Nocebo effects are stronger and more persistent than placebo effects in healthy individuals

Placebo and nocebo effects illustrate the profound influence of cognitive-affective processes on symptom perception and treatment outcomes, with the potential to significantly alter responses to medical interventions. Despite their clinical relevance, the question of how placebo and nocebo effects differ in strength and duration remains largely unexplored. Using a within-subject design in 104 healthy individuals, we investigated and directly compared the magnitude and persistence of placebo and nocebo effects on experimental pain. Effects were assessed immediately after their induction through verbal instructions and conditioning and at a 1-week follow-up. The study was preregistered in the German Clinical Trials Register (registration number: DRKS00029228). Significant placebo and nocebo effects were detected on days 1 and 8, but nocebo effects were stronger on both test days. Sustained effects after 1 week were primarily predicted by individuals’ experienced effects on day 1. Our findings underscore the enduring nature of placebo and nocebo effects in pain, with nocebo responses demonstrating consistently greater strength, which is consistent with an evolutionarily advantageous ‘better-safe-than-sorry’ strategy. These insights emphasise the significant impact of nocebo effects and stress the need to prioritise efforts to mitigate them in clinical practice.