In a new preregistered study, we set out to compare the magnitude and duration of placebo versus nocebo effects in healthy volunteers, and also to examine the different factors contributing to these effects. Despite the clinical relevance of these effects, the question of how placebo and nocebo effects differ in strength and duration remains largely unexplored.

In this preregistered study, we used a within-subject design in 104 healthy to investigate and directly compare 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 one-week follow-up.

Significant placebo and nocebo effects were detected on day 1 and day 8, but nocebo effects were stronger on both test days. Sustained effects after one 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.