Roles of administration route, expectation, and belief in placebos in a randomized controlled trial with open-label placebos

Recent reports challenge the view that placebos need to be given in deception. Numerous studies report remarkable effects when giving placebos honestly in an open way. However, the mechanisms of open-label placebos still remain to be cleared. For example, while expectation is often regarded as an important mechanism for concealed placebos, it is unclear whether this process may also account for open-label placebo effects. Thus, alternative theories based on, for example, the embodiment theory are also discussed. Here we examined possible mechanisms of open-label placebos including administration route (to address rituals or sensorimotor embodiment mechanisms), expectation, and belief in placebos. Healthy participants viewed emotional distressing pictures and were given an open-label placebo beforehand or were in the control group. Results replicated previous studies by showing that participants in the open-label placebo conditions felt less emotional distress. Route of administration did not affect the placebo response. Treatment expectancy did not predict the placebo effect but was linked to the strength of the placebo effect that participants self-reported (which was not related to the actual placebo effect). Belief in open-label placebos was related to the strength of the placebo effect. Interestingly, an affirmative attitude towards homeopathic treatments was linked to a positive treatment expectation, but not to the actual placebo effect. We discuss the results with respect to different theories explaining open-label placebo mechanisms and argue that open-label placebos may work predominantly in an unconscious way.