Two families of exocomets in the ß Pictoris system.

The young planetary system surrounding the star ß Pictoris harbours active minor bodies. These asteroids and comets produce a large amount of dust and gas through collisions and evaporation, as happened early in the history of our Solar System. Spectroscopic observations of ß Pictoris reveal a high rate of transits of small evaporating bodies, that is, exocomets. Here we report an analysis of more than 1,000 archival spectra gathered between 2003 and 2011, which provides a sample of about 6,000 variable absorption signatures arising from exocomets transiting the disk of the parent star. Statistical analysis of the observed properties of these exocomets allows us to identify two populations with different physical properties. One family consists of exocomets producing shallow absorption lines, which can be attributed to old exhausted (that is, strongly depleted in volatiles) comets trapped in a mean motion resonance with a massive planet. Another family consists of exocomets producing deep absorption lines, which may be related to the recent fragmentation of one or a few parent bodies. Our results show that the evaporating bodies observed for decades in the ß Pictoris system are analogous to the comets in our own Solar System.

[On the legalization debate of non-medical cannabis consumption : Position paper of the German Association for Psychiatry, Psychotherapy and Psychosomatics]. / Zur Legalisierungsdebatte des nichtmedizinischen Cannabiskonsums : DGPPN-Positionspapier.

Calls are increasing for the legalization of cannabis. Some legal experts, various politicians, political parties and associations are demanding a change in drug policy. The legalization debate is lively and receiving wide coverage in the media. The German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) comments on the most important questions from a medical scientific perspective: can cannabis consumption trigger mental illnesses, what consequences would legalization have for the healthcare system and where is more research needed?

[Normative definition of staff requirement for a guideline-adherent inpatient qualified detoxification treatment in alcohol dependence]. / Personalbedarfsermittlung für eine leitliniengerechte stationäre Qualifizierte Entzugsbehandlung bei Alkoholabhängigkeit.

The central element of the "qualified withdrawal treatment" of alcohol dependence is - in addition to physical withdrawal treatment - psychotherapy. The treatment of the underlying addictive disorder that is displayed by intoxication, harmful behaviour and withdrawal symptoms is only possible with a combination of somatic and psychotherapeutic treatment elements. The successfully established multimodal therapy of the "qualified alcohol withdrawal treatment", postulated in the current S3-Treatment Guidelines, requires a multi-disciplinary treatment team with psychotherapeutic competence. The aim of the present work is to calculate the normative staff requirement of a guideline-based 21-day qualified withdrawal treatment and to compare the result with the staffing regulations of the German Institute for Hospital Reimbursement. The present data support the hypothesis that even in the case of a hundred per cent implementation of these data, adequate therapy of alcohol-related disorders, according to the guidelines, is not feasible. This has to be considered when further developing the finance compensation system based on the described superseded elements of the German Institute for Hospital Reimbursement.

Strong association of serum- and glucocorticoid-regulated kinase 1 with peripheral and adipose tissue inflammation in obesity.

OBJECTIVE: The serum- and glucocorticoid-regulated kinase 1 (SGK1) is an early transcriptional target of glucocorticoids and is activated via insulin. Here we investigate the regulation of SGK1 expression in human obesity, diet-induced murine obesity and human monocytic cell line THP-1 monocytes. SUBJECTS AND METHODS: SGK1 expression was studied in subcutaneous and omental adipose tissue (AT) of 20 morbidly obese and 20 age- and gender-matched non-obese controls in murine diet-induced obesity and the THP-1 cell line. The regulation of SGK1 by inflammatory signals was tested in THP-1 cells. RESULTS: Murine diet-induced obesity is associated with a significant upregulation of Sgk1 in gonadal AT. Sgk1 expression is highest in the macrophage-rich stromal vascular fraction and lower in adipocytes. In humans, AT SGK1 is predominantly expressed in CD14(+) macrophages and significantly upregulated in omental and subcutaneous AT of obese subjects. SGK1 mRNA expression in both omental and subcutaneous AT correlates with body mass index, circulating leptin and C-reactive protein, and the local expression of inflammatory markers including monocyte chemotactic protein-1 and macrophage inflammatory protein-1α. The expression of SGK1 in THP-1 cells is upregulated by inflammatory signals, such as lipopolysaccharide and tumour necrosis factor-α, as well as during the induction of monocyte-to-macrophage maturation. CONCLUSIONS: Our data present the first link between SGK1 and obesity-associated inflammation. SGK1 expression is stimulated in response to inflammatory signals and increased in AT macrophages. The characterisation of SGK1 functions in obesity and immunity may help identify potential therapeutic targets in the treatment of obesity.

Intraperitoneal atrial natriuretic peptide attenuates anxiety-related behaviour during alcohol withdrawal in mice.

Converging evidence from both preclinical and clinical studies suggests atrial natriuretic peptide (ANP) as a potential target for treatment of alcohol withdrawal and dependence. Since ANP tightly interacts with hypothalamic-pituitary-adrenocortical (HPA) axis activity, especially the modulation of stress-related anxiety during alcohol withdrawal might mediate these effects. We have now evaluated the anxiolytic activity of intraperitoneal ANP application during alcohol withdrawal in alcohol-habituated mice (C57/Bl6J). Anxiety related behaviour was attenuated during ethanol withdrawal following application of ANP (60 µg/kg) vs. saline. Our results support that anxiolytic effects of ANP mediate ANP-related gene effects with clinical data on withdrawal symptomatology.

[Neurobiology of behavioral addictions]. / Neurobiologische Grundlagen der Verhaltenssüchte.

Reward learning represents a crucial mechanism in the acquisition and maintenance of addictive behavior. The underlying neurobiological foundations and associated neurobiological pathways are identified in this review and similarities between substance abuse and behavioral addictions will be discussed. In the second section current neuroimaging findings on neurobiological mechanisms of pathological gambling and computer and internet addiction are discussed. The main focuses are on changes in neurocognitive processes, such as cue reactivity, reward and punishment processing and behavioral control.

Impairment of inhibitory control in response to food-associated cues and attentional bias of obese participants and normal-weight controls.

OBJECTIVE: Starting from a model of impaired response inhibition and salience attribution for addictive behaviour we investigated whether obese participants show a greater impairment of inhibitory control in response to food-associated cues compared with neutral stimuli and whether this is seen in normal-weight control subjects. In addition, we questioned whether an attentional bias towards food-associated cues can be observed in an early stage of information processing. DESIGN: Control-group study including the administration of behavioural tasks (that is, go/no-go task with food-associated and neutral words, visual dot probe task with food-associated and neutral pictures) and self-reported measures of eating behaviour and impulsivity. RESULTS: Although self-reported measures indicated disinhibition of eating behaviour of obese patients, we found that food-associated stimuli induced an impairment of inhibitory control in both obese participants as well as normal-weight controls. Results from the visual dot-probe task indicated that food-associated cues did not modulate attention allocation in a very early stage of information processing, which suggests that the incentive salience of food-associated stimuli might be lower than that of drug-associated cues. CONCLUSION: These findings are not in line with hypotheses derived from models of addictive behaviour and call into question that an impairment of inhibitory control in response to food-associated cues and salience attribution might be at the core of obesity. Future studies using larger sample sizes and refined experimental procedures are warranted to further investigate mechanisms controlling food intake in obesity.

Assessment of automated craving across substances and across cultures: stability-analysis of the Craving Automated Scale (CAS).

BACKGROUND: The transition from hedonic to compulsive use in Substance Use Disorders (SUD) is a critical point in SUD progression and hence relevant for assessment and treatment. To measure the habitual patterns of substance consumption, the Craving Automated Scales (CAS) for alcohol (CAS-A), substances (CAS-S) and cigarette smoking (CAS-CS) were developed and introduced to different countries. In this study, we aimed to investigate the structural stability of CAS across substances and cultures. METHODS: This study analyzed the CAS-scores of a sample of 370 participants in Germany, China and the UK, including 262 opioid-users, 65 smokers and 43 alcohol-users. We performed stability analyses to check the stability (i. e. factorial invariance) of factor solutions. Based on confirmed stability of the general factor (gfactor) solution and the calculations rule obtained in the previous validation of CAS-alcohol (CAS-A), the factor structures of CAS-A, CAS-S and CAS-CS were compared. RESULTS: The gfactor solutions based on calculations rule shows good stability, with the mean stability coefficients of 0.990 and 0.977 for CAS-S and CAS-CS respectively. The gfactor patterns were similar for CAS-A, CAS-S and CAS-CS, as well as across samples (Germany, China and the UK), with most factor-loadings larger than 0.7. Based on these findings, CAS-S and CAS-CS were also associated with established clinical measures of SUD. CONCLUSIONS: Our findings suggest the two-gfactor solution based on a proposed calculation rule has a high stability across substances and cultures. This could be in line with common neurobiological mechanisms underlying habitual substance use. Moreover, comparing CAS with established clinical tools suggests that CAS might assess the automated behavior in substance consumption in a more sophisticated way.

• The two-gfactor solution of the Craving Automated Scale has a good stability.• The Craving Automated Scale can be used across substances.• The Craving Automated Scale is associated with established SUD measures.

Deciphering the heterogeneity of the Lyve1+ perivascular macrophages in the mouse brain.

Perivascular macrophages (pvMs) are associated with cerebral vasculature and mediate brain drainage and immune regulation. Here, using reporter mouse models, whole brain and section immunofluorescence, flow cytometry, and single cell RNA sequencing, besides the Lyve1+F4/80+CD206+CX3CR1+ pvMs, we identify a CX3CR1- pvM population that shares phagocytic functions and location. Furthermore, the brain parenchyma vasculature mostly hosts Lyve1+MHCII- pvMs with low to intermediate CD45 expression. Using the double Cx3cr1GFP x Cx3cr1-Cre;RosatdT reporter mice for finer mapping of the lineages, we establish that CD45lowCX3CR1- pvMs are derived from CX3CR1+ precursors and require PU.1 during their ontogeny. In parallel, results from the Cxcr4-CreErt2;Rosa26tdT lineage tracing model support a bone marrow-independent replenishment of all Lyve1+ pvMs in the adult mouse brain. Lastly, flow cytometry and 3D immunofluorescence analysis uncover increased percentage of pvMs following photothrombotic induced stroke. Our results thus show that the parenchymal pvM population is more heterogenous than previously described, and includes a CD45low and CX3CR1- pvM population.

Osteopontin deficiency protects against obesity-induced hepatic steatosis and attenuates glucose production in mice.

AIMS/HYPOTHESIS: Obesity is strongly associated with the development of non-alcoholic fatty liver disease (NAFLD). The cytokine osteopontin (OPN) was recently shown to be involved in obesity-induced adipose tissue inflammation and reduced insulin response. Accumulating evidence links OPN to the pathogenesis of NAFLD. Here we aimed to identify the role of OPN in obesity-associated hepatic steatosis and impaired hepatic glucose metabolism. METHODS: Wild-type (WT) and Opn (also known as Spp1) knockout (Opn (-/-)) mice were fed a high-fat or low-fat diet to study OPN effects in obesity-driven hepatic alterations. RESULTS: We show that genetic OPN deficiency protected from obesity-induced hepatic steatosis, at least in part, by downregulating hepatic triacylglycerol synthesis. Conversely, absence of OPN promoted fat storage in adipose tissue thereby preventing the obesity-induced shift to ectopic fat accumulation in the liver. Euglycaemic-hyperinsulinaemic clamp studies revealed that insulin resistance and excess hepatic glucose production in obesity were significantly attenuated in Opn (-/-) mice. OPN deficiency markedly improved hepatic insulin signalling as shown by enhanced insulin receptor substrate-2 phosphorylation and prevented upregulation of the major hepatic transcription factor Forkhead box O1 and its gluconeogenic target genes. In addition, obesity-driven hepatic inflammation and macrophage accumulation was blocked by OPN deficiency. CONCLUSIONS/INTERPRETATION: Our data strongly emphasise OPN as mediator of obesity-associated hepatic alterations including steatosis, inflammation, insulin resistance and excess gluconeogenesis. Targeting OPN action could therefore provide a novel therapeutic strategy to prevent obesity-related complications such as NAFLD and type 2 diabetes.

Involvement of the atrial natriuretic peptide transcription factor GATA4 in alcohol dependence, relapse risk and treatment response to acamprosate.

In alcoholism, both relapse to alcohol drinking and treatment response are suggested to be genetically modulated. This study set out to determine whether the top 15 single nucleotide polymorphisms (SNPs) of a recent genome-wide association (GWA) and follow-up study of alcohol dependence are associated with relapse behavior and pharmacological treatment response in 374 alcohol-dependent subjects who underwent a randomized, double-blind, placebo-controlled trial with acamprosate, naltrexone or placebo. The single nucleotide polymorphism, rs13273672, an intronic SNP in the gene for GATA-binding protein 4 (GATA4), was associated with relapse within the 90-day medical treatment period (P<0.01). Subsequent pharmacogenetic analyses showed that this association was mainly based on patients treated with acamprosate (P<0.01). In line with the observation that natriuretic peptide promoters are modulated by GATA4, a significant gene dose effect on the variance of atrial natriuretic peptide (ANP) plasma concentration in the different GATA4 genotypes (P<0.01) was found. Hence, genetic variations in GATA4 might influence relapse and treatment response to acamprosate in alcohol-dependent patients via modulation of ANP plasma levels. These results could help to identify those alcohol-dependent patients who may be at an increased risk of relapse and who may better respond to treatment with acamprosate.

B cell adaptor containing src homology 2 domain (BASH) links B cell receptor signaling to the activation of hematopoietic progenitor kinase 1.

The B cell adaptor containing src homology 2 domain (BASH; also termed BLNK or SLP-65), is crucial for B cell antigen receptor (BCR)-mediated activation, proliferation, and differentiation of B cells. BCR-mediated tyrosine-phosphorylation of BASH creates binding sites for signaling effectors such as phospholipase Cgamma (PLCgamma)2 and Vav, while the function of its COOH-terminal src homology 2 domain is unknown. We have now identified hematopoietic progenitor kinase (HPK)1, a STE20-related serine/threonine kinase, as a protein that inducibly interacts with the BASH SH2 domain. BCR ligation induced rapid tyrosine-phosphorylation of HPK1 mainly by Syk and Lyn, resulting in its association with BASH and catalytic activation. BCR-mediated activation of HPK1 was impaired in Syk- or BASH-deficient B cells. The functional SH2 domain of BASH and Tyr-379 within HPK1 which we identified as a Syk-phosphorylation site were both necessary for interaction of both proteins and efficient HPK1 activation after BCR stimulation. Furthermore, HPK1 augmented, whereas its kinase-dead mutant inhibited IkappaB kinase beta (IKKbeta) activation by BCR engagement. These results reveal a novel BCR signaling pathway leading to the activation of HPK1 and subsequently IKKbeta, in which BASH recruits tyrosine-phosphorylated HPK1 into the BCR signaling complex.

Newly identified adipose tissue macrophage populations in obesity with distinct chemokine and chemokine receptor expression.

OBJECTIVE: Infiltration by macrophages is a hallmark of obesity-related adipose tissue (AT) inflammation that is tightly linked to insulin resistance. Although CD11c+ AT macrophages (ATMs) have recently been shown to promote inflammation in obese mice, the knowledge on phenotype and function of different ATM populations is still very limited. This study aimed at identifying and characterizing ATM populations in obesity. METHODS: Isolation of ATM populations defined by CD11c and mannose receptor (MR) expression and analysis of gene expression in high-fat diet-induced obese mice. RESULTS: Obesity provoked a shift from a predominant MR+CD11c⁻ population ('MR-ATM') to two MR⁻ populations, namely MR⁻CD11c+ ('CD11c-ATM') and MR⁻CD11c⁻ (double negative, 'DN-ATM'). Although CD11c-ATMs were of a clear inflammatory M1 phenotype, DN-ATMs expressed few inflammatory mediators and highly expressed genes for alternative activation (M2) markers involved in tissue repair, such as arginase and YM1. In contrast, MR-ATMs marginally expressed M1 and M2 markers but highly expressed chemokines, including Mcp-1 (Ccl2) and Mcp-3 (Ccl7). Both CD11c-ATMs and DN-ATMs, but not MR-ATM, highly expressed a panel of chemokine receptors (namely Ccr2, Ccr5, Ccr3 and Cx3cr1), whereas the expression of Ccr7 and Ccr9 was selective for CD11c-ATMs and DN-ATMs, respectively. Notably, stressed adipocytes upregulated various chemokines capable of attracting CD11c-ATM and DN-ATM. CONCLUSION: This study identifies a novel ATM population with a putatively beneficial role in AT inflammation. This DN-ATM population could be attracted to the obese AT by similar chemokines such as inflammatory CD11c-ATM, on which only Ccr7 is uniquely expressed.

[Methylphenidate. Therapy option for adults with ADHD and comorbid substance use disorder?]. / Methylphenidat. Therapieoption bei ADHS und Suchterkrankung im Erwachsenenalter?

Attention-deficit/hyperactivity disorder (ADHD) in adults is often associated with a comorbid substance use disorder (SUD). To date, no treatment algorithms are available. The question of whether the administration of methylphenidate (MPH) is justified in the treatment of adult patients with ADHD and comorbid SUD still remains unclear. While animal studies indicate an addictive potential of intravenous application of the drug, controlled oral treatment with MPH does not seem to carry the potential for abuse in humans. It remains controversial whether MPH treatment of ADHD during childhood protects against the development of SUD during adulthood. Although data remain inconsistent, a small number of studies and our own clinical observations of ADHD patients with SUD treated with MPH support a reduction not only of ADHD-related symptoms, but also of craving and substance abuse. The treatment of the adult ADHD with comorbid SUD with MPH should be conducted after a risk-benefit assessment, taking into consideration the abused substances, the motivation to abstinence and the quality of the physician-patient relationship; it should be evaluated critically, monitored closely and accompanied by treatment of the SUD and specific psychotherapy/psychoeducation.

[Neurobiology and genetics of addiction]. / Neurobiologie und Genetik von Suchterkrankungen.

Recent results on the neurobiological bases of addictive disorders allow new insights into the etiopathogenesis of addiction to be made and allow targets for new therapeutic strategies to be defined. An important advancement in the understanding of the underlying pathophysiology derives from recent research results, showing similarities between addiction and physiological neural plasticity in learning and memory. These include basic mechanisms involving dopamine, glutamate, and their cellular and molecular targets leading to drug-induced synaptic alterations in the mesolimbic reward system. Genetic factors modulate the individual vulnerability. The challenge of future research will be to generate more efficient and individualized therapies based on the insights from neurobiology and genetics.

Interaction between behavioral inhibition and neural alcohol cue-reactivity in ADHD and alcohol use disorder.

RATIONALE: Compared to the general population, adult Attention-Deficit / Hyperactivity Disorder (ADHD) is more prevalent in patients with Alcohol Use Disorder (AUD). Impaired behavioral inhibition is a common characteristic in both ADHD and AUD. Relapse risk is increased in patients with AUD and comorbid, untreated ADHD and in AUD patients with increased neural cue-reactivity. OBJECTIVES: In this study, we examined the interaction between neural correlates of behavioral inhibition and alcohol cue-reactivity with a hybrid imaging task. METHODS: Out of 69 adult study participants, we included n = 49 in our final analyses: Individuals had a diagnosis of either AUD (n = 13), ADHD (n = 14) or both (n = 5), or were healthy controls (HC; n = 17). The functional magnetic resonance imaging paradigm aimed to examine the combined effects of both an interference-inhibition task ("Simon-task") and an alcohol cue-reactivity task. Instead of segregating by diagnostic group, we pursued a dimensional approach in which we compared measures of AUD and ADHD severity, as well as the interaction of both, using multiple regression analyses. RESULTS: The four groups did not differ on the behavioral level on either the inhibition task or the alcohol cue-reactivity task. However, brain activation in frontal control and reward-related regions during completion of the combined tasks were related to ADHD and AUD severity (symptom load). During presentation of both alcohol cues and the inhibition task, participants with higher AUD and ADHD symptom load exhibited greater BOLD (blood oxygen level dependent) responses in subcortical reward-related regions. CONCLUSIONS: Our findings support the hypothesis that ADHD additionally diminishes inhibition ability in individuals with AUD. This may increase relapse risk when confronted with alcohol cues. Further, it is crucial for patients with comorbid AUD and ADHD to take into account not only reduced cognitive control over behavioral inhibition but also simultaneously heightened alcohol cue-reactivity.

Ion thrusters for electric propulsion: Scientific issues developing a niche technology into a game changer.

The transition from old space to new space along with increasing commercialization has a major impact on space flight, in general, and on electric propulsion (EP) by ion thrusters, in particular. Ion thrusters are nowadays used as primary propulsion systems in space. This article describes how these changes related to new space affect various aspects that are important for the development of EP systems. Starting with a historical overview of the development of space flight and of the technology of EP systems, a number of important missions with EP and the underlying technologies are presented. The focus of our discussion is the technology of the radio frequency ion thruster as a prominent member of the gridded ion engine family. Based on this discussion, we give an overview of important research topics such as the search for alternative propellants, the development of reliable neutralizer concepts based on novel insert materials, as well as promising neutralizer-free propulsion concepts. In addition, aspects of thruster modeling and requirements for test facilities are discussed. Furthermore, we address aspects of space electronics with regard to the development of highly efficient electronic components as well as aspects of electromagnetic compatibility and radiation hardness. This article concludes with a presentation of the interaction of EP systems with the spacecraft.

Polyoma middle T-induced vascular tumor formation: the role of the plasminogen activator/plasmin system.

The middle T antigen of murine Polyomavirus (PymT) rapidly transforms endothelial cells, leading to the formation of vascular tumors in newborn mice. Transformed endothelial (End.) cell lines established from such tumors exhibit altered proteolytic activity as a result of increased expression of urokinase-type plasminogen activator (uPA) and are capable of inducing vascular tumors efficiently when injected into adult mice. In this study we have used mice lacking components of the PA/plasmin system to analyze the role of this system in the transformation process and in tumor growth. We found that the proteolytic status of the host is not a critical determinant for PymT-induced vascular tumor formation. In addition, the lack of either uPA or tissue-type PA (tPA) activity is not limiting for the establishment and proliferation of End. cells in vitro, although the combined loss of both PA activities leads to a marked reduction in proliferation rates. Furthermore, the in vitro morphogenetic properties of mutant End. cells in fibrin gels could only be correlated with an altered proteolytic status in cells lacking both uPA and tPA. However, in contrast with tumors induced by PymT itself, the tumorigenic potential of mutant and wild-type End. cell lines was found to be highly dependent on the proteolytic status of both the tumor cells and the host. Thus, genetic alterations in the PA/plasmin system affect vascular tumor development, indicating that this system is a causal component in PymTmediated oncogenesis.

Rivastigmine reduces tobacco craving in alcohol-dependent smokers.

INTRODUCTION: Although alcohol-dependent smokers represent an important group for applying smoking interventions, a sufficient pharmacotherapy has not been established in this high-risk group so far. METHODS: In order to examine the effect of the acetylcholinesterase inhibitor rivastigmine on tobacco dependence, we performed a 12-week, randomized, placebo-controlled trial. 26 alcohol-dependent smokers were randomized to rivastigmine 6 mg/day (n=14) or placebo (n=12). Assessments on addictive behavior included carbon monoxide (CO), severity of tobacco dependence (FTND), daily smoked cigarettes (diaries), and craving for tobacco (QSU) and alcohol (AUQ). RESULTS: ANOVA revealed a significant treatment-by-time interaction for tobacco consumption and tobacco craving (each p<0.0001). The rivastigmine group showed a decrease in daily smoked cigarettes (-30%), in exhaled carbon monoxide (-32%) and in tobacco craving (-18%) whereas controls did not show significant changes. ANCOVA revealed rivastigmine effects to be more prominent in smokers suffering from more severe tobacco dependence. None of the patients developed an alcohol relapse or an increase in alcohol craving. DISCUSSION: Our preliminary data indicate an effect of rivastigmine on tobacco craving and consumption. This pilot study encourages further investigation of acetylcholinesterase-inhibitors as a promising treatment approach regarding tobacco dependence.

Oxcarbazepine in combination with Tiaprid in inpatient alcohol-withdrawal--a RCT.

INTRODUCTION: Oxcarbazepine (OXC), a derivative of Carbamazepine (CBZ), may represent a solution to metabolic and side effects of CBZ treatment due to the fact that renal excretion is its major route of elimination. The goal of the study is to compare the efficacy and tolerability of OXC/Tiaprid (TIA) combination therapy to the well established Clomethiazole (CLO) therapy in an inpatient setting. METHODS: To investigate the efficacy of OXC/TIA in terms of lower alcohol withdrawal symptoms and better tolerability, 56 alcohol-dependent patients participated in a randomized open-label trial, where OXC/TIA and CLO treatments were compared. RESULTS: Following admission, we observed that severity of alcohol withdrawal syndrome was comparable between OXC/TIA and CLO-patients. Overall tolerability was good. However, significantly more patients in the OXC/TIA-group (48.1%) displayed no AE compared to the CLO-group (24.1%). We found no significant differences between groups regarding total number of recorded adverse events (AEs). DISCUSSION: OXC/TIA inpatient therapy proved to be as effective and participants demonstrated the same tolerance as with CLO. In medication-based alcohol withdrawal, OXC/TIA could have the potential to become a promising alternative for alcohol dependent patients unable to undergo inpatient withdrawal therapy with CLO. Our findings further indicate that it could be worthwhile testing OXC/TIA in alcohol withdrawal in daily care units and outpatient settings. This is an important question for national health care services, since outpatient therapy is more and more asked for as alternative to inpatient settings.