Gut Hormones in Obesity, Nicotine and Alcohol Dependence

Summary

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Obesity, smoking and alcohol dependence are major health burdens to society. Relapse after alcohol and smoking abstinence is common despite the use of combined behavioural support and current limited available medications. In obesity, nonsurgical interventions have also been disappointing in achievi...

Obesity, smoking and alcohol dependence are major health burdens to society. Relapse after alcohol and smoking abstinence is common despite the use of combined behavioural support and current limited available medications. In obesity, nonsurgical interventions have also been disappointing in achieving longterm weight loss. Therefore, there is a pressing need to develop novel drug treatments for addiction derived from knowledge of brain mechanisms related to relapse and reward responses to food and drugs. There is evidence in animals that some gut hormones, produced in the stomach and intestine, influence the consumption of food and desire for food, but also alcohol, nicotine and other drugs of abuse. Examples of such gut hormones are glucagon-like peptide1 (GLP1) and ghrelin. The influence of these hormones is exerted through brain systems involved in the core behavioural components of addiction: reward sensitivity, stress, impulsivity and compulsivity. These components are often also seen in obesity and food-related disorders such as binge eating disorder. It is unknown whether these gut hormones directly influence the core behavioural components of addiction in humans, particularly during abstinence. The investigators will examine the acute effects of Exenatide (mimics GLP1) and desacyl ghrelin (counteracts active acyl ghrelin), which are infused through a vein, on brain reward systems, craving for food, cigarettes and alcohol, and addictive and eating behaviours. The investigators will recruit adults with nicotine or alcohol dependence who have recently stopped smoking or drinking, and overweight/obese adults. The investigators will use functional magnetic resonance imaging (MRI) brain scans and computer-based test over 3 separate study days to study different aspects of eating and addictive behaviours.

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