The gut in the brain: the effects of bariatric surgery on alcohol consumption.

Obesity represents a major medical and public health problem worldwide. Efforts have been made to develop novel treatments, and among them bariatric surgery is used as an effective treatment to achieve significant, long-term weight loss and alleviate medical problems related to obesity. Alcohol use disorder (AUD) is also a leading cause of morbidity and mortality worldwide.

The CRF1 Antagonist Verucerfont in Anxious Alcohol-Dependent Women: Translation of Neuroendocrine, But not of Anti-Craving Effects.

Blockade of corticotropin-releasing factor receptor 1 (CRF1) suppresses stress-induced alcohol seeking in rodents, but clinical translation remains. Here, we first showed that the CRF1 antagonist verucerfont potently blocks hypothalamic-pituitary adrenal (HPA) axis activation in adrenalectomized rats. We then evaluated verucerfont for its ability to block HPA axis activation and reduce stress-induced alcohol craving in alcohol-dependent patients.

Targeting the Oxytocin System to Treat Addictive Disorders: Rationale and Progress to Date.

The neuropeptide oxytocin plays a role in reward, stress, social affiliation, learning, and memory processes. As such, there is increasing interest in oxytocin as a potential treatment for addictions. The endogenous oxytocin system is itself altered by short- or long-term exposure to drugs of abuse.

Relationship of plasma oxytocin levels to baseline symptoms and symptom changes during three weeks of daily oxytocin administration in people with schizophrenia.

Several clinical studies have found an inverse relationship between clinical symptoms and peripheral oxytocin (OT) levels in people with schizophrenia. As oxytocin is a putative treatment for schizophrenia, the effect of repeated dosing of OT on OT levels, clinical symptoms and the relationship between the two is of interest. In a, randomized, double blind, parallel group 3 week study (N=28) with daily administration of intranasal OT (20 IU twice daily) or placebo (PBO), we examined the effect of OT administration on the correlation between the change in peripheral OT levels and change in clinical symptoms in patients with schizophrenia.

What the alcohol doctor ordered from the neuroscientist: Theragnostic biomarkers for personalized treatments.

Major advances in the neuroscientific understanding of alcohol actions have so far not translated into measurably improved clinical outcomes in alcoholism. Future treatment development should be guided by accumulating insights into a diverse range of biological mechanisms that maintain the pathophysiology of alcoholism in different individuals, but also at different points in time within any given patient. This biological diversity calls for the development and use of biological markers predictive of treatment response in the individual case, at the specific stage of the disease, here called "theragnostics.

Transcranial magnetic stimulation of dorsolateral prefrontal cortex reduces cocaine use: A pilot study.

Unlabelled: Recent animal studies demonstrate that compulsive cocaine seeking strongly reduces prelimbic frontal cortex activity, while optogenetic stimulation of this brain area significantly inhibits compulsive cocaine seeking, providing a strong rationale for applying brain stimulation to reduce cocaine consumption. Thus, we employed repetitive transcranial magnetic stimulation (rTMS), to test if dorsolateral prefrontal cortex (DLPFC) stimulation might prevent cocaine use in humans. Thirty-two cocaine-addicted patients were randomly assigned to either the experimental group (rTMS) on the left DLPFC, or to a control group (pharmacological agents) during a 29-day study (Stage 1).

Management of Alcohol Use Disorder in Patients Requiring Liver Transplant.

Alcoholic liver disease is the second most common indication for orthotopic liver transplantation in western countries. The majority of patients with alcoholic liver disease, however, are not referred for transplant evaluation. If evaluated, a 6 month period of sobriety is required before waitlisting for transplant.

Leptin levels are reduced by intravenous ghrelin administration and correlated with cue-induced alcohol craving.

Increasing evidence supports the role of appetite-regulating pathways, including ghrelin and leptin, in alcoholism. This study tested the hypothesis that intravenous exogenous ghrelin administration acutely decreases endogenous serum leptin levels, and that changes in leptin levels negatively correlate with alcohol craving. This was a double-blind, placebo-controlled human laboratory study.

Effect of Functionally Significant Deiodinase Single Nucleotide Polymorphisms on Drinking Behavior in Alcohol Dependence: An Exploratory Investigation.

Background: Abnormalities of the hypothalamic-pituitary-thyroid (HPT) axis have been reported in alcoholism; however, there is no definitive agreement on the specific thyroid abnormalities and their underlying mechanisms in alcohol dependence. The biological activity of thyroid hormones or the availability of T3 is regulated by the three deiodinase enzymes: D1, D2, and D3. In the context of alcohol use, functionally significant single nucleotide polymorphisms (SNPs) of these deiodinase genes may play a role in HPT dysfunction.

The glucagon-like peptide-1 receptor as a potential treatment target in alcohol use disorder: evidence from human genetic association studies and a mouse model of alcohol dependence.

The hormone glucagon-like peptide-1 (GLP-1) regulates appetite and food intake. GLP-1 receptor (GLP-1R) activation also attenuates the reinforcing properties of alcohol in rodents. The present translational study is based on four human genetic association studies and one preclinical study providing data that support the hypothesis that GLP-1R may have a role in the pathophysiology of alcohol use disorder (AUD).

Roux-en-Y Gastric Bypass Alters Brain Activity in Regions that Underlie Reward and Taste Perception.

Background: Roux-en-Y gastric bypass (RYGB) surgery is a very effective bariatric procedure to achieve significant and sustained weight loss, yet little is known about the procedure's impact on the brain. This study examined the effects of RYGB on the brain's response to the anticipation of highly palatable versus regular food.

Methods: High fat diet-induced obese rats underwent RYGB or sham operation and were then tested for conditioned place preference (CPP) for the bacon-paired chamber, relative to the chow-paired chamber.

Role of the α1 blocker doxazosin in alcoholism: a proof-of-concept randomized controlled trial.

Evidence suggests that the norepinephrine system represents an important treatment target for alcohol dependence (AD) and the α1 -blocker prazosin may reduce alcohol drinking in rodents and alcoholic patients. The α1 -blocker doxazosin demonstrates a more favorable pharmacokinetic profile than prazosin, but has never been studied for AD. A double-blind placebo-controlled randomized clinical trial was conducted in AD individuals seeking outpatient treatment.

Relationship between the thyroid axis and alcohol craving.

Aims: A few studies have suggested a relationship between thyroid hormones and alcohol dependence (AD) such as a blunted increase of thyroid stimulating hormone (TSH) in response to thyrotropin-releasing hormone (TRH), lower levels of circulating free triiodothyronine (fT3) and free thyroxine (fT4) levels and down regulation of the TRH receptors. The current study aimed to explore the relationship between the hormones of the thyroid axis and alcohol-seeking behaviors in a sample of alcohol-dependent patients.

Methods: Forty-two treatment-seeking alcohol-dependent individuals enrolled in a 12-week treatment study were considered.

Baclofen for the Treatment of Alcohol Dependence and Possible Role of Comorbid Anxiety.

Aim: To conduct a double-blind, placebo-controlled randomized clinical trial of baclofen in the treatment of alcohol dependence.

Methods: Out of 69 participants consecutively screened, 42 alcohol-dependent patients were randomized to receive placebo, baclofen 30 mg/day or baclofen 60 mg/day for 12 weeks. All subjects were offered BRENDA, a structured psychosocial therapy for alcohol dependence that seeks to improve motivation for change, enhance strategies to prevent relapse and encourage compliance with treatment.

Ondansetron and sertraline may interact with 5-HTTLPR and DRD4 polymorphisms to reduce drinking in non-treatment seeking alcohol-dependent women: exploratory findings.

The purpose of this exploratory study was to examine the interaction of 5-HTTLPR and DRD4 exon III polymorphisms with gender in non-treatment seeking alcohol-dependent (AD) individuals while alternately taking ondansetron and sertraline. Evidence suggests that alcohol dependence may be influenced by a genetic interaction that may be gender-specific with temporal changes making pharmacological treatment with serotonergic drugs complex. The main trial was a within-subject double-blind placebo-controlled human laboratory study with 77 non-treatment-seeking AD individuals randomized (55 completed, 49 complete data) to receive 200 mg/day of sertraline or 0.

Pharmacotherapy for alcoholic patients with alcoholic liver disease.

Purpose: An update on pharmacotherapy for achieving and maintaining abstinence and mitigating hepatic damage in patients with alcoholic liver disease (ALD) is presented.

Summary: Currently there are limited pharmacotherapy options for managing ALD, which encompasses a broad spectrum of disorders ranging from steatosis and alcoholic hepatitis to fibrosis, cirrhosis, and hepatocellular cancer. Individual variation in the severity, presentation, and complex pathologenesis of ALD defines barriers to effective treatment.

A preliminary double-blind, placebo-controlled randomized study of baclofen effects in alcoholic smokers.

Rationale: There is presently no approved single treatment for dual alcohol and nicotine dependencies.

Objective: This pilot study investigated baclofen effects in alcoholic smokers.

Methods: This was a preliminary double-blind placebo-controlled randomized clinical study with 30 alcoholic smokers randomized to baclofen at 80 mg/day or placebo.

High ghrelin levels in post-treatment euthyroid patients with Hashimoto's thyroiditis: a case-control preliminary study.

Rationale: Hashimoto's thyroiditis is a chronic inflammatory condition often associated with changes in appetite and body composition. Ghrelin is an orexigenic peptide involved in the regulation of appetite and food intake. A possible role of ghrelin in mediating inflammation has been suggested.

Intravenous ghrelin administration increases alcohol craving in alcohol-dependent heavy drinkers: a preliminary investigation.

Background: There is a need to identify novel pharmacologic targets to treat alcoholism. Animal and human studies suggest a role for ghrelin in the neurobiology of alcohol dependence and craving. Here, we were the first to test the hypothesis that intravenous administration of exogenous ghrelin acutely increases alcohol craving.

Combined pharmacotherapies for the management of alcoholism: rationale and evidence to date.

Pharmacotherapies for alcohol use disorders (AUDs) have limited efficacy. One approach to improving treatment outcomes for AUDs is to combine pharmacotherapies that have shown some efficacy as individual agents. The rationale for combining medications rests on the following principles: a combination of medications can target more than one neurotransmitter system that is dysfunctional in AUDs, can target different drinking behaviors (i.

Roux-en-Y gastric bypass increases intravenous ethanol self-administration in dietary obese rats.

Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment for severe obesity. Clinical studies however have reported susceptibility to increased alcohol use after RYGB, and preclinical studies have shown increased alcohol intake in obese rats after RYGB. This could reflect a direct enhancement of alcohol's rewarding effects in the brain or an indirect effect due to increased alcohol absorption after RGYB.