Abstract

Clinical trials of psychedelic compounds like psilocybin, LSD and DMT have forced a reconsideration of how non-drug factors, like participant expectations, are measured and controlled in mental health research. As doses of these profoundly psychoactive substances increase, so does the difficulty in concealing the treatment condition in the classic double-blind, placebo-controlled trial design. As widespread public enthusiasm for the promise of psychedelic therapy grows, so do questions regarding whether, and how much, trial results are biased by positive expectancy. First, we review the key concepts related to expectancy and its measurement. Then, we review expectancy effects reported in both micro- and macrodose psychedelic trials from the modern era. Finally, we consider expectancy as a discrete physiological process that can be independent of, or even interact with, the drug effect. Expectancy effects can be harnessed to improve treatment outcomes, and can also be actively managed in controlled studies to enhance the rigor and generalizability of future psychedelic trials.

View details for DOI 10.1016/j.bpsc.2024.02.004

View details for PubMedID 38387698