Redefining the real problem in psychedelic trials: Why fighting the Lessebo matters more than blinding integrity.
The International journal on drug policy July 8, 2026 Laetitia Vanderijst, Jean-Luc Faillie, Thibault Mura et al.
Imperfect blinding is a common issue in randomized trials, not just in psychedelic research, yet it is rarely assessed outside this field. In mental health, uncertainties from imperfect blinding combine with those from patient-reported outcomes, which are often viewed skeptically despite clinician-rated scales having their own limitations. Maintaining reasonable doubt about treatment allocation, not perfect blinding, supports placebo-controlled designs. Expectancy bias in psychedelic trials may lead to a 'lessebo' effect—a negative placebo effect from expecting to receive a placebo—driven by disappointment rather than pre-treatment expectation alone. The authors argue for shifting focus from preserving imperfect blinding to mitigating disappointment through structured psychoeducation, therapeutic alliance, and realistic preparation, which would improve ethical rigor and clinical usefulness.