BDNF influences neural cue-reactivity to food stimuli and food craving in obesity.

There is increasing evidence that brain-derived neurotrophic factor (BDNF) impacts on the development of obesity. We are the first to test the hypothesis that BDNF levels might be associated with neural reactivity to food cues in patients suffering from obesity and healthy controls. We assessed visual food cue-induced neural response in 19 obese patients and 20 matched controls using functional magnetic resonance imaging and analyzed the associations between BDNF levels, food cue-reactivity and food craving. Whole-brain analysis in both groups revealed that food cues elicited higher neural activation in clusters of mesolimbic brain areas including the insula (food > neutral). Patients suffering from obesity showed a significant positive correlation between plasma BDNF levels and visual food cue-reactivity in the bilateral insulae. In addition, patients suffering from obesity with positive food cue-induced insula activation also reported significantly higher food craving than those with low cue-reactivity-an effect that was absent in normal weight participants. The present findings implicate that BDNF levels in patients suffering from obesity might be involved in food craving and obesity in humans. This highlights the importance to consider BDNF pathways when investigating obesity and obesity treatment.

Reliability of neural food cue-reactivity in participants with obesity undergoing bariatric surgery: a 26-week longitudinal fMRI study.

Obesity is highly prevalent worldwide and results in a high disease burden. The efforts to monitor and predict treatment outcome in participants with obesity using functional magnetic resonance imaging (fMRI) depends on the reliability of the investigated task-fMRI brain activation. To date, no study has investigated whole-brain reliability of neural food cue-reactivity. To close this gap, we analyzed the longitudinal reliability of an established food cue-reactivity task. Longitudinal reliability of neural food-cue-induced brain activation and subjective food craving ratings over three fMRI sessions (T0: 2 weeks before surgery, T1: 8 weeks and T2: 24 weeks after surgery) were investigated in N = 11 participants with obesity. We computed an array of established reliability estimates, including the intraclass correlation (ICC), the Dice and Jaccard coefficients and similarity of brain activation maps. The data indicated good reliability (ICC > 0.6) of subjective food craving ratings over 26 weeks and excellent reliability (ICC > 0.75) of brain activation signals for the contrast of interest (food > neutral) in the caudate, putamen, thalamus, middle cingulum, inferior, middle and superior occipital gyri, and middle and superior temporal gyri and cunei. Using similarity estimates, it was possible to re-identify individuals based on their neural activation maps (73%) with a fading degree of accuracy, when comparing fMRI sessions further apart. The results show excellent reliability of task-fMRI neural brain activation in several brain regions. Current data suggest that fMRI-based measures might indeed be suitable to monitor and predict treatment outcome in participants with obesity undergoing bariatric surgery.

Predictors of weight loss in participants with obesity following bariatric surgery - A prospective longitudinal fMRI study.

Prevalence rates of overweight and obesity are increasing worldwide and are amongst the leading causes of death. Participants with obesity also suffer from poorer mental health with a concomitant reduced quality of life. Bariatric surgery outperforms other existing weight optimization approaches. However, hitherto, it was not possible to identify factors predicting weight loss following surgery. Therefore, we aimed at investigating neural and behavioral predictors of weight loss, as well as the neurological underpinnings of food cue-induced craving before and after bariatric surgery. The total sample consisted of 26 participants with obesity (17 females and 9 males, mean age 41 ± 12 years, mean BMI 46 ± 6 kg/m2, 21 received Roux-en-Y gastric bypass and 5 sleeve gastrectomy). Participants with obesity were prospectively assessed using functional magnetic resonance imaging two weeks before, as well as eight and 24 weeks after surgery. Imaging data were available for 11 individuals; 10 received Roux-en-Y gastric bypass and one sleeve gastrectomy. Subjective cue-induced food craving correlated positively with brain activation in the amygdala, the parahippocampal gyrus, and hippocampus, and negatively with brain activation in frontal brain regions. In the total sample (N = 26), perceived feeling of hunger and YFAS sum score explained 50.6% of the variance (R2 = 0.506, F(1,23) = 10.759, p < 0.001) and in the imaging sample, cue-induced food craving at baseline before surgery explained 49.6% of the variance (R2 = 0.496, F(1,23) = 7.862, p = 0.023) of % total weight loss (%TWL). In other words, with respect to %TWL, bariatric surgery was most efficient in candidates characterized by high cue-induced food craving, high-perceived feeling of hunger and a low YFAS sum score.

Telecommunications Network Measurements of Online Gambling Behavior in Switzerland: A Feasibility Study.

BACKGROUND: Methodological shortcomings of gambling studies relying on self-report or on data sets derived from gambling operators tend to result in biased conclusions. The aim of this study was to analyze online gambling behavior using a novel network database approach. METHODS: From October 13 to October 26, 2014, telecommunications network data from a major telecommunications provider in Switzerland were analyzed. Netflows between mobile devices and a poker operator were quantified to measure the gambling duration and session number. RESULTS: Time spent gambling during night and working hours was compared between devices with longest (red group), intermediate (orange group), and shortest gambling time (green group). Online gambling behavior differed depending on overall gambling time, F (2, 3,143). Night and working hours gambling was the highest in the red group (53%), compared to the orange (50.1%) and the green groups (41.5%). Post hoc analyses indicated significant differences between the orange and green groups (p < 0.05). No differences were observed between the red and orange groups (p = 0.850), and the red and green groups (p = 0.053). CONCLUSIONS: On mobile devices, distinct gambling patterns were observed depending on the overall gambling time. This methodology could also be used to investigate online gaming, social media use, and online pornography.

The association of pineal gland volume and body mass in obese and normal weight individuals: a pilot study.

BACKGROUND: In obese individuals impaired sleep and neuroendocrine alterations such as melatonin deficits are associated with circadian rhythm disruption, altered circadian clock gene expression, and bright light at night. While the relation of pineal gland volume (PGV) and melatonin levels has recently been documented in humans, surprisingly little is known about the possible interference of the PGV and the pathophysiology of obesity in humans. SUBJECTS AND METHODS: We therefore compared the PGV of obese with non-obese individuals; both groups were matched by age and gender. Volumetric analyses were performed on the basis of 3 Tesla high resolution Magnetic Resonance Imaging (MRI). RESULTS: We found, that the PGV was significantly smaller in obese individuals than in lean controls (P=0.036). Moreover, PGV and waist-hip ratio showed a significant negative association in controls (P=0.018, rs=-0.602) whereas no association of both variables was found in obese individuals (P=0.856, rs=-0.051). CONCLUSIONS: Thus, the current pilot investigation suggests that pineal gland function, reflected by PGV might be involved in the energy homeostasis and pathophysiological mechanisms that contribute to the development and the maintenance of obesity in humans. Moreover, our data supports the notion that the replacement of melatonin deficits might be a novel strategy in the treatment of obesity.

Epigenetic alteration of the dopamine transporter gene in alcohol-dependent patients is associated with age.

Chronic alcohol abuse and dependence are associated with dysfunctional dopaminergic neurotransmission in mesocorticolimbic circuits. Genetic and environmental factors have been shown to modulate susceptibility to alcohol dependence, and both may act through epigenetic mechanisms that can modulate gene expression, e.g. DNA methylation at CpG sites. Recent studies have suggested that DNA methylation patterns may change over time. However, few data are available concerning the rate of these changes in specific genes. A recent study found that hypermethylation of the promoter of the dopamine transporter (DAT) gene was positively correlated with alcohol dependence and negatively correlated with alcohol craving. The aim of the present study was to replicate these findings in a larger sample of alcohol-dependent patients and population-based controls matched for age and sex. No difference in methylation level was observed between patients and controls, and no difference in methylation level was observed before and after alcohol withdrawal in patients. However, patients with more severe craving showed a trend towards lower DAT methylation levels (P = 0.07), which is consistent with previous findings. Furthermore, in our overall sample, DAT methylation levels increased with age. Interestingly, a separate analysis of patients suggested that this finding was mainly driven by the patient group. Although the present data do not clarify whether chronic alcohol abuse is responsible for this phenomenon or merely enhances an ageing-specific process, our findings suggest that hypermethylation in alcohol-dependent patients is a consequence, rather than a cause, of the disorder.

Pregabalin abuse among opiate addicted patients.

PURPOSE: Pregabalin is a novel GABA-analogue approved for the treatment of partial onset seizures, neuropathic pain, and general anxiety disorder. Pregabalin has been classified as a Schedule V drug with a low risk of inflicting abuse or addiction. However, some publications have indicated that pregabalin may have a potential for abuse among patients with past or current opiate addiction. Thus, we hypothesized that pregabalin might be abused by patients who were undergoing an opiate replacement therapy and never had an indication for taking pregabalin on medical grounds. METHODS: Urine specimens from 124 patients with opiate dependency syndrome and from 111 patients with other addiction disorders (alcohol, benzodiazepines, cannabis, amphetamines) were screened for pregabalin by means of a mass spectrometer analysis. RESULTS: We found 12.1 % of all urine specimens from patients with opiate addiction to be positive for pregabalin. None of the patients concerned had a medical indication for using pregabalin. In the control group, 2.7 % of the patients were tested positively for pregabalin, due to their taking it regularly for chronic pain or general anxiety. CONCLUSIONS: Our data suggest that pregabalin is liable to be abused among individuals with opiate dependency syndrome Thus, vigilance and caution are called for when patients with a past or current opiate dependency are exposed to treatment with pregabalin.

Insula-specific H magnetic resonance spectroscopy reactions in heavy smokers under acute nicotine withdrawal and after oral nicotine substitution.

The aim of this study was to clarify whether addiction-specific neurometabolic reaction patterns occur in the insular cortex during acute nicotine withdrawal in tobacco smokers in comparison to nonsmokers. Fourteen male smokers and 10 male nonsmokers were included. Neurometabolites of the right and the left insular cortices were quantified by magnetic resonance spectroscopy (MRS) on a 3-Tesla scanner. Three separate MRS measurements were performed in each subject: among the smokers, the first measurement was done during normal smoking behavior, the second measurement during acute withdrawal (after 24 h of smoking abstinence), and the third shortly after administration of an oral nicotine substitute. Simultaneously, craving, withdrawal symptoms, and CO levels in exhaled air were determined during the three phases. The participants in the control group underwent the same MR protocol. In the smokers, during withdrawal, the insular cortex showed a significant increase in glutamine (Gln; p = 0.023) as well as a slight increase not reaching significance for glutamine/glutamate (Glx; p = 0.085) and a nonsignificant drop in myoinositol (mI; p = 0.381). These values tended to normalize after oral nicotine substitution treatment, even though differences were not significant: Gln (p = 0.225), Glx (p = 0.107) and mI (p = 0.810). Overall, the nonsmokers (control group) did not show any metabolic changes over all three phases (p > 0.05). In smokers, acute nicotine withdrawal produces a neurometabolic reaction pattern that is partly reversed by the administration of an oral nicotine substitute. The results are consistent with the expression of an addiction-specific neurometabolic shift in the brain and confirm the fact that the insular cortex seems to play a possible role in nicotine dependence.

Hunger modulates behavioral disinhibition and attention allocation to food-associated cues in normal-weight controls.

Overeating, weight gain and obesity are considered as a major health problem in Western societies. At present, an impairment of response inhibition and a biased salience attribution to food-associated stimuli are considered as important factors associated with weight gain. However, recent findings suggest that the association between an impaired response inhibition and salience attribution and weight gain might be modulated by other factors. Thus, hunger might cause food-associated cues to be perceived as more salient and rewarding and might be associated with an impairment of response inhibition. However, at present, little is known how hunger interacts with these processes. Thus, the aim of the present study was to investigate whether hunger modulates response inhibition and attention allocation towards food-associated stimuli in normal-weight controls. A go-/nogo task with food-associated and control words and a visual dot-probe task with food-associated and control pictures were administered to 48 normal-weight participants (mean age 24.5 years, range 19-40; mean BMI 21.6, range 18.5-25.4). Hunger was assessed twofold using a self-reported measure of hunger and a measurement of the blood glucose level. Our results indicated that self-reported hunger affected behavioral response inhibition in the go-/nogo task. Thus, hungry participants committed significantly more commission errors when food-associated stimuli served as distractors compared to when control stimuli were the distractors. This effect was not observed in sated participants. In addition, we found that self-reported hunger was associated with a lower number of omission errors in response to food-associated stimuli indicating a higher salience of these stimuli. Low blood glucose level was not associated with an impairment of response inhibition. However, our results indicated that the blood glucose level was associated with an attentional bias towards food-associated cues in the visual dot probe task. In conclusion our results suggest that hunger induces an approach bias and is associated with an impairment of response inhibition when normal-weight participants are confronted with food-associated cues. These findings are important as these processes play a crucial role with regard to the control of food-intake and weight gain and are assumed to contribute to obesity. Thus, individualized treatment approaches taking into account the experience of hunger in everyday-life situations should be considered in addition to a training of response inhibition.

Functional social support within a medical supervised outpatient treatment program.

BACKGROUND: This study examined functional social support (FSS) and its impact on treatment outcome in alcohol-dependent outpatients treated with supervised disulfiram. METHOD: FSS was assessed cross-sectionally in 46 severe alcohol-dependent patients participating in a close-meshed biopsychosocial treatment program. The FSS was measured with the Medical Outcome Study Social Support Survey. RESULTS: We found significantly higher FSS levels in patients with a current partnership. No significant influence was found of the FSS on days until relapse and retention time. However, FSS was positively correlated with cumulative abstinence. In comparison with another patient sample, it can be shown that the patients of the close-meshed biopsychosocial treatment program seemed to perceive more FSS, presumably through the higher frequency of the outpatient treatment contacts. CONCLUSION: High FSS is associated with a current partnership and with a higher cumulative time of abstinence through close professional supervision. A better understanding of the underlying mechanisms of social relationships in alcohol-dependent patients would probably help to improve treatment outcome in the future.

Pregabalin use in forensic hospitals and prisons in German speaking countries-a survey study of physicians.

Background: Pregabalin is a gamma-aminobutyric acid (GABA) analog that was approved in the EU in 2004 for the treatment of neuropathic pain, generalized anxiety disorder and epilepsy. Since its introduction, pregabalin abuse and misuse has increased significantly. In Switzerland, clinical reports suggest that pregabalin misuse is common among patients in forensic hospitals and prisons. However, data on pregabalin use is scarce, especially in these settings. Therefore, we conducted a study to explore patterns of pregabalin use among prison and forensic patients. Methods: We used a questionnaire to survey physicians working in prison and forensic medicine in German-speaking countries. A total of 131 responses were received. Results: According to the physicians' subjective assessment, 82.5% of them had observed a recent increase in pregabalin use by their patients and 89.1% of them reported that their patients requested pregabalin without a clear medical indication. Patients misusing pregabalin in combination with other illicit substances were observed by 93.3% of the physicians surveyed. According to 73.5% of the physicians surveyed, they had already encountered patients on pregabalin doses of more than 600 mg/day (the maximum recommended daily dose); the highest dose reported was 4,200 mg/day. According to 85.0% of physicians surveyed, they have observed patients experiencing withdrawal symptoms from pregabalin, with the most commonly reported symptoms being displeasure and high aggression. Regarding the nationality of pregabalin-misusing patients, 58.3% of the interviewed physicians reported to be rather in contact with foreign patients, mainly from Northwest Africa (Maghreb). Only 45.0% of the surveyed physicians prescribe pregabalin. Among patients who developed behavioral problems while taking pregabalin, none of the physicians (0.0%) showed a tendency to continue pregabalin at the same dose; all respondents chose to reduce/substitute/discontinue. Conclusion: Our study has provided confirmatory evidence that the use of pregabalin presents a significant issue in forensic and prison medicine across German-speaking countries. Prescribing pregabalin in this field can compound use disorder problems and exacerbate challenges in daily life for those in forensic institutions or prisons. It is necessary that all physicians who prescribe pregabalin are clearly informed about the management (including the risks) of this drug.

Application of electronic diaries in patients with schizophrenia and bipolar disorders.

BACKGROUND: Despite the dissemination of second generation antipsychotics for schizophrenia and bipolar disorder, outcomes remain suboptimal, largely due to poor treatment and drug adherence. The primary aim of the current study was to assess the tolerability, validity and feasibility of the pocket-sized electronic diary Medicus®. SUBJECTS AND METHODS: Our case observations attempted to evaluate eighteen patients suffering from schizophrenia and bipolar disorder. All of the patients were treated with the second generation antipsychotic quetiapine. We followed them up in two German medical centers over two years. RESULTS: The present results display an improvement of mood-stability in all patients treated with quetiapine. All patients were in regular contact to their psychiatrist over a period of 24 months. A complete description of the coherences between the symptoms was essential for estimation, which was conducted by Medicus®. Moreover, Medicus® seem to be useful for improving compliance within a medication regimen. CONCLUSIONS: Although uncontrolled case observations can only be interpreted with caution, Medicus® seems to deserve further investigation and may hold the potential to optimize treatment and drug adherence in patients suffering from schizophrenia and bipolar disorders.

Involvement of orexin in the regulation of stress, depression and reward in alcohol dependence.

There is growing evidence from preclinical studies for an involvement of orexins (ORX) in the regulation of stress, affectivity and addictive behavior. The aim of our study was to gather corresponding clinical data and to elucidate the relationships between alcohol withdrawal stress, ORX plasma concentration and psychopathology. A consecutive sample of thirty-four alcohol-dependent inpatients was included in the study. Blood was drawn at onset of withdrawal and following 2 weeks of controlled abstinence in order to assess ORX, ACTH and cortisol plasma concentrations. In parallel, we assessed clinically relevant psychological distress symptoms applying the Brief Symptom Inventory (BSI). We found a significant positive correlation between ORX and global distress indices of the BSI (p ≤ 0.05). In a regression model, ORX concentration during acute withdrawal explained 24% of the variance of symptom severity (p<0.01). No association with craving, ACTH or cortisol plasma concentration was detected. Our results suggest an involvement of ORX in the affective dysregulation seen commonly in alcohol dependent patients during alcohol withdrawal. Moreover, the effects on global distress indices as well as the earlier studied effects on reinstatement of drug seeking behaviors may point on an involvement of ORX in impaired brain stress systems.

Psychological and hormonal features of smokers at risk to gain weight after smoking cessation--results of a multicenter study.

Preclinical and clinical data suggest modulating effects of appetite-regulating hormones and stress perception on food intake. Nicotine intake also interferes with regulation of body weight. Especially following smoking cessation gaining weight is a common but only partially understood consequence. The aim of this study was to examine the interaction between smoking habits, the appetite regulating hormone leptin, negative affectivity, and stress vulnerability on eating behavior in a clinical case-control study under standardized conditions. In a large population-based study sample, we compared leptin and cortisol plasma concentrations (radioimmunoassay) between current tobacco smokers with high cognitive restraint and disinhibition in eating behavior and smokers scoring low in both categories as assessed with the Three Factor Eating Questionnaire (TFEQ; Stunkard & Messick, 1985). As a measure for smoking effects on the stress axis, the saliva cortisol concentrations were compared before and after nicotine smoking. Additionally, stress perception was assessed with the Perceived Stress Scale (PSS), symptoms of depression and anxiety with the Beck Depression Inventory (BDI) and the State Trait Anxiety Inventory (STAI). In smokers showing high cognitive restraint and disinhibition we found significantly higher leptin concentrations than in the group of smokers scoring low in both categories. Furthermore there was a significant group difference in saliva cortisol concentrations after nicotine intake. Smokers showing high cognitive restraint and disinhibition were also characterized by significantly higher scores in the STAI, the PSS and the BDI. Our results suggest that smokers with a pathological eating behavior show an impaired neuroendocrine regulation of appetite and are prone to experience higher levels of stress and negative affectivity. This interaction of behavioral and neuroendocrinological factors may constitute a high risk condition for gaining weight following smoking cessation.

Implications from addiction research towards the understanding and treatment of obesity.

Recent research indicates similarities between obesity and addictive disorders on both the phenomenological and neurobiological level. In particular, neuroendocrine and imaging studies suggest a close link between the homeostatic regulation of appetite on the on hand, and motivation and reward expectancy on the other. In addition, findings from neuropsychological studies additionally demonstrate alterations of cognitive function in both obesity and addictive disorders that possibly contribute to a lack of control in resisting consumption. In this review, recent findings on overlapping neurobiological and phenomenological pathways are summarized and the impact with regard to new treatment approaches for obesity is discussed.

Disulfiram, an option for the treatment of pathological gambling?

AIM: Pathological gambling and comorbid alcohol dependence often occur in combination. Disulfiram is one of the proven drugs for alcohol dependence. In addition to its inhibiting acetaldehyde dehydrogenase, disulfiram inhibits dopamine beta-hydroxylase and may thereby increase dopamine and decrease norepinephrine cerebral concentrations. Because there may be common neurochemical substrates and neuronal circuits for pathological gambling and addiction, we wished to explore the effect of disulfiram in gambling. METHOD: We describe the outcome of a patient with alcohol dependence and pathological gambling treated with disulfiram D. RESULTS: During treatment with disulfiram, the patient reported that his desire to gamble disappeared entirely. Follow-up indicated that he has not gambled for >12 months. CONCLUSIONS: Although uncontrolled case observations should be interpreted with caution, disulfiram deserves further investigation in pathological gambling.

Supervised disulfiram in relapse prevention in alcohol-dependent patients suffering from comorbid borderline personality disorder--a case series.

AIMS: Disulfiram is widely used to prevent alcoholic relapse. However, due to the intended adverse reaction with ethanol, some believe that its use is dangerous for patients with personality disorders or psychiatric comorbidities because of their increased risk of impulsivity or suicidal behaviour. We examined the safety and efficacy in relapse prevention of a series of alcoholics with borderline personality disorder (BPD). METHODS: Case history study of patients diagnosed with BPD, prescribed disulfiram in a dose of 1.5-2.5 g/week, supervised by a physician in up to three brief contacts per week. RESULTS: Two out of eight patients remained completely abstinent during the supervised disulfiram therapy over a mean period of 9.25 months. Adherence to treatment was 18.44 +/- 21.78 months. The first relapse occurred after 1.38 +/- 1.41 months. The cumulated time of abstinence was 16.88 +/- 20.48 months. The overall tolerability was considered to be high; dizziness and fatigue appeared in all patients at the beginning of the therapy but did not persist. No serious adverse events or ethanol-disulfiram interactions were observed. No suicidal behaviour was reported. CONCLUSIONS: Although case observations should be interpreted with caution, supervised disulfiram seems to deserve further investigation in patients with comorbid BPD, for whom it appears to help prevent alcoholic relapse.

[Impact of functional social support for abstinence after inpatient detoxification]. / Zur Bedeutung der funktionellen sozialen Unterstützung für den Abstinenzverlauf nach Alkohol-Entzugsbehandlung.

OBJECTIVE: Several studies discovered an association between social support and therapy outcomes in patients suffering from alcoholism. However, less is known about the influence of functional social support (fss) on these outcomes. In this prospective study, we examined the impact of fss on different alcohol-dependence related variables in 132 alcohol-dependent patients. METHODS: The fss was measured with the Medical Outcome Study (MOS) Social Support Survey at baseline and at the end of the study. RESULTS: We found significantly higher fss levels in patients with a current partnership. However, there was no association between fss or its sub-dimensions (emotional, cognitive and practical social support) with days until relapse. Fss was stable in the 12 week interval, despite ongoing weekly therapy. However, controlling for the variables "partnership" and "time of first withdrawal symptoms", we found a negative correlation between perceived practical social support and number of previous inpatient detoxifications. CONCLUSIONS: Increased empirical understanding of the impact of social relationships in alcohol-dependent patients would help to improve treatment prognosis, in addition, optimizing the currently available therapeutic options.

Oxcarbazepine in rapid benzodiazepine detoxification.

OBJECTIVE: This study aims at evaluating the tolerability and efficacy of the antiepileptic drug oxcarbazepine in benzodiazepine detoxification in ten patients. METHODS: In this case study of an inpatient withdrawal program, each of the ten patients was detoxified using oxcarbazepine and completed withdrawal successfully without the occurrence of withdrawal symptoms. The detoxification program followed an outlined dosage scheme with oxcarbazepine increase and benzodiazepine tapering. RESULTS: The rapidity of benzodiazepine detoxification using oxcarbazepine was remarkable, benzodiazepine withdrawal being completed in as little as 11 days. CONCLUSIONS: The results support the assumption that oxcarbazepine is a valuable drug for inpatient benzodiazepine withdrawal programs.

[A new pharmacological treatment option for alcohol dependence discovered in transnational study: neurokinin-1 receptor antagonist as a possible therapy for alcoholism?]. / Neue potentielle pharmakologische Behandlung bei Alkoholabhängigkeit im transnationalen Forschungsansatz entdeckt: Neurokinin-1 Rezeptor Antagonist als mögliche Therapie der Alkoholabhängigkeit?

Today solid evidence is available that pharmacological treatments can prevent relapse and improve clinically relevant outcomes in alcoholism. In a preclinical and experimental-clinical study George and colleagues first investigated the role of Substance P and its receptor (NK1R) in the context of alcoholism. They could demonstrate that either the blockade of the receptor, or the lack of the receptors leds to a decreased alcohol intake as well as reduced alcohol tolerance and craving concomitantly accompanied by improved general well-beeing.