ends. Incubated and expanded craving occur with several drugs of abuse, and these forms of craving, can last for weeks to months and end in relapse. Voluntary physical exercise, blocked incubated cocaine craving, and expanded heroin craving elicited by multiple conditions was reduced in female and male rats. This review examines voluntary physical exercise as a long-term, self-initiated, and self-sustainable treatment that reduces long-term drug craving leading to relapse., (Copyright © 2021. Published by Elsevier Inc.)

Serious complications of drug abuse are frequently seen in acute care. When the clinical signs and symptoms of drug use are discordant with the expected clinical features of the intended substance used, it may involve misleading, contaminated and therefore dangerous illicit drugs. In 2014 and 2015, multiple young patients presented to several Dutch emergency departments in Amsterdam with an opioid toxidrome after supposed use of cocaine. However, it required months and multiple patient presentations, including fatalities, to discover that heroin was sold as cocaine, resulting in serious opioid toxidrome complications. The improvement and formalization of local collaboration and the instatement of an accessible central coordinating party enables early pattern recognition, treatment, sample testing and prevention of future cases of serious drug complications. This was demonstrated in a case of accidental fentanyl intoxication after alleged cocaine use in 2018. Extension of such collaborative networks to create a national coverage is desirable.

Background: The opioid crisis is a major public health emergency. Current data likely underestimate the full impact on mortality due to limitations in reporting and toxicology screening. We explored the relationship between opioid overdose and firearm-associated emergency department visits (ODED & FAED, respectively)., Methods: For the years 2010 to 2017, we analyzed county-level ODED and FAED visits in Kentucky using Office of Health Policy and US Census Bureau data. Firearm death certificate data were analyzed along with high-dose prescriptions from the Kentucky All Schedule Prescription Electronic Reporting records. Socioeconomic variables analyzed included health insurance coverage, race, median household earnings, unemployment rate, and high-school graduation rate., Results: ODED and FAED visits were correlated (Rho = 0.29, P< 0.01) and both increased over the study period, remarkably so after 2013 (P < 0.001). FAED visits were higher in rural compared to metro counties (P < 0.001), while ODED visits were not. In multivariable analysis, FAED visits were associated with ODED visits (Std. B = 0.24, P= 0.001), high-dose prescriptions (0.21, P = 0.008), rural status (0.19, P = 0.012), percentage white race (-0.28, P = 0.012), and percentage high school graduates (-0.68, P < 0.001). Unemployment and earnings were bivariate correlates with FAED visits (Rho = 0.42, P < 0.001 and -0.32, P < 0.001, respectively) but were not significant in the multivariable model., Conclusions: In addition to recognized nonfatal consequences of the opioid crisis, firearm violence appears to be a corollary impact, particularly in rural counties. Firearm injury prevention efforts should consider the contribution of opioid use and abuse., Competing Interests: Disclosures The authors have no conflicts of interest to report., (Copyright © 2021 Elsevier Inc. All rights reserved.)