Effects of prefrontal transcranial direct current stimulation on open-label placebo responses

Recent research has shown that placebos can have beneficial effects even when given without deception. Such effects have been reported for outcomes including pain, anxiety or emotional distress. However, the mechanisms behind these open-label placebo (OLP) effects still remain unclear. For conventionally concealed placebos, a central role of expectation has been discussed, which has been linked to an engagement of the dorsolateral prefrontal cortex. Evidence from non-invasive brain stimulation studies suggests that inhibition of this brain region abolishes the placebo effect, whereas its activation enhances it. Here, we applied prefrontal transcranial direct current stimulation (tDCS) to test the role of expectation for placebos without deception. A total of 112 participants were assigned either to an OLP group or to a control group prior to viewing emotionally distressing images. All participants completed both active and sham tDCS in two separate sessions. Our results replicated the OLP effect by showing reduced emotional distress for the placebo group during sham stimulation. TDCS alleviated emotional distress in the control group but did not enhance the placebo response in the OLP condition. The results suggest that expectation of treatment effects may play a more limited role in OLP responses than in conventionally concealed placebos. OLPs may therefore represent a multimodal behavioral intervention whose neural underpinnings differ, at least in part, from those underlying placebos with deception.