Blinding integrity in psychedelic research: Evidence from a comparative randomized controlled trial of psilocybin, MDMA, and methylphenidate in healthy volunteers.
L Belinger, N M Rieser, E J E Engeli, L Becciolini, M Clamote, M Pribis, F Saissi, G A Florineth, N L Hehl, M Herdener, K H Preller
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology May 28, 2026 Peer reviewed DOI: 10.1016/j.euroneuro.2026.112879 via PubMed
Summary
The study evaluated blinding integrity in 120 healthy volunteers who received psilocybin, MDMA, or methylphenidate in a double-blind, randomized controlled trial. Overall, blinding was found to be insufficient, with psilocybin showing the highest rates of unblinding, followed by MDMA and then methylphenidate. Methylphenidate was more effective at blinding participants regarding MDMA than psilocybin. The findings highlight the importance of comprehensive assessments of blinding in psychedelic research.
Study at a glance
| Design | randomized controlled trial |
|---|---|
| Sample size | 120 |
| Population | healthy volunteers |
| Key finding | Overall blinding was insufficient, with psilocybin showing the highest rates of functional unblinding. |
Abstract
Maintaining effective blinding is a major methodological challenge in psychedelic research. This study provides a comprehensive evaluation of blinding integrity in 120 healthy volunteers who received either psilocybin, MDMA, or methylphenidate (active placebo) in a double-blind, randomized controlled trial. Using a multi-level assessment incorporating forced-choice substance guesses, certainty ratings, decision factors, and subjective substance effects, the analyses characterize blinding integrity and its relation to the substance experience. Results indicate that overall blinding was insufficient, with psilocybin showing the highest rates of functional unblinding, MDMA moderate levels, and methylphenidate the lowest. As an active placebo, methylphenidate provided more effective blinding for MDMA than for psilocybin. Incorporating certainty levels of substance guesses revealed a more differentiated pattern, with lower functional unblinding rates. Decision factors and subjective substance experiences were associated with phenomenological substance effects. Prior substance experiences did not influence accuracy of forced-choice substance guesses. These findings provide empirical guidance for the design and reporting of blinding procedures in psychedelic trials and underscore the value of systematic, multi-level assessment of blinding integrity.