Blinding and expectancy confounds in psychedelic randomized controlled trials
Suresh Muthukumaraswamy, Anna Forsyth, Thomas Lumley
Expert Review of Clinical Pharmacology May 26, 2021 DOI: 10.1080/17512433.2021.1933434 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Peer reviewed |
|---|---|
| Topics | Psilocybin |
| Keywords | Blinding Expectancy theory Randomized controlled trial Context archaeology Placebo Meta-analysis Clinical trial Systematic review Medline Clinical psychology Alternative medicine Hallucinogen Pathology |
| Citations | 312 |
| Key findings | Effect sizes in psychedelic randomized controlled trials are likely overestimated due to participant de-blinding and high response expectancy. |
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.
Comparable studies
Other systematic reviews and meta-analyses on psilocybin, most cited first.
Citations in the library
Cited by 277
- Great Expectations: recommendations for improving the methodological rigor of psychedelic clinical trials Psychopharmacology April 1, 2022
- Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review Journal of Psychopharmacology August 26, 2022
- Ketamine for the treatment of major depression: a systematic review and meta-analysis EClinicalMedicine August 1, 2023
- Psychedelic-Assisted Psychotherapy—A Systematic Review of Associated Psychological Interventions Frontiers in Psychology June 10, 2022
- Psilocybin-assisted therapy for major depressive disorder: An exploratory placebo-controlled, fixed-order trial Journal of Psychopharmacology March 20, 2023
and 272 more in the library
Cites 47
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- 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 with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
and 42 more in the library