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Compass Pathways is developing COMP360, a synthetic psilocybin formulation, as an investigational treatment for treatment-resistant depression. The sponsor reported that both Phase 3 trials — COMP005 and COMP006 — met their primary endpoints in 2025 and 2026 respectively. [1] sponsor-press-release Compass Pathways Successfully Achieves Primary Endpoint in First Phase 3 Trial Evaluating COMP360 Psilocybin for Treatment-Resistant Depression Link → [2] sponsor-press-release Compass Pathways Successfully Achieves Primary Endpoint in Second Phase 3 Trial Evaluating COMP360 Psilocybin for Treatment-Resistant Depression Link → The FDA authorized a rolling NDA review and issued a Commissioner’s National Priority Voucher. [3] sponsor-press-release Compass Pathways Announces FDA Granted NDA Rolling Review Request and Awarded Commissioner's National Priority Voucher Link → As of mid-2026, no approval had been issued, the NDA was not yet complete, and full peer-reviewed publications of the Phase 3 data had not appeared. These findings apply to a specific indication, dose, and protocol. They do not speak to microdosing.
What COMP360 is
COMP360 is a proprietary synthetic formulation of psilocybin manufactured by Compass Pathways to pharmaceutical quality standards for use in clinical trials. In the TRD program, it is administered under structured clinical protocols with psychological support; COMP005 studied a single 25 mg administration and COMP006 studied two fixed 25 mg administrations separated by three weeks. The administration is not a microdosing protocol. The clinical program does not study repeated sub-perceptual doses or self-administered use.
The investigational compound’s Schedule I status under federal law has not changed. Clinical use under FDA-authorized IND protocols is an authorized, narrow exception for the clinical programs, not a general permission. The FDA’s 2023 guidance on psychedelic drug clinical investigations addresses the specific design and oversight requirements for this class of investigational programs. [4] primary-regulatory Psychedelic Drugs: Considerations for Clinical Investigations Link →
The Phase 2b foundation
The COMP360 TRD program built on the COMP001 Phase 2b study, which enrolled 233 participants and evaluated COMP360 at three doses. [5] Clinical trial Single-dose psilocybin for a treatment-resistant episode of major depression doi:10.1056/NEJMoa2206443 The Phase 2b results provided the evidentiary basis for the Phase 3 design: they showed the 25 mg dose was associated with a greater reduction in MADRS scores at three weeks compared to the 10 mg and 1 mg doses, and a response rate that warranted Phase 3 investigation. Phase 2b results are not a substitute for Phase 3; they are the basis for the Phase 3 design.
| Milestone | Date | What it represents |
|---|---|---|
| COMP001 Phase 2b publication | 2022 | Peer-reviewed Phase 2b results; basis for Phase 3 design |
| Breakthrough Therapy designation | 2018 | FDA development acceleration — not approval [6] primary-legal Breakthrough Therapy designation Link → |
| COMP005 top-line result | June 2025 | Sponsor-reported Phase 3 primary endpoint met |
| COMP006 top-line result | February 2026 | Sponsor-reported second Phase 3 primary endpoint met |
| Rolling NDA review authorized, CNPV issued | April 2026 | FDA process milestone — not approval |
| NDA complete / approval decision | Pending as of mid-2026 | Has not occurred as of lastReviewedDate |
COMP005 and COMP006: what the sponsor reported
The COMP005 trial was a randomized, double-blind, placebo-controlled Phase 3 study enrolling 258 participants with treatment-resistant depression at 32 sites in the United States. The pre-specified primary endpoint was the mean difference in change from baseline on the MADRS between the COMP360 25 mg arm and the placebo arm at week 6. Compass Pathways reported a mean treatment difference of minus 3.6 points, which was highly statistically significant. [1] sponsor-press-release Compass Pathways Successfully Achieves Primary Endpoint in First Phase 3 Trial Evaluating COMP360 Psilocybin for Treatment-Resistant Depression Link →
The COMP006 trial evaluated two fixed 25 mg administrations against a 1 mg comparator. Compass Pathways reported a mean MADRS treatment difference of minus 3.8 points at week 6, also highly statistically significant. [2] sponsor-press-release Compass Pathways Successfully Achieves Primary Endpoint in Second Phase 3 Trial Evaluating COMP360 Psilocybin for Treatment-Resistant Depression Link → COMP006 data also indicated a rapid onset of effect from the day after administration and durability through week 26 in participants who showed a clinically meaningful initial response.
These are sponsor-reported top-line results. They had not been published in a peer-reviewed journal as of the lastReviewedDate. The full dataset, statistical analysis plan compliance, secondary endpoint results, safety data granularity, and peer review conclusions are pending.
What these results do not establish
Positive Phase 3 top-line results in treatment-resistant depression are a significant development. They do not:
- Establish efficacy for major depressive disorder (studied separately in the Usona program)
- Establish efficacy for PTSD, anxiety, addiction, or any other indication
- Establish efficacy for psilocybin mushrooms, dietary supplements, or unprocessed plant products
- Establish safety or efficacy for unsupervised use
- Establish efficacy for microdosing or any sub-perceptual dose regime
- Constitute FDA approval of COMP360 or any other product
The FDA’s review of the rolling NDA — once the submission is complete — will evaluate the totality of the evidence, including manufacturing, labeling, safety, and whether the clinical benefit satisfies the approval standard for treatment-resistant depression.
The regulatory path forward
Compass Pathways received FDA authorization for a rolling NDA review and a Commissioner’s National Priority Voucher in April 2026. [3] sponsor-press-release Compass Pathways Announces FDA Granted NDA Rolling Review Request and Awarded Commissioner's National Priority Voucher Link → The CNPV can compress the standard 10-to-12-month review window to approximately one to two months once the complete application is filed. The sponsor was targeting NDA completion in Q4 2026. If the complete NDA is filed and the FDA’s review concludes favorably, an approval decision could come in late 2026 or early 2027, based on publicly stated timelines. None of these milestones is guaranteed.
See Is Psilocybin FDA Approved? for the current status. See How to Read Press Releases for a framework for evaluating future announcements. The legal-status guardrail article explains why regulatory status does not determine safety or efficacy. The Access cluster explains why state-level programs differ from FDA approval.
- Treatment-resistant depression (TRD)
- Defined as major depressive disorder that has not responded adequately to at least two antidepressant treatments. A narrower population than all patients with depression.
- MADRS (Montgomery-Åsberg Depression Rating Scale)
- A 0-to-60 clinician-rated scale measuring depression severity across ten symptom domains. Used as the primary endpoint in both COMP005 and COMP006.
- Top-line data
- The sponsor’s announcement of primary endpoint results before full data are available for peer review. Top-line data carries less evidentiary weight than a peer-reviewed publication of the complete trial results.
- Sponsor-reported vs. peer-reviewed
- A sponsor’s press release and a peer-reviewed journal publication are different objects at different evidentiary levels. Top-line results are a necessary interim communication; they become peer-reviewed evidence only after publication and independent review.