ERP correlates of placebo and 'anti-placebo' effects

Abstract

In the study we observed the effects of placebo and 'anti-placebo' messages on the neural activities registered through the event related potentials (ERP). Instead of commonly used term nocebo, we used the term 'anti-placebo', given that the message we delivered was not supposed to induce the negative effects, but just to diminish the effect of placebo. Thermal stimulus of 45 degrees of Celsius was applied on the skin of 29 students in a four different experimental situations: without analgesia, after receiving dermal analgesic EMLA Cream, after receiving neutral skin cream presented as an analgesic (placebo situation), and after receiving again EMLA Cream, but presented as the herbal analgesic not officially accepted as a medicament ('anti-placebo' situation). Immediately after stimulation, participants were asked to estimate the level of 'unpleasantness' of the stimuli on the subjective scale ranging from 1-10, and to start a cognitive experiment, during which the ERP responses were measured. Results showed three main ERP effects. In the early effect, we noticed that all three experimental situations with analgesia (that is, two conditions with the pharmaco-analgesia + the condition with the placebo analgesia) showed a different ERP effects in comparison to the condition with no analgesia. We interpreted these results as early expectancies that any analgesic (including placebo) should produce some effect in comparison to no-analgesic condition. In the medium effect, we observed significantly longer durations of the ERP effects in the situation of the 'anti-placebo' and no-analgesia, whereas in the analgesia and placebo condition these effects were much shorter. This result led us to the conclusion, that on the neural level, our suggestion of 'bad medicament' (similar to situation of no-medicament) caused a specific mental activity registered on ERP. This effect is the one which calls into a question doctors’ recommendations (which contain negative connotation) of medicaments, as they could potentially and unconsciously diminish a valuable impact that the placebo could have during a treatment. Finally, in the late effect, we also observed significant differences across the four experimental conditions, but these differences were directly correspondent with the order of presentation of experimental situations, and we interpret them as an artefact of the experimental design.