SynthesisPsychopharmacology2025
Incremental efficacy systematic review and meta-analysis of psilocybin-for-depression RCTs.
Synthesis in Psychopharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers, 1 of them a synthesis that pooled 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.
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
4 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The subtle science: a systematic review of psilocybin magic mushroom and truffle microdosing.Frontiers in psychiatry · 2026Pooled it
- Challenges with clinical trial participants in studies with classical psychedelics: A position statement from the National Network of Depression Centers' task group on psychedelics and related compounds.Journal of psychopharmacology (Oxford, England) · 2026Article
- Reframing sedation for existential suffering: A case for integrating rapid-relief strategies.Palliative & supportive care · 2026Article
- Inaugural year of regulated psilocybin services in Oregon: safety, motivations, and utilization.Frontiers in psychiatry · 2026Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationalePsilocybin is a potentially paradigm-shifting depression intervention. We conducted a systematic review and meta-analysis of psilocybin-for-depression randomized controlled trials (RCTs).
objectivesSystematically assess harm reporting, risk of bias, action mechanism specification, and incremental therapeutic effect sizes in the psilocybin-for-depression RCT literature.
methodsAssessed databases included PsycINFO, CINAHL, Embase, Medline, Web of Science, and Scopus. Search terms "Psilocybin" or "Psychedelic" were paired with "Depression", and "Randomized Controlled Trial" or "RCT".
resultsWe identified k = 9 RCTs (k = 10 subgroups) involving n = 602 participants (56% psilocybin). Five studies had low/very low harm quality reporting, opposed to two with high. Most studies demonstrated a high risk of bias. Therapeutic mechanisms of action (MoAs) were discussed in varying detail but rarely assessed in original publications. Psilocybin was moderately superior to controls at reducing depression (g = 0.62; 95% CI = 0.27, 0.98). Effects were heterogenous (τ = .47). Smaller studies evidenced stronger effects that favored psilocybin (Egger's b0 = 3.63, p = .014). Almost all studies documented financial conflicts of interests.
conclusionPsilocybin demonstrates significant depression reduction relative to controls. However, researchers, clinicians, and stakeholders should consider several contextual factors. Effects were moderate and attenuated in larger and better-controlled studies. Harms reporting and risk of bias was high, though partly driven by unique challenges of psilocybin research. MoAs were variably specified but rarely assessed; suggesting it is unclear how depression is reduced. We advise researchers conduct RCTs with active control conditions, larger samples, and include MoA assessments. Independent RCTs from researchers without financial conflicts of interest are needed.
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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.