The prevalence of overweight and obesity has increased rapidly in less than half a century. It is assumed that this development is due to interplay between behavioural, environmental and genetic factors. This increase in weight is associated with multiple-medical conditions, e.g. increased depression, and chronicle health conditions, like heart disease, cancer, and type 2 diabetes, and is associated with high health care costs. The UK has one of the highest rates of obesity in Europe, with 20% of the population defined as obese and over 50% defined as overweight. However treatment options for weight loss, and especially long-term weight maintenance are still limited. The development of safe and effective therapeutics is therefore imperative. An effective way to help weight loss, as part of a comprehensive program, is to prescribe drug treatments designed to reduce food consumption. However, at present, drug treatments for obesity are very limited.

mCPP appears to reduce food intake, and appetite in lean people. However it also seems to effect cognitive processes. Basic research to understand the interplay between these processes in relation to drug effects on appetite are of great interest because it can provide important insight into new development novel treatments for obesity. The investigators propose to test a model outlining that metabolic signals may reduce food intake by interfering with cognitive processes that underpin appetite.

It has been agreed upon that eating behaviour is affected by metabolic signals, e.g. serotonin, insulin and ghrelin, and influenced by food reward processes (Berthoud 2011). But the idea that these mechanisms are modulated via higher cognitive processes such as inhibitory control, attention, and memory is a relatively new domain to be explored. In humans, eating behaviour seems to be a more complex system; which also involves habits, long-term goals, and social interaction. Cognitive processes appear to play an important role in food consumption. Previous studies reported the anorectic effect of the drugs meta-chloriphenylpiperazine (mCPP), a 5-HT2C receptor agonist. Additionally mCPP has been shown to reduce appetite, increase satiety, and enhance memory for emotional material (word recall) and recognition memory (Thomas et al 2015). Preliminary results suggest that mCPP decreased intake of palatable snacks (hedonic eating) and when viewing food pictures appetite and reward related neural responses appear to be modulated by mCPP administration (Thomas et al in preparation). However the interaction between the drugs, neural responses and behaviour are still not known, and the effects of overweight on these responses is a very interesting question in relation to anti-obesity drug development.

In the proposed study the researchers want to investigate the effect of oral administrating mCPP, on neural responses and networks in relation to food reward, cognitive control and working memory and its impact on subsequent snack consumption, food and emotion related memory, and mood and appetite ratings, and additionally the interplay between all these processes in both lean and obese individuals. Participants will get an mCPP dose (30mg) and a placebo on different occasion, where after the neural activation (with fMRI) in response to food stimuli is assesed, inhibition tasks, and memory tests. This will be related to eating behaviour, memory performance, and mood and appetite ratings.