Expectancy effects in psychedelic trials
This review (2024) explores the impact of participant expectations on psychedelic clinical trials. It highlights the challenge of maintaining blinding as doses increase and discusses the potential bias introduced by positive expectancy. The review covers expectancy effects in both micro- and macrodose trials, suggesting that understanding and managing expectancy could enhance trial rigour and treatment outcomes in future psychedelic research.
Authors
- Balázs Szigeti
- Boris Heifets
Published
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.
Research Summary of 'Expectancy effects in psychedelic trials'
Introduction
Psychedelic clinical trials face a particular challenge with blinding because the strong psychoactive effects of compounds such as psilocybin, LSD and DMT make it difficult for participants to remain unaware of treatment allocation. Szigeti and colleagues note that when participants can infer their treatment condition, positive expectancy linked to media coverage and cultural enthusiasm may inflate apparent treatment benefits; they cite instances where the vast majority of participants correctly guessed allocation despite formal blinding procedures. This paper sets out to clarify how expectancy-related processes operate in psychedelic research. Rather than presenting new trial data, the authors review key conceptual distinctions (placebo response versus placebo effect; expectancy versus unblinding), summarise empirical findings from both macrodose and microdose studies, and consider neurophysiological pathways that might mediate expectancy. The stated aim is to identify measurement gaps and propose ways expectancy can be measured, manipulated, or accounted for in future trials to improve rigor and interpretability.
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Szigeti, B., & Heifets, B. D. (2024). Expectancy effects in psychedelic trials. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 9(5), 512-521. https://doi.org/10.1016/j.bpsc.2024.02.004
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