The development of adverse side effects after placebo intake has been reported for a variety of medical conditions often discontinued pill intake explicitly because of symptoms that were attributed to the medication. Nocebo responses, similar to placebo responses, are mediated through specific and interrelated mechanisms across different medical conditions and physiological systems. Nocebo responses are steered by patient expectations towards possible unwanted side effects of a treatment or medication, which in turn can be induced by an inappropriate doctor-patient communication and/or patients information systems such as drug information leaflets. In addition, associative learning and LY2835219 CDK inhibitor social observational learning can also play a role in the development of nocebo effects. These nocebo-induced side effects are not only of relevance for clinical trials, but also play a major role in drug discontinuation in clinical practice, thereby negatively affecting treatment efficacy as well as patient adherence and compliance. Since experimental and clinical data document a large interindividual variability in nocebo responses, one of the major challenges in this research area is to identify psychological and/or biological predictors for nocebo responses. Genetic variation had been identified that might predict placebo responses. The Met allele of a genetic polymorphism in the catechol-o-methyltransferase gene was associated with increased placebo responses in patients with irritable bowel syndrome. Previously, functional polymorphisms in the monoamine oxidase gene and the COMT predicted reduced placebo responses in depression. However these data were not significant. Moreover, a link between polymorphisms of genes of the serotonergic system, amygdala activity and social anxiety has been reported. More recently, the major degrading enzyme of endocannabinoids FAAH has been found to induce higher placebo analgesia for FAAH Pro129/ Pro129 homozygotes. However, data on genetic variables predicting nocebo responses are lacking. Psychological predictors for nocebo responses such as anticipatory anxiety for the experience of visceral pain, the trait pessimism for inducing unpleasant feelings after pill intake and a tendency towards somatization, as well as a higher somatosensory awareness and amplification have been identified. In a model of learned immunosuppressive placebo effects in healthy humans, we were able to identify biological and psychological predictor variables for the learned inhibition in cytokine release. Thus, employing this well-established paradigm of behaviorally conditioned immunosuppressive effects, the aim of the present study was to identify possible genetic predictors for nocebo responses. We focused on the COMT Val158Met polymorphism since it has been investigated most extensively. The valine form catabolizes dopamine three to four-times more efficiently than the methionine form.