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Background/Aims: Opioid dependence is a severe disease which is associated with a high risk of relapse, even in cases of successful withdrawal therapy. Studies have shown alterations of the hypothalamic-pituitary-gonadal axis in opioid-dependent patients, such as decreased testosterone serum levels in affected males. Sex hormones and the steroid 5-alpha-reductase 2 (SRD5A2) V89L polymorphism are associated with craving during alcohol withdrawal, but little is known about their impact on symptomatology of opioid dependence. Methods: In this study, we analyzed 2 independent male cohorts of opioid-dependent patients for possible alterations in testosterone serum levels compared to non-opioid-dependent controls. In one of the cohorts, we additionally investigated associations of testosterone serum levels and 3 SRD5A2 polymorphisms with symptoms of opioid dependence, measured by the Heroin Craving Questionnaire (HCQ). Results: In the patient groups, we found significantly decreased testosterone serum levels compared to the control groups. Furthermore, we found significant associations of both the testosterone serum levels and the SRD5A2 V89L polymorphism with opioid craving assessed by the HCQ. Conclusion: Our data show a possible role of testosterone metabolism in opioid dependence, which may be relevant for the establishment of future treatment strategies.

We present the case of a 35-year-old woman in heroin-assisted treatment (HAT) expressing the wish for the transition to oral opioid agonist treatment. After failed attempts to change to oral diacetylmorphine and slow-release oral morphine, respectively, she was induced on overlapping buprenorphine (BUP) treatment with the Bernese method. Gradual dose increases to BUP 48 mg per day did not result in attenuation of subjective effects of IV diacetylmorphine (DAM) 190 mg. Instead, the patient showed increased sedation. BUP was then reduced to 32 mg per day. After the gradual reduction of IV DAM, she reinitiated illicit substance use. IV DAM was again raised to an effective dose leading to stabilization and reduction of illicit substance use. BUP was subsequently reduced to 8 mg per day. This combination was continued as the patient felt comfortable and reported less early morning withdrawal than with exclusive DAM treatment. We discuss possible underlying mechanisms and explanations as well as clinical implications.

Clinical research has demonstrated the efficacy of injectable opioid treatment for long-term, treatment-refractory opioid-dependent patients. It has been hypothesized that compulsive drug use is particularly associated with neuroplasticity changes in the networks corresponding to withdrawal/negative affect and preoccupation/anticipation rather than binge/intoxication. However, as yet, no study has investigated the effect of long-term opioid treatment on key regions within these networks. Magnetic resonance imaging (MRI) was used to assess brain volumes changes during long-term (approximately 9 years) injectable opioid agonist treatment with diacetylmorphine (DAM) in 22 patients with opioid use disorder. Voxel-based morphometry was applied to detect volumetric changes within the networks of binge/intoxication (ventral/dorsal striatum, globus pallidus and thalamus), withdrawal/negative affect (amygdala and ventral striatum) and preoccupation/anticipation (hippocampus, orbitofrontal and anterior cingulate cortex). The relationships between significant volume changes and features of opioid use disorder were tested using Pearson correlation. Long-term opioid agonist treatment was associated with the enlargement of the right caudate nucleus, which was related to the duration of opioid use disorder. In contrast, reduced volume in the right amygdala, anterior cingulate cortex and orbitofrontal cortex were found that were related to opioid dose, onset of opioid consumption and state anxiety. These findings suggest that long-term opioid agonist treatment is related to structural changes in key brain regions underlying binge/intoxication, withdrawal/negative affect and preoccupation/anticipation, suggesting sustained interaction between these systems.

Aims: Posttraumatic stress disorder (PTSD) is a significant comorbidity in substance use disorders (SUDs). While most studies have addressed trauma/PTSD in abstinent patients, little is known about trauma/PTSD in early detoxification treatment. The current study therefore addresses the systematic evaluation of trauma/PTSD in early inpatient detoxification. Methods: A cross-sectional survey was accomplished in three German-speaking clinics (n = 134) specialized in inpatient detoxification and motivation treatment. All measures are based on self-report using trauma-specific questionnaires and measures for general psychopathological burden. Results: Participation rate was 60.1% and patients did not show clinically obvious psychological distress during or after assessment. DSM-IV traumatic events were reported by 66.4%. Of the total sample, 38.1% screened positive for PTSD, and 14.9% screened positive for subsyndromal PTSD. PTSD patients reported significantly more childhood adversities and significantly higher scores in depression and ­general psychopathology compared to subsyndromal PTSD and SUD-only patients. Conclusions: Early and systematic evaluation of PTSD in SUD inpatient detoxification treatment is largely safe and yields important information for individual treatment. The high PTSD-rate and the high symptom load in SUD patients during inpatient detoxification treatment highlight the need for a more stringent address of trauma/PTSD in early SUD treatment.

It is unclear whether post-traumatic stress disorder symptoms and reports of traumatic childhood experiences decline during substance withdrawal. A convenience sample of 34 inpatients of the Psychiatric University Clinics in Basel was recruited and general psychopathological and trauma-related symptoms were assessed with the Brief Symptom Checklist, Post-Traumatic Stress Diagnostic Scale, and Childhood Trauma Questionnaire in the 1st and 3rd week of substance use treatment. The average age of the sample was 41.9 (SD = 9.1) years, and 26.5% were female. Hyperarousal (Mt1 = 4.51 versus Mt2 = 3.61; z = -2.38, p = .017) and avoidance symptoms (Mt1 = 6.24 versus Mt2 = 4.27; z = -2.59, p = .010) declined significantly, but re-experiencing symptoms (Mt1 = 4.00 versus Mt2 = 3.45; z = -.50, p = .617) did not. Post-traumatic stress disorder assessment, according to the Diagnostic and Statistical Manual of Mental Disorders-4th edition criteria, remained constant for 28 of 34 patients. Likewise, self-reported childhood trauma experiences decreased, yet the number of elevated subscale scores remained stable. Post-traumatic stress disorder symptoms are not adequately treated by substance withdrawal alone. Trauma-specific diagnostics can be initiated with sufficient quality as early as the first week of withdrawal treatment.

Aims: The present study examined the association between pre-treatment drinking and smoking parameters and plasma testosterone levels before and after alcohol withdrawal. Methods: A total of 51 alcohol-dependent men and 43 age-matched healthy men were investigated. In alcoholics, free testosterone in plasma was measured on the day of admission, after detoxification and after 6 weeks of sobriety. Results: While the testosterone level of alcoholic men did not differ from healthy controls at the onset of withdrawal, it was significantly higher for the alcoholics after 6 weeks of sobriety than for the healthy controls. Higher alcohol consumption and higher tobacco use before detoxification led to higher levels of testosterone concentration before and after withdrawal. Conclusions: The effect of alcohol and tobacco is cumulative, with higher levels of alcohol and tobacco consumption being associated with higher levels of testosterone before and after alcohol withdrawal.

Background Cocaine has become one of the drugs of most concern in Switzerland, being associated with a wide range of medical, psychiatric and social problems. Available treatment options for cocaine dependence are rare. The study sought to compare combined prize-based contingency management (prizeCM) plus cognitive-behavioral therapy (CBT) to CBT alone in cocaine-dependent patients. Methods Sixty cocaine-dependent patients participated in a randomized, controlled trial with two treatment conditions. The participants were randomly assigned to the experimental group (EG; n = 29), who received CBT combined with prizeCM, or to the control group (CG; n = 31), who received CBT only during 24 weeks. The primary outcome measures were retention, at least 3 consecutive weeks of cocaine abstinence, the maximum number of consecutive weeks of abstinence and proportions of cocaine-free urine samples during the entire 24-week and at 6-month follow-up. Results Sixty-three percent of the participants completed the study protocol. Participants in both groups significantly reduced cocaine use over time. Overall, no difference in cocaine-free urine screens was found across the two treatment groups, except at weeks 8, 9, 10, 17 and 21 in favor of the EG. Conclusions The addition of prizeCM to CBT seems to enhance treatment effects, especially in the early treatment period, supporting results from previous studies. Both the combined intervention and CBT alone, led to significant reductions in cocaine use during treatment and these effects were sustained at 6-month follow-up. These findings underline the importance in implementing CM and CBT interventions as treatment options for cocaine dependence in the European context.

Exposure to traumatic events is common among patients with substance use disorders (SUD). In patients with non-substance-related disorders, especially with gambling disorders (GD) and internet addiction (IA), traumatic childhood experiences have not been investigated extensively. The objective of this study was to compare trauma histories in patients with GD and IA to patients with heroin dependence.Cross-sectional surveys including the childhood trauma questionnaire (CTQ) and clinical data among 107 participants; 59 patients with non-substance-related disorders (GD [n = 39]; IA [n = 20]) were compared to 28 patients prescribed injectable heroin for opioid dependence in heroin-assisted treatment (HAT) and to a healthy control group (HC) (n = 20).The findings revealed a high prevalence of trauma exposure in all three clinical groups, with 74.4% of patients with GD, 80.0% of patients with IA, and 93.0% of patients in HAT compared to 40% in HC. All three groups (GD, IA, HAT) reported significantly higher levels of "emotional neglect" compared to HC.The results provide clinically relevant information suggesting that the burden of childhood traumatic experiences may be as common in patients with GD and IA as in patients with heroin dependence. These findings could pose an important starting-point for treatment. (Am J Addict 2017;26:215-220).

Objective: Substance use treatment is often performed inside locked wards. We investigate the effects of adopting a policy of open-door treatment for a substance use treatment and dual diagnosis ward. Methods: This is a prospective open-label study investigating 3-month study periods before opening (P1), immediately after (P2), and 1 year after the first period (P3). Data on committed patients, coercion (seclusion, forced medication, absconding events with subsequent police search), violence, and substance use was collected daily. We applied generalised estimating equation models. Results: The mean daily number of patients with ongoing commitment changed from 2.64 (P1) to 2.12 (P2) to 0.96 (P3), corresponding to a reduction of relative risk (RR) for having an ongoing commitment by 20% in P2 (RR 0.80; 95% CI 0.66-0.98) and 67% in P3 (RR 0.33; 95% CI 0.25-0.42). The mean daily number of coercive events was 0.29, 0.13, and 0.05, corresponding to a risk for undergoing coercive measures reduced by 56% (RR 0.44; 95% CI 0.22-0.90) and 85% (RR 0.15; 95% CI 0.05-0.45). Substance use, violence or ward atmosphere did not differ significantly. Conclusions: Our results support findings from general psychiatric wards of reduced coercion after adopting a primarily open-door policy. However, coercive events were rare during all periods. The widespread practice of restricting the freedom of inpatients with substance use disorders by locking ward doors is highly questionable.

Background Among alcohol-dependent subjects tobacco smoking is very common and causes a variety of health risks. Therefore, it is necessary to reach this high-risk population early with appropriate smoking interventions. Methods Smokers in alcohol detoxification treatment were offered to participate in a smoking cessation study. A total of 103 patients was enrolled and randomly assigned to either the experimental group (EG) receiving a cognitive behavioral smoking cessation treatment (CBT) or the control group (CG) receiving autogenic training. Smoking outcomes were measured by self-report and carbon monoxide levels, directly after intervention and 6 months later, where additionally alcohol outcomes were recorded. Results There were no differences in smoking quit rates directly after intervention. However, patients in the EG were significantly more likely to reduce their daily cigarette use compared to CG ( p = .046). Sub-group analyses revealed that heavy smokers (FTND score ≥ 7) seemed to profit most in the EG regarding cigarette reduction. After 6 months, these positive effects had leveled out. No evidence was found that smoking cessation might jeopardize alcohol outcomes. Conclusions Results suggest that alcohol-dependent smokers are interested in smoking interventions even during alcohol detoxification. CBT is promising in short-term smoking outcomes and in the approach of harm reduction, however, long-term effects are desirable. These findings underline the feasibility and the importance to provide smoking cessation interventions to patients in alcohol detoxification treatments.

Objectives. Proteomic technologies based on mass spectrometry are increasingly used as a valuable tool in clinical research allowing high-throughput protein and peptide profi ling to be undertaken. Whilst previous research has focussed the application of this novel technology on the study of patients with disorders compared to comparable individuals from the healthy population, this current study seeks to determine the effect of successful treatment for alcoholism on the serum protein profi le obtained. Methods. Serum samples were collected from patients after initial treatment for alcohol abuse and also 6 months after treatment. The serum samples were prepared for analysis using reverse phase magnetic bead fractionation and the resulting peptides analysed by matrix assisted laser desorption ionisation time-of-fl ight (MALDI-ToF) mass spectrometry. Results. Whilst the majority of the peptides detected by this approach exhibited constant levels between the two time points, three peptides were elevated at the 6-month time point compared to the initial sampling. Conclusions. Whilst disorders with very clear biological causes (such as cancer) exhibit signifi cantly different peptide profi les, psychiatric disorders such as alcohol addiction which are multifactorial show less obvious changes. Despite this the two groups of samples could statistically be distinguished by certain peptides expression levels.

Many methadone patients and untreated heroin users have an ambivalent attitude toward methadone maintenance. This may be a result of the widespread belief that methadone produces various side effects not found with heroin. This study compared the symptom complaints of patients on oral methadone maintenance (MMT) with those of patients prescribed injectable heroin (IHT). A convenience sample of 117 (63 MMT, 54 IHT) patients was recruited from two maintenance clinics. With the use of a self-completion questionnaire, patients were interviewed about a range of symptoms they had experienced and which, in their view, were due to maintenance substance immediately after the last 10 opioid administrations, during the previous week and previous year. The complaints of the two groups overlapped considerably with only few significant differences; these appeared related to the route of administration. IHT patients reported a larger number of complications experienced immediately after administration than MMT patients (p = .007). From the patients' view, methadone does not produce many more or side effects very different from heroin and thus seems at least as tolerable as heroin for maintenance treatment.

Phosphatidylethanol (PEth) is a direct ethanol metabolite, and has recently attracted attention as biomarker of ethanol intake. The aims of the current study are: (1) to characterize the normalization time of PEth in larger samples than previously conducted; (2) to elucidate potential gender differences; and (3) to report the correlation of PEth with other biomarkers and self-reported alcohol consumption. Fifty-seven alcohol-dependent patients (ICD 10 F 10.25; 9 females, 48 males) entering medical detoxification at three study sites were enrolled. The study sample was comprised of 48 males and 9 females, with mean age 43.5. Mean gamma glutamyl transpeptidase (GGT) was 209.61 U/l, average mean corpuscular volume (MCV) was 97.35 fl, mean carbohydrate deficient transferrin (%CDT) was 8.68, and mean total ethanol intake in the last 7 days was 1653 g. PEth was measured in heparinized whole blood with a high-pressure liquid chromatography method, while GGT, MCV and %CDT were measured using routine methods. PEth levels at day 1 of detoxification ranged between 0.63 and 26.95 micromol/l (6.22 mean, 4.70 median, SD 4.97). There were no false negatives at day 1. Sensitivities for the other biomarkers were 40.4% for MCV, 73.1% for GGT and 69.2% for %CDT, respectively. No gender differences were found for PEth levels at any time point. Our data suggest that PEth is (1) a suitable intermediate term marker of ethanol intake in both sexes; and (2) sensitivity is extraordinary high in alcohol dependent patients. The results add further evidence to the data that suggest that PEth has potential as a candidate for a sensitive and specific biomarker, which reflects longer-lasting intake of higher amounts of alcohol and seemingly has the above mentioned certain advantages over traditional biomarkers.

Alcohol dependence is a heavy burden on patients, their families, and society. Epidemiological studies indicate that alcohol dependence will affect many individuals at some time in their lives, with men affected more frequently than women. Since alcohol-dependent patients often exhibit a lack of social skills and suffer from interpersonal problems, the aim of this study is to elucidate whether men and women experience the same interpersonal problems. Eighty-five alcohol-dependent patients (48 men; 37 women) after detoxification and 62 healthy controls (35 men; 27 women) were recruited. Interpersonal problems were measured with the Inventory of Interpersonal Problems (IIP-64). Additionally, alcohol-dependent patients were interviewed with the Alcohol Use Disorders Identification Test (AUDIT) and were subtyped according to Lesch’s Alcohol Typology (LAT). There were no significant gender differences in the AUDIT and LAT between alcohol-dependent men and women. Interpersonal problems of alcohol-dependent men differed significantly in one out of eight dimensions from controls; alcohol-dependent men perceive themselves as colder than male controls. Alcohol-dependent women differed in four out of eight interpersonal dimensions from female controls. Alcohol-dependent women rated themselves as significantly more vindictive, more introverted, more overly accommodating and more intrusive than female controls. Results suggest that alcohol-dependent men and women suffer from different interpersonal problems and furthermore alcohol-dependent women perceive more interpersonal problems, whereas the severity of alcohol dependence did not differ between the groups. Our findings indicate that alcohol-dependent women may profit more from a gender-specific treatment approach aimed at improving treatment outcome than alcohol-dependent men.

Background: Ghrelin is a 28-amino acid gut-brain peptide, mainly secreted by the gastric mucosa. Its effects are linked to energy homeostasis and particularly seem to increase hunger and food intake. In recent years, studies suggested that appetite-regulating peptides, such as ghrelin play a relevant role in alcoholism. Since data published to date on the potential role of ghrelin as state and/or trait marker in alcoholism and the association with craving are controversial, we aimed at further elucidating these aspects. Patients and Methods: One-hundred nine alcohol-dependent abstinent patients after withdrawal (27 f, 82 m), (ICD 10 F 10.25) and 45 healthy volunteers (12 f, 33 m) were included. Laboratory testing (Ghrelin RIA 90, Mediagnost Inc., Germany) was performed and several craving scales [Obsessive Compulsive Drinking Scale, Alcohol Urge Questionnaire and Visual Analogue Scale (VAS)] were applied at the beginning and at the end of the 3-week rehabilitation program. Results: (1) Ghrelin levels are significantly higher in female alcohol-dependent patients as compared to controls, not, however, in men alcoholics. (2) In several statistical subanalyses, an association of craving and ghrelin was found. The results, however, remain heterogeneous. Conclusion: The data suggest gender-dependent ghrelin levels in alcohol-dependent patients. We therefore conclude, that it might be useful to perform statistical analyses gender-specific. With regard to a potential correlation of ghrelin and craving the results seem to depend on gender, duration of the abstinence period and the instrument used.

Objectives: To compare markers of alcohol consumption. Design and methods: Measurement of urinary ethyl glucuronide, 5-hydroxytryptophol, 5-hydroxytryptophol glucuronide, 5-hydroxyindole acetic acid in 10 patients during alcohol withdrawal. Results: 5-Hydroxytryptophol glucuronide was measured by ELISA with good analytical precision, its diagnostic specificity and sensitivity was better than that of 5-hydroxytryptophol and its correlation was closer to ethyl glucuronide than to 5-hydroxytryptophol. Conclusion: Determination of 5-hydroxytryptophol glucuronide by ELISA offers promising results in detection of previous alcohol consumption.

Heroin addiction is a severe relapsing brain disorder associated with impaired cognitive control, including deficits in attention allocation. The thalamus has a high density of opiate receptors and is critically involved in orchestrating cortical activity during cognitive control. However, there have been no studies on how acute heroin treatment modulates thalamic activity. In a cross‐over, double‐blind, vehicle‐controlled study, 29 heroin‐maintained outpatients were studied after heroin and placebo administration, while 20 healthy controls were included for the placebo condition only. Resting‐state functional magnetic resonance imaging was used to analyze functional integration of the thalamus by three different resting state analysis techniques. Thalamocortical functional connectivity (FC) was analyzed by seed‐based correlation, while intrinsic thalamic oscillation was assessed by analysis of regional homogeneity (ReHo) and the fractional amplitude of low frequency fluctuations (fALFF). Relative to the placebo treatment and healthy controls, acute heroin administration reduced thalamocortical FC to cortical regions, including the frontal cortex, while the reductions in FC to the mediofrontal cortex, orbitofrontal cortex, and frontal pole were positively correlated with the plasma level of morphine, the main psychoactive metabolite of heroin. Furthermore, heroin treatment was associated with increased thalamic ReHo and fALFF values, whereas fALFF following heroin exposure correlated negatively with scores of attentional control. The heroin‐associated increase in fALFF was mainly dominated by slow‐4 (0.027–0.073 Hz) oscillations. Our findings show that there are acute effects of heroin within the thalamocortical system and may shed new light on the role of the thalamus in cognitive control in heroin addiction. Future research is needed to determine the underlying physiological mechanisms and their role in heroin addiction. Hum Brain Mapp 36:5287–5300, 2015. © 2015 Wiley Periodicals, Inc.

Aims: Self-help groups such as Alcoholics Anonymous (AA) are widely recommended for aftercare of alcohol- dependent persons, even though scientific knowledge of its effectiveness is inconsistent. The aim of the present analysis was to elucidate whether persons attending AA groups regularly after detoxification have lower relapse rates within 1 year, compared to persons without self-help group attendance. Methods: Data for the present analysis were derived from the placebo-group of a multi-centre study in Germany (Wiesbeck et al., 2001). Patients were free to choose either self-help group attendance (N = 50) or no support (N = 28). Results: After 1-month of follow-up, there was a lower relapse rate in patients attending a self-help group as compared to the control group, a difference, however, that leveled off during the following months. Moreover, relapse rates did not differ significantly at any point of time between both groups. Levels of social functioning improved in both groups over 1 year. Conclusions: The present study was unable to show an advantage of self-help group attendance in reducing relapses compared to the control group.

Background Ethyl sulphate (EtS), a direct ethanol metabolite, appears to offer potential as a biomarker for recent alcohol consumption. Although its window of assessment is similar to that of ethyl glucuronide (EtG), there are differences between the two markers in their pathways for formation and degradation. Aims (a) To assess the excretion of EtS compared to EtG and ethanol in drinking experiments with healthy volunteers, and (b) to elucidate the possibility of using the two metabolites for monitoring abstinence in substance use disorder patients during rehabilitation treatment. Design, setting, participants (a) Nine drinking experiments were performed by six healthy volunteers (two females, four males), with a mean age of 34.1 years (20–62), average oral intake of 0.2 g/kg ethanol (0.1–0.61), and having 74 spot urine samples. (b) Thirty-six substance abuse patients (mean age 41.9 years, 20–59; 22 males, 14 females) in a rehabilitation programme after withdrawal, producing 98 urine samples. Ethyl glucuronide and ethyl sulphate were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) using d5-EtG and d5-EtS, respectively, as an internal standard. Findings (a) Volunteers: EtG and EtS were detectable for up to 36 hours and reached the limits of determination in urine at 20.6 hours and 21.2 hours (median), respectively, after ethanol intake. EtG-100 (standardized to a creatinine of 100 mg/dl) reached its maximum level at 2.8 hours and EtS-100 at 2.1 hours (median) after the beginning of the experiment. Of the ethanol ingested, 0.022% was excreted as EtS in one volunteer. Eight samples were positive for EtS only and six for EtG only. Spearman's rank correlation coefficients of 0.84 (P

Alcohol-dependent patients face a substantial risk of relapse after detoxification. Though psychosocial stress and coping strategies are regarded as major contributing factors in returning to drinking, the direct effects of coping styles on relapse are not clear. In this treatment outcome study, a mixed gender sample of 130 detoxified and well-characterized alcohol-dependent patients (37 women) was followed up over a period of 12 months after 6 weeks of inpatient treatment. Patients had completed a comprehensive baseline assessment, including a stress coping questionnaire (SVF120). We hypothesized that these individual stress coping styles would contribute to treatment outcome. A logistic regression analysis was used to evaluate the impact of stress coping styles, as well as the effect of pretreatment drinking and social characteristics on relapse. Approximately half the patients (49%) relapsed within 1 year after treatment. In contrast to our hypothesis, stress coping styles did not predict relapse. However, significant predictors of relapse were social factors related to living situation (living alone), marital status (being separated from the spouse) and pretreatment frequency of alcohol intake. These findings suggest that a partnership is more relevant for the risk of relapse than stress coping styles.

As, for ethical reasons, it is difficult to investigate by an experiment the effect of acute intoxication on leptin levels in alcoholics, we tested the hypothesis of lowered levels as an effect of acute ethanol intake inhealthy volunteers. The subjects comprised (1) 17 healthy male participants, recruited via newspaper advertisements [age 29 + 3.75 years, body mass index (BMI) 24.3 + 3.5, leptin at baseline 3.3 + 3.1 ng/ml]; (2) for comparison, leptin levels of 16 male alcoholic patients at day I of withdrawal were used. They were characterized as follows: (mean, median, standard deviation and range) age in years (41.1, 40.5, 10.2, 24, 57), BMI (23.3, 21.7, 5.4, 16.6, 37.5), 1032g of ethanol (median) consumed within the last 7 days, leptin levels 2.3mglml. A placebo-controlled double-blind trial teas performed. Leptin levels of blood samples were taken at baseline (t 1 ), before ethanol intake (t 2 ), when blood alcohol had reached its maximum (t 3 ) and the morning after (t 4 ). The oral dose of ethanol administered was 0.6 g/kg ethanol. (1) Volunteers: (a) the ethanol and placebo group exhibited leptin levels corresponding closely with levels measured at baseline (t 1 ) (rs = 0.85, p < 0.0001) and follow-up (t 4 ) (r s = 0.768, p < 0.0001). (b) Leptin levels for the placebo and the alcohol-consuming (verum) group did not differ significantly at baseline, after ethanol intake or on the morning after [Mann - Whitney U-test (p = 0.669, p = 1.0 and p = 0.887, respectively)]. (2) Leptin levels in relation to BMI did not significantly differ at any measurement time in either group. (3) Leptin levels/BMI of the healthy volunteers at t 1 and t 4 were not significantly different from those of 16 alcoholics. The data do not support the hypothesis of a significant effect of acute moderate alcohol intake on leptin levels in healthy volunteers.

Background: Ethyl glucuronide (EtG), a direct ethanol metabolite, seems to meet the need for a sensitive and specific marker for monitoring recent alcohol consumption in different settings. Our aim was to study sensitivity, specificity, and the influence of various parameters on EtG levels in urine. Patients and Methods: Urine samples for a total of 453 patients (373 male, 80 female) were statistically analyzed. The mean age was 37.1 years (median 36, SD 12.59), body mass index was 24.7, total ethanol consumed last month was 1817.66 g (each median), and 80 patients reported cannabis use within the last 30 days. Determination of EtG was performed with a liquid chromatography-tandem mass spectrometry method with deuterium-labeled EtG as internal standard. Results: For EtG in urine, a good correlation was found with other state markers and days of sobriety. In a regression analysis, age, gender, marijuana use, kidney disease, and total grams of ethanol consumed last month were the variables that significantly influenced EtG levels in contrast to race, smoking, body mass index, cirrhosis of liver, age began drinking regularly, packs of cigarettes smoked last month, and total body water. Furthermore, in a receiver operating characteristic curve analysis to distinguish between nondrinkers and individuals sober >4 days versus individuals drinking in the recent 4 days, area under the curve was 0.834. At a cutoff of 0.145 mg/liter, sensitivity was 83.5% and specificity 68.3%. A receiver operating characteristic curve was calculated for lifetime alcohol abuse or dependence against those who had never been abusers or dependent. In this case, subjects were either never dependent or lifetime dependent, but those currently dependent were excluded. The resulting area under the curve was 0.694. At a cutoff of 0.145 mg/liter, sensitivity was 73.8% and specificity 60.3%. For those with a self-reported sobriety of less than 24 hr, the area under the curve was 0.899, sensitivity was 90.8%, and specificity was 76.5% at a cutoff of 0.435 mg/liter when we calculated nondrinkers and light drinkers against heavy drinkers and drinkers needing treatment. Cannabis-using patients showed significant differences with regard to almost all state markers when compared with nonconsuming subjects. Conclusions: Age, gender, marijuana use, kidney disease, and total grams of ethanol consumed last month should be taken into consideration when interpreting results of EtG in urine. Sensitivity and specificity seem promising. Cannabis use can be regarded as an indicator for other serious mental problems in alcohol-using subjects.

It is well established that genetic factors play a major role in the development of alcoholism in both sexes. Several twin studies demonstrated a nearly equally high magnitude of genetic influence for men and women. However, the genetic sources of vulnerability are supposed to only partially overlap in men and women. Therefore, we evaluated the gender-specific effects of two single nucleotide polymorphisms affecting dopaminergic neurotransmission (dopamine D2 receptor: -141C Ins/Del polymorphism; Dopamine D3 receptor: Bal I) in our large sample of primary alcoholics. Only a gender-specific analysis of subgroups with a putatively high genetic load, e.g., family-history-positive or presence of severe withdrawal complications, revealed significant differences in allele-/genotype-frequency. Our results demonstrate that a varying sex distribution in the samples investigated might contribute to the heterogeneous results reported in association studies for candidate genes in alcoholism and, therefore, should be taken into account in future studies.

¶The topic gender and personality in alcoholism is discussed on the background of a research project on clinical aspects of alcoholism at the University of Wurzburg, Germany. The data of this study are presented in the context of two questions: Which personality differences are there between women and men dependent on alcohol, and is there a connection between these personality differences and features of the alcohol dependence? Additionally, we take a look at gender-related differences in the development of alcoholism. In a first step, gender differences in the development and the course of alcoholism are investigated. The data revealed only weak differences between female and male alcoholics when important confounding variables like age and education are taken into consideration. Secondly, the female and male alcoholics are matched according to age and education and their personality structures are compared by using several well-established and standardized self-report questionnaires. No serious gender differences concerning the main characteristics of alcohol dependence could be discovered. However, some remarkable personality differences between female and male alcoholics are found: women scored significantly higher on Neuroticism and Harm-Avoidance while men reached significantly higher scores on Venturesomeness and Sensation-Seeking. In order to detect a possible connection between alcoholism and gender-related personality differences, both males and females are subdivided into two groups using the scores of Neuroticism, Harm-Avoidance, Venturesomeness and Sensation-Seeking, respectively. We have found no indication for a gender-specific relevance of personality differences between female and male alcoholics with regard to Harm-Avoidance, Venturesomeness or Sensation-Seeking. However, differences in Neuroticism have revealed a greater relevance in alcohol-dependent women than in men.

Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy.

A single dose of heroin can reduce stress responses in heroin-dependent patients. Schmidt et al. report that increased amygdala-related functional connectivity during fearful face processing in heroin-dependent patients transiently normalises after a single dose of heroin. This measure may help to assess the efficacy of maintenance treatments in drug addiction., 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.

The serotonergic neurotransmission seems to be involved in the neuropsychobiology of alcoholism. The intensity dependence of the N1/P2 component of auditory-evoked potentials is discussed as an indicator of the central serotonergic neurotransmission in healthy subjects. The aim of this study was to verify this correlation between intensity dependence and serotonergic neurotransmission, as indicated by the personality trait "harm avoidance" (HA) within the Temperament and Character Inventory (TCI) in alcohol-dependent patients. The intensity dependence was measured in 25 alcohol-dependent patients, 10 and 40 days after detoxification. The personality trait HA was assessed, which is supposed to reflect the serotonergic neurotransmission. The intensity dependence was negatively correlated with the temperament trait HA of the TCI (r = - .55, P

Personality disorders (PD) and substance use disorders (SUD) lead to high violent criminality. The influence of co-morbidity on recidivism remains unclear. Recidivism of 379 offenders was assessed at 8 years of follow-up. Sixty-nine percent of PD+SUD, 45% of SUD- and 33% of PD- subjects showed any recidivism. However, violent recidivism was highest in the PD- group.

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.

Summary BACKGROUND/AIMS: Switzerland’s drug policy model has always been unique and progressive, but there is a need to reassess this system in a rapidly changing world. The IMPROVE study was conducted to gain understanding of the attitudes and beliefs towards opioid maintenance therapy (OMT) in Switzerland with regards to quality and access to treatment. To obtain a “real-world” view on OMT, the study approached its goals from two different angles: from the perspectives of the OMT patients and of the physicians who treat patients with maintenance therapy. The IMPROVE study collected a large body of data on OMT in Switzerland. This paper presents a small subset of the dataset, focusing on the research design and methodology, the profile of the participants and the responses to several key questions addressed by the questionnaires. METHODS: IMPROVE was an observational, questionnaire-based cross-sectional study on OMT conducted in Switzerland. Respondents consisted of OMT patients and treating physicians from various regions of the country. Data were collected using questionnaires in German and French. Physicians were interviewed by phone with a computer-based questionnaire. Patients self-completed a paper-based questionnaire at the physicians’ offices or OMT treatment centres. RESULTS: A total of 200 physicians and 207 patients participated in the study. Liquid methadone and methadone tablets or capsules were the medications most commonly prescribed by physicians (60% and 20% of patient load, respectively) whereas buprenorphine use was less frequent. Patients (88%) and physicians (83%) were generally satisfied with the OMT currently offered. The current political framework and lack of training or information were cited as determining factors that deter physicians from engaging in OMT. About 31% of OMT physicians interviewed were ≥60 years old, indicating an ageing population. Diversion and misuse were considered a significant problem in Switzerland by 45% of the physicians. CONCLUSION: The subset of IMPROVE data presented gives a present-day, real-life overview of the OMT landscape in Switzerland. It represents a valuable resource for policy makers, key opinion leaders and drug addiction researchers and will be a useful basis for improving the current Swiss OMT model.

Flupenthixol, with its broad receptor profile, interacts with a variety of dopamine and serotonin binding sites which are important in the neurobiology of alcohol dependence. Its pharmacology, together with encouraging results from both animal studies and clinical trials with cocaine users, led us to postulate that flupenthixol would significantly prevent relapse in detoxified alcohol-dependent individuals. We conducted a prospective, randomized, double-blind, placebo-controlled, multi-centre trial with two parallel groups and appropriate statistical evaluation. Subjects met criteria for moderate to severe alcohol dependence (DSM-III-R), without any concomitant psychiatric disorder. After complete detoxification, 281 women and men received either 10 mg of flupenthixol decanoate or placebo as i.m. injection every second week for 6 months on an out-patient basis, followed by 6 months of follow-up. Efficacy was based on absolute abstinence, with relapse being defined as consumption of any alcohol after inclusion in the study. In contrast to the hypothesis, flupenthixol did not reduce, but was associated with more, relapses. Though well tolerated, relapse rates after 6 months of treatment were 85.2% (flupenthixol) versus 65.5% (placebo), a highly significant difference from the medication. Flupenthixol was also inferior to placebo with regard to other secondary criteria of efficacy (cumulative abstinence duration, relapse rate after 12 months). These results indicate that a 10 mg dose of flupenthixol decanoate does not have a beneficial effect on abstinence maintenance in alcohol-dependent individuals.

Novelty Seeking including impulsive behaviour is a personality dimension which has been shown to be related to early-onset alcoholism and to high relapse rates. The cued Continuous Performance Test (CPT) is an experimental paradigm for active response control requiring a choice reaction between execution (Go) and inhibition (NoGo) of a prepared motor response. Metabolic functional methods have shown right frontal brain activation throughout the period of a CPT, and the spatial analysis of the associated event-related brain electrical (ERP) field potentials revealed that this right frontal activation was due to the NoGo subset of the task. The ERP fields allow distinction between the Go and NoGo conditions with one spatial parameter (NoGo-anteriorization) in single cases. and the magnitude of this parameter is thought to be related to inhibitory frontal lobe control. Twenty patients with severe alcohol dependence and 20 age- and sex-matched healthy controls were included in the study and investigated with a 21-channel electroencephalogram while performing a cued CPT. Consistent with previous studies, NoGo-anteriorization was present in every case in both groups. The ERP field differed between alcoholics and controls in the Go condition (P < 0.05) and NoGo-anteriorization in alcoholics was correlated inversely with Novelty Seeking in Cloninger's Temperament and Character Inventory (r= 0.67, P < 0.01). This indicates a reduced frontal lobe contribution during response control in alcoholics with impulsive behaviour and identifies a possible biological marker for the clinical evaluation of the risk of relapse in alcoholism.

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.

The level of intensity of response to a drug is likely to influence the future pattern of intake of the substance. This article evaluates a simple Self-Rating of the Effects (SRE) of alcohol form, and reports the relationship between a person's estimate of the amounts of alcohol usually required for four possible effects during three different time frames and his subjective feelings reported during an alcohol challenge.SRE forms and results of a challenge with 0.9 ml/kg (0.72 g/kg) of ethanol were available for 18 to 29 year old drinking, but not alcohol dependent, men (N = 98). A subset of 40 subjects completed a second SRE form approximately 1 year later.The correlation between the two SRE administration was .82 (p.0001), and the results on the SRE were internally consistent, with a higher number of drinks associated with more intense alcohol effects. Focusing on the subjective feelings reported at the 60-minute timepoint during the alcohol challenge, 11 of the 12 alcohol effect categories on the SRE correlated in the predicted direction, including eight that were statistically significant. Evaluating all seven timepoints during the drinking experiment, the average number of drinks on the SRE correlated significantly with the Subjective High Assessment Scale (SHAS) total score at all but the final timepoint. Sons of alcoholics and controls demonstrated similar levels of correlation between SRE and alcohol challenge results. Finally, the SRE correctly identified 79% of the individuals whose levels of response to alcohol fell into the lowest third of intensity during the alcohol challenge, and it correctly classified 60% to 67% of the alcohol challenge subjects who did not fall into that low response category.The SRE is a simple and reliable measure of a person's estimate of the number of drinks required to achieve a response. The form might be helpful in educating people about the intensity of their response to alcohol and might be useful as a point of discussion in curricula focusing on genetic aspects of alcoholism. When alcohol challenges are not possible in a research protocol, the SRE might help identify a less heterogeneous subgroup of individuals at high risk for alcoholism who have a common mechanism increasing their vulnerability.

Mean manganese superoxide dismutase (Mn-SOD) concentrations in the serum of patients suffering from alcohol dependence is almost twice as high as in serum of non-dependent controls. In order to investigate the time course of this parameter during abstinence, we determined it at different time points. Patients had mean Mn-SOD serum concentrations (+/-S.D.) of 150.4 +/- 76.3, 121.1 +/- 40.7, 94.6 +/- 37.8 micrograms/ml at 1, 10 and 40 days after abstinence compared to 76.3 +/- 16.9 micrograms/ml as mean Mn-SOD value in the control group. Although the Mn-SOD concentration tended to normalise during abstinence, the differences between index and control group remained significant up to the last measurement at day 40.

Pathological gambling is defined as inappropriate, persistent, and maladaptive gambling behaviour. It is a non-pharmacological addiction classified as an impulse control disorder. However, pathological gambling has been associated with dopamine agonist use. Here we report of a 28-year-old man with a first major depressive episode and a post-traumatic stress disorder who has been treated with a combination of the serotonine/noradrenaline reuptake inhibitor duloxetine and the tricyclic antidepressant maprotiline. The administration of antipsychotic flupentixole (up to 7 mg) turned this slight online poker gambler into an excessive gambler. Only after the discontinuation of the antidopaminergic agents and the switch to bupropion did this gambling behaviour stop which suggests a causal relationship between dopamine antagonists and pathological gambling.

Benzodiazepine (BZD) use is widespread among opioid-maintained patients worldwide. We conducted a cross-sectional survey to investigate motives and patterns of BZD use and psychiatric comorbidity in a convenience sample of patients (n=193) maintained on oral opioid agonists or diacetylmorphine (DAM). Prolonged BZD use and high-risk behaviors like parenteral use were common. After principal component analysis, motives were divided into those related to negative affect regulation, positive affect regulation (i.e. reward-seeking) and somato-medical problems. Negative affect regulation and somato-medical motives were associated with prolonged use. Psychiatric comorbidity was associated with several self-therapeutic motives, most importantly to lose anxiety. Patients maintained on DAM were more likely to be ex-users of BZD and report high positive affect regulation. Therefore, patients maintained on different agonists may have deviating motives for BZD use, which could be of importance when addressing this issue. Treatment of psychiatric comorbidity, in particular anxiety, depressive and sleeping disorders, may be helpful in reducing BZD use, particularly in patients maintained on oral opioids.

Heroin dependence is a chronic relapsing brain disorder characterized by the compulsion to seek and use heroin. Heroin itself has a strong potential to produce subjective experiences characterized by intense euphoria relaxation and release from craving. The neurofunctional foundations of these perceived effects are not well known. In this study we have used pharmacological magnetic resonance imaging (phMRI) in 15 heroin dependent patients from a stable heroin assisted treatment program to observe the steady state effects of heroin (60 min after administration). Patients were scanned in a cross over and placebo controlled design. They received an injection of their regular dose of heroin or saline (placebo) before or after the scan. As phMRI method we used a pulsed arterial spin labeling (ASL) sequence based on a flow sensitive alternating inversion recovery (FAIR) spin labeling scheme combined with a single shot 3D GRASE (gradient spin echo) readout on a 3 Tesla scanner. Analysis was performed with Statistical Parametric Mapping (SPM 8) using a general linear model for whole brain comparison between the heroin and placebo conditions. We found that compared to placebo heroin was associated with reduced perfusion in the left anterior cingulate cortex (ACC) the left medial prefrontal cortex (mPFC) and in the insula (both hemispheres). Analysis of extracted perfusion values indicate strong effect sizes and no gender related differences. Reduced perfusion in these brain areas may indicate self and emotional regulation effects of heroin in maintenance treatment.

Preclinical study results suggest that neurotrophic peptides like nerve growth factor (NGF) and vascular endothelial growth factor A (VEGF-A) may be associated with symptoms of addictive behavior like withdrawal symptoms and rewarding effects. We investigated alterations in NGF and VEGF-A serum levels in opiate-dependent patients (25 male patients), who received diamorphine (DAM, heroin) treatment within a structured opiate maintenance program, and compared the results with the NGF and VEGF-A serum levels of healthy controls (23 male controls). NGF and VEGF-A serum levels were assessed before and after DAM administration twice a day (in the morning (16 h after last application – t1) and in the afternoon (7 h after last application – t3)) in order to detect a possible immediate or summative (in the afternoon) heroin effect on these two neuropeptides. Moreover, we investigated possible associations between the serum levels of these neurotrophic growth factors and psychometric dimensions of addictive behavior, e.g. craving, withdrawal, depression. Whereas there was no direct effect of DAM application on the serum levels of both neurotrophic growth factors neither in the morning nor in the afternoon, the NGF serum levels of the patient group were found to be significantly increased at all four time points of investigation compared with the healthy controls. In contrast, VEGF-A serum levels did not differ significantly in the patient and control groups. We found a significant positive association between the NGF serum levels and several items of the short opiate withdrawal scale as well as a negative association between self-reported mood (measured by visual analogue scale) and mood before heroin application (in the morning as in the afternoon). Moreover, we found a significant positive association between the NGF serum levels (t1 and t3) and the self-reported craving for methadone. In contrast, we found a negative association between the VEGF-A serum levels and avoidance, anxiety, suicide intentions of the SCL-90 as well as a positive association between the VEGF-A serum levels and the subscales of the heroin craving questionnaire measuring the rewarding effects of heroin. In conclusion, the results of this pilot study show that there might be an association between symptoms of opiate dependence and withdrawal and serum levels of VEGF-A and NGF.

Heroin dependence is associated with a stressful environment and with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. The present study examined the acute effects of intravenous heroin versus placebo on the HPA axis response in heroin-dependent patients.Twenty-eight heroin-dependent patients in heroin-assisted treatment and 20 age- and sex-matched healthy participants were included in a controlled trial in which patients were twice administered heroin or saline in a crossover design, and healthy controls were only administered saline. The HPA axis response was measured by adrenocorticotropic hormone (ACTH) levels and by cortisol levels in serum and saliva before and 20 and 60 minutes after substance administration. Craving, withdrawal, and anxiety levels were measured before and 60 minutes after substance application. Plasma concentrations of heroin and its main metabolites were assessed using high-performance liquid chromatography.Heroin administration reduces craving, withdrawal, and anxiety levels and leads to significant decreases in ACTH and cortisol concentrations (P < 0.01). After heroin administration, cortisol concentrations did not differ from healthy controls, and ACTH levels were significantly lower (P < 0.01). In contrast, when patients receive saline, all hormone levels were significantly higher in patients than in healthy controls (P < 0.01).Heroin-dependent patients showed a normalized HPA axis response compared to healthy controls when they receive their regular heroin dose. These findings indicate that regular opioid administration protects addicts from stress and underscore the clinical significance of heroin-assisted treatment for heroin-dependent patients.

Animal experiments suggest that endogenous substances that could result from the interaction between neurotransmitters (dopamine and indoleamines) and ethanol and its metabolite acetaldehyde might be involved in the pathogenesis and maintenance of alcohol dependence. Therefore, aromatic beta-carbolines (norharman and harman) were investigated repeatedly in 24-hr urine of 13 male severe alcoholics without any psychiatric comorbidity during a controlled inpatient abstention program of up to 8 weeks. Harman excretion was approximately 2-fold above levels in control subjects, with a steady decline after 3 weeks of abstinence and lower levels in patients with a longer duration of alcohol dependence. Severity of withdrawal symptoms and actual feelings of anxiety/depression were negatively associated with urinary harman excretion. Positive associations could be established with daily ethanol consumption the month before admission and the score on the scale "reward dependence" according to Cloninger's Tridimensional Personality Questionnaire. Moreover, patients without alcohol-dependent first-degree relatives and higher "reward dependence" exhibited an increased excretion of harman. Therefore, harman levels might characterize a distinct subgroup of alcoholic patients, who in part resemble the so-called type l alcoholics of Cloninger. However, this awaits further study in a larger number of individuals. In contrast, norharman excretion was elevated up to 6-fold, compared with nonalcoholics over 6 to 8 weeks of controlled abstention. No correlations to demographic or clinical variables could be observed. Therefore, increased norharman levels might be proposed as a "residual marker" or a trait variable. Whether the observed changes are specific markers of at least certain aspects of alcoholism or dependence remain to be elucidated.

Cocaine dependence has proved difficult to treat, whether it occurs alone or in combination with opiate dependence. No intervention has been demonstrated to be uniquely effective. Patients might benefit most from combined pharmacotherapeutic and psychotherapeutic interventions. The present study sought to evaluate the feasibility, tolerability, and efficacy of methylphenidate (MP) and cognitive-behavioral group therapy (CBGT) for cocaine dependence in diacetylmorphine-maintained patients. Sixty-two cocaine-dependent diacetylmorphine-maintained patients participated in a dual-site, double-blind, placebo-controlled pilot trial with 4 treatment conditions. The participants were randomly assigned to receive MP or a placebo each combined with either CBGT or treatment as usual for 12 weeks. Methylphenidate 30 mg and a placebo in identical capsules were administered onsite twice daily under supervision in a fixed-dose regimen without titration. Manual-guided CBGT consisted of 12 weekly sessions. Participation in the CBGT sessions was voluntary. Primary outcome measures were retention in pharmacologic treatment, cocaine-free urine samples, self-reported cocaine use, and adverse effects. Urine screens were performed thrice weekly. Seventy-one percent of the participants completed the study protocol. Methylphenidate was well tolerated with similar retention rates compared with the placebo. No serious adverse effects occurred. No difference in cocaine-free urine screens was found across the 4 treatment groups. Self-reported cocaine use was reduced in all 4 study groups. Methylphenidate and CBGT did not provide an advantage over a placebo or treatment as usual in reducing cocaine use. There were no signs of additive benefits of MP and CBGT. Because of the small sample size, the results are preliminary.

Fifteen alcohol dependent men with an alcohol dependent first degree relative (i.e. family history positive or FHP), 15 well matched alcohol dependent men without a family history for alcohol dependence (i.e. family history negative or FHN), and 15 healthy controls (CONTR) participated in this study. The three groups were compared according to their postsynaptic D2 dopamine receptor function as assessed by growth hormone release after stimulation with the dopamine receptor agonist apomorphine. Statistical evaluation was done by planned comparisons within a one-way ANOVA. Alcohol dependent subjects significantly differed from CONTRs as long as family history was not taken into account (t(42) = 2.38; P = 0.022*). When differentiating according to family history, both FHPs and FHNs maintained a blunted growth hormone response. However, the difference between FHNs and CONTRs, though present, dropped out of statistical significance (t(42) = 1.65; P = 0.105); at the same time, the difference between FHPs and CONTRs became slightly stronger (t(42) = 2.47; p = 0.017*). In conclusion, our data give neuroendocrinological support to the assumption that a reduced D2 dopamine receptor function in alcohol dependent men is not only a state marker of residual heavy drinking but also a genetically determined trait marker.

Preclinical studies suggest that chronic drug abuse profoundly alters stress-responsive systems. The best studied of the stress-responsive systems in humans is the hypothalamic-pituitary-adrenal (HPA) axis. Apart from cortisol, arginine vasopressin peptide (AVP), and atrial natriuretic peptide (ANP) are known to directly impact upon the HPA axis in addictive behavior. We investigated alterations in ANP, AVP and cortisol serum levels in opiate-dependent patients who received diacetylmorphine treatment within a structured opiate maintenance program. ANP serum levels were significantly increased in opiate-dependent patients as compared to healthy controls, whereas AVP and cortisol serum levels were reduced. The ANP, AVP and cortisol serum levels were not significantly associated with the psychometric dimensions of heroin craving. In conclusion, chronic drug abuse profoundly alters stress-responsive systems like the HPA axis. Alterations of AVP, ANP and cortisol appear to constitute an important component in the neurobiology of opiate-dependent patients.

Preclinical study results suggest that brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) are involved in the modulation of addictive behaviour. We investigated alterations in serum levels of BDNF and GDNF in opiate-dependent patients (28 males) who received diacetylmorphine treatment within a structured opiate maintenance programme. BDNF ( T = 2.735, p = 0.009) serum levels were significantly increased in the opiate-dependent patients as compared with healthy controls (21 males), whereas GDNF serum levels ( T = 1.425, p = 0.162) did not differ significantly from GDNF serum levels of the healthy controls. BDNF serum levels were significantly associated with craving for heroin (measured by the Heroin Craving Questionnaire ( r = 0.420, p = 0.029) and by the General Craving Scale ( r = 0.457, p = 0.016), whereas GDNF serum levels were not associated with psychometric dimensions of heroin craving. In conclusion, our results show a positive association between BDNF serum levels and opiate craving in opiate-dependent patients.

Patients with borderline personality disorder (BPD) suffer from affective instability, impulsivity, and identity disturbance which particularly manifest in an unstable or insecure self-image. One main problem for studies of core psychopathology in BPD is the complex subject of identity disturbance and self-image. The purpose of this study was to investigate the self-image of BPD patients with a qualitative research approach. Twelve patients with BPD were compared to 12 patients with remitted major depressive disorder (MDD) without personality disorder, using the Structured Interview of Personality Organization (STIPO). The transcribed interviews were analyzed using a combination of content analysis and grounded theory. BPD patients described themselves predominantly as helpful and sensitive; reported typical emotions were sadness, anger, and anxiety. MDD patients on the other hand reported numerous and various characteristics and emotions, including happiness, as well as sadness and anxiety. Other persons were characterized by the BPD group as egoistic and satisfied, while the MDD group described others as being balanced and secretive. BPD patients displayed an altruistic, superficial, and suffering self-image. Aggressive tendencies were only seen in other persons. Our findings support the concept of a self and relationship disturbance in BPD which is highly relevant for psychotherapy treatment.

Background Data from the US indicates that methadone-maintained populations are aging, with an increase of patients aged 50 or older. Data from European methadone populations is sparse. This retrospective cohort study sought to evaluate the age trends and related developments in the methadone population of Basel-City, Switzerland. Methods The study included methadone patients between April 1, 1995 and March 31, 2003. Anonymized data was taken from the methadone register of Basel-City. For analysis of age distributions, patient samples were split into four age categories from '20-29 years' to '50 years and over'. Cross-sectional comparisons were performed using patient samples of 1996 and 2003. Results Analysis showed a significant increase in older patients between 1996 and 2003 (p < 0.001). During that period, the percentage of patients aged 50 and over rose almost tenfold, while the proportion of patients aged under 30 dropped significantly from 52.8% to 12.3%. The average methadone dose (p < 0.001) and the 1-year retention rate (p < 0.001) also increased significantly. Conclusions Findings point to clear trends in aging of methadone patients in Basel-City which are comparable, although less pronounced, to developments among US methadone populations. Many unanswered questions on medical, psychosocial and health economic consequences remain as the needs of older patients have not yet been evaluated extensively. However, older methadone patients, just as any other patients, should be accorded treatment appropriate to their medical condition and needs. Particular attention should be paid to adequate solutions for persons in need of care.

Risk factors for osteoporosis are prevalent in chronic heroin users who often start using opiates in their late teens. This study was the first to evaluate bone mineral density (BMD) in relatively young heroin-dependent patients on injectable heroin maintenance.Using cross-sectional design, BMD was assessed in a convenience sample of 19 patients (mean age ± SD = 33.9 ± 5.4; 13 men) prescribed injectable diacetylmorphine for heroin dependence. BMD of the lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometry. Substance use and menstrual history, psychopathology and risk factors for low BMD were assessed by questionnaire-based interviews.According to World Health Organisation criteria almost three-quarters (74%) of the sample had osteopenia (n = 11) or osteoporosis (n = 3) at one or more sites of measurement. All patients showed multiple risk factors for bone loss, with pack-years of tobacco use and years of heroin use reaching marginally significant associations with spine Z-scores. Moreover, BMD Z-scores correlated significantly negatively with increasing age at all sites, indicating that the older the patient, the greater the BMD deviation from an age-controlled population.Prolonged heroin dependence appears to be associated with lower-than-normal bone mass already at early age and these individuals might be at greater risk for fracture with advancing age. The negative correlation of age-adjusted Z-scores with increasing age suggests factors other than age for low BMD in this population (e.g. smoking, heroin use). Prospective studies are warranted to determine the necessity for diagnostic and preventive measures.

Research suggests that alpha-synuclein (SNCA) and NACP-Rep1, a polymorphic complex microsatellite repeat ~10 kb upstream of the SNCA gene translational start, may be involved in substance-use behaviors and craving. This study was the first to examine the effects of diacetylmorphine (DAM) on peripheral SNCA protein expression along with craving in opiate-dependent patients and to compare their NACP-Rep1 allele lengths with those of healthy controls. Using an experimental design, opiate-dependent patients on injectable heroin maintenance were investigated at four time points, twice pre- and post-injection of DAM. SNCA protein levels of 30 DAM-maintained patients were measured using enzyme-linked immunosorbent assay. Participant-rated effects were assessed in 42 patients by Tiffany's Heroin Craving Questionnaire (HCQ), Gossop's Short Opiate Withdrawal Scale and Visual Analogs. NACP-Rep1 alleles of 42 patients and 101 controls were analyzed. One-way repeated-measures ANOVAs provided significant overall effects for SNCA protein content (P = 0.028), craving (P0.001), withdrawal symptomatology (P0.001) and mood (P0.001), indicating that DAM injections may not only reduce craving but also SNCA protein expression. However, there was no association between protein expression and craving. Relative to controls, patients had significantly longer NACP-Rep1 alleles (P0.001). NACP-Rep1 allele lengths correlated positively with HCQ total scores averaged across all time points (r = 0.420; P = 0.006) as well as with post-DAM HCQ total scores in the morning (r = 0.488, P = 0.001) and afternoon (r = 0.423, P = 0.005). The findings provide evidence of a contributory role of SNCA and NACP-Rep1 for opiate dependence.

A substantial proportion of therapists will at some point in their professional life experience the loss of a patient to suicide. Our aims were to assess how therapists react to patient's suicide over time and which factors contribute to the reaction. One third of the therapists, mostly women, suffer from severe distress. The impact is not different for therapists in institutional settings and therapists in private practice. The item "overall distress" immediately after the suicide predicts emotional reactions and changes in behavior. Our data suggest that identifying the severely distressed subgroup could be done using a visual analogue scale for overall distress. As a consequence, more specific and intensified help could be provided to these individuals.