Blinding integrity in psychedelic research: Evidence from a comparative randomized controlled trial of psilocybin, MDMA, and methylphenidate in healthy volunteers.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology May 28, 2026 L Belinger, N M Rieser, E J E Engeli et al.
In a double-blind randomized trial with 120 healthy volunteers who received psilocybin, MDMA, or methylphenidate (active placebo), overall blinding was insufficient. Psilocybin had 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 effects. Prior substance experiences did not influence accuracy of forced-choice guesses. These findings offer empirical guidance for designing and reporting blinding procedures in psychedelic trials.