Chronic Heroin Research Articles

Direct effects of heroin and methadone on T cell function

Opioid addiction presents a relevant health challenge, with chronic heroin use linked to detrimental effects on various aspects of physical, mental, and sociological health. Opioid maintenance therapy (OMT), particularly using methadone, is the primary treatment option for heroin addiction. Previous studies using blood samples from current heroin addicts and OMT patients have shown immunomodulatory effects of heroin and methadone on T cell function. However, various additional factors beyond heroin and methadone affect these results, including the consumption of other substances, a stressful lifestyle, comorbid psychological and somatic disorders, as well as additional medications. Therefore, we here investigated the direct effects of heroin and methadone on purified human T cells in vitro. Our results reveal that both, heroin and methadone directly suppress Tcell activation and proliferation. Strikingly, this inhibitory effect was markedly stronger in the presence of methadone, correlating with a decrease in secretion of pro-inflammatory cytokines. While heroin did not interfere with the in vitro differentiation and expansion of regulatory Tcells (Tregs), methadone significantly impaired the proliferation of Tregs. Overall, our findings suggest a direct inhibitory impact of both opioids on effector T cell function in vitro, with methadone additionally interfering with Treg induction and expansion in contrast to heroin.

Orally Administered N-Oleoyl Alanine Blocks Acute Opioid Withdrawal Induced-Conditioned Place Preference and Attenuates Somatic Withdrawal following Chronic Opioid Exposure in Rats

(1) Background: Intraperitoneal injections of the endogenous N-acyl amino acid N-Oleoyl alanine (OlAla) effectively reduces both the affective and somatic responses produced by opioid withdrawal in preclinical models. To increase the translational appeal of OlAla in clinical drug applications, the current experiments tested whether oral OlAla pretreatment also attenuates opioid withdrawal in rats. (2) Methods: In Experiment 1, to assess its impact on affective withdrawal behavior, OlAla (0, 5, 20 mg/kg) was orally administered during the conditioning phase of an acute naloxone-precipitated morphine withdrawal conditioned place avoidance task. In Experiment 2, to assess its impact on somatic withdrawal behavior, OlAla (5–80 mg/kg) was orally administered prior to naloxone-precipitated withdrawal from chronic heroin exposure. (3) Results: Pretreatment with oral OlAla at the higher (20 mg/kg), but not lower (5 mg/kg) dose, reduced the establishment of an acute morphine withdrawal-induced conditioned place aversion. Instead, the lower dose of oral OlAla (5 mg/kg) reduced heroin withdrawal-induced abdominal contractions and diarrhea, whereas higher doses were without effect. (4) Conclusions: The results suggest a dose-dependent reduction of opioid withdrawal responses by orally administered OlAla, and further highlight the potential utility of this compound for opioid withdrawal in clinical populations.

Dorsal hippocampal astrocytes mediate the development of heroin withdrawal-enhanced fear learning

There is a significant co-occurrence of opioid use disorder (OUD) and post-traumatic stress disorder (PTSD) in clinical populations. However, the neurobiological mechanisms linking chronic opioid use, withdrawal, and the development of PTSD are poorly understood. Our previous research has shown that proinflammatory cytokines, expressed primarily by astrocytes in the dorsal hippocampus (DH), play a role in the development of heroin withdrawal-enhanced fear learning (HW-EFL), an animal model of PTSD-OUD comorbidity. Given the role of astrocytes in memory, fear learning, and opioid use, our experiments aimed to investigate their involvement in HW-EFL. Experiment 1 examined the effect of withdrawal from chronic heroin administration on GFAP surface area and volume, and identified increased surface area and volume of GFAP immunoreactivity in the dentate gyrus (DG) following 24-hour heroin withdrawal. Experiment 2 examined astrocyte morphology and synaptic interactions at the 24-hour withdrawal timepoint using an astroglial membrane-bound GFP (AAV5-GfaABC1D-lck-GFP). Although we did not detect significant changes in surface area and volume of GfaABC1D-Lck-GFP labelled astrocytes, we did observe a significant increase in the colocalization of astrocyte membranes with PSD-95 (postsynaptic density protein 95) in the DG. Experiment 3 tested if stimulating astroglial Gi signaling in the DH alters HW-EFL, and our results demonstrate this manipulation attenuates HW-EFL. Collectively, these findings contribute to our current understanding of the effects of heroin withdrawal on astrocytes and support the involvement of astrocytes in the comorbid relationship between opioid use and anxiety disorders.

Insula Connectivity Abnormalities Predict Impulsivity in Chronic Heroin Use Disorder: A Cross-Sectional Resting-State fMRI Study.

Patients with heroin use disorder (HUD) often exhibit trait impulsivity, which may be an important factor in and a good predictor of addiction. However, the factor structure of HUD trait impulsivity (motor, attentional, and nonplanning) and its neural correlates are not yet known. A total of 24 male volunteers with HUD and 16 healthy control volunteers were recruited for this cross-sectional study. The Barratt Impulsiveness Scale (BIS-11) and resting-state functional magnetic resonance imaging (rs-fMRI) were employed using the insula as a seed point in an effort to understand the association between trait impulsivity and its intrinsic factors and functional connectivity (FC) between the insula and the whole brain. The HUD group in this study exhibited higher total trait impulsivity scores, motor impulsivity, and nonplanning impulsivity than the control group. Changes in FC between the right insula and the lateral occipital cortex and the right angular gyrus were significantly positively correlated with total trait impulsivity scores, motor impulsivity, and nonplanning impulsivity, whereas changes in the FC between the left insula and the left superior frontal gyrus and left frontopolar brain region were significantly negatively correlated with trait impulsivity. Thus, the insula may serve as an important biomarker for identifying trait impulsivity and its intrinsic factor structure in patients with HUDs.

The Impact of Heroin Self-Administration and Environmental Enrichment on Ventral Tegmental CRF1 Receptor Expression.

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. 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. 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. 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.

A pilot study examining the relationship between chronic heroin use and telomere length among individuals of African ancestry

BackgroundPrior research has suggested a possible link between heroin use and shortened telomere length (TL), a marker of cellular aging and genomic stability. We sought to replicate these findings by examining the relationship between TL and heroin use among individuals of African ancestry. MethodsThis cross-sectional study examined TL among 57 participants [17.5 % female; mean age 48.0 (±6.80) years] of African ancestry with Opioid Use Disorder (OUD) and a mean heroin use duration of 18.2 (±10.7) years. Quantitative polymerase chain reaction (qPCR) was used to calculate TL as the ratio between telomere repeat copy number (T) and a single-copy gene, copy number (S). The primary dependent variable was TL (T/S Ratio) measured in kilobase pairs. Covariates included heroin use years and personality traits. Using a hybrid approach, multiple linear regression and Bayesian linear regression examined the association of chronological age, heroin use years and personality traits with TL. ResultsThe multiple linear regression model fit the data well, R2 = 0.265, F(7,49) = 2.53, p < .026. Chronological age (β = −0.36, p = .017), neuroticism (β = 0.46, p = .044), and conscientiousness (β = 0.52, p = .040) were significant predictors of TL. Bayesian linear regression provided moderate support for the alternate hypothesis that chronological age and TL are associated, BF10 = 5.77, R2 = 0.120. The posterior summary of the coefficient was M = 0.719 (SD = 0.278, 95 % credible interval [−1.28, −0.163]). ConclusionsContrary to prior studies, these findings suggest that heroin use duration may not be significantly associated with TL among individuals of African ancestry, highlighting the need for more rigorous research to elucidate the complexity of this relationship.

Towards adherence monitoring using breath or oral fluid as a matrix in a methadone maintenance treatment program for patients with a chronic heroin use disorder: issues and interpretation of the results.

Urine has been the preferred matrix for monitoring heroin and methadone adherence due to its large detection window. Drawbacks such as privacy concerns and adulteration require however other matrices. The study aims to determine if oral fluid and exhaled breath are suitable alternatives for heroin and methadone monitoring and to assess the detection time in exhaled breath. Forty-three participants, all on methadone and heroin-assisted treatment, were studied. Participants were monitored after the first and right before the second dosage of heroin. At both time points oral fluid and exhaled breath samples were collected with urine at the second time point. All samples were screened for opiates, methadone and other drugs using immunoassay and LC-MSMS. At the second time point, 98 percent of oral fluid samples and all exhaled breath samples tested positive for 6-monoacetylmorphine (6-MAM). Regarding morphine detection, the findings were reversed (100 percent in oral fluid, 98 percent in exhaled breath). Methadone-related results were 100 percent positive across all matrices, as expected. Notable is the detection of the heroin marker acetylcodeine in oral fluid and exhaled breath samples, which resulted in relatively low negative predictive value (average 54.6 percent). Oral fluid and exhaled breath are suitable alternatives for heroin and methadone maintenance monitoring. Clinicians should consider ease of collection, adulteration risk, costs, turn-around time, and the substance of interest while choosing a matrix. In addition, even in cases when medicinal heroin is used, medical professionals should be aware of the presence of acetylcodeine in these alternate matrices.

Heroin-Induced Transverse Myelitis in a Chronic Heroin User: A Case Report

Heroin-Induced Transverse Myelitis in a Chronic Heroin User: A Case Report

Enhanced heroin analgesic effect in male offspring of sires who self-administered heroin.

Introduction: A growing body of evidence suggests that parental substance abuse, even prior to conception, may induce phenotypic changes in offspring. Parental opioid exposure has been shown to affect developmental processes, induce memory deficits, and lead to psycho-emotional disorders in offspring. However, how parental, especially paternal, chronic drug exposure affects offspring remains unexplored. Methods: Adult male rats were subjected to 31days of heroin self-administration followed by mating with naïve females. Litter size and body weight of F1 offspring were recorded. Object-based attention tests, cocaine self-administration tests, and hot plate tests were used to test for potential effects of chronic paternal heroin seeking on cognition, reward, or analgesic sensitivity in the offspring. Results: Body weight and litter size of the heroin F1 generation were not altered compared to the saline F1 generation. Furthermore, paternal chronic heroin self-administration experience had no significant effect on object-based attention tests or cocaine self-administration behavior in either sex. However, in the hot plate test, although no difference in basal latency was found between the two groups in either sex, a significant increase in the analgesic effect of heroin was observed in the male heroin F1 generation. Conclusions: Taken together, these data provide evidence that paternal chronic heroin self-administration experience could sex-dimorphically increase the analgesic effect of heroin in male offspring, but had no significant effect on response to cocaine reinforcement or attentional behavior.

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

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

Cognitive Enhancer Donepezil Attenuates Heroin-Seeking Behavior Induced by Cues in Rats.

Opioid use disorder is a significant global problem. Chronic heroin use is associated with impairment of cognitive function and conscious control ability. The cholinergic system can be disrupted following heroin administration, indicating that activation of the cholinergic system may prevent chronic heroin misuse. Donepezil as an inhibitor of cholinesterase has been reported to clinically improve cognition and attention. In this study, the inhibition of heroin self-administration and heroin-seeking behaviours by donepezil were evaluated in rats. Rats were trained to self-administer heroin every four hours for 14 consecutive days under a fixed ratio 1 (FR1) reinforcement schedule, then underwent withdrawal for two weeks. A progressive ratio schedule was then used to evaluate the relative motivational value of heroin reinforcement. After withdrawal, a conditioned cue was introduced for the reinstatement of heroin-seeking behaviour. Donepezil (0.3-3 mg/kg, i.p.) was used during both the FR1 heroin self-administration and progressive ratio schedules. Immunohistochemistry was used to investigate the mechanism of action of donepezil in the rat brain. Pre-treatment with high dose donepezil (3 mg/kg) but not low doses (0.3-1 mg/kg) significantly inhibited heroin self-administration under the FR1 schedule. Donepezil decreased motivation values under the progressive ratio schedule in a dose-dependent manner. All doses of donepezil (1-3 mg/kg) decreased the reinstatement of heroin seeking induced by cues. Correlation analysis indicated that the inhibition of donepezil on heroin-seeking behaviour was positively correlated with an increased expression of dopamine receptor 1 (D1R) and dopamine receptor 2 (D2R) in the nucleus accumbens (NAc) and increased expression of choline acetyltransferase (ChAT) in the ventral tegmental area (VTA). The present study demonstrated that donepezil could inhibit heroin intake and heroin-seeking behaviour. Further, donepezil could regulate dopamine receptors in the NAc via an increase of acetylcholine. These results suggested that donepezil could be developed as a potential approach for the treatment of heroin misuse.

Sex-differences in anxiety, neuroinflammatory markers, and enhanced fear learning following chronic heroin withdrawal

Post-traumatic stress disorder (PTSD) and opioid use disorder (OUD) are comorbid in clinical populations. However, both pre-clinical and clinical studies of these co-occurring disorders have disproportionately represented male subjects, limiting the applicability of these findings. Our previous work has identified chronic escalating heroin administration and withdrawal can produce enhanced fear learning. This behavior is associated with an increase in dorsal hippocampal (DH) interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and glial fibrillary acidic protein (GFAP) immunoreactivity. Further, we have shown that these increases in IL-1β and TNF-α are mechanistically necessary for the development of enhanced fear learning. Although these are exciting findings, this paradigm has only been studied in males. The current studies aim to examine sex differences in the behavioral and neuroimmune effects of chronic heroin withdrawal and future enhanced fear learning. In turn, we determined that chronic escalating heroin administration can produce withdrawal in female rats comparable to male rats. Subsequently, we examined the consequence of heroin withdrawal on future enhanced fear learning and IL-1β, TNF-α, and GFAP immunoreactivity. Strikingly, we identified sex differences in these neuroimmune measures, as chronic heroin administration and withdrawal does not produce enhanced fear learning or immunoreactivity changes in females. Moreover, we determined whether heroin withdrawal produces short-term and long-term anxiety behaviors in both female and males. Collectively, these novel experiments are the first to test whether heroin withdrawal can sensitize future fear learning, produce neurobiological changes, and cause short-term and long-term anxiety behaviors in female rats.

S1980 Cocaine-Induced Pseudomembranous Colitis With Negative Clostridium difficile Infection

Introduction: Pseudomembranous colitis (PMC) is most commonly caused by Clostridium difficle (C.Diff). The incidence of C.Diff related PMC is 3-8% and increasing. Other than Clostridium difficile, ischemia, infections, medications, and inflammatory conditions can cause PMC. We report a case of pseudomembranous colitis-tested negative PCR for C. difficile. Case Description/Methods: A 52-year-old female with a past medical history of hypothyroidism, asthma, and polysubstance abuse (history of chronic heroin, cocaine, benzodiazepine, alcohol, and cigarette use) with Hx of chronic intermittent diarrhea due to opioid withdrawal presented to the emergency department with bloody watery diarrhea of 3-4 times in a day for 5 days. On initial evaluation, the patient's vital signs are stable. The abdomen is diffusely tender on physical examination with increased tenderness in the left lower quadrant. Labs showed WBC count of 15,900/μL, 90.2% neutrophils, AST of 80 U/L, ALT of 41 U/L, ALP of 97 U/L, total bilirubin of 0.5 mg/dL, lactic acid of 0.9 mmol/L and c-reactive protein of 11.9 mg/dL. The urine drug screen was positive for benzodiazepine, cocaine, opiate, and methadone. CT scan of the abdomen showed mild diffuse concentric colonic wall thickening representing colitis. The patient was empirically treated with IV ceftriaxone, IV metronidazole, and PO vancomycin. Stool for C. difficile PCR was negative 3 times on 3 different days. Stool culture was negative for Salmonella, Shigella, Campylobacter, or E. coli O157:H7. Fecal lactoferrin quantification was 320.72 μg/mL. The patient underwent sigmoidoscopy, which showed discontinuous areas of ulcerated mucosa covered with yellowish punctate membrane with stigmata of recent bleeding in the entire examined colon. Biopsy of the colon showed focal active colitis with superficial crypt erosion and focal adherent mucopurulent material negative for crypt abscesses and granulomas, consistent with pseudomembranous colitis. The patient was continually treated with supportive care including IV fluids and bowel rest. Her diet was advanced, and her diarrhea improved (Figure). Discussion: Other than C. difficile, we propose keeping other differentials of pseudomembranous colitis is essential. Other infections from S. aureus, E. coli, Shigella and Strongyloides may also cause PMC. Non-infectious causes of PMC include chemical endoscope cleaning agents, intestinal ischemia, drug abuse from cocaine, inflammatory bowel disease, and microscopic colitis to avoid over-usage of antibiotics and focus on targeted therapy.Figure 1.: Discontinuous areas of ulcerated mucosa covered with yellowish punctate membrane with stigmata of recent bleeding in the entire examined colon.

Evidence on the Heroin-Mediated Impairment of the Oxidative Status of Erythrocytes.

Away from hemorheological properties, the effect of heroin addiction on erythrocytes is poorly investigated. This study aimed to investigate the oxidative impacts of heroin administration on erythrocytes. Study subjects included chronic intravenous heroin addicts and control subjects. Hematological analysis and redox parameters were measured, including serum concentration of methemoglobin ([MethHb]), serum glutathione peroxidase-1 ([GPX-1]), serum glutathione peroxidase (GPX) activity, erythrocytic protein carbonyl content, and oxidized to reduced glutathione (GSSG/GSH) ratio. Hematological analysis revealed that addicts had a significantly higher red cell distribution width, consistent with the mild anisocytosis and poikilocytosis of erythrocytes. As compared to control subjects, significantly higher levels of serum [Met-Hb], [GPX-1], and GPX activity (p < 0.001) were reported among addicted subjects. A significant association between [MetHb] and GPX activity was observed with r = 0.764 (p < 0.001). Furthermore, significantly higher erythrocytic protein carbonyl contents and GSSG/GSH ratio were evident among heroin addicts (p < 0.005) that were significantly associated with r = 0.429 (p=0.01). Results demonstrate preliminary evidence that heroin addiction is implicated in impaired redox status of erythrocytes. Considering the pharmacokinetics of heroin, erythrocytic antioxidant mechanisms, and turnover rate, further investigation is required to evaluate the extent and clinical outcomes, especially upon over-dose administration.

The subjective experience of heroin effects among individuals with chronic opioid use: Revisiting reinforcement in an exploratory study

Aims: Consistent with the opponent process theory individuals with chronic opioid use should predominantly endorse the avoidance of aversive negative emotional and/or physiological states as the motivation for continued opioid use (source of reinforcement: reductions in negative states). The primary aim of this study was to explore whether this view is supported by the subjective effects of heroin reported by individuals with opioid use disorder (OUD). Methods: Responses during in-person interviews of participants to the question “What do you like about heroin?” were categorized as positive, negative, or mixed (positive and negative) reinforcement. In addition, we examined differences between these “reinforcement groups” in sociodemographic and clinical variables. Results: Participants (N = 307) with OUD were predominantly male (78.1%), with chronic heroin use (M = 15.8 years, SD=11.5), and 46.1% currently used heroin and were not enrolled in treatment. Agreement between two raters concerning the categorization of participant-reported effects of heroin into reinforcement categories was high, κ=0.924, p<.0005. Approximately half (49.8%) of participant-reported effects of heroin were categorized as attributable to positive reinforcement. About one-fourth (22.8%) were categorized as negative reinforcement and 9.0% as “mixed”. There were no statistically significant differences between the three reinforcement groups in any of the socio-demographic variables, duration of heroin use, or treatment status/interest. Conclusions: The results of this study indicate marked heterogeneity of heroin effects experienced by individuals with OUD and their source of reinforcement, respectively. Better integration of how individuals construe their drug use is important to understand the psychological—and neurobiological—processes in the development and maintenance of OUD.

Altered Accumbal Dopamine Terminal Dynamics Following Chronic Heroin Self-Administration.

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.

Heroin Regulates Orbitofrontal Circular RNAs.

The number of drug overdose deaths involving opioids continues to rise in the United States. Many patients with opioid use disorder (OUD) that seek treatment still experience relapse. Perseverant opioid seeking behaviors represent a major challenge to treating OUD and additional therapeutic development will require insight into opioid-induced neurobiological adaptations. In this study, we explored the regulation of a novel class of RNAs, circular RNAs (circRNAs), by the addictive opioid heroin in the rat orbitofrontal cortex (OFC), a brain region that mediates behavioral responses to rewarding stimuli. Microarray analysis identified 76 OFC circRNAs significantly regulated in male rats after heroin self-administration. We evaluated the specificity of these findings by measuring heroin-associated circRNA expression in female rats after heroin self-administration and in rats that self-administered sucrose. We identify circGrin2b, circUbe2cp, circAnks1a, circAdcy5 and circSlc24A2 as heroin-responsive circRNAs in the OFC. Linear mRNA levels of heroin-associated circRNAs were unchanged except for Grin2b and Adcy5. An integrated bioinformatics analysis of regulated circRNAs identified microRNAs predicted to bind heroin-associated circRNAs and downstream targets of circRNA: microRNA sponging. Thus, heroin regulates the expression of OFC RNA splice variants that circularize and may impact cellular processes that contribute to the neurobiological adaptations that arise from chronic heroin exposure.

Effects of cocaine and/or heroin use on resting cardiovascular function

BackgroundRegular cocaine and/or heroin use is associated with major health risks, especially cardiovascular disease, but confounded by other factors. We examined effects of chronic (years regular use) and recent (past-month) cocaine and heroin use, controlling for other factors, on resting cardiovascular function. MethodsIn a sample of 292 cocaine and/or heroin users, we assessed demographics, body mass index (BMI), substance use history, electrocardiogram, heart rate (HR) and blood pressure (BP). Three-block (1: demographics, BMI; 2: tobacco, alcohol, cannabis; 3: cocaine, heroin) regression analyses were conducted to predict cardiovascular measures. ResultsHigher BMI predicted increased systolic and diastolic BP (as did older age), increased supine HR, and longer QRS duration, QTc interval, PR interval, and P-wave duration. Past-month cannabis-use days predicted higher systolic BP, lower supine HR, and greater likelihood of early repolarization and ST elevation; average daily cannabis use predicted shorter QTc interval. Average daily alcohol use predicted higher diastolic BP, higher supine HR and lower likelihood of sinus bradycardia (HR < 60 bpm). Past-month tobacco-use days predicted shorter QTc interval and lower lower likelihood of profound bradycardia (HR < 50 bpm). Past-month heroin-use days predicted lower seated HR, greater likelihood of sinus bradycardia and lower likelihood of left ventricular hypertrophy. More years of regular cocaine use and past-month cocaine-use days predicted longer QTc interval. ConclusionsCocaine and heroin use incrementally predicted modest variance in resting bradycardia and QTc interval. Clinicians should first consider demographics and recent use of tobacco, alcohol and cannabis before assuming cocaine and heroin affect these measures.

Heroin induced acute myelopathy, rhabdomyolysis and chronic globus pallidus ischemia: Uncommon complications of heroin abuse

Heroin or diacetylmorphine is widely consumed illegal opioid. Neurological manifestations of heroin include Spongiform lekoencephalopathy, ischemia, botulism, myelopathy, neuropathy and cerebral atrophy. Heroin myelopathy is a very rare manifestation seen in relation to first episode of heroin usage or following consumption after a period of abstinence. Neurovascular ischemia is the most common complication involving Globus pallidus, periventricular and subcortical regions. We describe a rare case of acute myelopathy, rhabdomyolysis and Globus pallidus ischemia in a chronic heroin user.

β-Arrestin 2 (ARRB2) Polymorphism is Associated With Adverse Consequences of Chronic Heroin Use.

β-arrestin 2 is an intracellular protein recruited during the activation of G-protein-coupled receptors. In preclinical studies, β-arrestin 2 has been implicated in µ-opioid receptor desensitization and internalization and the development of opioid tolerance and dependence. The present study investigated relationships between variants in the gene encoding β-arrestin 2 (ARRB2) and clinically relevant phenotypes among individuals with opioid use disorder (OUD). We hypothesized that ARRB2 variants would be associated with the negative effects of long-term heroin use. Chronic heroin users (N = 201; n = 103 African American; n = 98 Caucasian) were genotyped for ARRB2 r1045280 (synonymous, also affecting binding motif of transcription factor GTF2IRD1), rs2036657 (3'UTR) and rs3786047 (intron) and assessed for the past-month frequency of use, injection use, and lifetime duration of heroin use, number of heroin quit-attempts, and heroin use-related consequences. Lifetime heroin-use consequences (especially occupational and health-related) were significantly lower for African American ARRB2 r1045280 C-allele carriers compared withthe TT genotype. There was no significant genotype difference in the Caucasian group. ARRB2 rs2036657 was in strong linkage disequilibrium with rs1045280. These results, consistent with extant data, illustrate a role for ancestry-dependent allelic variation in ARRB2 r1045280 on heroin-use consequences. The ARRB2 r1045280 C-allele played a protective role in African-descent participants. These first-in-human findings, which should be replicated, provide support for mechanistic investigations of ARRB2 and related intracellular signaling molecules in OUD etiology, treatment, and relapse prevention. (Am J Addict 2021;00:00-00).