In recent years, placebos have evolved from a mean to control for 'therapeutic chaff' to something that has clinically relevant effects with biological underpinning and that is considered to have clinical as well as scientific potential. However, the wealth of scientific placebo research is conceptualized in a biomedical context, i.e. based on placebos provided with a biomedical treatment rationale, whereas little is known about effects and mechanisms of placebos provided with a psychological treatment rationale. This has important repercussions not only on placebo research, but also on attempts to establish specificity of psychological interventions, such as psychotherapy. Therefore, we set out to assess the effects and possible components of placebos provided with a psychological treatment rationale in three experiments on healthy subjects. We show that placebos provided with a psychological treatment rationale are effective in short- as well as mid-term, but only when provided by a trustworthy, friendly and empathetic experimenter. These findings indicate that placebos are effective outside the medical context and thus need be controlled for in non-medical trials. Furthermore, it highlights and confirms the importance of a plausible psychological treatment rationale in the context of a therapeutic alliance for psychological interventions, such as psychotherapy.