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Updated: Nov 4, 2025

Dissociation of the Confounding Influences of Expectancy and Integrative Difficulty Residing in Anomalous Sentences in Event-related Potential Studies

Dissociation of the Confounding Influences of Expectancy and Integrative Difficulty Residing in Anomalous Sentences in Event-related Potential Studies

Published on: May 9, 2019

Blinding and expectancy confounds in psychedelic randomized controlled trials.

Suresh D Muthukumaraswamy¹, Anna Forsyth¹, Thomas Lumley²

¹School of Pharmacy, The University of Auckland, Auckland, New Zealand.

Expert Review of Clinical Pharmacology

|May 26, 2021

Summary

This summary is machine-generated.

Psychedelic drug trials for mental health may overestimate effectiveness. High participant expectancy and de-blinding can inflate results, suggesting a need for better trial designs and reporting of these factors.

Keywords:

LSD Psychedelics blinding causation ketamine masking placebo effect psilocybin randomized controlled trials

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Area of Science:

Psychopharmacology
Clinical Psychology
Medical Research Methodology

Background:

Growing interest in psychedelic therapies (psilocybin, LSD, ketamine) for mental health disorders.
Previous literature indicates potential confounding factors in psychedelic randomized controlled trials (RCTs) due to expectancy and de-blinding.
Current psychedelic RCTs often lack reporting on pre-trial expectancy and blinding success.

Purpose of the Study:

To review literature on expectancy and blinding in psychedelic RCTs.
To systematically review psychedelic RCTs for reporting of expectancy and blinding.
To assess the impact of expectancy and de-blinding on reported effect sizes in psychedelic research.

Main Methods:

Systematic review of randomized controlled trials (RCTs) using Medline, PsychInfo, and EMBASE databases (January 1990 - November 2020).
Analysis of literature concerning expectancy effects and blinding procedures in psychedelic research.
Evaluation of reporting standards for expectancy and blinding in published psychedelic RCTs.

Main Results:

Psychedelic RCTs frequently report large effect sizes for therapeutic outcomes.
A significant proportion of reviewed psychedelic RCTs do not report pre-trial participant expectancy.
Success of blinding procedures is rarely reported in psychedelic RCTs, indicating a potential for de-blinding.

Conclusions:

Reported effect sizes in psychedelic RCTs may be overestimated due to participant expectancy and de-blinding.
Routine measurement of de-blinding and expectancy is recommended for future psychedelic RCTs.
Improved clinical trial design and participant instructions are crucial to mitigate and account for confounding factors in psychedelic research.