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Background: Studies have shown that contamination of surfaces by illicit drugs frequently occurs in forensic laboratories when manipulating seized samples as well as in pharmacies and hospitals when preparing medicinal drugs. In this project, we extended these studies to a Drug Consumption Room to investigate drug levels and possible exposure of the staff members. Methods: We investigated pre and post cleaning contamination by heroin and cocaine and their degradation products 6-monoacetylmorphine and benzoylecgonine on different surfaces (tables, counters, computers and door handles) and in the ambient air. We also collected urine and hair samples from staff members to check for potential short and long term contaminations. Results: Medium to heavy contamination has been detected on most surfaces and door handles; as expected, air contamination was particularly high in the smoking room. Drug levels were < LOD to very low in the urine and the hair samples of staff members tested. Conclusion: The cleaning efficiency of the surfaces, carried out by staff and drug users after drug consumption, was often not satisfactory. The very low drug levels in hair indicate that acute health risks for staff members are low. [ABSTRACT FROM AUTHOR]

The emergence of compulsive drug‐seeking habits, a hallmark feature of substance use disorder, has been shown to be predicated on the engagement of dorsolateral striatal control over behaviour. This process involves the dopamine‐dependent functional coupling of the anterior dorsolateral striatum (aDLS) with the nucleus accumbens core, but the mechanisms by which this coupling occurs have not been fully elucidated. The striatum is tiled by a syncytium of astrocytes that express the dopamine transporter (DAT), the level of which is altered in individuals with heroin use disorder. Astrocytes are therefore uniquely placed functionally to bridge dopamine‐dependent mechanisms across the striatum. Here we tested the hypothesis that exposure to heroin influences the expression of DAT in striatal astrocytes across the striatum before the development of DLS‐dependent incentive heroin seeking habits. Using Western‐blot, qPCR, and RNAscope™, we measured DAT protein and mRNA levels in whole tissue, culture and in situ astrocytes from striatal territories of rats with a well‐established cue‐controlled heroin seeking habit and rats trained to respond for heroin or food under continuous reinforcement. Incentive heroin seeking habits were associated with a reduction in DAT protein levels in the anterior aDLS that was preceded by a heroin‐induced reduction in DAT mRNA and protein in astrocytes across the striatum. Striatal astrocytes were also shown to be susceptible to direct dopamine‐ and opioid‐induced downregulation of DAT expression. These results suggest that astrocytes may critically regulate the striatal dopaminergic adaptations that lead to the development of incentive heroin seeking habits. [ABSTRACT FROM AUTHOR]

Abnormal genetic polymorphism of trace amine-associated receptor 1 (TAAR1) rs8192620 site has been confirmed to induce methamphetamine (MA) use and drug craving. However, the genetic susceptibility difference between MA addicts and heroin addicts is unknown. This study evaluated genetic heterogeneity of TAAR1 rs8192620 between MA and heroin addicts and elucidated whether rs8192620 genotypes associated with discrepancy in emotional impulsivity, which would help to instruct individualized treatment in addiction via acting on TAAR1 and evaluate risk of varied drug addiction. Participants consisting of gender-matched 63 MA and 71 heroin abusers were enrolled in the study. Due to mixed drug usage in some MA addicts, MA users were further subdivided into 41 only-MA (only MA taking) and 22 mixed-drug (Magu composed of about 20% MA and 70% caffeine) abusers. Via inter-individual single nucleotide polymorphism (SNP) analysis and two-sample t tests, respectively, the genotypic and Barratt Impulsiveness Scale-11 (BIS-11) scores differences between groups were completed. With following genotypic stratification, the differences in BIS-11 scores between groups were analyzed through two-sample t test. Individual SNP analysis showed significant differences in alleles distribution of rs8192620 between MA and heroin subjects (p = 0.019), even after Bonferroni correction. The TT homozygotes of rs8192620 dominated in MA participants, while C-containing genotypes in heroin (p = 0.026). There was no association of genotypes of TAAR1 rs8192620 with addicts' impulsivity. Our research indicates that the TAAR1 gene polymorphism might mediate the susceptibility discrepancy between MA and heroin abuse. [ABSTRACT FROM AUTHOR]

Introduction: Heroin use disorder (HUD) is a seriously increasing health issue, accounting for most deaths among drug abusers. Studying non-coding ribonucleic acid gene expression among drug abusers is a promising approach, as it may be used in diagnosis and therapeutics. Participants and methods: A total of 49 male heroin-dependent patients and 49 male control participants were recruited from Kasr Al Ainy Psychiatry and Addiction outpatient clinics, Faculty of Medicine, Cairo University. Sera were gathered. qRT-PCR was utilized for the detection of gene expression of non-coding RNAs such as "HOX transcript antisense RNA" (HOTAIR), micro-RNA (miRNA-206), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), mechanistic target of rapamycin (mTOR), and Activity Regulated Cytoskeleton Associated Protein (Arc). Sera Brain-Derived Neurotrophic Factor (BDNF) levels were assessed using ELISA. Using a western blot made it possible to determine the protein expression of PI3K, AKT, and mTOR. Results: The study demonstrated that gene expressions of HOTAIR, AKT, PI3K, and Arc were considerably lowered between cases and controls, while gene expressions of miR-206 and mTOR1 were significantly raised. PI3K and AKT protein expressions were downregulated, while mTOR expressions were upregulated. BDNF levels were significantly decreased in some cases. Conclusion: The results of this study suggest that decreased HOTAIR in HUD relieves miR-206 inhibition, which thus increases and affects downstream PI3K/AKT/mTOR, ARC, and BDNF expression. This may be shared in addictive and relapsing behaviors. [ABSTRACT FROM AUTHOR]

Magnusiomyces capitatus (M. capitatus) is an emerging opportunistic yeast, rarely found as a causal agent of invasive fungal infection. In this study, we report a 31-year-old man infected with M. capitatus in the oral cavity, with a history of heroin and amphetamine abuse. M. capitatus was isolated through culture and microscopic analysis and identified by PCR amplification of the ITS DNA region. Based on the in vitro antifungal susceptibility test, the lowest MICs for M. capitatus were recorded for nystatin, itraconazole, and amphotericin, while higher MICs were observed for caspofungin and fluconazole. Treatment with nystatin successfully eliminated M. capitatus and relieved the clinical symptoms. This study presents the first case of M. capitatus in a patient with substance use disorder, manifesting as a plaque-like ulcer in the oral cavity. [ABSTRACT FROM AUTHOR]

Gloriosa superba (GSb), or Glory Lily, is not an uncommon plant found in Sri Lanka. Every part of the plant is poisonous, especially the rhizome. It contains mainly colchicine and gloriocine which are toxic alkaloids. Fatalities following ingestion are rarely reported with current medical management. A 37-year-old male, with history of cannabis dependence and heroin abuse, ingested one and half of GSb rhizomes following a family dispute, witnessed by his family. He was hospitalized nearly eighteen hours later and he developed severe gastro-enteritis associated with nausea and vomiting. The patient's presenting condition necessitated intensive care management for severe liver and renal failure. On the second day following admission he underwent haemodialysis and one cycle of plasma paresis but he ultimately succumbed due to unresponsive cardiac failure with arrhythmia. Subsequent autopsy examination revealed inflamed stomach and small intestinal mucosa with erosions, severe diffuse pulmonary haemorrhages with oedema, necrosis of liver and myocardium, and acute tubular necrosis. Multi-organ failure due to ingestion of GSb attributed to his death and manner of death was concluded as suicide following an inquest. This case report highlights the severity of effects of GSb poisoning including the effects on myocardium which is rarely encountered in clinical practice. [ABSTRACT FROM AUTHOR]

Background There is a strong link between chronic stress and vulnerability to drug abuse and addiction. Corticotropin releasing factor (CRF) is central to the stress response that contributes to continuation and relapse to heroin abuse. Chronic heroin exposure can exacerbate CRF production, leading to dysregulation of the midbrain CRF-dopamine-glutamate interaction. Methods Here we investigated the role of midbrain CRF1 receptors in heroin self-administration and assessed neuroplasticity in CRF1 receptor expression in key opioid addiction brain regions. Results Infusions of antalarmin (a CRF1 receptor antagonist) into the ventral tegmental area (VTA) dose dependently reduced heroin self-administration in rats but had no impact on food reinforcement or locomotor activity in rats. Using RNAscope in situ hybridization, we found that heroin, but not saline, self-administration upregulated CRF1 receptor mRNA in the VTA, particularly on dopamine neurons. AMPA GluR1 and dopamine reuptake transporter mRNA in VTA neurons were not affected by heroin. The western-blot assay showed that CRF1 receptors were upregulated in the VTA and nucleus accumbens. No significant changes in CRF1 protein expression were detected in the prefrontal cortex, insula, dorsal hippocampus, and substantia nigra. In addition, we found that 15 days of environmental enrichment implemented after heroin self-administration does not reverse upregulation of VTA CRF1 receptor mRNA but it downregulates dopamine transporter mRNA. Conclusions Overall, these data suggest that heroin self-administration requires stimulation of VTA CRF1 receptors and upregulates their expression in brain regions involved in reinforcement. Such long-lasting neuroadaptations may contribute to continuation of drug use and relapse due to stress exposure and are not easily reversed by EE exposure. [ABSTRACT FROM AUTHOR]

Background: Opioids, defined as medicines that stimulate opioid receptors, are primarily used in the treatment of moderate to severe pain. They induce central nervous system (CNS) adverse effects. This study aimed to assess the effect of opioids on brain electrical activity, the effect of opioids on cognitive functions, and corroborate whether there was any correlation between changes in brain electrical activity and cognitive functions that may do in opioid addicts. Methods: This cross-sectional case–control study was performed on 80 cases (divided into two groups 40 cases with tramadol use disorders and 40 cases with heroin use disorders) and 40 age-/sex-matched healthy control. All subjects were subordinated to neuropsychiatric evaluation, assessment of opioid use complaint through history from the case and his relatives, substance monitoring in urine, medicine abuse screening test (DAST), electroencephalography (EEG), and cognitive assessment by Montreal Cognitive Assessment (MOCA). Results: Opioid dependence convinced global cognitive function impairment, specific cognitive disciplines impairment that included visual-conceptual, visual-motor tracking, visual-constructional skills, language function, attention, memory, and orientation. Additionally, affection of the brain's electrical activities with significant changes compared with control. Comparison of cognitive impairment substantiated by lower cognitive scores in relation to abnormal EEG changes among studied case groups revealed significant differences. Conclusions: Opioid abusers had a significant impairment of cognitive functions and EEG changes with a significant correlation between changes in brain electrical activity and impairment of cognitive functions. [ABSTRACT FROM AUTHOR]

Introduction: Heroin use disorder (HUD) is commonly accompanied by gut dysbiosis, but the roles of gut microbiota in HUD treatment, such as compulsory detoxification and methadone maintenance treatment (MMT), remain poorly understood. Methods: In this study, we performed 16 s rDNA and whole metagenome sequencing to analyze the gut microbial profiles of HUD patients undergoing heroin addiction, heroin withdrawal (compulsory detoxification), and MMT. Results: Our findings revealed that, compared to healthy controls, microbial diversity was significantly decreased in HUD patients who were in a state of heroin addiction and withdrawal, but not in those receiving MMT. We observed significant alterations in 10 bacterial phyla and 20 bacterial families in HUD patients, while MMT partially restored these changes. Whole metagenome sequencing indicated gut microbiota functions were significantly disrupted in HUD patients experiencing heroin addiction and withdrawal, but MMT was found to almost reverse these dysfunctions. In addition, we identified 24 featured bacteria at the genus level that could be used to effectively distinguish between healthy individuals and those with heroin addiction, heroin withdrawal, or receiving MMT. Furthermore, we found the relative abundance of Actinomyces, Turicibacter and Weissella were positively associated with the Hamilton Depression Scale score in different states of HUD patients. Discussion: This study provides evidence from the gut microbiota perspective that MMT is a more effective approach than compulsory detoxification for HUD treatment. [ABSTRACT FROM AUTHOR]

Opioid addiction is a major public health problem. Through a commitment to individualized treatment plans meant to help patients meet personal goals, behavioral therapy can encourage abstinence and help prevent relapses that can have debilitating consequences. This case describes a 31-year-old male with heroin relapse who presented with flaccid quadriparesis as well as loss of sensation below the T2-3 spinal level, loss of rectal tone, and urinary retention. A urine drug screen (UDS) was positive for opiates and amphetamines. Autoimmune serologies were negative. Cerebrospinal fluid (CSF) analysis was negative for any acute ongoing infectious process. Magnetic resonance imaging (MRIs) of the cervical and thoracic spine showed increased intramedullary signals with spinal cord expansion from C2-T2, indicating acute transverse myelitis. Upon completion of the aforementioned work-up, idiopathic transverse myelopathy (TM) was diagnosed, and the patient was started on intravenous (IV) methylprednisolone; he also received five sessions of plasmapheresis. By process of elimination, suspicion remained of a diagnosis of opioid-induced myelopathy. The patient showed mild improvement in his original sensory deficits and flaccid quadriplegia.

Opioids are killing America's youth. New data confirms that children under 18 who are prescribed opioids by a medical doctor develop a heightened risk of future drug addiction. Currently, there are no national prescribing guidelines for opioids in the pediatric population. However, doctors recently started to administer an over‐the‐counter medicine combination of Advil and Tylenol to patients because it is more effective at relieving pain than prescription opioids and prevents addiction. Thus, drafting national legislation to limit the circumstances under which a child is eligible to receive an opioid prescription will save countless children from a life of future addiction. Key Points for the Family Law Community: Pediatric medical practices have been largely derived from adult practices.Dentists are the second‐highest prescribers of opioids in the medical profession.20% of American children take at least one prescription medication for pain management.6% of people who misuse prescription opioids transition to heroin.A 2017 study revealed a 33% drop in opioid prescriptions by oncologists. [ABSTRACT FROM AUTHOR]

We explore how precarious livelihoods intersect with precarious treatments for heroin dependency in a setting affected by longstanding conflicts and an illicit drug economy as well as by recent events of pandemic and political change. Working with 33 qualitative interviews with people who inject drugs in Kachin State, northern Myanmar, we explore how drug dependency treatment, especially methadone substitution, is made to work in efforts to sustain everyday livelihoods. Our analysis attends to the work that is done to enable therapeutic trajectories to emerge as "generous constraints" in precarity. We trace methadone substitution as an emergent intervention of livelihood survival. [ABSTRACT FROM AUTHOR]

In this work, a novel biosensing platform was fabricated based on modification of a rotating glassy carbon electrode (GCE) with chitosan-ionic liquid (Ch-IL) composite film, electrochemical synthesis of gold palladium platinum trimetallic three metallic alloy nanoparticles (AuPtPd NPs) onto its surface, and electrosynthesis of dual templates molecularly imprinted polymers (MIPs) where morphine (MO) and codeine (COD) used as template molecules. The AuPtPd NPs were synthesized under different electrochemical conditions, and surfaces of electrodes were investigated by digital image processing, and the best electrode was chosen. Effects of experimental variables on response of the biosensor to MO and COD were optimized by a central composite design (CCD), and under optimized conditions (concentration of the phosphate buffered solution (PBS): 0.09 M, pH of the PBS: 3.21–3.2, time of immersion: 204.8–205 s, and rotation rate: 2993.51–3000 rpm) the biosensor responses to MO and COD were individually calibrated (1–20 pM for MO and 0.5–12 pM for COD), three-way calibrated by PARASIAS, PARAFAC2, and MCR-ALS, and validated in the presence of ascorbic acid and uric acid as uncalibrated interference. Finally, performance of the biosensor in simultaneous determination of MO and COD in the presence of ascorbic acid and uric acid as uncalibrated interference in human serum samples were verified and compared with the results of HPLC-UV as the reference method which guaranteed it as a reliable method. • A novel electrochemical biosensor was fabricated for simultaneous determination of morphine and codeine. • Image processing, experimental design, and multi-way calibration supported the biosensor. • Interference caused by ascorbic acid and uric acid were tackled by exploiting second-order advantage. • The biosensor assisted by MCR-ALS was successful in analysis of serum samples. • Performance of the intelligent biosensor was admirable and comparable with the reference method. [ABSTRACT FROM AUTHOR]

When a human body ingests a lethal1 dose of heroin, the body goes through an enormous physiological transformation.2 The functions of the central nervous system begin to depress, breathing is shallowed, the pulse is weakened, and the skin turns blue or gray with dark lips and fingernails.3 An alert person must quickly administer naloxone, an opioid antagonist, to reverse the effects of a heroin overdose, as symptoms typically begin after ten minutes.4 For many, however, their lives end with an overdose, despite this outcome being preventable. 5 This paper will establish that drug overdose deaths are preventable for an entirely different set of reasons. [ABSTRACT FROM AUTHOR]

Heroin, a semisynthetic opioid drug synthesized from morphine, is the 3,6‐diacetyl ester of morphine (diacetylmorphine). The post‐mortem diagnosis of heroin‐related death could be an issue and usually rely on a combination of investigations, including the autopsy, histological and toxicological analysis. We conducted the present study to evaluate the correlation between the heroin concentration in biological fluids (peripheral blood, bile and urine) and the post‐mortem anti‐6‐MAM antibody expression in various tissues (brain, heart, lung, liver and kidney) using immunohistochemical staining. A quantitative analysis of the immunohistochemical reaction was carried out. 45 cases of heroin‐related death investigated at the Forensic Pathology Institutes of the University of Rome, Foggia and Pisa were included. The control group was composed of 15 cases of death due to other causes, without brain lesions and negative toxicological analysis for drugs. We found a positive immunohistochemical reaction in different organs and it was related to the timing of heroin metabolization. No reaction was found in the control group. Our findings show that immunohistochemistry can be a valuable tool for the post‐mortem diagnosis of acute heroin abuse. A better understanding of the timing of heroin's metabolism can be useful in the forensic field and for future therapeutic applications. [ABSTRACT FROM AUTHOR]

Objective. To explore the potential link between gut damage and proinflammatory cytokines in heroin-dependent patients. Methods. We retrospectively analyzed and compared partial blood counts and biomarkers of intestinal injury and their potential correlations in 38 male heroin abuse patients and 29 healthy male participants. In addition, we compared and assessed proinflammatory cytokines and immune cells in 10 heroin abuse patients and 10 healthy participants. Results. Neutrophil counts, platelets/lymphocytes (PLR), neutrophils/lymphocytes (NLR), gut injury biomarkers, and proinflammatory cytokines, CD19+B in patients compared with healthy subjects' cells increased significantly. The number of lymphocytes, CD3 CD4 T cells, and CD3 CD8 T cells decreased in patients compared to healthy individuals. When distinguishing between heroin addicts and healthy people, ROC/AUC analysis showed that a cutoff of 142.42 for PLR and 2.18 for NLR yielded a sensitivity of 65% and 85% and a specificity of 96.5% and 89.7%, respectively (p = 0.001 , p < 0.001). For predicting intestinal injury, ROC/AUC analysis showed that a cutoff of 135.7 for PLR and 0.15 for NLR yielded a sensitivity of 52% and 60% and a specificity of 82% and 86.4%, respectively (p = 0.003 , p = 0.009). Male heroin addicts are subject to intestinal injury and present with increased proinflammatory cytokine levels. Conclusion. NLR and PLR are possible indirect biomarkers for heroin dependence based on intestinal injury. [ABSTRACT FROM AUTHOR]

Among the various causes of heroin addiction, the use of prescription opioids is one of the main reasons. In this article, we introduce and analyze a two-strain epidemic model with the superinfection for modeling the effect of prescribed opioids abuse on heroin addiction. Our model contains the impact of relapse of individuals under treatment/rehabilitation to drug abuse in each strain. We extract the basic reproductive ratio, the invasion numbers and study the occurrence of backward bifurcation in strain dominance equilibria, i.e., boundary equilibria. Also, we explore both the local and global stability of DFE and boundary equilibria under suitable conditions. Furthermore, we study the existence of the coexistence equilibrium point. We prove that when R0 < 1, the coexistence equilibrium point can exist, i.e., backward bifurcation occurs in coexistence equilibria. Finally, we use numerical simulation to describe the obtained analytical results. [ABSTRACT FROM AUTHOR]

Background and Aims: Tracking specific drugs contributing to drug overdose deaths is limited when relying on death certificate (DC) data alone. This study aimed to determine whether integrating DC data with medical examiner/coroner reports, including postmortem toxicology and death investigation findings, would enhance identification of (1) heroin and pharmaceutical morphine involvement in overdose deaths and (2) fentanyl source (illicitly manufactured versus pharmaceutical). Design Retrospective analysis of heroin, pharmaceutical morphine, illicitly manufactured fentanyl (IMF) and pharmaceutical fentanyl involvement in fatal overdoses. DC and toxicology data were compared with enhanced definitions integrating overdose scene, witness and toxicology evidence. Setting: United States: 38 states and the District of Columbia, participating in Centers for Disease Control and Prevention (CDC)‐funded opioid overdose death surveillance. Cases Opioid overdose decedents from funded jurisdictions; deaths during 1 January 2018–31 December 2019. Measurements Using medical examiner/coroner report data, deaths with 6‐acetylmorphine and/or morphine detected by postmortem toxicology were defined as confirmed, probable or suspected heroin deaths, or probable pharmaceutical morphine deaths. Fentanyl was defined as probable or suspected IMF or probable pharmaceutical fentanyl. Findings The enhanced definition defined 18 393 deaths as confirmed, probable, or suspected heroin deaths (including 2678 with morphine listed as cause of death on the DC) and 404 as probable pharmaceutical morphine deaths. Among deaths with fentanyl detected, 89.3% were defined as probable or suspected IMF and 1.0% as probable pharmaceutical fentanyl. Fentanyl source could not be determined for 9.7% of deaths. Conclusions: Integrating drug overdose scene, witness and toxicology findings can improve identification of specific drugs contributing to overdose deaths and enhance overdose intervention targeting. [ABSTRACT FROM AUTHOR]

Heroin dependency has become a global problem and has caused significant clinical and socioeconomic burdens along with devastating medical consequences. Chronic drug exposure alters the expression and functional activity of 5-hydroxytryptamine (serotonin) 2A receptors (5-HT2ARs) in the brain. Furthermore, pharmacological blockade of 5-HT2ARs reduces cue-induced cocaine craving behaviors. In this study, we explored the influence of 5-HT2ARs on heroin-withdrawal behaviors in mice. Black C57BL/6J mice were given gradually increasing (10–50 mg/kg over 4.5 days) doses of heroin to induce heroin dependency, after which naloxone was given to precipitate withdrawal symptoms. MDL100907, a selective and potent 5-HT2AR antagonist, attenuated naloxone-precipitated withdrawal symptoms in these mice. In addition, 5-HT2AR protein levels increased significantly in the medial prefrontal cortex (mPFC), while phosphorylation of extracellular signal-regulated kinase (p-ERK) decreased in the mPFC after heroin exposure. In conclusion, these results suggest that 5-HT2ARs might be involved in the development of opioid dependency and that pharmacological blocking of 5-HT2ARs might be a new therapeutic strategy for heroin dependency. [ABSTRACT FROM AUTHOR]

Background: Renal infarctions as a result of recreational drug use are rare and are commonly associated with cocaine use. Although amphetamines have a similar mechanism of action as cocaine, there are few reports linking them to ischemic events, and only one to renal infarction. Similarly, few reports link heroin use with infarcts, but never in the kidney. Although uncommon, several mechanisms have been implicated in heroin and amphetamine-induced infarction, including vasculopathy, vasculitis and the activation of the coagulation cascade.Case Presentation: 47-year-old female with a past medical history of non-intravenous heroin and amphetamine abuse, chronic obstructive pulmonary disease, hypertension, hyperlipidemia presented with right lower extremity swelling and rash, which was diagnosed as cellulitis and treated appropriately. Incidentally, the patient was found to have an acute kidney injury and further workup identified multiple renal infarcts in the right kidney. The patient had no past medical history of clotting disorders. Blood culture and urine cultures were sterile; autoimmune and hypercoagulable workup were negative. Urinalysis was unremarkable. Urine toxicology was only positive for opiates and amphetamines, which were thought to be the most likely cause of the renal infarct. Patient was lost to outpatient follow up due to noncompliance, but returned to the hospital for re-emergence of her cellulitis, during which no new infarcts were discovered, and the previous renal infarct had scarred over.Conclusion: There are very few reports of heroin and amphetamine-induced infarctions. This case report describes a rare but important complication of heroin/amphetamine abuse that could be easily overlooked. [ABSTRACT FROM AUTHOR]

This case study seeks to demonstrate the Cincinnati Enquirer's use of the public health model of reporting and public health news frames. The Enquirer created the first newspaper heroin beat in January 2016. Enquirer reporters framed the heroin epidemic as a public health issue, focusing on solutions, contextualizing the issue through societal determinants of health, and incorporating the voices of constituent groups. Findings are discussed using news framing and the public health model of reporting. [ABSTRACT FROM AUTHOR]

The US opioid crisis came in three waves -- prescription opioids, heroin, and illicitly manufactured fentanyls -- Centers for Disease Control and Prevention Centers for Disease Control and Prevention resulting in the deaths of nearly 500,000 people from 1996 to 2019. In 2009, drug overdose deaths exceeded those involving automobiles. Opioid overdose deaths contributed to the decrease in life expectancy for Americans from 78.8 to 78.5 during 2014 to 2017. The overprescribing of a schedule II prescription opioid was escalated by pharmaceutical companies promoting a growing belief that pain was an undertreated condition. In 2012, the number of opioid prescriptions peaked at 255 million and deaths exceeded 11,000 per year. The typical prescription opioid abuser was white, male, and 45--55 years of age. The hardest-hit states were in Appalachia and the Northeast. When an abuse-resistant formulation was introduced for OxyContin, the most prevalent prescription opioid, users turned to heroin. From the early 1980s, a new pizza delivery style of Mexican trafficking in black tar heroin infiltrated many of the same states hit hardest by prescription opioids. Heroin overdose deaths reached 14,495 in 2017. As heroin abuse increased in states supplied with black tar heroin, fentanyl-contaminated white powder heroin began to appear in the Northeast. Fentanyl was quickly followed by fentanyl analogs. While heroin deaths continued to escalate through 2017, they were soon overshadowed by fentanyl overdose deaths. Finally, prescription opioid and heroin overdose deaths started to decline in 2017, though fentanyl deaths continued to increase. In late 2019, it appeared that restrictions on transportation and travel due to the COVID-19 pandemic had resulted in decreased availability of illicit drugs, but by 2020 drug abuse had escalated in many countries. Globally, heroin was the primary opioid of abuse and only a few countries -- including Canada, Germany, Austria, and Belgium -- have experienced a significant increase in prescription opioids. However, illicitly manufactured fentanyls are a growing problem in North America, Europe, Australia, and Asia. [ABSTRACT FROM AUTHOR]

Introduction. Cerebral air embolism is a rare, yet serious neurological occurrence with unclear incidence and prevalence. Here, we present a case of fatal cerebral arterial and venous cerebral gas embolism in a patient with infective endocarditis and known large right-to-left shunt and severe tricuspid regurgitation following pressurized fluid bolus administration. Case Presentation. A 32-year-old female was admitted to the medical intensive care unit from a long-term acute care facility with acute on chronic respiratory failure. Her medical history was significant for intravenous heroin and cocaine abuse, methicillin-sensitive Staphylococcus aureus tricuspid valve infective endocarditis on vancomycin, patent foramen ovale, septic pulmonary embolism with cavitation, tracheostomy with chronic ventilator dependence, multifocal cerebral infarction, hepatitis C, nephrolithiasis, anxiety, and depression. After intravenous fluid administration, she became unresponsive with roving gaze, sluggish pupils, and hypotensive requiring vasopressors. CT of the brain showed diffuse arterial and venous cerebral air embolism secondary to accidental air administration from fluid bolus. Magnetic resonance imaging of the brain showed diffuse global anoxic injury and flattening of the globe at the optic nerve insertion. Given poor prognosis, her family chose comfort measures and she died. Conclusions. Fatal cerebral air embolism can occur through peripheral intravenous routes when the lines are inadequately primed and fluids administered with pressure. Caution must be exercised in patients with right-to-left shunting as air may gain access to systemic circulation. [ABSTRACT FROM AUTHOR]

Background: α7 Nicotinic acetylcholine receptors are implicated in the reinstatement of drug-seeking, an important component of relapse. We showed previously that the α7 nicotinic acetylcholine receptor antagonist, methyllycaconitine, specifically attenuated morphine-primed reinstatement of conditioned place preference in rodents and this effect was mediated in the ventral hippocampus. Aims: The purpose of this study was to evaluate α7 nicotinic acetylcholine receptor antagonism in reinstatement of the conditioned place preference for the more widely abused opioid, heroin, and to compare the effect of α7 nicotinic acetylcholine receptor blockade on reinstatement of heroin-seeking and heroin self-administration in an intravenous self-administration model of addictive behaviour. Methods: Rats were trained to acquire heroin conditioned place preference or heroin self-administration; both followed by extinction of responding. Methyllycaconitine or saline was given prior to reinstatement of drug-primed conditioned place preference, or drug-prime plus cue-induced reinstatement of intravenous self-administration, using two protocols: without delivery of heroin in response to lever pressing to model heroin-seeking, or with heroin self-administration, using fixed and progressive ratio reward schedules, to model relapse. Results: Methyllycaconitine had no effect on acquisition of heroin conditioned place preference or lever-pressing for food rewards. Methyllycaconitine blocked reinstatement of heroin-primed conditioned place preference. Methyllycaconitine did not prevent drug-prime plus cue-induced reinstatement of heroin-seeking, reinstatement of heroin self-administration, or diminish the reinforcing effect of heroin. Conclusions: The α7 nicotinic acetylcholine receptor antagonist, methyllycaconitine, prevented reinstatement of the opioid conditioned place preference, consistent with a role for α7 nicotinic acetylcholine receptors in the retrieval of associative memories of drug liking. The lack of effect of methyllycaconitine in heroin-dependent rats in two intravenous self-administration models suggests that α7 nicotinic acetylcholine receptors do not play a role in later stages of heroin abuse. [ABSTRACT FROM AUTHOR]

An 11‐month‐old intact male boxer cross was presented unconscious following oral heroin consumption. At home, intramuscular naloxone given by the owner showed no obvious improvements. Intravenous naloxone given in the hospital quickly reversed the clinical signs. The owners were not able to afford hospitalisation and the animal was discharged against medical advice. No signs of rebound opioid toxicity were reported. This case report describes the clinical presentation and treatment of a case of heroin intoxication in a dog. [ABSTRACT FROM AUTHOR]

Opioid-dependent patients frequently show deficits in multiple cognitive domains that might impact on their everyday life performance and interfere with therapeutic efforts. To date, the neurobiological underpinnings of those deficits remain to be determined. We investigated working memory performance and gray matter volume (GMV) differences in 17 patients on opioid maintenance treatment (OMT) and 17 healthy individuals using magnetic resonance imaging and voxel-based morphometry. In addition, we explored associations between substance intake, gray matter volume, and working memory task performance. Patients on OMT committed more errors during the working memory task than healthy individuals and showed smaller insula and putamen GMV. The duration of heroin use prior to OMT was associated with working memory performance and insula GMV in patients. Neither the substitution agent (methadone and buprenorphine) nor concurrent abuse of illegal substances during the 3 months prior to the experiment was significantly associated with GMV. Results indicate that impaired working memory performance and structural deficits in the insula of opioid-dependent patients are related to the duration of heroin use. This suggests that early inclusion into OMT or abstinence-oriented therapies that shorten the period of heroin abuse may limit the impairments to GMV and cognitive performance of opioid-dependent individuals. [ABSTRACT FROM AUTHOR]

Heroin dependence may result in suppression of adaptive immune responses. Previously, we demonstrated an increase in relative numbers of inhibitory CD4+ regulatory T cells (Tregs) and impaired proliferative activity of CD4+ T cells from heroin‐addicted patients in contrast to patients in opioid maintenance therapy and healthy controls. However, it remains elusive whether heroin has a direct impact on the CD4+ T cell compartment or whether observed effects result from stressful living conditions. Here, we analyzed the frequencies of Tregs and the proliferation as well as the cytokine production of stimulated CD4+ T cells from heroin‐addicted patients with use of illicit heroin, patients in heroin‐assisted treatment (HAT), and patients in methadone maintenance therapy (MMT). Relative numbers of CD4+ Tregs were significantly enhanced in patients with illicit heroin abuse compared with patients in HAT or MMT. Notably, CD4+ T cells from patients in HAT and from persons using illicit heroin showed significant reduced proliferation and secretion of the pro‐inflammatory cytokines IFN‐γ and IL‐6 upon stimulation in vitro. From these results, we conclude that structured programs such as HAT and MMT dampen elevated frequencies of Tregs in heroin‐addicted patients, whereas chronic heroin administration irrespective of using illicit heroin or receiving HAT has a direct impact on the proliferative activity and cytokine production of CD4+ T cells. [ABSTRACT FROM AUTHOR]