Expectancy Effects in Psychedelic Trials.

Clinical trials of psychedelics such as psilocybin, LSD, and DMT have challenged how nondrug factors like participant expectations are measured and controlled in mental health research. Higher doses of these psychoactive substances make it harder to conceal treatment conditions in double-blind, placebo-controlled designs. Growing public enthusiasm for psychedelic therapy raises questions about whether trial results are biased by positive expectancy. This review covers key concepts of expectancy and its measurement, examines expectancy effects reported in modern microdose and macrodose trials, and considers expectancy as a physiological process that can be independent of or interact with drug effects. Expectancy can be harnessed to improve outcomes and managed to enhance trial rigor.

Study at a glance

Abstract

Clinical trials of psychedelic compounds like psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltrptamine (DMT) have forced a reconsideration of how nondrug factors, such as 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 that have been 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.