Personalised and Standardised Wafer-Based Open-Label Placebos Reduce Perceived Stress: A Three-Arm Randomised Controlled Trial

Background: Open-label placebos (OLPs) are placebos administered transparently, without deception, that can nonetheless yield beneficial effects. We tested a novel OLP delivery format—printed edible wafers, with or without individualised coaching-based personalisation, in highly stressed university students.Methods: N = 137 highly stressed university students were randomly assigned for three weeks to a personalised OLP (personalised printed image, label, desired effects) a standardised OLP (standardised for stress reduction), or waitlist. The primary outcome was perceived stress; secondary outcomes included anxiety, depression, sleep, well-being, and life satisfaction; moderators were treatment expectancy (TE) and general self-efficacy (GSE). Results: Both OLP arms reduced perceived stress vs. waitlist; effects maintained at follow-up. Anxiety decreased only in the personalised arm. The OLP arms did not differ significantly. In the standardised arm, lower GSE predicted larger depressive-symptom reductions and higher TE predicted greater well-being gains (vs waitlist). Conclusions: Wafers may be a versatile OLP delivery method with potential for mechanism-guided refinement and targeted personalisation in preventive and clinical contexts.