"Recent data suggest the placebo effect to be a powerful demonstration of how mental activity that is shaped by expectation and experience can influence physiological functions. The current strategy to minimize potential placebo effects largely ignores the positive effects of the placebo response. The current proposal postulates a radically different approach: Instead of considering placebo effects a nuisance, we will explicitly investigate the mechanisms behind expectation and experience (i.e. placebo response) to develop its use for the benefit of the patient. Importantly, the same applies to the effect of negative expectations (i.e. nocebo response) that can be responsible for negative effects of treatment. Understanding the mechanisms and circumstances that promote these effects will allow us to adjust medical treatments to minimize these nocebo effects. We will investigate the mechanisms of placebo and nocebo responses in traditional fields such as pain, but also in respiratory medicine and in “cognitive enhancement”. Using functional magnetic resonance imaging (fMRI), pharmacological interventions and formal models we will in particular address the neuronal mechanisms underlying placebo and nocebo responses. Combining the data from all three fields (pain, respiration and cognitive enhancement) will allow us to identify domain general and domain specific mechanisms of placebo responses. These projects will be supported by a methodological work-package which will provide neuroimaging techniques to improve the assessment of placebo and nocebo relevant brain structures. Finally a large cohort of volunteers will be investigated, to assess the relationship between placebo responses, personality variables and genetic polymorphisms using a genome-wide association analysis. Insights gained in this project could have the potential to formally place placebo responses and related mechanisms such as experience and expectation into the mainstream of evidence based medicine."