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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
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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.

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HumansHallucinogensPsilocybinDouble-Blind MethodMethylphenidateN-Methyl-3,4-methylenedioxyamphetamineMaleFemaleAdultYoung AdultHealthy VolunteersAdolescentBlinding assessmentBlinding integrityMDMAPsychedelic researchJournal ArticleRandomized Controlled TrialComparative Study

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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. 2026-05-28. Blinding integrity in psychedelic research: Evidence from a comparative randomized controlled trial of psilocybin, MDMA, and methylphenidate in healthy volunteers.. https://doi.org/10.1016/j.euroneuro.2026.112879

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