In the new era of psychedelic assisted therapy: A systematic review of study methodology in randomized controlled trials.
Paul S Soliman, Dallece E Curley, Christy Capone, Erica Eaton, Carolina L Haass-Koffler
Psychopharmacology June 1, 2024 DOI: 10.1007/s00213-024-06598-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Placebo-controlled Peer reviewed |
|---|---|
| Sample size | 16 |
| Population | Randomized controlled trials of psychedelics for psychiatric disorders |
| Topics | MDMA Psychedelic-assisted therapy |
| Keywords | Assisted therapy Placebo Psychadelics Clinical research Mental health treatment Drug trials Therapeutic breakthroughs |
| Citations | 22 |
| Key findings | Traditional placebo administration is insufficient to control for expectancy confounds in psychedelic-assisted therapy trials; active placebos and methods to limit unblinding are important design considerations. |
Abstract
Recent years have seen a resurgence in randomized, placebo controlled trials (RCTs) utilizing non-classical psychedelics (e.g. 3,4-methyl enedioxy methamphetamine [MDMA]), and classical psychedelics (e.g. psilocybin, lysergic acid diethylamide [LSD], and N,N-dimethyltryptamine [DMT/ayahuasca]) in conjunction with assisted therapy (AT) for psychiatric disorders. A notable methodological challenge in psychedelic AT, however, is the complexity of blinding procedures. The lack of efficacious blinding can introduce considerable response bias, reduce internal validity, and compromise participant retention. This systematic review examines design and blinding techniques in RCTs utilizing psychedelics and placebo for the treatment of psychiatric disorders. The aim of this work is to identify factors that may inform future RTC design for conducting psychedelics research. We conducted a systematic review of PubMed, MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Psycinfo, Embase, and Web of Science Core Collection to examine: (1) placebo selection, (2) study design, and (3) integrity of blinding measures. Sixteen publications were identified as meeting the criteria for a systematic review. Our findings suggest that traditional placebo administration is insufficient to control for expectancy confounds. Consequently, experimental methodology that limits personnel unblinding and the use of an active placebo are important considerations when designing prospective clinical studies involving psychedelics.
Comparable studies
Other systematic reviews and meta-analyses on MDMA and psychedelic-assisted therapy, most cited first.
Citations in the library
Cited by 18
- Randomized Controlled Trials of Psilocybin‐Assisted Therapy in the Treatment of Major Depressive Disorder: Systematic Review and Meta‐Analysis Acta Psychiatrica Scandinavica December 3, 2024
- Treating posttraumatic stress disorder and alcohol use disorder comorbidity: Current pharmacological therapies and the future of MDMA-integrated psychotherapy. Journal of Psychopharmacology December 1, 2023
- From Efficacy to Effectiveness: Evaluating Psychedelic Randomized Controlled Trials for Trustworthy Evidence‐Based Policy and Practice Pharmacology Research & Perspectives April 1, 2025
- What should constitute a control condition in psychedelic drug trials? Nature Mental Health October 1, 2024
- [Psychedelic and dissociative agents in psychiatry: challenges in the treatment]. Der Nervenarzt September 1, 2024
and 13 more in the library
Cites 31
- 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 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
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
and 26 more in the library