ArticleBJPsych open2023
Psilocybin for treatment-resistant depression without psychedelic effects: study protocol for a 4-week, double-blind, proof-of-concept randomised controlled trial.
Article in BJPsych open, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Psychedelics as an intervention for psychological, existential distress in terminally ill patients: A systematic review and network meta-analysis.Journal of psychopharmacology (Oxford, England) · 2026Pooled it
- Ten practical suggestions for setting up a psychedelic study.Journal of psychopharmacology (Oxford, England) · 2026Article
- Mechanistic insights toward dissociating therapeutic from psychedelic effects: bridging the gap between psychedelic research and mental health care.Translational psychiatry · 2026Review
- Psilocybin ameliorates neuropathic pain-like behaviour in mice and facilitates gabapentin-mediated analgesia.Communications biology · 2026Article
- Psychedelic Therapies for Comorbid Major Depressive Disorder and Chronic Pain: A Review of Putative Mechanisms of Action.Pharmacology research & perspectives · 2026Review
- The HPA axis and kynurenine pathway: exploring the role of stress and neuroinflammation in treatment-resistant depression.Pharmacological reports : PR · 2026Review
- Considerations and cautions for the integration of psilocybin into routine clinical care: a consensus statement from the US National Network of Depression Centers' Task Group on Psychedelics and Related Compounds.EClinicalMedicine · 2025Review
- The Role of Psychedelics in Contemporary Psychological and Interdisciplinary Inquiry.Journal of personalized medicine · 2025Review
- Biased agonism in psychopharmacology: an opportunity to improve efficacy and safety of treatments.CNS spectrums · 2025Review
- The Causal Role of Consciousness in Psychedelic Therapy for Treatment-Resistant Depression: Hypothesis and Proposal.ACS pharmacology & translational science · 2025Article
- Are "mystical experiences" essential for antidepressant actions of ketamine and the classic psychedelics?European archives of psychiatry and clinical neuroscience · 2025Review
- Psilocybin mitigates behavioral despair and cognitive impairment in treatment-resistant depression model using wistar kyoto rats.Scientific reports · 2025Article
- Pharmacokinetics of Psilocybin: A Systematic Review.Pharmaceutics · 2025Review
- Psilocybin: From Psychiatric Pariah to Perceived Panacea.The American journal of psychiatry · 2025Review
- Recent advances in the synthesis of antidepressant derivatives: pharmacologic insights for mood disorders.3 Biotech · 2024Review
- Comparison between Single-Dose and Two-Dose Psilocybin Administration in the Treatment of Major Depression: A Systematic Review and Meta-Analysis of Current Clinical Trials.Brain sciences · 2024Review
- Neural effects of psychedelics: Complexity the key word.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- A Critical View on New and Future Antidepressants.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2024Review
- Review of Psilocybin Use for Depression among Cancer Patients after Approval in Oregon.Cancers · 2024Review
- The mechanistic divide in psychedelic neuroscience: An unbridgeable gap?Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundRandomised controlled trials (RCTs) of psilocybin have reported large antidepressant effects in adults with major depressive disorder and treatment-resistant depression (TRD). Given psilocybin's psychedelic effects, all published studies have included psychological support. These effects depend on serotonin 2A (5-HT2A) receptor activation, which can be blocked by 5-HT2A receptor antagonists like ketanserin or risperidone. In an animal model of depression, ketanserin followed by psilocybin had similar symptomatic effects as psilocybin alone.
aimsTo conduct a proof-of-concept RCT to (a) establish feasibility and tolerability of combining psilocybin and risperidone in adults with TRD, (b) show that this combination blocks the psychedelic effects of psilocybin and (c) provide pilot data on the antidepressant effect of this combination (compared with psilocybin alone).
methodIn a 4-week, three-arm, 'double dummy' trial, 60 adults with TRD will be randomised to psilocybin 25 mg plus risperidone 1 mg, psilocybin 25 mg plus placebo, or placebo plus risperidone 1 mg. All participants will receive 12 h of manualised psychotherapy. Measures of feasibility will include recruitment and retention rates; tolerability and safety will be assessed by rates of drop-out attributed to adverse events and rates of serious adverse events. The 5-Dimensional Altered States of Consciousness Rating Scale will be a secondary outcome measure.
resultsThis trial will advance the understanding of psilocybin's mechanism of antidepressant action.
conclusionsThis line of research could increase acceptability and access to psilocybin as a novel treatment for TRD without the need for a psychedelic experience and continuous monitoring.
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What OpenQuestion holds
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.