Heroin-dependent Patients Research Articles

Predictors of Outcome During a 6-Month Follow-Up Among Heroin Dependent Patients Receiving Buprenorphine/Naloxone Maintenance Treatment

Objective: The aim of this study was to evaluate the predictors of outcome during a 6-month follow-up among heroin dependent patients receiving buprenorphine/naloxone (BN) maintenance treatment.Methods: Three hundred and ninety-two heroin dependent patients, who were consecutively admitted to the clinic (n=106, 27.04%) or accepted as outpatients for BN maintenance treatment (n=286, 72.96%) were included in the study. Patients were investigated with the Bakirkoy Opioid Withdrawal Scale (BOWS), the Substance Craving Scale (SCS), the Drug Use Disorders Identification Test (DUDIT), the Drug Abuse Screening Test (DAST-10) and the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) at baseline evaluation.Results: Among 392 heroin dependent patients, 287 (73.21%) were considered to have relapsed to substance use or to have dropped out of treatment, whereas 105 (26.79%) were considered to be compliant to the BN maintenance treatment. Rates of having a first degree relative with substance abuse, being under probation and having a history of suicide attempts were higher in relapsed/dropout group (RDG) when compared with the maintenance group. Other sociodemographic variables did not differ between these two groups. Mean scores on the BOWS and SCS were higher in the RDG than the maintenance group at the first month, whereas the DUDIT, DAST-10, SOCRATES scores and mean dose of BN did not differ between the groups. Among items of the SCS, “severity of craving” predicted a negative outcome. When type of treatment was included in these regression analyses as an independent variable, outpatient treatment predicted negative outcome together with history of suicide attempt and being under probation.Conclusions: Since the dose of BN did not differ between the RDG and those retained in maintenance treatment, the present study suggests that those with severe withdrawal symptoms, particulary those with a high severity of craving, may need a higher dose of BN. A history of suicide attempt and being under probation are high risks for a negative outcome, particularly among those in outpatient treatment. Thus, more observed (supervised) use of BN in the first two weeks, which is more available during inpatient treatment, may improve outcome in outpatient maintenance treatment.

Differentiating Between the Course of Illness in Bipolar 1 and Chronic-Psychotic Heroin-Dependent Patients at Their First Agonist Opioid Treatment

In an effort to inquiry the “self-medication hypothesis” in heroin-dependent patients suffering from chronic psychosis and bipolar disorder, a naturalistic comparative cohort study was designed with the aim of comparing, according to the presence of dual diagnosis, the clinical characteristics of heroin-dependent patients presenting for their first agonist opioid treatment. The main finding was that addictive (heroin) illness was more severe in bipolar 1 patients and less severe in chronic psychotic patients when compared with heroin-dependent patients without dual diagnoses. In the case of chronic psychotic patients, these differences do not allow us to exclude a therapeutic heroin use, at least at the beginning of their toxicomanic career, with limited progression of their addictive disease. This occurrence seems to be excluded for bipolar 1 heroin-dependent patients, who come to their first agonist opioid treatment with a more severe addictive disease.

Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity.

Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treatment. Furthermore, this study suggests that the assessment of amygdala-related connectivity during fear processing may provide a prognostic tool to assess stress levels in heroin-dependent patients and to quantify the efficacy of maintenance treatments in drug addiction.

Psychometric evaluation, using Rasch analysis, of the WHOQOL-BREF in heroin-dependent people undergoing methadone maintenance treatment: further item validation.

BackgroundThe brief version of World Health Organization Quality of Life assessment (WHOQOL-BREF), a useful outcome measure for clinical decision making, has been evaluated using classical test theory (CTT) for psychometric properties on heroin-dependent patients. However, CTT has a major disadvantage of invalid summated score, and using Rasch models can overcome the shortcoming. The purpose of this study was using Rasch models to evaluate the psychometric properties of the WHOQOL-BREF for heroin-dependent patients, and the hypothesis was that each WHOQOL-BREF domain is unidimensional.MethodsTwo hundred thirty six participants (24 females, mean [SD] age = 38.07 [7.44] years, first used heroin age = 26.13 [6.32] years), with a diagnosis of opioid dependence, were recruited from a methadone maintenance treatment program. Each participant filled out the WHOQOL-BREF. Parallel analysis (PA) and Rasch rating scale models were used for statistical analyses.ResultsBased on the PA analyses, four domains of the WHOQOL-BREF were unidimensional. The Rasch analyses showed three negatively worded items (2 in Physical and 1 in Psychological) reported as misfits that may not contribute to the Physical and Psychological domains; one positively worded item in the Physical domain may be redundant. All values for the separation indices were above 2 except for the person separation index in the Physical domain (1.93). Category functioning and item independency of four WHOQOL-BREF domains were supported by the Rasch analyses, and there were 5 items showing the differential item function (DIF) for positive versus negative HIV (human immunodeficiency virus) infection.ConclusionsThe WHOQOL-BREF is a valid outcome measure for assessing general quality of life for substance abusers in terms of physical, psychological, social, and environmental factors. It can also be used as a treatment outcome measure to evaluate the effect of treatments for substance abusers. However, the three misfit negatively worded items should be used with caution because the substance abuser may not fully understand their meaning. Future research may apply cognitive interviews to determine the cognitive functioning of substance abusers and their interpretation of negatively worded items.

P.1.a.011 Polymorphism of cytochrome P450 2D6 and its clinical significance in a sample of 73 consecutive patients

The activity of cytochrome P-450 enzyme 2D6 (CYP2D6) could be related to heroin-dependent patient satisfaction with methadone maintenance treatment. We sought to compare satisfaction with the usual methadone treatment in patients who are ultrarapid, extensive or poor metabolizers, according to CYP2D6 genotyping.Two hundred and five heroin-dependent patients filled out the Verona Service Satisfaction Scale for methadone maintenance treatment (VSSS-MT), before CYP2D6 genotyping.VSSS-MT overall scores were comparable in the poor metabolizer (N = 9) and extensive metabolizer (N = 185) groups, although they were higher in poor metabolizers and extensive metabolizers taken together than in the ultrarapid metabolizers (N = 11) (p < 0.003). Likewise, ultrarapid metabolizers scored higher than the rest of the sample on the VSSS-MT Basic Interventions subscale (p < 001). Regarding this subscale, no poor metabolizers felt dissatisfied, and ultrarapid metabolizer males (N = 7) reported lower satisfaction than ultrarapid metabolizer females (N = 4) (p < 0.022). Ultrarapid metabolizer genotype accounted for 4.2% of the variance on the VSSS-MT total scores, and 5.0% on the Basic Intervention scores.Heroin-dependent patients who are CYP2D6 ultrarapid metabolizers according to genotyping present deficient satisfaction with methadone maintenance treatment.

Predicting subsequent relapse by drug-related cue-induced brain activation in heroin addiction: an event-related functional magnetic resonance imaging study.

Abnormal salience attribution is implicated in heroin addiction. Previously, combining functional magnetic resonance imaging (fMRI) and a drug cue-reactivity task, we demonstrated abnormal patterns of subjective response and brain reactivity in heroin-dependent individuals. However, whether the changes in cue-induced brain response were related to relapse was unknown. In a prospective study, we recruited 49 heroin-dependent patients under methadone maintenance treatment, a gold standard treatment (average daily dose 41.8 ± 16.0 mg), and 20 healthy subjects to perform the heroin cue-reactivity task during fMRI. The patients' subjective craving was evaluated. They participated in a follow-up assessment for 3 months, during which heroin use was assessed and relapse was confirmed by self-reported relapse or urine toxicology. Differences between relapsers and non-relapsers were analyzed with respect to the results from heroin-cue responses. Compared with healthy subjects, relapsers and non-relapsers commonly demonstrated significantly increased brain responses during the processing of heroin cues in the mesolimbic system, prefrontal regions and visuospatial-attention regions. However, compared with non-relapsers, relapsers demonstrated significantly greater cue-induced craving and the brain response mainly in the bilateral nucleus accumbens/subcallosal cortex and cerebellum. Although the cue-induced heroin craving was low in absolute measures, the change in craving positively correlated with the activation of the nucleus accumbens/subcallosal cortex among the patients. These findings suggest that in treatment-seeking heroin-dependent individuals, greater cue-induced craving and greater specific regional activations might be related to reward/craving and memory retrieval processes. These responses may predict relapse and represent important targets for the development of new treatment for heroin addiction.

P-52 * SLOW-RELEASE ORAL MORPHINE (SROM) AS FURTHER MEDICATION IN OPIOID SUBTITUTION TREATMENT (OST): RESULTS FROM A REGISTRATION STUDY

Since 50 years oral methadone is the gold standard in OST. However, some of the heroin dependent patients refrain from this kind of treatment due to different reasons (e.g. no injections, limited well-being, excessive sweating). Additionally the prolongation of the QTc poses a clinical problem in double diagnosed patients as many medications that are necessary in the treatment of these patients, add to the QTc prolongation. Unconfirmed reports from different countries suggested that SROM could be a useful addition to the in Switzerland already registered substitution medications methadone, diamorphine, and buprenorphine. In order to test this assumption we conducted a prospective, multi-dose, open label, non-inferiority, cross-over study in a bi-national, multicentre setting over 11 weeks, in which methadone and SROM were compared (ITT population n = 276). Beyond this time-point, the participants were observed another 25 weeks. Main results were: The proportion of heroin-positive urine samples and retention rates under SROM was equal to the ones under methadone. The mean QTc-interval under methadone was significantly longer than that under SROM. Higher treatment satisfaction, fewer cravings for heroin, and lower mental stress were reported by patients under SROM. More Details will be presented. SROM is now registered in Switzerland as an OST medication.

Outcomes of adult heroin users v. abstinent users four years after presenting for heroin detoxification treatment

&lt;p&gt;&lt;strong&gt;Background. &lt;/strong&gt;There are no studies in South Africa (SA) on the outcomes following detoxification and psychosocial rehabilitation of heroin-dependent patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective. &lt;/strong&gt;To compare the demographic, clinical, forensic and treatment data of active heroin users v. users who were abstinent at the time of interview 4 years after attending the Opioid Detoxification Unit at Stikland Hospital in the Western Cape Province, SA. &lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method.&lt;/strong&gt; Participants included patients above the age of 16 years who had been admitted to the Opioid Detoxification Unit at Stikland Hospital for heroin detoxification between July 2006 and June 2007. Participants were individually interviewed (either in person or tele­phonically) using a structured self-report questionnaire to collect demographic, clinical, forensic and treatment data 4 years following heroin detoxification treatment at this unit. &lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results.&lt;/strong&gt; Of the participants, 60% were abstinent and a large portion (34%) attributed this to social support. Furthermore, there was a significant (&lt;em&gt;p&lt;/em&gt;=0.04) difference in the longest period of abstinence between the past user group and active users, with more participants in the past user group being abstinent for 18 months or longer (&lt;em&gt;n&lt;/em&gt;=24, 57%) than in the active users group (&lt;em&gt;n&lt;/em&gt;=8, 29%). Active users (&lt;em&gt;n&lt;/em&gt;=18, 64%) had significantly (&lt;em&gt;p&lt;/em&gt;=0.03) more legal problems than abstinent users (&lt;em&gt;n&lt;/em&gt;=14, 33%). Most participants (&lt;em&gt;n&lt;/em&gt;=38, 54%) relapsed within 3 months after index detoxification and rehabilitation.&lt;strong&gt; &lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion.&lt;/strong&gt; Active users had more legal problems than abstinent users, with social support structures playing a pivotal role in abstinence. Future research should assess the impact of interventions such as post-discharge social support programmes on criminality and heroin use in those that relapse following treatment.&lt;/p&gt;

Quantitation of methadone and metabolite in patients under maintenance treatment.

Gas chromatography-mass spectrometry quantitative method was developed to monitor concentrations of methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in plasma and urine of patients. The developed method was simple, accurate and reproducible to quantify methadone and EDDP in plasma and urine samples in the concentration range of 15-1,000 and 50-2,000 ng/mL, respectively. The proposed analytical method was applied to plasma and urine samples obtained from 96 patients undergoing methadone maintenance treatment (MMT) with daily methadone doses of 2-120 mg/day. Urinary methadone excretion was observed to be significantly affected by pH, in which the ratio of methadone to EDDP was two times higher in acidic urine (P = 0.029). The findings of this study further enhance the guidelines for monitoring of methadone treatment among outpatients. Methadone-to-EDDP ratio in urine was found to be consistent at 24 and 4 h, hence suggesting the possibility that outpatients may be monitored with single urine sample in order to check for compliance. This study which provides data on peak concentrations of methadone and EDDP as well as the ratio of both compounds has added to the body of knowledge regarding pharmacokinetic properties of methadone among heroin-dependent patients under MMT.

A Double-Blind, Placebo-Controlled Trial of Dextromethorphan Combined With Clonidine in the Treatment of Heroin Withdrawal

Dextromethorphan has been reported to ameliorate opioid withdrawal symptoms in both animal and human subjects. In the present study, we investigated the efficacy of dextromethorphan as an add-on medication in heroin detoxification treatment in a double-blind, placebo-controlled design. Sixty-five heroin-dependent patients (male, 63; female, 2) participated in this inpatient detoxification trial after giving informed consent. Clonidine 0.075 mg 4 times a day was given as an antiwithdrawal medication at baseline. Each patient was then randomly assigned to treatment with either dextromethorphan 60 mg or placebo 4 times a day as additional medication. Flurazepam 30 mg was given before bedtime for insomnia. Other medications that were allowed included loperamide for diarrhea and lorazepam for agitation. Participants were monitored using the Objective Opioid Withdrawal Scale 3 times a day as the primary outcome to compare drug efficacy between groups. Generalized estimating equation model analysis revealed that the Objective Opioid Withdrawal Scale had no group difference between dextromethorphan and placebo group overall (P = 0.29), whereas a significant difference between groups was found during day 3 to day 6 (P = 0.04) by post hoc analysis. There was no difference in the Clinical Global Impression Scale, patient's impression of treatment, and use of ancillary medications between groups. No severe adverse effects were noticed. We suggest that dextromethorphan has some beneficial effect in attenuating the severity of opioid withdrawal symptoms and can be used as an adjunction medication in the treatment of opioid withdrawal, whereas the exact efficacy needs further investigation.

Outcomes of adult heroin users v. abstinent users four years after presenting for heroin detoxification treatment

Background. There are no studies in South Africa (SA) on the outcomes following detoxification and psychosocial rehabilitation of heroin-dependent patients. Objective. To compare the demographic, clinical, forensic and treatment data of active heroin users v. users who were abstinent at the time of interview 4 years after attending the Opioid Detoxification Unit at Stikland Hospital in the Western Cape Province, SA. Method. Participants included patients above the age of 16 years who had been admitted to the Opioid Detoxification Unit at Stikland Hospital for heroin detoxification between July 2006 and June 2007. Participants were individually interviewed (either in person or tele­phonically) using a structured self-report questionnaire to collect demographic, clinical, forensic and treatment data 4 years following heroin detoxification treatment at this unit. Results. Of the participants, 60% were abstinent and a large portion (34%) attributed this to social support. Furthermore, there was a significant ( p =0.04) difference in the longest period of abstinence between the past user group and active users, with more participants in the past user group being abstinent for 18 months or longer ( n =24, 57%) than in the active users group ( n =8, 29%). Active users ( n =18, 64%) had significantly ( p =0.03) more legal problems than abstinent users ( n =14, 33%). Most participants ( n =38, 54%) relapsed within 3 months after index detoxification and rehabilitation. Conclusion. Active users had more legal problems than abstinent users, with social support structures playing a pivotal role in abstinence. Future research should assess the impact of interventions such as post-discharge social support programmes on criminality and heroin use in those that relapse following treatment.

Development and validation of the scale to assess satisfaction with medications for addiction treatment-methadone for heroin addiction (SASMAT-METHER)

ObjectiveTo develop and examine the psychometric properties of a scale to specifically assess satisfaction with methadone in heroin-dependent patients. MethodsThe 44-item preliminary version of the scale to assess satisfaction with medications for addiction treatment–methadone for heroin addiction (SASMAT–METHER) was obtained from a pool of items designed to assess satisfaction with any medication-addiction combination. Theoretical domains of the initial SASMAT–METHER were overall satisfaction, pharmacotherapy, initiation, anti-addictive effect on heroin, mental state, physical state, personal functioning, acceptability, and anti-addictive effect on secondary substances. The Treatment Satisfaction Questionnaire for Medication 1.4 version (TSQM 1.4) and the Verona Service Satisfaction Scale for Methadone Treatment (VSSS-MT) were used for concurrent validation. Participants included heroin-dependent patients receiving methadone treatment for at least the last 3 months. ResultsThe preliminary version of the SASMAT–METHER scale was completed by 241 patients, with 180 surveys considered suitable for factor analysis. Principal component analysis of these SASMAT–METHER surveys revealed a 3-factor structure that accounted for 40.4% of total variance. Based on similarities between empirically-obtained factors and theoretical domains, factors 1 through 3 were named ‘Personal Functioning and Well-Being’ (7 items), ‘Anti-Addictive Effect on Heroin’ (5 items), and ‘Anti-Addictive Effect on Other Substances’ (5 items). All factors showed good to excellent internal consistency (Cronbach's α: 0.83–0.92) and test–retest reliability (intraclass correlation coefficients: 0.66–0.89). Correlations between overall SASMAT–METHER and TSQM 1.4 scores were stronger (Pearson r=0.69) than correlations between overall SASMAT–METHER and VSSS-MT scores (Pearson r=0.26). ConclusionThese results present evidence for the validity and reliability of SASMAT–METHER.

O9: Segmental hair analysis from patients in opiate substitution treatment is useful to investigate drug use history, abstinence and compliance with treatment

Introduction The present study aimed to use the syringe exchange setting in order to facilitate transfer or heroin users into evidence-based substitution treatment with methadone or buprenorphinenaloxone. Out-of-treatment heroin-dependent patients were recruited from a syringe exchange program and actively referred to a research substitution treatment facility. Among 75 patients who were included and underwent baseline evaluation, 71 were successfully referred and started treatment. Segmental hair analysis was used to investigate previous drug abuse, abstinence from drugs of abuse during treatment as well as to confirm compliance to substitution treatment. Hair samples were taken at admission and then after approximately 3 months of treatment. Methods Hair samples were segmented into 5 segments (5, 5, 5, 10, 10 mm) and subjected to qualitative UHPLC-TOF screening for 30 drugs of abuse to elucidate previous drug use patterns. Hair samples were also segmented into 5 segments, washed and quantitation of mu-agonists and sedatives were performed using LC-MSMS including the substitution medications methadone and buprenorphine. Results Base line results from the UHPLC-TOF screening indicated an extensive poly-drug abuse of different opioids including heroin (74%), methadone (79%), fentanyl (16%), buprenorphine (16%) and tramadol (26%) as well as use of stimulants such as amphetamine (32%) together with sedatives (74%) of both the common benzodiazepine group and zopiclone and zolpidem. The segmental analysis showed even or decreasing concentrations of 6-acetylmorphine in the hair confirming continuous use of heroin but suggesting infrequent use or lower doses prior to inclusion. After the initiation of treatment the use of illicit opioids decreased dramatically and most subjects abstained from heroin when given methadone or buprenorphine. 50% had no positive segment during the treatment period and 15% were only positive in one or two of the distal segments which could be interpreted as remnants from dormant hair. However, the use of benzodiazepines and other sedatives (80%) was very common during treatment with alprazolam and clonazepam as the most frequent encounters. The mean methadone dose was 85 mg/d (N=12) and the mean concentrations of EDDP and methadone were 0.46 ng/mg and 8.8 ng/mg, respectively. The concentrations of methadone in hair did not correlate to the dose between subjects but there were clear relationships within patients when doses were escalated during titration. Three patients continued to use heroin and two continued their use of amphetamine. In two of these subjects the methadone concentrations from decreased to half the initial concentrations suggesting that the prescribed dose was diverted rather than taken. Buprenorphine was only detected in 1 patient and norbuprenorphine in 3 patients even though doses between 8 and 24 mg/d was given (N=7). Conclusion We conclude that segmental hair analysis was a good clinical tool to assess drug use histories prior to inclusion into substitution treatment and to prove abstinence from other drugs during treatment. The dose concentration relationship was weak but may be used within a patient to investigate dose changes or non-compliance for methadone. We believe that data from living subjects entering treatment may provide a basis for interpretation of acute heroin overdoses where abstinence have been suggested as a major factor contributing to death.

Severity of Impulsivity and Aggression at a 12-Month Follow-Up Among Male Heroin Dependent Patients

Objective: The aim of this study was to evaluate the changes in impulsivity and aggression scores among male heroin dependent patients using buprenorphine/naloxone as a maintenance treatment and th...

Increased serum brain-derived neurotrophic factor levels during opiate withdrawal

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of opiate addiction. Both increased and decreased serum BDNF levels have been reported in heroin addicts. Moreover, the role of BDNF in heroin-dependent patients during withdrawal has not been studied. This study aimed to explore the differences in serum BDNF levels of heroin addicts and healthy controls, and investigate the changes of serum BDNF levels in heroin addicts at baseline and at one month after heroin cessation. Seventy-two heroin-dependent patients and ninety age- and gender-matched healthy controls were enrolled in this study. We measured serum BDNF levels at baseline (both heroin addicts and healthy controls) and one month after heroin cessation (heroin addicts only). A total of 37 (51.4%) heroin addicts completed the one-month study. We found that baseline serum BDNF levels were significantly higher in heroin addicts compared to controls (F=36.5, p=0.001). There was no difference in serum BDNF levels among heroin addicts at baseline and one month after heroin cessation (F=1.101, p=0.301). These results indicate that BDNF may play a critical role in the course of opiate addiction and withdrawal.

Assessment of CYP450 genetic variability effect on methadone dose and tolerance.

Methadone dose is related to treatment success in individuals under methadone maintenance treatment (MMT). We constructed a gene matrix using previously identified genetic polymorphisms in CYP450 and determined their genetic influence on methadone dose or tolerance. The allelic combinations of CYP450 genetic variants (two from CYP2C19, four from CYP2B6 and five from CYP3A4) were analyzed in 366 MMT heroin dependent patients as possible determinants of methadone dose and tolerance using analysis of covariance. Methadone dose (p = 0.007) and tolerance (p = 0.06) were mainly influenced by CYP2C19 gene dose. Moreover, dominant influence of the CYP2C19 gene dose on methadone dose and tolerance was only found among MMT patients with negative urine morphine test results, but not among those with positive results. The findings suggest that CYP2C19 gene dose may serve as a potential indicator for assessing methadone dose and tolerance in MMT patients.

Orbitofrontal response to drug-related stimuli after heroin administration

The compulsion to seek and use heroin is frequently driven by stress and craving during drug-cue exposure. Although previous neuroimaging studies have indicated that craving is mediated by increased prefrontal cortex activity, it remains unknown how heroin administration modulates the prefrontal cortex response. This study examines the acute effects of heroin on brain function in heroin-maintained patients. Using a crossover, double-blind, placebo-controlled design, 27 heroin-maintained patients performed functional magnetic resonance imaging 20 minutes after the administration of heroin or placebo (saline) while drug-related and neutral stimuli were presented. Images were processed and analysed with statistical parametric mapping. Plasma concentrations of heroin and its main metabolites were assessed using high-performance liquid chromatography. Region of interest analyses showed a drug-related cue-associated blood-oxygen-level-dependent activation in the orbitofrontal cortex (OFC) in heroin-dependent patients during both treatment conditions (heroin and placebo). This activation of the OFC was significantly higher after heroin than after placebo administration. These findings may indicate the importance of OFC activity for impulse control and decision-making after regular heroin administration and may emphasize the benefit of the heroin-assisted treatment in heroin dependence.

The association of 5-HTR2A-1438A/G, COMTVal158Met, MAOA-LPR, DATVNTR and 5-HTTVNTR gene polymorphisms and borderline personality disorder in female heroin-dependent Chinese subjects

To explore the association between the 5-HTR2A-1438A/G, COMTVal158Met, MAOA-LPR, DATVNTR and 5-HTTVNTR polymorphisms with co-morbid borderline personality disorder (BPD) in female heroin-dependent patients. In a case control study, we compared the polymorphic distributions of 5-HTR2A-1438A/G, COMTVal158Met, MAOA-LPR, DATVNTR and 5-HTTVNTR in 296 female heroin-dependent patients (including 61 patients with BPD and 235 without BPD) and 101 normal females by genotypes, alleles, and interaction between genes. Female heroin-dependent subjects with BPD have lower frequency of the high activity allele (L: 4 repeats (4R)) of MAOA-LPR than those female heroin-dependent subjects without BPD, and have higher 5-HTTVNTR 10R/10R genotype frequency than normal female controls, with adjusted P-value<0.05 (after adjusted for multiple testing by 1000-fold permutation tests) respectively. By MDR (Multifactor Dimensionality Reduction) analyses, the interactive effects between MAOA-LPR and 5-HTTVNTR, and among MAOA-LPR, 5-HTTVNTR and rs6311 were close to the significance level (P=0.05) in predicting the risk of co-morbidity of BPD and heroin dependence relative to normal female controls, with 1000-fold permutation testing P-value<0.06 however >0.05 respectively. 5-HTTVNTR and MAOA-LPR may have independent predictive effects on co-morbid BPD in female heroin-dependent patients; the gene-gene interactions between MAOA-LPR and 5-HTTVNTR, and among MAOA-LPR, 5-HTTVNTR and rs6311 might also be involved in the etiology of this co-morbidity.

Towards a unitary perspective between Post-Traumatic Stress Disorder and Substance Use Disorder. Heroin use disorder as case study

BackgroundGenetic, neurobiological, environmental and psychosocial mechanisms have received considerable attention in exploring the mechanisms that underlie comorbid PTSD and SUD. PTSD and SUD are not necessarily linked by a causal relationship, as the self-medication hypothesis had supposed. They might, in fact, both be caused by a third factor that predisposes these subjects to develop the two disorders (so allowing a unitary perspective). MethodsUsing a conceptualization of the PTSD spectrum, we studied the PTSD–SUD unitary perspective by testing the correlation between severity of heroin addiction, dose of opioid medication and severity of PTSD spectrum in 82 methadone-treated, heroin-dependent patients. ResultsCanonical correlation analysis (Wilks Lambda=0.125F=1.41 p=0.014), univariate and multivariate comparisons between subgroups, identified on the basis of addiction severity, showed a highly positive correlation between the PTSD spectrum and the severity of heroin addiction. In addition, negative correlations were found between PTSD spectrum severity and methadone dose (r=0.225; p=0.042). ConclusionsThis strength and breadth of the correlations encourage us to move towards a unified vision of the two disorders.

Altered prefrontal connectivity after acute heroin administration during cognitive control

Neuroimaging studies have reported reduced activity in a broad network of brain regions during response inhibition in heroin-dependent patients. However, how heroin in an acute dose modulates the neural correlates of response inhibition and the underlying brain connectivity has not yet been investigated. In this double-blind placebo-controlled study, we used functional magnetic resonance imaging to examine whether acute heroin administration changed whole brain activity during response inhibition in 26 heroin-dependent patients. We then applied dynamic causal modelling to investigate the effect of an acute dose of heroin on the functional interactions between the dorsal anterior cingulate cortex (dACC) and the bilateral inferior frontal gyri (IFG). Heroin acutely reduced dACC activity, as well as the inhibition-induced modulation of connectivity from the dACC to the right IFG compared with placebo. Furthermore, dACC activity was positively related to false alarm rates after placebo but not heroin administration. These results suggest that acute heroin administration impairs cognitive control in dependent patients by reducing the activity in the dACC activity and the functional connectivity from the dACC to the right IFG.