Blinding and expectancy confounds in psychedelic randomized controlled trials

Summary

Treatment effects for Major Depression from psychedelic clinical trials may be significantly overestimated. A systematic review of Randomized Controlled Trials (RCTs) using MEDLINE revealed many studies on psilocybin and similar psychedelics lacked effective blinding. Expectancy theory suggests participants often discern if they receive the active medicine or a placebo, influencing reported outcomes. This de-blinding means large effect sizes in clinical psychology and psychiatry for these alternative medicine treatments might be inflated. Future drug studies must improve blinding to accurately assess therapeutic potential.

Abstract

Introduction: There is increasing interest in the potential for psychedelic drugs such as psilocybin, LSD and ketamine to treat several mental health disorders, with a growing number of randomized controlled trials (RCTs) being conducted to investigate the therapeutic effectiveness of psychedelics.Areas covered: We review previous literature on expectancy effects and blinding in the context of psychedelic RCTs - literature which strongly suggest that psychedelic RCTs might be confounded by de-blinding and expectancy. We conduct systematic reviews of psychedelic RCTs using Medline, PsychInfo and EMBASE (Jan 1990 - Nov 2020) and show that currently reported psychedelic RCTs have generally not reported pre-trial expectancy, nor the success of blinding procedures.Expert opinion: While psychedelic RCTs have generally shown promising results, with large effect sizes reported, we argue that treatment effect sizes in psychedelic RCTs are likely over-estimated due to de-blinding of participants and high levels of response expectancy. We suggest that psychedelic RCTs should routinely measure de-blinding and expectancy. Careful attention should be paid to clinical trial design and the instructions given to participants to allow these confounds to be reduced, estimated and removed from effect size estimates. We urge caution in interpreting effect size estimates from extant psychedelic RCTs.

Tags