What four peer-reviewed psilocybin trials in depression reported, and where COMPASS Pathways' phase 3 program and FDA approval stand.
Four peer-reviewed psilocybin clinical trials tested psilocybin plus psychological support in depression. Three reported larger symptom reductions than their comparison condition. The fourth, against escitalopram, found no significant difference on its primary measure. Adverse events were more common with psilocybin than with niacin placebo in the Raison trial. Most trials excluded people with higher-risk histories, and follow-up was short. As of October 20, 2026, we found no FDA approval of a psilocybin product in the sources reviewed.
We reviewed the PubMed abstracts of those four trials, two ClinicalTrials.gov records for phase 3 studies, and the COMPASS Pathways second-quarter 2026 press release filed with the Securities and Exchange Commission (SEC) on August 5, 2026. We completed this desk review of published documents on October 20, 2026. Sponsor-reported phase 3 results exist for COMP360, but we found no peer-reviewed publication of them in the sources reviewed.
The four completed peer-reviewed trials all tested psilocybin with psychological support in adults with depression, and they differ in what psilocybin was compared against. Three reported a larger drop in depression scores with psilocybin than with the comparison condition. The fourth, against an antidepressant, found no statistically significant difference on its primary measure.
Davis and colleagues at Johns Hopkins Bayview Medical Center randomized 27 adults with major depressive disorder (MDD) to immediate treatment or an 8-week waiting list. At week 4, the immediate group averaged 8.5 on the GRID-Hamilton Depression Rating Scale (GRID-HAMD), against 23.5 for the waiting list group.
Goodwin and colleagues, in a trial funded by COMPASS Pathfinder, gave 233 adults with treatment-resistant depression one of three doses of a synthetic psilocybin formulation, with the lowest dose serving as the control. MADRS scores fell 6.6 points more with the highest dose than with the control at week 3. The middle dose did not differ significantly.
Raison and colleagues randomized 104 adults with MDD at 11 research sites in the United States to a single dose of psilocybin or a niacin placebo (JAMA 2023). By day 43, psilocybin led placebo by 12.3 MADRS points.
Carhart-Harris and colleagues compared psilocybin with escitalopram, a selective serotonin reuptake inhibitor (SSRI), in 59 patients over 6 weeks (New England Journal of Medicine 2021). The 2.0-point difference between groups on the primary self-report scale was not statistically significant (P=0.17).
Our guide to psilocybin for depression covers the condition-level questions these trials raise.
The Johns Hopkins trial, published by Davis and colleagues in JAMA Psychiatry in 2021, randomized 27 adults aged 21 to 75 with MDD (ClinicalTrials.gov NCT03181529). Participants were not using antidepressants and had no history of psychotic disorder, serious suicide attempt or hospitalization. Fifteen started treatment right away and 12 waited 8 weeks first.
Treatment was two psilocybin sessions with about 11 hours of supportive psychotherapy. The mean GRID-HAMD score at baseline was 22.8, and at weeks 1 and 4 the immediate group averaged 8.0 and 8.5. The waiting list group averaged 23.8 and 23.5 at the comparable time points.
Of the 27 people randomized, 24 (89%) completed the week 1 and week 4 assessments.
Seventeen participants (71%) had a clinically significant response, meaning a reduction of 50% or more, at week 1 and at week 4. Fourteen (58%) at week 1 and 13 (54%) at week 4 were in remission, defined as a score of 7 or lower. The authors concluded the findings suggest psilocybin with therapy is efficacious in MDD.
The trial was small and ran at a single site. It used a waiting list in place of a blinded placebo, and its outcome window ended at 4 weeks.
The COMPASS phase 2 trial, published by Goodwin and colleagues in the New England Journal of Medicine in 2022, was a double-blind study of 233 adults with treatment-resistant depression (ClinicalTrials.gov NCT03775200). Each participant received a single dose of a proprietary synthetic psilocybin formulation with psychological support. Seventy-nine received the highest dose, 75 a middle dose, and 79 the lowest dose that served as the control.
The primary endpoint was change on the MADRS, a 0 to 60 scale, from baseline to week 3, and baseline means were 32 or 33 in each group. Least-squares mean changes were -12.0 for the highest dose, -7.9 for the middle dose and -5.4 for the control dose.
The difference between the highest dose and the control was -6.6 points (95% confidence interval [CI] -10.2 to -2.9; P<0.001). The middle dose differed from the control by -2.5 points (95% CI -6.2 to 1.2; P=0.18), which was not statistically significant.
In the highest-dose group, response and remission at 3 weeks were generally supportive of the primary result. Sustained response at 12 weeks was not.
Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. The authors concluded that larger and longer trials, including comparison with existing treatments, are required.
The phase 2 trial by Raison and colleagues, published in JAMA in 2023, enrolled 104 adults aged 21 to 65 with MDD lasting at least 60 days at 11 research sites in the United States (ClinicalTrials.gov NCT03866174). Participants were randomized 1:1, 51 to psilocybin and 53 to niacin placebo, each given as a single dose with psychological support. Participants, staff, raters and statisticians were all blinded.
Exclusions included a history of psychosis or mania, active substance use disorder and active suicidal ideation with intent. People taking psychotropic medication could enroll after a medication taper.
On the primary outcome, change in MADRS from baseline to day 43, the mean difference between groups was -12.3 points (95% CI -17.5 to -7.2; P<.001). At day 8 the mean difference was -12.0 points (95% CI -16.6 to -7.4). More psilocybin participants than niacin participants had sustained response, and the same was not found for remission.
No serious treatment-emergent adverse events occurred. Psilocybin was associated with a higher rate of overall adverse events and of severe adverse events. The authors concluded the findings add to increasing evidence that psilocybin with psychological support "may hold promise" for MDD.
The trial against escitalopram, published by Carhart-Harris and colleagues in the New England Journal of Medicine in 2021, enrolled 59 patients with long-standing, moderate-to-severe MDD (ClinicalTrials.gov NCT03429075). It was a phase 2 double-blind randomized trial over 6 weeks, with 30 patients in the psilocybin group and 29 in the escitalopram group. Funding came from the Alexander Mosley Charitable Trust and Imperial College London's Centre for Psychedelic Research.
The primary outcome was change at week 6 on QIDS-SR-16, a self-report depression scale scored 0 to 27. Mean scores fell 8.0 points with psilocybin and 6.0 points with escitalopram. The between-group difference of 2.0 points (95% CI -5.0 to 0.9; P=0.17) was not statistically significant.
Secondary outcomes showed response in 70% of the psilocybin group versus 48% of the escitalopram group, and remission in 57% versus 28%. Those secondary results were not corrected for multiple comparisons. The incidence of adverse events was similar in the two groups.
The authors concluded the trial did not show a significant difference in antidepressant effects between psilocybin and escitalopram in a selected group of patients. They also wrote that larger and longer trials are required. Our psilocybin vs antidepressants guide sets this trial beside the wider comparison.
Phase 3 results for COMP360 come from COMPASS Pathways' own statements, and we found no peer-reviewed publication of them in the sources reviewed. In a second-quarter 2026 press release filed with the SEC on Form 8-K on August 5, 2026, COMPASS Pathways says COMP360 "has Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA)".
The filing says that across two phase 3 trials, "39% in COMP006 and 25% of participants in 005, achieved a clinically meaningful reduction in MADRS". It says the benefit was maintained "on average, through at least Week 26". These statements come from a corporate filing, and they are not an FDA decision.
The same filing says the FDA granted COMPASS Pathways' request in April for rolling submission and review of a New Drug Application (NDA). COMPASS Pathways says some modules have been submitted and all modules are on track to complete in the fourth quarter.
ClinicalTrials.gov lists two phase 3 studies sponsored by COMPASS Pathways in treatment-resistant depression (TRD). NCT05624268, "Efficacy, Safety, and Tolerability of COMP360 in Participants With TRD", is completed with 258 participants enrolled. NCT05711940, "Efficacy, Safety, and Tolerability of Two Administrations of COMP360 in Participants With TRD", is active, not recruiting, with 572 enrolled.
We have not matched either registry record to the COMP005 or COMP006 names used in the filing. Each NCT page linked above carries the registry's current status for that study.
The FDA granted Breakthrough Therapy designation to COMP360 for treatment-resistant depression in October 2018 and to the Usona Institute for psilocybin in MDD in November 2019. The designation speeds development and review, and it is neither an approval nor a legal change. As of October 20, 2026, we found no FDA approval of a psilocybin product for any condition in the sources reviewed. Check current status on the FDA website.
A peer-reviewed phase 3 paper or an FDA decision on the COMP360 application would change this summary of where approval stands.
The published trials cannot show how psilocybin performs over many months, because their primary outcomes were measured between week 1 and day 43. The Goodwin trial's 12-week sustained response did not support the primary result. The 26-week figure comes only from the COMPASS Pathways filing.
The trials screened out people with certain histories. The Davis trial excluded anyone with a history of psychotic disorder, serious suicide attempt or hospitalization, and the Raison trial excluded psychosis, mania, active substance use disorder and active suicidal ideation with intent.
Three of the trial abstracts we reviewed report adverse events. The Goodwin trial found them in 77% of participants, the Raison trial found higher overall and severe rates with psilocybin, and the escitalopram trial found a similar incidence in both arms.
Psilocybin is a Schedule I controlled substance under the federal Controlled Substances Act. Oregon and Colorado run state-regulated adult-access programs, and those programs are not treatment programs for depression. Our guide on whether mushrooms are legal carries the state-by-state detail.
SSRIs and other medications may interact with psilocybin, and trial protocols often require people to stop or taper certain medicines under medical supervision. Take medication questions to your prescriber, and read our psychedelic medication safety guide. If you are in crisis, use our crisis resources page.
To look for psilocybin clinical trials you could join, start with our clinical trial finder.
Yes, trials have been run in the United States: the Raison trial ran at 11 US research sites. ClinicalTrials.gov also lists two phase 3 COMP360 studies sponsored by COMPASS Pathways, one completed and one active but not recruiting. The sources we reviewed do not say whether any trial is currently enrolling. Search our clinical trial finder for current studies.
COMPASS Pathways says "39% in COMP006 and 25% of participants in 005, achieved a clinically meaningful reduction in MADRS", with benefit maintained "on average, through at least Week 26". Those figures come from an August 5, 2026 company filing with the SEC. They are sponsor statements that had no peer-reviewed publication in the sources we reviewed, and they are not an FDA decision.
No psilocybin product had FDA approval for any condition as of October 20, 2026, in the sources we reviewed. COMP360 and the Usona Institute's psilocybin were granted Breakthrough Therapy designation, which speeds development and review but is not approval. COMPASS Pathways says its New Drug Application is under rolling submission, with all modules on track to complete in the fourth quarter. Check current status on the FDA website.
The one head-to-head trial we reviewed found no statistically significant difference on its primary measure. Carhart-Harris and colleagues compared psilocybin with escitalopram in 59 patients and found a 2.0-point difference in QIDS-SR-16 change at week 6 (P=0.17). Response and remission rates were higher with psilocybin, but those secondary outcomes were not corrected for multiple comparisons.
The Goodwin trial reported adverse events in 179 of 233 participants (77%), including headache, nausea and dizziness, and suicidal ideation or behavior or self-injury occurred in all dose groups. The Raison trial reported no serious treatment-emergent adverse events but higher rates of overall and severe adverse events with psilocybin than with niacin. The escitalopram trial found a similar incidence of adverse events in both groups.
Eligibility differs by study. Completed trials excluded, for example, a history of psychotic disorder (Davis trial) and psychosis or active suicidal ideation with intent (Raison trial). Our clinical trial finder and ClinicalTrials.gov list studies. Trial protocols often require stopping or tapering certain medicines under medical supervision, so talk to your prescriber before you apply.
Psilocybin is a Schedule I controlled substance under federal law. Oregon and Colorado run state-regulated adult-access programs, and those programs are not treatment programs for depression. Our guide on whether mushrooms are legal carries the state-by-state detail.
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