Placebo effects account for a significant and clinically relevant percentage of clinical outcomes in various somatic and mental disorders and the administration of pure or impure placebos in clinical practise is common among physicians. However, the use of deceptive placebos is ethically not justifiable in clinical settings as well as legally forbidden, as it disregards the key principles of openness and transparency in the Code of Medical Ethics. Therefore, the potential and novel treatment with open-label placebos would provide an ethically acceptable way to harness placebo effects, without violating key principles of openness and transparency. Objectives of the project: The proposed projects will examine the effects of open-label placebo in comparison to well-established and highly controlled placebo paradigms as well as test the clinical significance and applicability of open-label placebos.Methods: To elucidate the effects and the effectiveness of open-label placebos two randomized controlled trials in healthy participants (study 1) as well as in subjects with premenstrual syndrome (study 2) will be conducted. Primary outcomes are expectancy-induced analgesia (study 1) and percentage change from baseline in symptoms intensity (study 2). Significance of the study: The proposed studies will help to test effects and applicability of open-label placebo in both healthy as well as in clinical subjects. Assuming that the administration of open-label placebo is ethical, the proposed studies could help to better understand the possibilities and limits of this novel treatment approach.