Expectancy Effects in Psychedelic Trials.
Balázs Szigeti, Boris D. Heifets
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging May 1, 2024 DOI: 10.1016/j.bpsc.2024.02.004 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Topics | Microdosing |
| Keywords | Hallucinogen therapy Clinical-trials trial design Psychedelic-therapy psychedelic medicine Psychedelic treatment Placebo-effect expectancy bias Suggestion effect Belief influence Research methodology Blinding procedures |
| Citations | 62 |
| Key findings | Expectancy effects in psychedelic trials can bias results, but can also be harnessed to improve treatment outcomes and managed to enhance rigor. |
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.
Comparable studies
Other narrative reviews on microdosing, most cited first.
Citations in the library
Cited by 61
- Expectancy Effects, Failure of Blinding Integrity, and Placebo Response in Trials of Treatments for Psychiatric Disorders: A Narrative Review. JAMA Psychiatry May 1, 2025
- Addressing blinding in classic psychedelic studies with innovative active placebos. The International Journal of Neuropsychopharmacology April 1, 2025
- In the new era of psychedelic assisted therapy: A systematic review of study methodology in randomized controlled trials. Psychopharmacology June 1, 2024
- Modifying Informed Consent to Help Address Functional Unmasking in Psychedelic Clinical Trials. JAMA Psychiatry March 1, 2025
- Psychedelic Therapy vs Antidepressants for the Treatment of Depression Under Equal Unblinding Conditions JAMA Psychiatry March 18, 2026
and 56 more in the library
Cites 38
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Psychological Medicine June 15, 2018
- Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases The Journal of Nervous and Mental Disease March 4, 2014
and 33 more in the library