Addressing blinding in classic psychedelic studies with innovative active placebos.
Int J Neuropsychopharmacol April 1, 2025 Jacob S Aday, Otto Simonsson, Emmanuelle A D Schindler et al. 25 citations
Classic psychedelics show promise for treating neuropsychiatric disorders, but weak blinding integrity in clinical trials limits the interpretability of therapeutic effects, making alternative active placebos necessary. This review describes drawbacks of current placebos, proposes criteria for suitable active placebos—including acute psychoactive and physiological effects, matched onset and duration, safety, and lack of therapeutic effects for the target disease—and identifies several pharmacological agents that may serve as active placebos for moderate-to-high doses of short- and long-acting psychedelics, as well as low-dose and microdosing regimens. Future research should apply a thoughtful selection process and ancillary strategies to improve blinding.