Evidence map›Paper›PMID 35359159›Full record

ReviewPsychopharmacology2022

Great Expectations: recommendations for improving the methodological rigor of psychedelic clinical trials.

Jacob S Aday, Boris D Heifets, Steven D Pratscher, Ellen Bradley, Raymond Rosen, Joshua D Woolley

Registry-linked trialOpen access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Psychopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07479550 (A Phase 2 Randomized Study Examining the Safety, Feasibility, and Effectiveness of Masking Psilocybin Therapy With General Anesthesia in Major Depressive Disorder), which is not on this map. Cited by 102 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed, 12 pooled it
36.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07479550 phase2not yet recruitingnot on this mapstarted 2026, after this paper: background citation

A Phase 2 Randomized Study Examining the Safety, Feasibility, and Effectiveness of Masking Psilocybin Therapy With General Anesthesia in Major Depressive Disorder

TypeinterventionalSponsorStanford UniversityRan2026 to 2027Enrolled10ConditionsMajor DepressionArmsPsilocybin (Usona Institute), Propofol, Placebo
3 · Its place in the literature

Who cites it

102 citing papers in PubMed, 12 syntheses or guidelines pooled it, 201 citations in OpenAlex.

  1. Pooled it
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  3. Magnitude of response in treatment and control groups within psychedelic trials for psychiatric disorders: A meta-analysis.European psychiatry : the journal of the Association of European Psychiatrists · 2026
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  13. Trial
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  15. Psilocybin therapy for mood dysfunction in Parkinson's disease: an open-label pilot trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
    Trial
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  18. The entropic brain today.Brain : a journal of neurology · 2026
    Review
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  20. Article

42 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Jacob S AdayDepartment of Psychiatry and Behavioral Sciences, San Francisco VA Medical Center, University of California, 401 Parnassus Ave., San Francisco, CA, 94143, USA. jacob.aday@ucsf.edu.ORCID http://orcid.org/0000-0003-0578-8530
Boris D HeifetsDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, USA.
Steven D PratscherDepartment of Community Dentistry and Behavioral Science, Pain Research and Intervention Center of Excellence, University of Florida, Gainesville, FL, USA.
Ellen BradleyDepartment of Psychiatry and Behavioral Sciences, San Francisco VA Medical Center, University of California, 401 Parnassus Ave., San Francisco, CA, 94143, USA.
Raymond RosenDepartment of Psychiatry and Behavioral Sciences, San Francisco VA Medical Center, University of California, 401 Parnassus Ave., San Francisco, CA, 94143, USA.
Joshua D WoolleyDepartment of Psychiatry and Behavioral Sciences, San Francisco VA Medical Center, University of California, 401 Parnassus Ave., San Francisco, CA, 94143, USA.
San Francisco VA Medical Center · USStanford Medicine · USUniversity of Florida · US

Funding

the Integrative and Multidisciplinary Pain and Aging Research Training (IMPART) ProgramT32AG049673 · NIA · UNIVERSITY OF FLORIDA · PI FILLINGIM, ROGER B · 2015 to 2024
$3.2M
CSR&D Research Career Development Transition Award ApplicationIK4CX002090 · VA · VETERANS AFFAIRS MED CTR SAN FRANCISCO · PI WOOLLEY, JOSH · 2020 to 2024
–
CSRD VA IK4 CX002090NIA NIH HHS T32 AG049673
6 · The paper itself

Abstract

rationalePsychedelic research continues to garner significant public and scientific interest with a growing number of clinical studies examining a wide range of conditions and disorders. However, expectancy effects and effective condition masking have been raised as critical limitations to the interpretability of the research.

objectiveIn this article, we review the many methodological challenges of conducting psychedelic clinical trials and provide recommendations for improving the rigor of future research.

resultsAlthough some challenges are shared with psychotherapy and pharmacology trials more broadly, psychedelic clinical trials have to contend with several unique sources of potential bias. The subjective effects of a high-dose psychedelic are often so pronounced that it is difficult to mask participants to their treatment condition; the significant hype from positive media coverage on the clinical potential of psychedelics influences participants' expectations for treatment benefit; and participant unmasking and treatment expectations can interact in such a way that makes psychedelic therapy highly susceptible to large placebo and nocebo effects. Specific recommendations to increase the success of masking procedures and reduce the influence of participant expectancies are discussed in the context of study development, participant recruitment and selection, incomplete disclosure of the study design, choice of active placebo condition, as well as the measurement of participant expectations and masking efficacy.

conclusionIncorporating the recommended design elements is intended to reduce the risk of bias in psychedelic clinical trials and thereby increases the ability to discern treatment-specific effects of psychedelic therapy.

Indexed as

HallucinogensHumansMotivationPsychotherapyResearch DesignHallucinogensClinical trialsExpectanciesMaskingPlacebo effectPsychedelicsPsychedelic therapyRecommendationsTreatment expectations

Identifiers

PMID35359159
PMCPMC10184717
OpenAlexW4226207502

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.