Psilocybin is not FDA-approved for depression. What the Johns Hopkins and COMPASS trials found, where COMP360 stands, and how federal and state law treat it.
Psilocybin for depression is not approved by the Food and Drug Administration (FDA).
This page covers two clinical trials of psilocybin for depression. The first trial evaluated adults diagnosed with major depressive disorder, while the second trial studied participants with treatment-resistant depression.
Psilocybin remains classified as a Schedule I controlled substance under federal law. Clinical trials are the route for depression-specific study. State-regulated programs in Oregon and Colorado allow adult access at state-regulated service centers, but those programs do not operate as depression treatment programs.
Two clinical trials report reductions in depressive symptom scores, but psilocybin is not approved by the Food and Drug Administration (FDA) for any depressive disorder.
The first study was conducted at Johns Hopkins University by Davis et al. (2021) and registered on ClinicalTrials.gov as NCT03181529. This randomized, waiting-list-controlled trial enrolled 27 adults aged 21 to 75 diagnosed with major depressive disorder (MDD). Participants were randomized into an immediate treatment group of 15 individuals or an 8-week delayed waiting-list control group of 12 individuals. A total of 24 participants completed the full study protocol. The intervention consisted of two psilocybin sessions delivered in conjunction with approximately 11 hours of supportive psychotherapy.
Investigators evaluated depressive symptom severity using the GRID-Hamilton Depression Rating Scale (GRID-HAMD), which required a baseline score of 17 or higher for enrollment. The mean baseline GRID-HAMD score across participants was 22.8. At weeks 1 and 4 following treatment, the immediate treatment group scored 8.0 and 8.5 on the GRID-HAMD, compared with scores of 23.8 and 23.5 in the waiting-list group at the comparable assessment points.
Clinically significant response, defined as a reduction of 50% or more on the GRID-HAMD score from baseline, occurred in 17 of 24 participants (71%) at week 1 and week 4. Remission, defined as a score of 7 or lower on the GRID-HAMD, occurred in 14 participants (58%) at week 1 and 13 participants (54%) at week 4. The study authors concluded that the findings suggest psilocybin administered with therapy is efficacious in MDD.
Several design characteristics limit how these findings can be applied. The trial was small and conducted at a single academic medical center. The study used a waiting-list control design rather than a blinded placebo control, meaning that participants knew they would receive active psilocybin sessions. The trial protocol excluded people using antidepressant medications and people with a history of psychotic disorder, serious suicide attempt or hospitalization. The published data cover an outcome window limited to 4 weeks post-treatment.
The second study was conducted across multi-site centers by Goodwin et al. (2022) in the New England Journal of Medicine and registered on ClinicalTrials.gov as NCT03775200. This double-blind phase 2 clinical trial was funded by COMPASS Pathfinder and investigated a proprietary synthetic psilocybin formulation from COMPASS Pathways. The trial enrolled 233 adults diagnosed with treatment-resistant depression. Participants were randomized to receive a single dose across three comparative arms: 25 mg (79 participants), 10 mg (75 participants), or a 1 mg control dose (79 participants), all delivered with psychological support.
The primary efficacy endpoint was the change from baseline to week 3 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score, which is scored from 0 to 60 points. Baseline mean scores across the treatment arms were 32 or 33 points. At week 3, the least-squares mean changes from baseline were -12.0 points for the 25 mg group, -7.9 points for the 10 mg group, and -5.4 points for the 1 mg control group.
Statistical analysis revealed a difference of -6.6 points between the 25 mg group and the 1 mg control group (95% confidence interval [CI], -10.2 to -2.9; P<0.001). The difference between the 10 mg group and the 1 mg control group was -2.5 points (95% CI, -6.2 to 1.2; P=0.18), which was not statistically significant. Response and remission at week 3 were generally supportive in the 25 mg group, but a sustained response was not observed at 12 weeks.
Safety outcomes in the trial revealed common adverse events across participants. Adverse events occurred in 179 of 233 participants (77%), including headache, nausea, and dizziness. Suicidal ideation, suicidal behavior, or intentional self-injury occurred across all dose groups during the study. The study authors concluded that larger and longer trials, including direct comparisons with existing treatments, are required.
The two clinical studies evaluated psilocybin under distinct protocols, diagnostic definitions, and control conditions.
| Trial Parameter | Johns Hopkins Trial | COMPASS Pathways Trial |
|---|---|---|
| Citation | Davis et al. (2021) | Goodwin et al. (2022) |
| Population | 27 adults with major depressive disorder (24 completed) | 233 adults with treatment-resistant depression |
| Study Design | Randomized, waiting-list-controlled trial | Multi-site, double-blind phase 2 randomized trial |
| Comparison | Immediate treatment vs delayed 8-week waiting list | Single dose of 25 mg vs 10 mg vs 1 mg control |
| Primary Outcome | GRID-HAMD score change at weeks 1 and 4 | MADRS score change from baseline to week 3 |
| Main Result | Immediate group scored 8.5 vs 23.5 in the waiting-list group at week 4; 71% response | 25 mg showed a -6.6 point difference over 1 mg at week 3; 10 mg vs 1 mg difference not significant |
| Key Caution | Small single-site cohort with waiting-list control; excluded antidepressant users | Sustained response not shown at 12 weeks; adverse events in 77%; suicidal ideation across all arms |
The Johns Hopkins study evaluated major depressive disorder in participants who were not taking antidepressant medications, using a waiting-list control. The COMPASS Pathways trial investigated treatment-resistant depression across multiple clinical sites with a 1 mg control dose. Sustained response was not seen at week 12.
Psilocybin is not FDA-approved for any depressive disorder as of September 30, 2026.
FDA has granted two separate active Breakthrough Therapy designations for psilocybin development programs. In 2018, FDA granted Breakthrough Therapy status to COMPASS Pathways for its COMP360 formulation in treatment-resistant depression. The FDA also granted Breakthrough Therapy designation to the Usona Institute for psilocybin in major depressive disorder. A Breakthrough Therapy designation speeds development and review. This designation is not FDA approval. For an overview, read our guide to psilocybin.
COMPASS Pathways made these statements in its August 5, 2026 press release, filed on SEC Form 8-K. In that disclosure, COMPASS Pathways stated that COMP360 holds FDA Breakthrough Therapy designation and that a rolling New Drug Application (NDA) submission and initial review are underway. COMPASS Pathways stated that initial application modules have been submitted, with all remaining modules on track for completion in the fourth quarter of 2026.
COMPASS Pathways also reported results from its phase 3 clinical program, which includes trials COMP005 and COMP006. In the press release, COMPASS Pathways reported that 25% of participants in COMP005 and 39% of participants in the 25 mg arm of COMP006 achieved a clinically meaningful reduction on the MADRS depression scale at Week 6.
These phase 3 figures represent sponsor statements announced in corporate financial disclosures. They are not peer-reviewed scientific publications, and they do not constitute an approval decision by the FDA.
In the COMPASS phase 2 trial, adverse events were common.
Clinical trial data show that adverse events can occur after psilocybin dosing. In the COMPASS Pathways phase 2 study, 179 of 233 participants (77%) reported adverse events, including headache, nausea, and dizziness. In the phase 2 trial, suicidal ideation, suicidal behavior, or self-injury occurred in all dose groups, including the 1 mg control group and both active dose groups. Individuals experiencing severe distress or thoughts of self-harm should immediately access professional support through our crisis resources page.
The Johns Hopkins trial excluded people with a history of psychotic disorder, serious suicide attempt or hospitalization.
Selective serotonin reuptake inhibitors (SSRIs) and other medications may interact with psilocybin. The Johns Hopkins trial required participants not to be using antidepressants. That was a trial rule.
Medication questions go to a prescriber. See our guide to psychedelic medication safety and the medication safety checker.
Psilocybin is a Schedule I controlled substance under federal law and is not approved for depression treatment.
Under federal statute 21 U.S.C. § 812, psilocybin is placed on Schedule I of the Controlled Substances Act. Federal law classes Schedule I substances as having no currently accepted medical use and a high potential for abuse. Clinical trials are the route for depression-specific study.
Oregon (Measure 109, a program run by the Oregon Health Authority) and Colorado (Proposition 122) allow adult access at state-regulated service centers. Those programs are not depression treatment programs.
Statutes governing psilocybin continue to change by jurisdiction and date. To verify current law, check our state-by-state legal status tool and read our guide on where psilocybin mushrooms are legal.
To find research studies evaluating psilocybin for depression, search for enrolling studies through our clinical trial finder. If you or someone you know is experiencing acute distress or suicidal thoughts, connect with immediate help through our crisis resources. For comparison, see our guide to ketamine vs psilocybin.
This guide provides general educational information and is not medical or legal advice. Psilocybin is a Schedule I controlled substance under federal law and remains illegal outside authorized channels. Consult a qualified physician or healthcare provider about any medical condition or psychiatric medication.
Psilocybin is not FDA-approved for depression and remains Schedule I federally. In the Johns Hopkins trial, participants given psilocybin with psychotherapy scored lower on the GRID-HAMD than the waiting-list group at weeks 1 and 4. In the COMPASS phase 2 trial, 25 mg beat 1 mg at week 3, but sustained response was not seen at 12 weeks.
No. The Food and Drug Administration (FDA) has not approved psilocybin for major depressive disorder or treatment-resistant depression as of September 30, 2026. While two drug development programs hold FDA Breakthrough Therapy designations, a Breakthrough designation is not an approval.
Not as an approved treatment. Psilocybin is a Schedule I controlled substance under 21 U.S.C. § 812. Oregon and Colorado allow adult access at state-regulated service centers, but those programs are not depression treatment programs. Clinical trials are the route for depression-specific study. Verify current law with the legal status tool.
The COMPASS Pathways phase 2 trial evaluated 233 adults with treatment-resistant depression. A single 25 mg dose produced a statistically significant reduction in MADRS depression scores compared with a 1 mg control dose at week 3. However, the 10 mg vs 1 mg difference was not statistically significant, sustained response was not observed at 12 weeks, and adverse events occurred in 77% of participants.
The COMPASS phase 2 trial reported suicidal ideation, suicidal behavior, or self-injury in all dose groups, including the 1 mg control group, and adverse events in 77% of participants. Anyone experiencing acute suicidal distress should immediately contact professional support through our crisis resources page.
SSRIs and other medications may interact with psilocybin. Ask a prescriber. Review our guide to psychedelic medication safety and use our medication safety checker.
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