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.

Methadone maintenance treatment is more effective than compulsory detoxification in addressing gut microbiota dysbiosis caused by heroin abuse.

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.

Left Ventricular Noncompaction in Concomitance With Heroin Use Disorder.

Left ventricular noncompaction (LVNC) is a rare congenital condition defined by the presence of prominent trabeculations in the myocardial layer of the left ventricle. The clinical presentation is varied as some patients are asymptomatic and others have symptoms of decompensated heart failure, arrhythmias, or thromboembolism. We present the case of a 42-year-old female with a past medical history of asthma and substance use disorder who presented to the Emergency Department following a syncopal event. The patient had used heroin intranasally, following which she became unresponsive for several minutes. Her husband witnessed the event and initiated chest compressions. When examined by emergency medical services (EMS), she had a palpable pulse and was given naloxone. The patient underwent further evaluation and was admitted for the treatment of aspiration pneumonia. Throughout her hospital stay, she complained of chest pain with musculoskeletal characteristics, likely secondary to chest compressions. However, due to the persistence of pain, she had further cardiac evaluation done. Her electrocardiography (EKG) revealed a normal sinus rhythm with no acute ischemic changes. Her echocardiography revealed left ventricular apical trabeculations with normal systolic and diastolic function, in line with the diagnosis of LVNC. Upon discharge, she was extensively counseled to abstain from substance use and to follow up with cardiology for a cardiac event monitor. Given her initial syncopal event and high-risk substance use behavior, she would benefit from close follow-up for the presence of arrhythmias.

Inhalational Heroin Use and Leukoencephalopathy: A Case Report.

Heroin-induced leukoencephalopathy (HLE) is a rare condition with acute and chronic outcomes ranging from mild neurological symptoms to severe neurological deficits and death. HLE is caused by cerebral white matter damage secondary to exposure to toxic agents such as chemotherapeutic drugs, environmental toxins, and drugs of abuse. Here, we present the case of a 20-year-old woman with a past medical history significant for bipolar disorder and opioid use who presented to the emergency department with ataxia, involuntary movements, and altered mental status secondary to inhalational heroin use. The patient presented with symptoms including agitation, tremors, speech difficulty, confusion, memory loss, and weakness. Magnetic resonance imaging (MRI) showed diffuse cerebral atrophy and electroencephalography (EEG) was significant for cerebral dysfunction in the left hemisphere and diffuse encephalopathy. The patient was treated with intravenous (IV) steroids, vitamins, and fluids but failed to show improvement. She was subsequently discharged to hospice 17 days after admission. There are few reported cases of toxic leukoencephalopathy due to heroin inhalation. The patient's young age and presentation following one month of abstinence are particularly unique as she suffered an acute decompensation with severe, lasting neurological deficits. This case highlights a potential presentation of HLE and seeks to increase clinical recognition in patients with a recent history of substance use and unexplained neurological symptoms.

Severe Tricuspid Regurgitation in a Patient With Previous Tricuspid Valve Surgery for Infective Endocarditis Secondary to Intravenous Drug Use: A Case Report.

Tricuspid regurgitation (TR) is an important but underappreciated disease in medical practice, and the severity can vary from moderate to severe. Right-sided infective endocarditis (RSIE) is more common in intravenous drug users (IVDUs), and the vast majority of these involve the tricuspid valve (TV). It is worth mentioning that right-sided valves are challenging to scan compared to left-sided valves. The incidence of severe tricuspid regurgitation (TR) immediately post-repair is not tangible, but it is considered to be rare. We present a case of a 47-year-old patient who had previous TV septal leaflet reconstruction using a bovine pericardial patch using 6/0 prolene, and an annuloplasty was performed by placing an annuloplasty ring in 2017 for infective endocarditis. The patient developed moderate to severe tricuspid regurgitation within a few weeks following the surgery. She was readmitted to the hospital four years later with a reduced consciousness level, and a subsequent repeat echocardiogram showed possible tricuspid valve vegetation. In addition, transoesophageal echocardiogram (TOE) demonstrated biventricular dysfunction and severe tricuspid regurgitation, along with moderate to severe mitral regurgitation (MR) that was variable depending on the rate of atrial fibrillation. The patient was not suitable for surgical intervention and was medically managed accordingly.

Heroin assisted treatment for key health outcomes in people with chronic heroin addictions: A context-focused systematic review.

BACKGROUND AND AIMS: Randomised controlled trials in Europe and Canada have shown that supervised heroin assisted treatment (HAT) is an effective treatment option for people with long-term heroin addictions for whom the standard opioid substitution treatments (OST) have not been effective. This review aims to evaluate the effectiveness of supervised HAT and analyse the significance of context and implementation in the design of successful HAT programmes. METHODS: PubMed, CENTRAL, Embase, and Web of Science were searched to identify randomised controlled trials (RCT) and systematic reviews evaluating supervised HAT compared to any other OST. Studies were eligible for inclusion if they were published in English, evaluated a supervised form of HAT, and included illegal drug use and/or health as a primary outcome measure. There were no restrictions on publication date. The following outcomes of the included studies were analysed using narrative synthesis and meta-analysis where possible: retention, street drug use, health, and social functioning. RESULTS: Nine randomised controlled trials spanning eight studies (n = 2331) and three systematic reviews met the inclusion criteria. Seven of the eight studies compared HAT to methadone maintenance treatment (MMT). One study compared HAT to injectable hydromorphone in a double-blind non-inferiority trial. Meta-analysis was performed on pooled results of retention across all included studies and found that HAT has a statistically significant effect on retention [Z = 7.65 (P > 0.0001)]. Five of the eight included studies found that supervised HAT reduces participants' use of illegal drugs more significantly than MMT. Evidence of improved health in participants receiving supervised HAT compared to other OSTs was inconsistent; positive effects were observed in three of the included studies (n = 1626). CONCLUSION: When compared to methadone maintenance treatment (MMT), heroin assisted treatment (HAT) more consistently retains people with heroin addictions in treatment and reduces their consumption of illicit drugs. TRIAL REGISTRATION: PROSPERO registration: CRD42022341306.

Functional neuroanatomy of craving in heroin use disorder: voxel-based meta-analysis of functional magnetic resonance imaging (fMRI) drug cue reactivity studies.

Background: The neuroanatomy of craving, typically investigated using the functional magnetic resonance imaging (fMRI) drug cue reactivity (FDCR) paradigm, has been shown to involve the mesocorticolimbic, nigrostriatal, and corticocerebellar systems in several substances. However, the neuroanatomy of craving in heroin use disorder is still unclear.Objective: The current meta-analysis examines previous research on the neuroanatomy of craving in abstinent individuals with opioid use disorder (OUD).Method: Seven databases were searched for studies comparing abstinent OUD versus healthy controls on drug > neutral contrast interaction at the whole-brain level. Voxel-based meta-analysis was performed using seed-based d mapping with permuted subject images (SDM-PSI). Thresholds were set at a family-wise error rate of less than 5% with the default pre-processing parameters of SDM-PSI.Results: A total of 10 studies were included (296 OUD and 187 controls). Four hyperactivated clusters were identified with Hedges' g of peaks that ranged from 0.51 to 0.82. These peaks and their associated clusters correspond to the three systems identified in the previous literature: a) mesocorticolimbic, b) nigrostriatal, and c) corticocerebellar. There were also newly revealed hyperactivation regions including the bilateral cingulate, precuneus, fusiform gyrus, pons, lingual gyrus, and inferior occipital gyrus. The meta-analysis did not reveal areas of hypoactivation.Conclusion: Recommendations based on the functional neuroanatomical findings of this meta-analysis include pharmacological interventions such as buprenorphine/naloxone and cognitive-behavioral treatments such as cue-exposure combined with HRV biofeedback. In addition, research should utilize FDCR as pre- and post-measurement to determine the effectiveness and mechanism of action of such interventions.

Extensive subcutaneous needle fragment retention due to injecting drug use.

Deaths in those with a history of injecting drug use commonly come to the attention of forensic pathologists, and therefore, one must have knowledge of possible findings and hazards of performing autopsies in these cases. This case demonstrates the finding of extensive retained broken needles in the subcutis of the arms and femoral region in a man with a long history of injecting drug use. While few or single broken needles are not uncommonly encountered, the multiplicity of needles in this case is noteworthy. We have demonstrated the findings both radiologically with PMCT and by conventional autopsy.

Transition from nonmedical prescribed opioids to non-injection heroin use among young integrated Thai male users in Bangkok.

Opioid use and misuse are understudied in Thailand despite evidence suggesting that a portion of young Thai male integrated drug users are initiating use of non-medical prescribed opioids with some transitioning to heroin. This study aims to capture and analyze the individual and social factors influencing these transitions. Twenty in-depth semi-structured interviews were conducted between December 2019 and January 2020 in the Bangkok metropolitan area with young male opioid users who transitioned to heroin. Sixteen respondents initiated opioid through a Tramadol cocktail named "YaPro" and tended to transition to heroin use within 21 months. The interaction of specific social and individual factors such as joining recreational activities, curiosity or experimentation gradually modified the opioid-related meanings, attitude and practices of Thai users, who ultimately transition to heroin use. These results indicate that drug prevention programs in Thailand should encompass young opioid users in their intervention and further research need to focus on nonmedical use of prescription opioids in Thailand.

Improving geographic access to methadone clinics.

INTRODUCTION: Opioid misuse is a nationwide public health crisis. Methadone treatment is proven to be highly successful in preventing opioid use disorder, reducing the use of illicit drugs, and preventing overdoses. Clients acquire methadone daily from clinics, making geographic access crucial for the initiation of and adherence to treatment. METHODS: This work estimates unsatisfied methadone demand due to lack of geographic access at a census tract level and models the problem of identifying optimal locations to open new methadone clinics. The objective function of the model is a weighted combination of providing access to individuals with unmet methadone demand and improving the travel time of individuals currently attending a clinic. Data on existing methadone clinics and statewide methadone demand is acquired from Substance Abuse and Mental Health Services Administration (SAMHSA) surveys from 2019. Unsatisfied demand is estimated through a linear regression model after aggregating the population, heroin use, and satisfied methadone demand at the state level. RESULTS: Nationwide, we find 18.2 % of the United States population does not have geographic access to a methadone clinic and estimate 77,973 individuals in these areas would attend a clinic if geographic access barriers were removed (95 % CI: 67,413-88,532). In a case study of six Midwestern states, we find that geography significantly contributes to the value of opening additional clinics and we see large differences in expected gains between states sharing similar characteristics such as population and satisfied methadone demand. The number of additional clients served by opening one new clinic ranges from 180 to 804 across these six states, representing between 8.4 % and 16.2 % of state unmet demand. Between 1.2 % and 14.1 % of existing clients were reassigned with a single newly opened clinic, with a one-way average travel distance improvement between 6.3 and 11.9 miles / person / day for these clients. CONCLUSIONS: The results demonstrate the large unserved methadone demand in the United States, the significant improvement in methadone access for new and existing clients that can be achieved by opening new clinics, and the important role state-specific geography plays in these decisions.

Abnormal brain oscillations and activation of patients with heroin use disorder during emotion regulation: The role of delta- and theta-band power.

BACKGROUND: Emotion dysregulation is a crucial component of substance use disorders in predisposition, maintenance, and relapse. Emotional regulation strategies are an important factor in emotion dysregulation. However, studies on heroin use disorder (HUD) patients' ability to use emotion regulation strategies are scarce. METHODS: Time-frequency-based analyses were used to compare the power of 33 patients with HUD and 28 healthy controls to elucidate whether patients with HUD have abnormal neural oscillations during passive viewing and emotion regulation strategies. Using the standardized low-resolution brain electromagnetic tomography algorithm (sLORETA), we estimated the possible sources of the anomalous band power. RESULTS: Compared to patients with HUD, healthy controls showed a stronger decrease in the power of the delta/theta band across all task conditions. The effect peaked at approximately 1300-1900 ms after stimulus onset and varied by task condition. The estimation of sLORETA suggested the frontal, parietal, and limbic lobes as possible generators. LIMITATIONS: We cannot exclude the potential influence of additional factors, such as sex, depression and anxiety levels, and polysubstance use, on the results. CONCLUSIONS: Patients with HUD have blunted arousal and impaired ability to use emotion regulation strategies. The abnormal patterns described above may be the underlying neurophysiological basis for this dysfunction. Future studies could combine different approaches to improve emotion dysregulation in patients with HUD to promote treatment outcomes.

Modeling the Dynamics of Heroin and Illicit Opioid Use Disorder, Treatment, and Recovery.

Opioid use disorder (OUD) has become a serious leading health issue in the USA leading to addiction, disability, or death by overdose. Research has shown that OUD can lead to a chronic lifelong disorder with greater risk for relapse and accidental overdose deaths. While the prescription opioid epidemic is a relatively new phenomenon, illicit opioid use via heroin has been around for decades. Recently, additional illicit opioids such as fentanyl have become increasingly available and problematic. We propose a mathematical model that focuses on illicit OUD and includes a class for recovered users but allows for individuals to either remain in or relapse back to the illicit OUD class. Therefore, in our model, individuals may cycle in and out of three different classes: illicit OUD, treatment, and recovered. We additionally include a treatment function with saturation, as it has been shown there is limited accessibility to specialty treatment facilities. We used 2002-2019 SAMHSA and CDC data for the US population, scaled to a medium-sized city, to obtain parameter estimates for the specific case of heroin. We found that the overdose death rate has been increasing linearly since around 2011, likely due to the increased presence of fentanyl in the heroin supply. Extrapolation of this overdose death rate, together with the obtained parameter estimates, predict that by 2038 no endemic equilibrium will exist and the only stable equilibrium will correspond to the absence of heroin use disorder in the population. There is a range of parameter values that will give rise to a backward bifurcation above a critical saturation of treatment availability. We show this for a range of overdose death rate values, thus illustrating the critical role played by the availability of specialty treatment facilities. Sensitivity analysis consistently shows the significant role of people entering treatment on their own accord, which suggests the importance of removing two of the most prevalent SAMHSA-determined reasons that individuals do not enter treatment: financial constraints and the stigma of seeking treatment for heroin use disorder.

Difference in topological organization of white matter structural connectome between methamphetamine and heroin use disorder.

The psychological symptoms caused by heroin and methamphetamine are significantly different in people with substance use disorders. The topological organization of structural connections that may underlie these differences remains unknown. The study sample consisted of 23 males with methamphetamine use disorder (MAUD), 20 males with heroin use disorder (HUD), and 21 male healthy controls (HCs) who were demographically matched. Diffusion tensor imaging and probabilistic tractography were used for white matter network construction. Psychological symptoms were evaluated by the Symptom Checklist-90. Using graph theoretical analysis, we examined the difference in graph-level and nodal-level properties among the groups. The network Hubs distribution and the relationship between the network alterations and psychological symptoms were identified. The MAUD group demonstrated significantly higher scores on anxiety, hostility, and symptoms of schizophrenia than the HUD and HCs groups. The HUD group showed significantly higher global efficiency and network strength than the HCs group, and higher network strength than the MAUD group. Compared with the HUD group, the MAUD group showed significantly lower Nodal Strength and efficiency, distributed mainly in the temporal, parietal, and occipital regions. We also found the network Hubs were decreased in the MAUD group, but increased in the HUD group. The Nodal Strength in the right superior temporal gyrus was significantly correlated with psychological symptoms in the MAUD group. These findings reflect the significant differences in topological structural connection between HUD and MAUD. This evidence helps shed some light on the neurobiological mechanisms of the psychological differences between HUD and MAUD, and extend our understanding of the structural disruption underlying MAUD-related psychological symptoms.

The influence of methadone on cerebral gray matter and functional connectivity.

BACKGROUND: Methadone maintenance treatment (MMT) is widely used for heroin use disorder. Although its curative effect is remarkable, there are problems associated with its use. While previous studies have found that methadone use may have certain effects on cerebral white matter, its effect on gray matter (GM) and its related neural networks is unclear. This study aimed to observe the effects of long-term methadone use on cerebral GM and the changes in related neural networks. METHODS: Patients receiving MMT treatment for heroin use disorder (N=50) were recruited. Longitudinal self-control was adopted, and the voxel-based morphometry (VBM) was used to compare the difference in cerebral GM volume before and after 1 year of methadone use, then we select the brain region where the GM volume changed as the region of interest (ROI), and use the DPARSF software for the whole brain function connection, and the differences in brain function connections before and after 1year MMT treatment were compared. RESULTS: Our results demonstrated that, after 1 year of MMT, patients showed smaller GM volume in the bilateral insula, occipital lingual gyrus, right cingulate gyrus, middle temporal gyrus, left inferior parietal lobule, caudate nucleus, temporal, and occipital regions, and the resting neural network of the brain also changed. CONCLUSIONS: We speculate that long-term methadone use can lead to damage to GM structure and adaptive changes in the neural network of patients with heroin use disorder, mainly involving emotional perception, spatial localization, working memory, and other related functions.

Reduced midbrain functional connectivity and recovery in abstinent heroin users.

Dopaminergic pathways from the midbrain to striatum as well as cortex are involved in addiction. However, the alternations of these pathways and whether the recoveries of aberrant circuits would be detected after prolonged abstinence in heroin users are rarely known. The resting-state functional connectivity (RSFC) patterns of midbrain (i.e., the ventral tegmental area (VTA) and substantia nigra (SN)) were compared between 40 abstinent heroin users with opioid use disorder (HUs) and 35 healthy controls (HCs). Then, we tested the functional recovery hypothesis by both cross-sectional and longitudinal design. For cross-sectional design, HUs were separated into short-term abstainers (STs) (3-15 days) and long-term abstainers (LTs) (>15 days). With regard to longitudinal design, 22 subjects among HUs were followed up for 10 months. A sandwich estimator method was used to analyze the differences between baseline HUs and follow-up HUs. HUs showed lower RSFC between midbrain and several cortical areas (medial orbitofrontal cortex (mOFC) and anterior cingulate cortex) compared with HCs. Besides, lower RSFC of VTA-right nucleus accumbens circuit as well as right SN- caudate circuit was also found in HUs. The enhanced RSFC value of VTA-left mOFC circuit was observed in LTs, compared with STs. Additionally, longitudinal design also revealed the increased RSFC values of the midbrain with frontal cortex after 10 months prolonged abstinence. We revealed abnormal functional organizations of midbrain-striato and midbrain-cortical circuits in HUs. More importantly, partially recovery of these dysfunctions can be found after long-term abstinence.

The ineffective emotion regulation strategies of heroin use disorder patients: An event-related potential study.

BACKGROUND: People with substance use disorders (SUDs) usually experience emotion dysregulation, which may be a consequence of or a risk factor for the development and maintenance of substance misuse. Despite growing evidence on emotion dysregulation among people with SUDs, relatively few studies have explored emotion dysregulation in heroin use disorder (HUD) patients. METHODS: Using event-related potentials (ERP), we compared the emotion regulation ability of 33 HUD patients and 30 healthy controls according to their average electroencephalogram amplitudes of the late positive potential (LPP) component in 400-1000 ms and 1000-2000 ms time windows, while viewing neutral and unpleasant emotional pictures, and using emotion regulation strategies (expressive suppression, cognitive reappraisal, and a combination) while viewing unpleasant pictures. We recorded their mood states and how successfully they used emotion regulation strategies in each block using 7-point scales. RESULTS: Relative to healthy controls, the LPP amplitudes of HUD patients were significantly lower when viewing emotional stimuli (pearlyLPP < 0.05) and using emotion regulation strategies (all p < 0.05). The left hemisphere was more active in healthy controls (pearlyLPP < 0.05, plateLPP < 0.01); there were no differences in scalp position activation among HUD patients. DISCUSSION: Compared to healthy controls, HUD patients' emotional arousal and emotion regulation ability were impaired, as reflected by the LPP component. Their abnormal scalp activation pattern may imply abnormal brain activity. Future research could explore this with electroencephalogram source analysis techniques, functional magnetic resonance imaging, or other technologies. Intervention effects for emotion dysregulation in HUD treatment are also worth exploring.

Clostridium botulinum Type B Isolated From a Wound Botulism Case Due to Injection Drug Use Resembles Other Local Strains Originating From Hawaii.

Clostridium botulinum produces botulinum neurotoxin (BoNT), which can lead to death if untreated. In the United States, over 90% of wound botulism cases are associated with injection drug use of black tar heroin. We sought to determine the phylogenetic relatedness of C. botulinum isolated from an injection drug use wound botulism case and isolates from endogenous infant botulism cases in Hawaii. Nineteen C. botulinum type B isolates from Hawaii and one type B isolate from California were analyzed by whole-genome sequencing. The botulinum toxin gene (bont) subtype was determined using CLC Genomics Workbench, and the seven-gene multi-locus sequence type (MLST) was identified by querying PubMLST. Mashtree and pairwise average nucleotide identity were used to find nearest neighbors, and Lyve-SET approximated a phylogeny. Eighteen of the isolates harbored the bont/B5 gene: of those, 17 were classified as sequence type ST36 and one was classified as ST104. A single isolate from Hawaii harbored bont/B1 and was determined to belong to ST110, and the isolate from California harbored bont/B1 and belonged to ST30. A tree constructed with Lyve-SET showed a high degree of homology among all the Hawaiian C. botulinum isolates that harbor the bont/B5 gene. Our results indicate that the bont/B-expressing isolates recovered from Hawaii are closely related to each other, suggesting local contamination of the drug paraphernalia or the wound itself with spores rather than contamination of the drug at manufacture or during transport. These findings may assist in identifying interventions to decrease wound botulism among persons who inject drugs.

Heroin-Induced Acute Pancreatitis.

Heroin-induced pancreatitis (HIP) is rare with only a few cases reported previously in the literature and the pathophysiology mechanism is yet to be investigated. We present two cases of acute pancreatitis (AP) in the setting of acute heroin (diacetylmorphine) intoxication. Both patients presented with nausea, vomiting and severe abdominal pain after intranasal heroin use. On laboratory analysis were found to have elevated serum lipase, positive urine toxicology for opioids, without any other obvious causes for AP. Both patients had a full recovery with supportive treatment. As a general approach, drug-induced pancreatitis is a diagnosis of exclusion and a high index of suspicion is required when the most common etiologies are ruled out.

Differences in cue-induced brain activation between long-term methadone maintenance treatment and protracted abstinence in heroin use disorder patients: a functional magnetic resonance imaging study.

BACKGROUND: Heroin use disorder (HUD) remains one of the gravest public health issues in China. Methadone maintenance treatment (MMT) and protracted abstinence (PA) are the most commonly used treatments for HUD. Although both treatment approaches can alleviate heroin cravings, a previous study found that MMT patients had stronger cue-induced brain activation than patients undergoing PA; however, the changes associated with long-term treatment are unclear. METHODS: Male patients with HUD who had been undergoing either PA (n=24) or MTT (n=21) for approximately 12 months, together with 20 demographically matched healthy controls, completed an event-related functional magnetic resonance imaging (fMRI) task. The subjective craving for heroin was evaluated using a visual analog scale. RESULTS: Compared to the healthy controls, the MMT and PA groups demonstrated significantly higher brain activation in the left pallidum, middle occipital gyrus, postcentral gyrus, anterior cingulate cortex, middle cingulate cortex, inferior parietal lobule, superior parietal lobule, amygdala, hippocampus, right inferior temporal gyrus, inferior frontal gyrus triangularis, and caudate during exposure to heroin-related cues. Compared to those undergoing PA, patients in the MMT group demonstrated significantly higher brain activation in all of these regions. Except for the left inferior parietal lobule and left superior parietal lobule, there were no statistically significant differences between the PA and healthy control groups. The MMT patients showed significantly higher subjective cravings before and after exposure to heroin cues than the PA group, but there was no significant difference in the change in subjective cravings between the 2 groups. CONCLUSIONS: The results suggested that although the HUD patients receiving long-term MMT complied with the treatment, they still had higher subjective cravings and cue-induced brain activation than those undergoing PA. Therefore, long-term PA appears to be more beneficial than MMT in reducing the salience value of drug cues in patients with HUD.

Association study of Catechol-o-methyltransferase and Alpha-1-adrenergic receptor gene polymorphisms with multiple phenotypes of heroin use disorder.

Heroin use disorder is a chronic relapsing brain disease containing multiple phenotypes. These phenotypes vary among heroin users and might be influenced by genetic factors. Single-nucleotide polymorphisms (SNPs) of catechol-O-methyltransferase (COMT) and alpha-1-adrenergic receptor (ADRA1A) genes are associated with heroin use disorder. However, it has not been clarified which phenotypes of heroin use disorder are related to these genes. To address this question, we recruited 801 unrelated heroin users and divided them into different subgroups according to four important phenotypes of heroin use disorder. Then 7 SNPs in the functional region of these genes were systematically screened and genotyped using a SNaPshot assay. We found that the A allele of ADRA1A rs1048101 was associated with a shorter duration of transition from first use to addiction. Subjects with the C allele of ADRA1A rs3808585 were more susceptible to memory impairment after heroin use disorder. Subjects with the G allele of COMT rs769224 were more likely to take a higher dose of heroin every day. Our study confirmed the association between polymorphisms of COMT and ADRA1A with those specific phenotypes of heroin use disorder, which will be instructive for the precise treatment of the disease.