Open-label placebo effects on psychological distress and hair cortisol in a randomized controlled trial – the moderating role of the five-factor personality traits

Objectives Open-label placebo (OLP) treatments have shown promising effects on various health outcomes, but evidence regarding physiological measures is still limited. Personality traits have been proposed as important moderators of treatment responsiveness, yet their role in OLP effects remains largely unclear. This study therefore investigated whether the five-factor personality traits moderate the effect of a four-week OLP intervention to reduce hair cortisol concentrations (HCC) and psychological distress in the context of oral university exams as real-life stressor. Methods In a randomized controlled trial, 202 healthy university students were assigned to either a four-week OLP treatment or a no-treatment control group. Psychological distress was assessed repeatedly across the intervention period, while HCC was measured pre- and within the intervention. Moderated regression analyses examined the influence of personality traits on OLP responsiveness, with conscientiousness and neuroticism as hypothesized moderators. Results Compared to the control group, the OLP group reported significantly lower psychological distress and showed a significant decrease in HCC. Conscientiousness moderated group effects on psychological distress, with higher trait levels predicting stronger reductions in the OLP group. Neuroticism moderated group effects on HCC, with highly neurotic individuals in the OLP group showing the strongest decreases. Exploratory analyses indicated no significant moderation effects of extraversion, agreeableness, or openness. Conclusion These findings demonstrate that OLPs can reduce both subjective and physiological distress measures in a naturalistic stress context. Personality traits play a differential moderating role across subjective and physiological measures, suggesting that OLPs may be particularly beneficial for vulnerable individuals.