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.

Systematic review of Pharmacogenomics Knowledgebase evidence for pharmacogenomic links to the dopamine reward pathway for heroin dependence.

Genetics play an important role in opioid use disorder (OUD); however, few specific gene variants have been identified. Therefore, there is a need to further understand the pharmacogenomics influences on the pharmacodynamics of opioids. The Pharmacogenomics Knowledgebase (PharmGKB), a database that links genetic variation and drug interaction in the body, was queried to identify polymorphisms associated with heroin dependence in the context of opioid related disorders/OUD. Eight genes with 22 variants were identified as linked to increased risk of heroin dependence, with three genes and variants linked to decreased risk, although the level of evidence was moderate to low. Therefore, continued exploration of biomarker influences on OUD, reward pathways and other contributing circuitries is necessary to understand the true impact of genetics on OUD before integration into clinical guidelines.

Brain responses to drug cues predict craving changes in abstinent heroin users: A preliminary study.

BACKGROUND: Loss of control over drug intake occurring in drug addiction is believed to result from disruption of reward circuits, including reduced responsiveness to natural rewards (e.g., monetary, sex) and heightened responsiveness to drug reward. Yet few studies have assessed reward deficiency and related brain responses in abstinent heroin users with opioid use disorder, and less is known whether the brain responses can predict cue-induced craving changes following by prolonged abstinence. METHOD: 31 heroin users (age: 44.13±7.68 years, male: 18 (58%), duration of abstinence: 85.2 ± 52.5 days) were enrolled at a mandatory detoxification center. By employing a cue-reactivity paradigm including three types of cues (drug, sexual, neutral), brain regional activations and circuit-level functional coupling were extracted. Among the 31 heroin users, 15 were followed up longitudinally to assess cue induced craving changes in the ensuing 6 months. RESULTS: One way analysis of variance results showed that heroin users have differential brain activations to the three cues (neutral, drug and sexual) in the left dorsolateral prefrontal cortex (DLPFC), insula, orbiotofrontal cortex (OFC) and the bilateral thalamus. Drug cue induced greater activations in left DLPFC, insula and OFC compared to sexual cue. The psychophysiological interactions (PPI) analysis revealed negative couplings of the left DLPFC and the left OFC, bilateral thalamus, putamen in heroin users during drug cue exposure. In the 6-month follow-up study, both drug cue induced activation of the left DLPFC and the functional coupling of the left DLPFC-bilateral thalamus at baseline was correlated with craving reductions, which were not found for sexual cues. CONCLUSION: Our preliminary study provided novel evidence for the reward deficiency theory of opioid use disorder. Our findings also have clinical implications, as drug cue induced activation of the left DLPFC and functional coupling of left DLPFC-bilateral thalamus may be potential neuroimaging markers for craving changes during prolonged abstinence. Evidently, the findings in the current preliminary study should be confirmed by large sample size in the future.

Contrasting effects of the α7 nicotinic receptor antagonist methyllycaconitine in different rat models of heroin reinstatement.

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.

Functional evaluation of NK1 antagonism on cue reactivity in opiate dependence; An fMRI study.

BACKGROUND: Opiate addiction is a major health challenge with substantial societal cost. Though harm minimisation strategies have been effective, there is a growing need for new treatments for detoxification and relapse prevention. Preclinical research has found neurokinin 1 (NK1) receptors have prominent effects on opiate reward and reinforcement, and human studies have found NK1 antagonism led to reductions in craving and withdrawal. However, its effect on brain mechanisms in opiate addiction has not yet been examined. METHODS: This study aims to assess the impact of NK1 antagonist aprepitant on heroin cue-elicited changes in blood-oxygenation level dependent (BOLD) signal in opiate dependent individuals undergoing detoxification. Participants will attend two scanning sessions and receive a single dose of aprepitant (320 mg) and a placebo in a randomised, cross-over design. During functional magnetic resonance imaging participants will undergo two runs of a cue reactivity task, which consists of passive viewing of drug cues or neutral cues in a block design fashion. We hypothesise that NK1 antagonism will attenuate the BOLD response to drug cues in the caudate nucleus and amygdala. Regions of interest were selected based on NK1 receptor density and their role in cue reactivity and craving.

Reduced thalamic resting-state functional connectivity and impaired cognition in acute abstinent heroin users.

As a critical component of cortico-striato-thalamo-cortical loop in addiction, our understanding of the thalamus in impaired cognition of heroin users (HU) has been limited. Due to the complex thalamic connection with cortical and subcortical regions, thalamus was divided into prefrontal (PFC), occipital (OC), premotor, primary motor, sensory, temporal, and posterior parietal association subregions according to white matter tractography. We adopted seven subregions of bilateral thalamus as regions of interest to systematically study the implications of distinct thalamic nuclei in acute abstinent HU. The volume and resting-state functional connectivity (RSFC) differences of the thalamus were investigated between age-, gender-, and alcohol-matched 37 HU and 33 healthy controls (HCs). Trail making test-A (TMT-A) was adopted to assess cognitive function deficits, which were then correlated with neuroimaging findings. Although no significant different volumes were found, HU group showed decreased RSFC between left PFC_thalamus and middle temporal gyrus as well as between left OC_thalamus and inferior frontal gyrus and supplementary motor area relative to HCs. Meanwhile, the higher TMT-A scores in HU were negatively correlated with PFC_thalamic RSFC with inferior temporal gyrus, fusiform, and precuneus. Craving scores were negatively correlated with OC_thalamic RSFC with accumbens, hippocampus, and insula. Opiate Withdrawal Scale scores were negatively correlated with left PFC/OC_thalamic RSFC with orbitofrontal cortex and medial PFC. We indicated two thalamus subregions separately involvement in cognitive control and craving to reveal the implications of thalamic subnucleus in pathology of acute abstinent HU.

Association studies of dopamine synthesis and metabolism genes with multiple phenotypes of heroin dependence.

BACKGROUND: Heroin dependence is a complex disease with multiple phenotypes. Classification of heroin users into more homogeneous subgroups on the basis of these phenotypes could help to identify the involved genetic factors and precise treatments. This study aimed to identify the association between genetic polymorphisms of DA synthesis and metabolism genes, including tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), solute carrier family 6 member 3 (SLC6A3) and DA beta-hydroxylase (DBH), with six important phenotypes of heroin dependence. METHODS: A total of 801 heroin dependent patients were recruited and fourteen potential functional single nucleotide polymorphisms (SNPs) were genotyped by SNaPshot. Associations between SNPs with six phenotypes were mainly assessed by binary logistic regression. Generalized multifactor dimensionality reduction was used to analyze the gene-by-gene and gene-by-environment interactions. RESULTS: We found that DBH rs1611114 TT genotype had a protective effect on memory impairment after heroin dependence (P = 0.002, OR = 0.610). We also found that the income-rs12666409-rs129915-rs1611114 interaction yielded the highest testing balance accuracy and cross-validation consistency for memory change after heroin dependence. CONCLUSIONS: Our results suggest that the memory change after heroin dependence was a result of a combination of genetics and environment. This finding could lead to a better understanding of heroin dependence and further improve personalized treatment.

Heroin-induced respiratory depression and the influence of dose variation: within-subject between-session changes following dose reduction.

BACKGROUND AND AIMS: Globally, more than 100 000 people die annually from opioid overdose. Opportunities to study physiological events in at-risk individuals are limited. This study examined variation of opioid dose and impact on respiratory depression in a chronic injecting heroin user at separate time-points during his long-term diamorphine maintenance treatment. DESIGN: A single-subject study over 5 years during which participant underwent experimental studies on diamorphine-induced respiratory depression, at changing maintenance doses. SETTING: A clinical research facility. Participant Male subject on long-term injectable diamorphine (pharmaceutical heroin) maintenance treatment for heroin addiction. MEASUREMENTS: Physiological measures of oxygen saturation (SpO2 ), end-tidal carbon dioxide (ETCO2 ) and respiratory rate (RR) were used to indicate severity of respiratory depression. FINDINGS: (1) After diamorphine injection, respiratory regulation became abnormal, with prolonged apnoea exceeding 20 sec (maximum 56 sec), elevated ETCO2 (maximum 6.9%) and hypoxaemia (minimum SpO2 80%). (2) Abnormalities were greater with highest diamorphine dose: average SpO2 was 89.3% after 100 mg diamorphine versus 93.6% and 92.8% for the two 30-mg doses. (3) However, long apnoeic pauses and high levels of ETCO2 % were also present after lower doses. CONCLUSIONS: With marked inter-session variability, these findings corroborate observations of inconsistent relationships between opioid dose and overdose risk.

The role of the paraventricular nucleus of the thalamus in the augmentation of heroin seeking induced by chronic food restriction.

Drug addiction is a chronic disorder that is characterized by compulsive drug seeking and involves cycling between periods of compulsive drug use, abstinence, and relapse. In both human addicts and animal models of addiction, chronic food restriction has been shown to increase rates of relapse. Previously, our laboratory has demonstrated a robust increase in drug seeking following a period of withdrawal in chronically food-restricted rats compared with sated rats. To date, the neural mechanisms that mediate the effect of chronic food restriction on drug seeking have not been elucidated. However, the paraventricular nucleus of the thalamus (PVT) appears to be a promising target to investigate. The objective of the current study was to examine the role of the PVT in the augmentation of heroin seeking induced by chronic food restriction. Male Long-Evans rats were trained to self-administer heroin for 10 days. Rats were then removed from the training chambers and experienced a 14-day withdrawal period with either unrestricted (sated) or mildly restricted (FDR) access to food. On day 14, rats underwent a 1-hour heroin-seeking test under extinction conditions, during which neural activity in the PVT was either inhibited or increased using pharmacological or chemogenetic approaches. Unexpectedly, inhibition of the PVT did not alter heroin seeking in food-restricted or sated rats, while enhancing neural activity in the PVT-attenuated heroin seeking in food-restricted rats. These results indicate that PVT activity can modulate heroin seeking induced by chronic food restriction.

A case report illustrating the effects of repetitive transcranial magnetic stimulation on cue-induced craving in an individual with opioid and cocaine use disorder.

Nationally, it was estimated that 11.4 million people misused opioids in 2017 with more than 47,000 opioid-related deaths. Although medication-assisted treatment (MAT) has been effective in enhancing treatment retention and decreasing frequency of opioid use, relapse rates for opioids and other substances remain high, emphasizing the importance of investigating novel interventions to augment MAT. One potential treatment approach is repetitive transcranial magnetic stimulation (rTMS)-a noninvasive, electrophysiological method of neuromodulation. Recently published studies of rTMS in individuals with alcohol, nicotine, and cocaine use disorder have suggested that this treatment shows promise in reducing cravings and substance use. The literature specific to rTMS and opioid use disorder (OUD) is limited to a single published study in heroin users, which showed that a single session of rTMS to the left dorsolateral prefrontal cortex (DLPFC) reduced cue-induced craving, with a further reduction following 5 consecutive days of rTMS. The following case report involved a 25-year-old Caucasian male diagnosed with OUD and cocaine use disorder. This subject continued to demonstrate ongoing substance use despite participating in comprehensive MAT with buprenorphine/naloxone in combination with psychosocial interventions. He was administered 7 separate sessions of rTMS targeting the left DLPFC. Substance-related cues were presented prior to, during, and following these rTMS administration sessions and the subject rated his substance cravings via a 100-point Visual Analog Scale. When compared with his cue-induced craving ratings, there was a mean reduction in craving for heroin and cocaine by ∼60% to 82% following the 7 administration sessions. Although this is a single case, further investigation of rTMS as an augmentation strategy for OUD and polysubstance use is warranted. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Basolateral amygdala is required for reconsolidation updating of heroin-associated memory after prolonged withdrawal.

Postretrieval extinction procedures are effective nonpharmacological interventions for disrupting drug-associated memories. Nonetheless, the conditioned stimulus (CS) memory retrieval-extinction procedure is ineffective in inhibiting drug craving and relapse after prolonged withdrawal, which significantly undermines its therapeutic potential. In the present study, we showed that, unlike the CS memory retrieval-extinction procedure, noncontingent heroin injections (unconditioned stimulus [UCS]) 1 hour before the extinction sessions decreased the heroin-priming-induced reinstatement, renewal, and spontaneous recovery of heroin seeking after 28 days of withdrawal (ie, remote heroin-associated memories) in rats. The UCS retrieval manipulation induced reactivation of the basolateral amygdala (BLA) after prolonged withdrawal, and this reactivation was absent with the CS retrieval manipulation. Chemogenetic inactivation of the BLA abolished the inhibitory effect of the UCS memory retrieval-extinction procedure on heroin-priming-induced reinstatement after prolonged withdrawal. Furthermore, the combination of chemogenetic reactivation of BLA and CS retrieval-extinction procedure resembled the inhibitory effect of UCS retrieval-extinction procedure on heroin seeking after prolonged withdrawal. We also observed that the inhibitory effect of the UCS retrieval-extinction procedure is mediated by regulation of AMPA receptor endocytosis in the BLA. Our results demonstrate critical engagement of the BLA in reconsolidation updating of heroin-associated memory after prolonged withdrawal, extending our knowledge of the boundary conditions of the reconsolidation of drug-associated memories.

Screening Heroin Smokers Attending Community Drug Clinics for Change in Lung Function: A Cohort Study.

BACKGROUND: Heroin smokers have high rates of COPD, respiratory morbidity, hospital admission, and mortality. We assessed the natural history of symptoms and lung function in this population over time. METHODS: A cohort of heroin smokers with COPD was followed for 18 to 24 months. At baseline and follow-up, respiratory symptoms were measured by the Medical Research Council Dyspnea Scale (MRC) and the COPD Assessment Tool (CAT), and postbronchodilator spirometry was performed. Frequency of health-care-seeking episodes was extracted from routine health records. Parametric, nonparametric, and linear regression models were used to analyze the change in symptoms and lung function over time. RESULTS: Of 372 participants originally recruited, 161 were assessed at follow-up (mean age, 51.0 ± 5.3 years; 74 women [46%]) and 106 participants completed postbronchodilator spirometry. All participants were current or previous heroin smokers, and 122 (75.8%) had smoked crack. Symptoms increased over time (MRC score increased by 0.48 points per year, P < .001; CAT score increased by 1.60 points per year, P < .001). FEV1 declined annually by 90 ± 190 mL (P < .001). This deterioration was not associated with change in tobacco or heroin smoking status or use of inhaled medications. CONCLUSIONS: Heroin smokers experience a high and increasing burden of chronic respiratory symptoms and a decline in FEV1 that exceeds the normal age-related decline observed among tobacco smokers with COPD and healthy nonsmokers. Targeted COPD diagnostic and treatment services hosted within opiate substitution services could benefit this vulnerable, relatively inaccessible, and underserved group of people.

Machine learning: assessing neurovascular signals in the prefrontal cortex with non-invasive bimodal electro-optical neuroimaging in opiate addiction.

Chronic and recurrent opiate use injuries brain tissue and cause serious pathophysiological changes in hemodynamic and subsequent inflammatory responses. Prefrontal cortex (PFC) has been implicated in drug addiction. However, the mechanism underlying systems-level neuroadaptations in PFC during abstinence has not been fully characterized. The objective of our study was to determine what neural oscillatory activity contributes to the chronic effect of opiate exposure and whether the activity could be coupled to neurovascular information in the PFC. We employed resting-state functional connectivity to explore alterations in 8 patients with heroin dependency who stayed abstinent (>3 months; HD) compared with 11 control subjects. A non-invasive neuroimaging strategy was applied to combine electrophysiological signals through electroencephalography (EEG) with hemodynamic signals through functional near-infrared spectroscopy (fNIRS). The electrophysiological signals indicate neural synchrony and the oscillatory activity, and the hemodynamic signals indicate blood oxygenation in small vessels in the PFC. A supervised machine learning method was used to obtain associations between EEG and fNIRS modalities to improve precision and localization. HD patients demonstrated desynchronized lower alpha rhythms and decreased connectivity in PFC networks. Asymmetric excitability and cerebrovascular injury were also observed. This pilot study suggests that cerebrovascular injury in PFC may result from chronic opiate intake.

2Hz-electroacupuncture attenuates heroin-seeking behaviors via adjusts CB1-Rs and CB2-Rs expression in relapse-relevant brain regions of heroin self-administration rats.

Opiate addiction has a high rate of relapse. The accumulating evidence shows that electroacupuncture (EA) may be effective for the treatment of opiate relapse. However, the change of expression of CB1-Rs and CB2-Rs involve in 2Hz EA anti-relapse pathway is still unclear. To explore the changes of expression of CB1-Rs and CB2-Rs, heroin self-administration (SA) model rats were adopted and treated using 2Hz EA. The expressions of CB1-Rs and CB2-Rs were observed using immunohistochemistry method. The results showed that, compared with the control group, active pokes in the heroin-addicted group increased, while the active pokes decreased significantly in 2Hz EA group compared with heroin-addicted group. Correspondingly, the expression of CB1-Rs in prefrontal cortex (PFC), hippocampus (Hip), nucleus accumbens (NAc) and ventral tegmental area (VTA) all increased significantly while the expression of CB2-Rs in those relapse-relevant brain regions decreased obviously in heroin-addicted group when compared with the control group. In addition, the expression of CB1-Rs obviously decreased in the 2Hz EA group while the expression of CB2-Rs in those relapse-relevant brain regions increased significantly when compared with the heroin-addicted group. It indicated that 2Hz EA could attenuate the heroin-evoked seeking behaviors effectively. The anti-relapse effects of 2Hz EA might be related to the decrease of CB1-Rs and increase of CB2-Rs expression in relapse-relevant brain regions of heroin SA rats.

Atypical frontal midline theta activity during cognitive control in heroin addicts.

Deficiency in cognitive control has been proposed as a core issue in addictive behavior, and recent advancements in cognitive neuroscience have suggested that frontal midline theta is a mechanism for cognitive control. This study examined frontal midline theta deficits in patients with heroin dependence during a Go/No-go task which explicitly involved cognitive control. Electroencephalography readings were collected from 15 male heroin addicts and 17 demographically matched healthy controls during an equal probability Go/No-go task. The findings revealed that heroin addicts responded significantly slower to the Go stimulus as compared to the healthy control. Heroin addicts also showed less frontal midline theta modulations between the Go and No-go conditions. These findings provided further evidence toward understanding the nature of drug addiction-related cognitive dysfunction.

Opioid-related compartment syndrome and associated morbidity.

INTRODUCTION: Opioid-related compartment syndrome (ORCS) is an understudied complication related to opioid overdose. We hypothesized that ORCS would be associated with worse clinical outcomes, including higher amputation rates, need for multiple surgical procedures, and rhabdomyolysis on admission, compared with nonopioid-related compartment syndrome (NORCS). METHODS: We used Current Procedural Terminology codes for fasciotomy as a proxy marker for cases of compartment syndrome treated at 1 health system from January 1, 2016, to December 21, 2018. We excluded patients younger than 18 years, those treated for exertional compartment syndrome, and those who underwent elective fasciotomies. Seventy-four patients met our inclusion criteria. Data reviewed included patient characteristics, cause of compartment syndrome, time until evaluation for compartment syndrome, peak creatinine kinase levels, number of surgical procedures required, duration of hospital stay, and postoperative inpatient morbidity and death. Patients were categorized as having ORCS (n = 8) or NORCS (n = 66). Alpha = .05. RESULTS: All cases of ORCS occurred in men. Opioid use was the third most common cause of compartment syndrome. Two patients underwent amputation, both in the ORCS group (p <  0.01). The median number of debridements was significantly higher for the ORCS group (median, 4; interquartile range [IQR]: 3-6) than for the NORCS group (median, 3; IQR 2-4) (p =  0.03). Duration of hospital stay was longer for the ORCS group (median, 27 days; IQR 16-38) compared with the NORCS group (median, 9 days; IQR: 5-13) (p <  0.001). Mean (± standard deviation) peak creatinine kinase level was significantly higher in the ORCS group (224,000 ± 225,052 U/L) compared with the NORCS group (7550 ± 32,500) (p <  0.001). The proportion of patients who underwent hemodialysis was higher in the ORCS group (88%) than in the NORCS group (35%) (p <  0.001). All ORCS patients presented >8 h after immobilization in a dependent position. CONCLUSION: Patients in the ORCS group had delayed presentations and significantly more morbidity compared with patients in the NORCS group.

The polymorphism of dopamine D2 receptor TaqIA gene is associated with brain response to drug cues in male heroin-dependent individuals during methadone maintenance treatment.

BACKGROUND: Polymorphism of the dopamine D2 receptor TaqIA gene is related to reward response, relapse risks and effect of therapy for drug addiction. Whether the cue-induced craving and brain response was related to dopamine D2 receptor TaqIA gene is unknown. METHODS: Forty-nine male heroin-dependent individuals [31 with A1 allele of the TaqIA (A1+), 18 A2 allele carriers (A1-)] under methadone maintenance treatment and 20 healthy control subjects performed a heroin cue-reactivity task during functional magnetic resonance imaging. Cue-elicited craving was measured. Difference in cue induced craving and brain response were analyzed among the three groups. Correlation analyses between craving and differential brain response, heroin use and treatment history were performed within A1+ and A1- group respectively. RESULTS: Compared with A1- group, A1+ group showed greater cue-induced response in the ventrolateral prefrontal cortex, medial orbitofrontal gyrus, dorsomedial prefrontal cortex, pallidum, putamen, thalamus, superior parietal lobule and superior occipital gyrus. No difference in craving was found. The response in right thalamus positively correlated with daily heroin and methadone dose in A1+ group. For A1- group, response in left ventral orbitofrontal cortex, medial orbitofrontal gyrus, ventral anterior cingulate cortex, caudate, precuneus, calcarine and bilateral pallidum negatively correlated with duration of heroin use. The response in left ventral orbitofrontal cortex, medial orbitofrontal gyrus, bilateral calcarine and right cerebellum negatively correlated with duration of methadone maintenance treatment in A1- group. CONCLUSIONS: The findings supported that A1 allele of the TaqIA is associated with higher salience allocation to heroin-related cues in heroin-dependent patients.

Craving for heroin: difference between methadone maintenance therapy patients with and without ADHD.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder persisting in adulthood in 40-60% of cases. Clinical and neuroimaging studies suggest that patients affected by both drug addiction and ADHD show higher rates of craving for drug than patients without ADHD. We designed a pilot open-label study to investigate the effects of ADHD on craving for heroin in methadone maintenance therapy patients. METHOD: Patients were recruited from outpatient facilities in an addiction treatment unit in the municipality of Alba, Italy. They were assessed using the Structured Clinical Interview for DSM-5 (SCID-5), the SCID-5 for Personality Disorders (SCID-5-PD), the Diagnostic Interview for Adult ADHD, second edition (DIVA 2.0), and the Clinical Opiate Withdrawal Scale (COWS). Categorical variables were examined using the chi-square test, and continuous variables, the t-test and Mann-Whitney's U test for normally and non-normally distributed data, respectively. Data distribution was evaluated using Shapiro-Wilk's test. Significance was set at p=0.05. Bonferroni correction was applied (0.0063) to avoid type I error. RESULTS: A total of 104 patients were included in the study: 14 affected by ADHD (13.5%) and 90 were not affected (86.5%). Patients with ADHD showed higher intensity of craving for heroin than patients without ADHD in the absence of withdrawal symptoms. CONCLUSION: Drug addiction and ADHD share various neurobiological mechanisms that mutually influence the evolution of both disorders. In particular, dopamine dysfunction within various brain circuits may influence impulsivity levels, motivation, inhibitory control, executive functions, and behavior and, consequently, the intensity of craving.

Heroin addiction engages negative emotional learning brain circuits in rats.

Opioid use disorder (OUD) is associated with the emergence of persistent negative emotional states during drug abstinence that drive compulsive drug taking and seeking. Functional magnetic resonance imaging (fMRI) in rats identified neurocircuits that were activated by stimuli that were previously paired with heroin withdrawal. The activation of amygdala and hypothalamic circuits was related to the degree of heroin dependence, supporting the significance of conditioned negative affect in sustaining compulsive-like heroin seeking and taking and providing neurobiological insights into the drivers of the current opioid crisis.

Craving for heroin: difference between methadone maintenance therapy patients with and without ADHD / Fissura por heroína: diferença entre pacientes em terapia de manutenção com metadona com e sem TDAH

Abstract Introduction Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder persisting in adulthood in 40-60% of cases. Clinical and neuroimaging studies suggest that patients affected by both drug addiction and ADHD show higher rates of craving for drug than patients without ADHD. We designed a pilot open-label study to investigate the effects of ADHD on craving for heroin in methadone maintenance therapy patients. Method Patients were recruited from outpatient facilities in an addiction treatment unit in the municipality of Alba, Italy. They were assessed using the Structured Clinical Interview for DSM-5 (SCID-5), the SCID-5 for Personality Disorders (SCID-5-PD), the Diagnostic Interview for Adult ADHD, second edition (DIVA 2.0), and the Clinical Opiate Withdrawal Scale (COWS). Categorical variables were examined using the chi-square test, and continuous variables, the t-test and Mann-Whitney's U test for normally and non-normally distributed data, respectively. Data distribution was evaluated using Shapiro-Wilk's test. Significance was set at p=0.05. Bonferroni correction was applied (0.0063) to avoid type I error. Results A total of 104 patients were included in the study: 14 affected by ADHD (13.5%) and 90 were not affected (86.5%). Patients with ADHD showed higher intensity of craving for heroin than patients without ADHD in the absence of withdrawal symptoms. Conclusion Drug addiction and ADHD share various neurobiological mechanisms that mutually influence the evolution of both disorders. In particular, dopamine dysfunction within various brain circuits may influence impulsivity levels, motivation, inhibitory control, executive functions, and behavior and, consequently, the intensity of craving.

Resumo Introdução O transtorno de déficit de atenção e hiperatividade (TDAH) é um transtorno do neurodesenvolvimento que persiste na idade adulta em 40-60% dos casos. Estudos clínicos e de neuroimagem sugerem que pacientes afetados tanto por adição quanto por TDAH apresentam maiores índices de fissura (craving) por droga do que pacientes sem TDAH. Este estudo piloto aberto investigou os efeitos do TDAH sobre fissura por heroína em pacientes em terapia de manutenção com metadona. Método Os pacientes foram recrutados em serviços ambulatoriais em uma unidade de tratamento de adição na cidade de Alba, Itália. Eles foram avaliados usando os seguintes instrumentos: Structured Clinical Interview for DSM-5 (SCID-5), SCID-5 for Personality Disorders (SCID-5-PD), Diagnostic Interview for Adult TDAH, second edition (DIVA 2.0) e Clinical Opiate Withdrawal Scale (COWS). Variáveis categóricas foram examinadas utilizando o teste do qui-quadrado, e variáveis contínuas, o teste t e o teste U de Mann-Whitney para dados com distribuição normal e não normal, respectivamente. A distribuição dos dados foi avaliada usando o teste de Shapiro-Wilk. O nível de significância foi estabelecido em p=0,05. A correção de Bonferroni foi aplicada (0,0063) para evitar erro tipo I. Resultados Um total de 104 pacientes foram incluídos no estudo: 14 com TDAH (13,5%) e 90 sem (86,5%). Pacientes com TDAH mostraram maior intensidade de fissura por heroína do que pacientes sem TDAH na ausência de sintomas de abstinência. Conclusão Adição e TDAH compartilham mecanismos neurobiológicos que influenciam mutuamente a evolução dos dois transtornos. Em particular, a disfunção da dopamina em vários circuitos cerebrais pode influenciar os níveis de impulsividade, motivação, controle inibitório, funções executivas e comportamento, e, portanto, a intensidade da fissura.