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Background: Over the past 15 years, comparative assessments of psychoactive substance harms to both users and others have been compiled by addiction experts. None of these rankings however have included synthetic cannabinoids or non-opioid prescription analgesics (NOAs, e.g., gabapentinoids) despite evidence of increasing recreational use. We present here an updated assessment by German addiction medicine experts, considering changing Western consumption trends–including those of NOAs.Methods: In an initial survey, 101 German addiction medicine physicians evaluated both physical and psychosocial harms (in 5 dimensions) of 33 psychoactive substances including opioids and NOAs, to both users and others. In a second survey, 36 addiction medicine physicians estimated the relative weight of each health and social harm dimension to determine the overall harm rank of an individual substance. We compared our ranking with the most recent European assessment from 2014.Results: Illicit drugs such as methamphetamine, heroin, cocaine and also alcohol were judged particularly harmful, and new psychoactive drugs (cathinones, synthetic cannabinoids) were ranked among the most harmful substances. Cannabis was ranked in the midrange, on par with benzodiazepines and ketamine—somewhat more favorable compared to the last European survey. Prescribed drugs including opioids (in contrast to the USA, Canada, and Australia) were judged less harmful. NOAs were at the bottom end of the ranking.Conclusion: In Germany, alcohol and illicit drugs (including new psychoactive substances) continue to rank among the most harmful addictive substances in contrast to prescribed agents including opioid analgesics and NOAs. Current laws are incongruent with these harm rankings. This study is the first of its kind to include comparative harm rankings of several novel abused substances, both licit/prescribed and illicit.

Open doors in psychiatry have been a subject of controversy in recent years. While some studies postulate the clinical necessity of closed doors, others challenge the theoretical advantages of this setting, mention numerous drawbacks of closed wards, and focus on the advantages of open-door settings. With regard to patients diagnosed with substance use disorders (SUD), other standards may apply. Very little research has been done on this topic. Some studies adopted a consumer perspective (i.e. asking involved parties about their experience of the door status). To the authors' knowledge, no study has so far addressed the ideal setting for the treatment of SUD. With our data from the opening of a specialized SUD ward, we take one step to closing this knowledge gap. Applying a qualitative design, we asked patients and health care professionals (HCP) to report changes following the opening of the ward. The results are mainly in line with the literature on the general psychiatric population. The newly introduced open-door setting was mostly perceived as positive, but some disadvantages were mentioned (e.g. less protection of patients, less control over who enters/leaves the ward, the theoretically increased risk of patients absconding). Moreover, HCP (but not patients) mentioned potentially increased substance use on the ward as an additional disadvantage that could arise. Opening a previously closed ward was generally perceived as a positive and progressive decision. These findings support the trend towards an overall open-door policy in psychiatry.

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.

Aims: Alcohol dependent patients in withdrawal display a wide spectrum of neurological and neuropsychological symptoms that complicate diagnosis. We report the case of a 53-year-old male alcoholic with disorientation, ataxia and nystagmus in alcohol withdrawal probably due not to initial supposed Wernicke's encephalopathy (WE) but rather due to multiple cerebral metastases of a non-small cell cancer of the lung. Results: The findings illustrate the importance of initially maintaining a tentative attitude toward causation of symptoms and the role of brain imaging in formulating an accurate diagnosis. ( Received 27 February 2006; first review notified 9 March 2006; in revised form 15 June 2006; accepted 15 June 2006)

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.

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.

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.

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.

Background: The aim of this study was to estimate the prevalence of cannabis use among Swiss students and to assess their attitudes regarding health and safety issues associated with drug use. Subjects and methods: After a workshop, 173 students (23.1% male, 75.7% female; 44.4% age 16, 43.8% age 17 and 11.8% age 18) from a Swiss school were surveyed by questionnaire. Results: 59.3% (n=103) of all participants had tried cannabis, and 30.1% of those who reported cannabis use had consumed more than 100 joints. Of those 103 students with cannabis experience, 6.8% rated the risk of cannabis-related psychic effects as low, and 9.8% were not concerned about driving under the influence of cannabis. In cases of heavy cannabis use, the chance of increased tobacco, alcohol or other drug use is higher than for those with less or no cannabis use at all (odds ratios of 4.33-10.86). Conclusions: This paper deals primarily with cannabis prevalence data in adolescents from previous studies and sources, and shows that our findings deviate significantly - and surprisingly - from past research. Our data from a school survey indicates higher cannabis use than data from official drug policy studies. Additionally, our data shows that the students’ self-reported attitudes towards health and safety issues were mostly realistic. The examination of methodological issues that might impact prevalence estimates should be added to the cannabis literature.

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.

Some patients on steady-state methadone occasionally crave for extra opioids for different reasons (eg, cue-elicited craving, stress). This study examined the acute-on-chronic effects on heroin craving, mood, and opioid-like symptoms of a single, extra half-dose on top of the patient's prescribed daily methadone dosage. A randomized, double-blind, placebo-controlled, counterbalanced crossover design was used to test the safety of this practice and the hypotheses that extra methadone would reduce heroin craving and improve mood, with greater responses in lower-dose (20-60 mg/d) as compared with higher-dose patients (80-120 mg/d). Fourteen stabilized methadone-maintained volunteers of each dose group were examined predrug and postdrug on 2 separate days using a range of self-report measures (Heroin Craving Questionnaire, visual analogs, Befindlichkeits-Skala, Short Opiate Withdrawal Scale, and Opioid Agonist Scale). Additionally, patients' expectations and guesses regarding treatment were assessed predrug and postdrug, respectively. No adverse effects occurred after extra methadone. Participants could not reliably distinguish between extra methadone and placebo. Repeated-measures analyses of variance showed no effects of extra methadone on heroin craving and opioid agonist effects. However, extra methadone improved mood on the Befindlichkeits-Skala (F1/24 = 4.71, P = 0.04), with marginally greater effects in lower-dose patients ((F1/24 = 2.94, P = 0.099). A single 50% extra methadone dose is most likely safe in patients on stable methadone doses of 20 to 120 mg/d and may improve patients' mood. Extra methadone may constitute an important factor in the attractiveness of maintenance treatment and may enhance treatment outcome.

BACKGROUND: Heavy alcohol consumption may accelerate the progression of hepatitis C (HCV)-related liver disease and/or limit efforts at antiviral treatment. As most of the patients in methadone maintenance treatment (MMT) suffer from hepatitis C infection, this study was conducted to identify the alcohol intake among these patients at a Swiss Psychiatric University Clinic by self-reports and direct ethanol metabolites as biomarkers of ethanol consumption. PATIENTS AND METHODS: A convenience sample of 40 MMT patients (15 women, 25 men; median age 39 years) of the total 124 patients was asked and consented to participate in this study. This sample was not different in age, gender distribution, and rate of hepatitis C infection from the total sample. The Alcohol Use Disorders Identification Test (AUDIT) and self-reported ethanol intake during the previous 7 days were assessed. In addition, ethyl glucuronide (EtG) in urine, and fatty acid ethyl esters (FAEEs) and EtG in hair were determined using LC-MS/MS and gas chromatograph/mass spectrometer. The limit of quantitation for UEtG, HEtG, and FAEEs were 0.1 mg/l, 2.3 pg/mg, and 0.1 ng/mg, respectively. RESULTS: Fourteen participants reported abstinence from alcohol for the previous 7 days. AUDIT scores were > or =8 in 15 male and >5 in 5 female participants. Direct ethanol metabolites were as follows (median, min, max, standard deviation): UEtG (19 positives; 9.91, 1.38 to 251, 62.39 mg/l); the values of HEtG were 17.65, 0 to 513, 105.62 pg/mg [in 2 cases no material, 8 abstinent (up to 7 pg/mg), 15 social drinkers (up to 50 g per day), and 15 excessive users (>50/60 g/d)]. For the 13 cases, where enough material for additional determination of HFAEEs was available, the values were 0.32, 0 to 1.32, 0.44 ng/mg. Among the 30 HEtG-positive participants, 20 had not reported the corresponding ethanol intake using question 1 (frequency) and 2 (quantity) of the AUDIT. Of the 14 participants reporting no alcohol intake during the previous 7 days, 4 were UEtG-positive. HEtG and AUDIT correlated significantly (r = 0.622, p < 0.0001), but this was not the case for UEtG and self-reported ethanol intake during the previous 7 days. CONCLUSION: (1) HEtG identified 20 cases of daily ethanol intake of more than 20 g, that would have been missed by the sole use of question 1 (frequency) and 2 (quantity) of the AUDIT. (2) Using the total score of the AUDIT, HEtG confirmed 10 more cases positive for alcohol intake. (3) Episodic heavy drinking is with 22.5% more frequent than in general population, and (4) of the 14 participants who reported no alcohol intake during the previous 7 days, 4 were UEtG positive. Improved detection of alcohol consumption, which is hazardous or harmful in the context of HCV and opiate dependence, would allow for earlier intervention in this population which is at particular risk of liver disease and fatal respiratory-depressed overdose. The combined use of self-reports and direct ethanol metabolites seems promising.

Personality traits are important individual characteristics modifying responses to therapy in various diseases. The aim of this study was to identify personality traits that may predict treatment outcome in alcohol-dependent patients. The present analysis was based on a total of 146 alcohol-dependent patients (109 male, 37 female) after detoxification. The variable of interest was treatment outcome (abstinence/relapse) after a 1-year follow-up. To identify personality traits as predictors of treatment outcome, 5 personality questionnaires (NEO 5-Factor Inventory, Temperament and Character Inventory, Eysenck Personality Questionnaire, Eysenck Impulsiveness-Venturesomeness-Empathy Scale and Sensation-Seeking Scale) were applied. Data analysis was performed by using a classification and regression tree analysis (CART; a nonparametric technique for data with a complex structure) in order to find a decision rule to predict treatment outcome from personality traits. The CART model identified psychoticism and persistence as the 2 most relevant discriminatory parameters, of which psychoticism was used as the first node in the model, classifying 64% of the patients correctly as relapsed and 12% correctly as abstinent. In addition, the risk of relapse was even higher in patients with a substantial score in psychoticism and a low score in persistence. When comparing relapsed and abstinent patients, further variables, such as scores for novelty seeking (20.9 ± 5.5 vs. 18.5 ± 5.9) and impulsiveness (8.4 ± 3 vs. 7.2 ± 3.5), showed significance. In addition, relapsed patients lived alone more often than abstinent patients (52 vs. 25%, p = 0.004). In conclusion, this analysis demonstrated that specific personality characteristics, namely psychoticism and persistence, are usable predictors for the risk of relapse in alcohol-dependent patients.

Chronic alcohol abuse results in morphological, metabolic, and functional brain damage which may, to some extent, be reversible with early effects upon abstinence. Although morphometric, spectroscopic, and neuropsychological indicators of cerebral regeneration have been described previously, the overall amount and spatial preference of early brain recovery attained by abstinence and its associations with other indicators of regeneration are not well established. We investigated global and local brain volume changes in a longitudinal two-timepoint study with T1-weighted MRI at admission and after short-term (6-7 weeks) sobriety follow-up in 15 uncomplicated, recently detoxified alcoholics. Volumetric brain gain was related to metabolic and neuropsychological recovery. On admission and after short-term abstinence, structural image evaluation using normalization of atrophy (SIENA), its voxelwise statistical extension to multiple subjects, proton MR spectroscopy (1H-MRS), and neuropsychological tests were applied. Upon short-term sobriety, 1H-MRS levels of cerebellar choline and frontomesial N-acetylaspartate (NAA) were significantly augmented. Automatically detected global brain volume gain amounted to nearly two per cent on average and was spatially significant around the superior vermis, perimesencephalic, periventricular and frontal brain edges. It correlated positively with the percentages of cerebellar and frontomesial choline increase, as detected by 1H-MRS. Moreover, frontomesial NAA gains were associated with improved performance on the d2-test of attention. In 10 age- and gender-matched healthy control subjects, no significant brain volume or metabolite changes were observed. Although cerebral osmotic regulations may occur initially upon sobriety, significant increases of cerebellar choline and frontomesial NAA levels detected at stable brain water integrals and creatine concentrations, serum electrolytes and red blood cell indices in our patient sample suggest that early brain recovery through abstinence does not simply reflect rehydration. Instead, even the adult human brain and particularly its white matter seems to possess genuine capabilities for regrowth. Our findings emphasize metabolic as well as regionally distinct morphological capacities for partial brain recovery from toxic insults of chronic alcoholism and substantiate early measurable benefits of therapeutic sobriety. Further understanding of the precise mechanisms of this recovery may become a valuable model of brain regeneration with relevance for other disorders.

Background Concomitant cocaine use is a major problem in clinical practice in methadone maintenance treatment (MMT) and may interfere with successful treatment. Data from European methadone populations is sparse. This register-based study sought to explore the association between prescribed methadone dose and concomitant cocaine and heroin use in the methadone population of Basel City. Methods The study included 613 methadone patients between April 1, 2003 and March 31, 2004. Anonymized data was taken from the methadone register of Basel City. For analysis of the prescribed methadone dose distribution, the patient sample was split into three methadone dosage groups: a low dose group (LDG) (n = 200; < 60 mg/day), a medium dose group (MDG) (n = 273; 60 to 100 mg/day), and a high dose group (HDG) (n = 140; > 100 mg/day). Concomitant drug use was based on self-report. Results Analysis showed a significant difference in self-reported cocaine use between groups (p