In 233 adults with treatment-resistant depression, the highest of three single psilocybin doses lowered depression scores more than a very low control dose at week 3 (difference 6.6 points); the middle dose did not. Suicidal ideation, behavior or self-injury occurred in all groups.
Adults with treatment-resistant depression (multinational) · Outcome: MADRS change at week 3
Confidence applies to this claim and context.
AttentionNot assessedNo current independent attention assessment
EvidenceNo mapped studiesNo reviewed experiment families currently mapped
ConfidenceNot assessedFor: In 233 adults with treatment-resistant depression, the highest of three single psilocybin doses lowered depression scores more than a very low control dose at week 3 (difference 6.6 points); the middle dose did not. Suicidal ideation, behavior or self-injury occurred in all groups.. No current reviewed confidence assessment for this claim.
The GapAttention not measured
Attention describes reviewed public attention, evidence shows study types, and confidence applies only to the stated claim. There is no overall score.
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Why we checked it
Very high, steady interest. In September 2026 English Wikipedia's Psilocybin and Psilocybin mushroom articles had 40,762 and 49,701 views. PubMed added 49 psilocybin records in the 30 days to Oct 11 2026. A pending FDA filing adds news attention (company-reported timeline). Federal attention is also rising: an April 2026 executive order set a policy to speed research on and access to psychedelic drugs, and the FDA held a public hearing on their possible future therapeutic use on September 14, 2026.
Here's where it actually stands
Psilocybin is the main psychedelic compound in so-called magic mushrooms. In the US it is a Schedule I controlled substance, and no psilocybin medicine is FDA-approved. Researchers are testing it, with psychological support, for depression that other treatments have not helped. Compass Pathways says two phase 3 trials of its synthetic psilocybin were positive. These results come from the company and are not yet peer-reviewed. The company expects to finish its application for FDA approval in late 2026. Any US launch would also need the DEA to reclassify the approved drug. Common short-term side effects in trials include headache, nausea and dizziness. Suicidal thoughts and self-harm were also reported, and rare lasting changes in perception have occurred. Oregon licenses supervised psilocybin services under state law. That is not FDA approval, and federal law still lists psilocybin in Schedule I.
What we know
In 233 adults with treatment-resistant depression, the highest of three single psilocybin doses lowered depression scores more than a very low control dose at week 3 (difference 6.6 points); the middle dose did not. Suicidal ideation, behavior or self-injury occurred in all groups.
What we don't know
For adults with treatment-resistant depression, does psilocybin keep working for months, and how does it compare with standard care?
Claims
In 233 adults with treatment-resistant depression, the highest of three single psilocybin doses lowered depression scores more than a very low control dose at week 3 (difference 6.6 points); the middle dose did not. Suicidal ideation, behavior or self-injury occurred in all groups. · headlineAdults with treatment-resistant depression (multinational) · Outcome: MADRS change at week 3Confidence: Not assessed · source checked
Would change this claim: If peer-reviewed COMP005/COMP006 results confirm the company-reported effects and durability, we would upgrade the opening from "being tested" to "shown in phase 3".
Source: Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. · PMID 36322843 · N Engl J Med · Abstract, Results: difference -6.6 (95% CI -10.2 to -2.9) highest vs control; -2.5 (-6.2 to 1.2) middle dose; AEs in 179/233 (77%); suicidal ideation/behavior/self-injury in all dose groups · Verify ↗Source: The Safety and Efficacy of Psilocybin in Participants With Treatment Resistant Depression · NCT NCT03775200 · COMPASS Pathways · Abstract, Results: difference -6.6 (95% CI -10.2 to -2.9) highest vs control; -2.5 (-6.2 to 1.2) middle dose; AEs in 179/233 (77%); suicidal ideation/behavior/self-injury in all dose groups · Verify ↗
A meta-analysis of 17 depression trials found that control groups improved less in psilocybin trials than in SSRI or esketamine trials, which may make psilocybin look more effective than it is.Randomized trials of psilocybin (4), esketamine (2) and SSRIs (11) for depression · Outcome: Pre-post change in control arms; response ratesConfidence: Not assessed · source checkedSource: Control Group Outcomes in Trials of Psilocybin, SSRIs, or Esketamine for Depression: A Meta-Analysis. · PMID 40736734 · JAMA Netw Open · Abstract, Results: control response rates 14 points higher in SSRI trials and 23 points higher in esketamine trials than in psilocybin trials; Conclusions: efficacy "might" be overestimated · Verify ↗
In 104 adults with major depressive disorder, a single psilocybin dose lowered depression scores more than an active placebo (niacin) by day 43 (difference 12.3 points). There were no serious treatment-related adverse events, but overall and severe adverse events were more common with psilocybin.Adults 21-65 with MDD (11 US sites) · Outcome: MADRS change to day 43Confidence: Not assessed · source checkedSource: Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. · PMID 37651119 · JAMA · Abstract, Results: mean difference -12.3 (95% CI -17.5 to -7.2); day 8 -12.0; higher rate of overall and severe AEs · Verify ↗Source: A Study of Psilocybin for Major Depressive Disorder (MDD) · NCT NCT03866174 · Usona Institute · Abstract, Results: mean difference -12.3 (95% CI -17.5 to -7.2); day 8 -12.0; higher rate of overall and severe AEs · Verify ↗
In 59 adults with moderate-to-severe depression, psilocybin was not significantly better than the antidepressant escitalopram on the main depression measure at week 6 (difference 2.0 points, P = 0.17). Secondary measures favored psilocybin but were not corrected for multiple comparisons.Adults with long-standing moderate-to-severe MDD · Outcome: QIDS-SR-16 change at week 6Confidence: Not assessed · source checkedSource: Trial of Psilocybin versus Escitalopram for Depression. · PMID 33852780 · N Engl J Med · Abstract, Results: -8.0 vs -6.0; difference 2.0 (95% CI -5.0 to 0.9), P=0.17 · Verify ↗Source: Psilocybin vs Escitalopram for Major Depressive Disorder: Comparative Mechanisms · NCT NCT03429075 · Imperial College London · Abstract, Results: -8.0 vs -6.0; difference 2.0 (95% CI -5.0 to 0.9), P=0.17 · Verify ↗
In a German trial of 144 adults with treatment-resistant depression, one high-dose psilocybin session with psychotherapy did not significantly increase response at week 6 compared with an active placebo (nicotinamide) (17.0% vs 10.6%). Suicidal thoughts on dosing days were more common with psilocybin (4% vs 1–2%), and one person developed lasting perceptual disturbances (hallucinogen persisting perception disorder).Adults aged 25-65 with treatment-resistant depression (2 German centers) · Outcome: Response at week 6 (primary)Confidence: Not assessed · source checkedSource: Efficacy and Safety of Psilocybin in Treatment-Resistant Major Depression: The EPISODE Randomized Clinical Trial. · PMID 41848690 · JAMA Psychiatry · Abstract, Results: response 17.0% / 12.5% / 10.6%; adjusted OR 1.73 (0.53-6.23), P=.19; suicidal ideation on dosing days 4% vs 1%-2%; 2 serious adverse reactions incl. 1 HPPD · Verify ↗Source: Efficacy and Safety of Psilocybin in Treatment-Resistant Major Depression · NCT NCT04670081 · Central Institute of Mental Health, Mannheim · Abstract, Results: response 17.0% / 12.5% / 10.6%; adjusted OR 1.73 (0.53-6.23), P=.19; suicidal ideation on dosing days 4% vs 1%-2%; 2 serious adverse reactions incl. 1 HPPD · Verify ↗
Mapped studies / experiment families
One experiment counts once, even with several registrations or publications. Counts above describe the headline claim.
No reviewed experiment families mapped yet.
Studies & active trials
Only papers and registered trials an editor reviewed for this page. Being listed is not a finding; the claims above say what they show.
Efficacy and Safety of Psilocybin in Treatment-Resistant Major Depression: The EPISODE Randomized Clinical Trial.PMID 41848690 · DOI 10.1001/jamapsychiatry.2026.0132Study · Published · May 1, 2026 · JAMA PsychiatryOpen source ↗
Control Group Outcomes in Trials of Psilocybin, SSRIs, or Esketamine for Depression: A Meta-Analysis.PMID 40736734 · DOI 10.1001/jamanetworkopen.2025.24119Study · Published · Jul 1, 2025 · JAMA Netw OpenOpen source ↗
Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial.PMID 37651119 · DOI 10.1001/jama.2023.14530Study · Published · Sep 5, 2023 · JAMAOpen source ↗
Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression.PMID 36322843 · DOI 10.1056/NEJMoa2206443Study · Published · Nov 3, 2022 · N Engl J MedOpen source ↗
Trial of Psilocybin versus Escitalopram for Depression.PMID 33852780 · DOI 10.1056/NEJMoa2032994Study · Published · Apr 15, 2021 · N Engl J MedOpen source ↗
Redefine Study: A Study Evaluating the Efficacy, Safety, and Tolerability of COMP360 in Participants With Post-traumatic Stress Disorder (Redefine)NCT NCT07570654Trial · Recruiting · Oct 6, 2026 · COMPASS PathwaysOpen registry record ↗
Psilocybin Intervention for Veterans Overcoming Treatment-Resistant Depression (PIVOT)NCT NCT07226232Trial · Recruiting · Aug 14, 2026 · VA Office of Research and DevelopmentOpen registry record ↗
Efficacy, Safety, and Tolerability of Two Administrations of COMP360 in Participants With TRDNCT NCT05711940Trial · Active, not recruiting · Aug 10, 2026 · COMPASS PathwaysOpen registry record ↗
A Study of Psilocybin for Major Depressive Disorder (MDD)NCT NCT03866174Trial · Completed · Usona InstituteOpen registry record ↗
Efficacy and Safety of Psilocybin in Treatment-Resistant Major DepressionNCT NCT04670081Trial · Completed · Central Institute of Mental Health, MannheimOpen registry record ↗
Efficacy, Safety, and Tolerability of COMP360 in Participants With TRDNCT NCT05624268Trial · Completed · COMPASS PathwaysOpen registry record ↗
Psilocybin vs Escitalopram for Major Depressive Disorder: Comparative MechanismsNCT NCT03429075Trial · Completed · Imperial College LondonOpen registry record ↗
The Safety and Efficacy of Psilocybin in Participants With Treatment Resistant DepressionNCT NCT03775200Trial · Completed · COMPASS PathwaysOpen registry record ↗
What would change our mind
If peer-reviewed COMP005/COMP006 results confirm the company-reported effects and durability, we would upgrade the opening from "being tested" to "shown in phase 3".
If FDA approves a psilocybin product and DEA reschedules it, we would update the legal-status sentence on the same day.
If blinded or active-controlled trials show much smaller effects, we would say expectation explains part of the earlier results.
Efficacy and Safety of Psilocybin in Treatment-Resistant Major DepressionCentral Institute of Mental Health, Mannheim · checked Oct 11, 2026 · NCT NCT04670081; status:COMPLETED
Efficacy, Safety, and Tolerability of Two Administrations of COMP360 in Participants With TRDCOMPASS Pathways · checked Oct 11, 2026 · NCT NCT05711940; status:ACTIVE_NOT_RECRUITING; primary completion 2025-11-13
Psilocybin Intervention for Veterans Overcoming Treatment-Resistant Depression (PIVOT)VA Office of Research and Development · checked Oct 11, 2026 · NCT NCT07226232; status:RECRUITING; primary completion 2030-12-02 (estimated)
Psilocybin vs Escitalopram for Major Depressive Disorder: Comparative MechanismsImperial College London · checked Oct 11, 2026 · NCT NCT03429075; status:COMPLETED
Redefine Study: A Study Evaluating the Efficacy, Safety, and Tolerability of COMP360 in Participants With Post-traumatic Stress Disorder (Redefine)COMPASS Pathways · checked Oct 11, 2026 · NCT NCT07570654; status:RECRUITING; primary completion 2028-11 (estimated)
The Safety and Efficacy of Psilocybin in Participants With Treatment Resistant DepressionCOMPASS Pathways · checked Oct 11, 2026 · NCT NCT03775200; status:COMPLETED
Control Group Outcomes in Trials of Psilocybin, SSRIs, or Esketamine for Depression: A Meta-Analysis.JAMA Netw Open · checked Oct 11, 2026 · PMID 40736734; DOI 10.1001/jamanetworkopen.2025.24119
Efficacy and Safety of Psilocybin in Treatment-Resistant Major Depression: The EPISODE Randomized Clinical Trial.JAMA Psychiatry · checked Oct 11, 2026 · PMID 41848690; DOI 10.1001/jamapsychiatry.2026.0132
Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression.N Engl J Med · checked Oct 11, 2026 · PMID 36322843; DOI 10.1056/NEJMoa2206443
Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial.JAMA · checked Oct 11, 2026 · PMID 37651119; DOI 10.1001/jama.2023.14530
For adults with treatment-resistant depression, does psilocybin keep working for months, and how does it compare with standard care?
Peer-reviewed trials lasted 3 to 6 weeks for their main result. Compass reports 26-week phase 3 data, but these are company-reported and not peer-reviewed. The second phase 3 trial is still active.
What would answer it: Peer-reviewed publication of the COMP005 (NCT05624268) and COMP006 (NCT05711940) phase 3 results, and the VA PIVOT trial (NCT07226232; 240 veterans; est. 2030-12).
In phase 2 randomized trials, a single psilocybin session with psychological support usually lowered depression scores more than a very low dose or an active placebo over 3 to 6 weeks, but a 2026 trial of 144 people missed its main goal. Against a standard antidepressant (escitalopram), it was not clearly better on the main measure. Trials are hard to blind because people can tell they got the drug. Peer-reviewed phase 3 results are not yet published.
How much of the benefit is the drug, and how much is expectation from knowing you received it?FDA guidance notes that intense perceptual effects make blinding hard. A meta-analysis found control groups in psilocybin trials improve unusually little.What would answer it: Trials using active comparators or blinding checks, reporting both, in a peer-reviewed phase 3 publication.