A randomized trial that compared brain activity, efficacy and plausibility of open-label placebo treatment and cognitive repappraisal for reducing emotional distress.

Placebo pills can reduce emotional distress even when recipients have been informed about the inert nature of the treatment. However, before such open-label placebos (OLPs) can be recommended for general clinical use, their efficacy and acceptability need to be further investigated and compared with established methods for emotion regulation, such as cognitive reappraisal (CR). The current study with functional magnetic resonance imaging compared the effects of an OLP pill with CR for reducing a specific form of emotional distress: disgust. Participants (150 healthy females) were randomly allocated to one of three groups, all of which were exposed to disgusting and neutral images (OLP, CR, PV: passive viewing). It was tested whether the three groups would differ in brain activity and reported disgust. Ratings for the perceived efficacy and plausibility of treatment were also compared between OLP and CR. Both OLP and CR increased the activity in a cognitive control region, the ventrolateral prefrontal cortex. Relative to PV and OLP, CR reduced activity in the putamen and pallidum. These regions play an important role in decoding disgust signals from different modalities. Self-reports indicated that CR was perceived as a more effective and plausible intervention strategy than OLP. In conclusion, CR was a superior method for disgust regulation compared to OLP, both on the subjective as well as the neurobiological level. Future OLP studies are needed to test whether the observed effects generalize to other forms of emotional distress.