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Usona Institute, a Wisconsin-based nonprofit research organization, received FDA Breakthrough Therapy designation for psilocybin in major depressive disorder in 2019 and launched its Phase 3 uAspire trial (NCT06308653) in 2024. [1] sponsor-press-release FDA grants Breakthrough Therapy Designation to Usona Institute's psilocybin program for major depressive disorder Link → [2] trial-registry Psilocybin for Major Depressive Disorder (MDD) (uAspire) Link → The trial’s primary completion date was January 2026. As of mid-2026, no Phase 3 results had been publicly announced. FDA’s April 2026 announcement said national priority vouchers were issued to companies studying psilocybin for treatment-resistant depression, psilocybin for major depressive disorder, and methylone for PTSD. [3] primary-regulatory FDA Accelerates Action on Treatments for Serious Mental Illness Following Executive Order Link → Major depressive disorder and treatment-resistant depression are different indications requiring separate clinical evidence.
Who Usona Institute is
Usona Institute is a 501(c)(3) nonprofit medical research organization. Its mission is to develop psilocybin as a potential treatment for depression. Unlike commercial sponsors, Usona operates under a nonprofit structure and makes pharmaceutical-grade synthetic psilocybin available to researchers worldwide for no charge — a logistically significant contribution to the broader research field.
Usona’s program addresses major depressive disorder, a broader diagnostic category than treatment-resistant depression. MDD encompasses a far larger patient population: it does not require prior antidepressant failures, and the definition of the patient population and the clinical thresholds differ materially from the TRD definition used in the Compass Pathways trials.
From Phase 2 to Phase 3
Usona’s Phase 2 study, PSIL201 (NCT03866174), enrolled approximately 80 participants with MDD and compared a single 25 mg psilocybin dose to an active placebo. It was a randomized, double-blind design completed in June 2022. Published results in JAMA reported a clinically significant sustained reduction in depressive symptoms and functional disability over the six-week primary follow-up window. [4] Clinical trial Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial doi:10.1001/jama.2023.14530
Phase 2 results informed the Phase 3 design but are a separate stage of evidence. The regulatory pathway requires Phase 3 confirmation in a larger, pre-specified design before a marketing application can be filed.
The uAspire Phase 3 trial
The uAspire Phase 3 trial (PSIL301, NCT06308653) launched in March 2024. [2] trial-registry Psilocybin for Major Depressive Disorder (MDD) (uAspire) Link → It is a randomized, double-blind, multicenter study evaluating psilocybin in adults with MDD. The trial evaluates three arms: psilocybin 25 mg, psilocybin 5 mg, and placebo. Enrollment targeted approximately 240 participants across academic institutions and research settings; this page does not list or route readers to trial sites. The primary completion date in the registry was listed as January 2026.
| Feature | Usona uAspire | Compass COMP005/006 |
|---|---|---|
| Indication | Major depressive disorder (MDD) | Treatment-resistant depression (TRD) |
| Sponsor type | Nonprofit | Commercial biotech |
| Dose arms | 25 mg, 5 mg, placebo | COMP005: 25 mg vs placebo; COMP006: two 25 mg doses vs 1 mg comparator |
| Enrollment target | ~240 | 258 (COMP005); 568 planned (COMP006) |
| Phase 3 results status | Not yet announced as of mid-2026 | Sponsor top-line announced 2025–2026 |
What “pending results” means
The primary completion date of January 2026 in the registry reflects when the last participant completed their primary outcome assessment, not when results are reported. Data cleaning, analysis, and public reporting have their own timelines. As of mid-2026, Usona had not publicly announced Phase 3 top-line results. The CNPV issued by the FDA in April 2026 accelerates the review process once an NDA is filed [3] primary-regulatory FDA Accelerates Action on Treatments for Serious Mental Illness Following Executive Order Link → — but an NDA cannot be filed until Phase 3 results are available and the application is prepared.
This means the Usona MDD program is at a different stage than the Compass TRD program. Both are advancing, but they are at different evidentiary and regulatory milestones as of the lastReviewedDate.
The distinction between MDD and TRD matters
Positive results in TRD do not imply efficacy in general MDD. The two conditions are defined differently, the patient populations differ substantially, and the regulatory applications are separate. A drug approved in TRD would be approved for TRD — patients without prior antidepressant failures would require a separately conducted and approved MDD program. This is not a technicality; it reflects the principle that evidence in one clinical context does not generalize automatically to another.
See the Legal Status guardrail for the relationship between regulatory status and safety or efficacy. See Is Psilocybin FDA Approved? for current FDA status. See the Access cluster for the distinction between state programs and federal approval.
- Major depressive disorder (MDD)
- A diagnostic category characterized by persistent depressive symptoms affecting functioning, without the prior treatment-failure criterion required for TRD. MDD encompasses a broad spectrum of severity and prior treatment history.
- Primary completion date vs. results reporting
- The primary completion date in a trial registry marks when the last enrolled participant finishes primary outcome assessments. Data collection, analysis, and public reporting follow on a separate timeline.
- Nonprofit clinical sponsor
- An organization conducting clinical research under a nonprofit structure, as opposed to a commercial company. Regulatory pathways and standards are the same regardless of sponsor type.