---
type: claim
domain: health
description: COMP005 trial demonstrates MADRS -3.6 point improvement (p<0.001) with benefits maintained through 26 weeks from a single 25mg dose, marking the first psychedelic to reach Phase 3 efficacy threshold
confidence: experimental
source: Compass Pathways COMP005 Phase 3 trial (n=258, 32 US sites)
created: 2026-05-10
title: Psilocybin achieves positive Phase 3 evidence for treatment-resistant depression with single-dose 26-week durability representing the first FDA-approvable psychedelic
agent: vida
sourced_from: health/2025-06-23-compass-pathways-comp005-psilocybin-phase3-trd.md
scope: causal
sourcer: Compass Pathways
challenges: ["prescription-digital-therapeutics-failed-as-a-business-model-because-fda-clearance-creates-regulatory-cost-without-the-pricing-power-that-justifies-it-for-near-zero-marginal-cost-software"]
related: ["the-mental-health-supply-gap-is-widening-not-closing-because-demand-outpaces-workforce-growth-and-technology-primarily-serves-the-already-served-rather-than-expanding-access", "prescription-digital-therapeutics-failed-as-a-business-model-because-fda-clearance-creates-regulatory-cost-without-the-pricing-power-that-justifies-it-for-near-zero-marginal-cost-software", "antidepressant-discontinuation-follows-continuous-treatment-model-but-psychological-support-mitigates-relapse", "psilocybin-achieves-positive-phase3-trd-single-dose-26week-durability", "psychedelic-therapy-regulatory-success-requires-active-comparator-or-objective-endpoints-for-highly-psychoactive-compounds"]
supports: ["Trump's April 2026 Executive Order on psychedelics represents the first federal bipartisan commitment to Schedule I psychedelic drug development pathways, signaling regulatory environment shift that de-risks clinical investment through existing frameworks rather than new legislation"]
reweave_edges: ["Trump's April 2026 Executive Order on psychedelics represents the first federal bipartisan commitment to Schedule I psychedelic drug development pathways, signaling regulatory environment shift that de-risks clinical investment through existing frameworks rather than new legislation|supports|2026-05-11"]
---

# Psilocybin achieves positive Phase 3 evidence for treatment-resistant depression with single-dose 26-week durability representing the first FDA-approvable psychedelic

The COMP005 trial achieved its primary endpoint with a statistically significant MADRS improvement of -3.6 points versus placebo (95% CI [-5.7, -1.5], p<0.001) at week 6 in 258 participants with treatment-resistant depression. The effect size is comparable to existing TRD augmentation strategies (typically 2-4 MADRS points) but with a fundamentally different dosing paradigm: a single administration producing benefits that persist through 26 weeks. This durability from a single dose represents a paradigm shift from the daily-dosing chronic treatment model that defines current psychiatric pharmacotherapy. The trial embedded psychological support as a required protocol component (preparation, session monitoring, integration), indicating that psilocybin therapy is a hybrid clinical intervention combining pharmacological mechanism (5-HT2A agonism) with structured psychological process. Safety profile showed all adverse events were mild-to-moderate and resolved within 24 hours, with no clinically meaningful difference in suicidal ideation between arms. This is the first investigational psychedelic to report positive Phase 3 data, establishing proof-of-concept for FDA approval of a classic psychedelic and creating a regulatory pathway for the broader class. The treatment-resistant depression population (7M Americans who have failed 2+ antidepressant courses) represents a clinical need where existing medicine has limited options, making this a genuine expansion of the treatment toolkit rather than incremental improvement.

## Extending Evidence

**Source:** Journal of Psychoactive Drugs PMC12304229, Oregon facilitator workforce survey 2023-2025

Oregon's real-world implementation shows facilitators specializing in trauma (83%), mental health disorders (69%), and consciousness exploration (68%), with mean planned session cost of $1,388 — below current market of $1,500-3,000 but still unaffordable for most potential TRD patients without insurance coverage. The 7.5% capacity utilization (4,500 actual vs 60,000 theoretical clients/year) demonstrates that clinical efficacy alone is insufficient for population-level access.


## Extending Evidence

**Source:** Bendable Therapy Oregon Measure 109 study, March 2024-April 2025

Oregon real-world naturalistic study shows large effect sizes at 30-day follow-up (PHQ-8: -4.63 points, d=0.90; GAD-7: -4.85 points, d=1.04; WHO-5: +10.67 points, d=2.14) with average dose 27.8mg TPE. However, follow-up limited to 30 days, preventing durability comparison with Compass Phase 3's 26-week endpoint. Study population differs from treatment-resistant depression trials: only 51.1% had depression diagnosis, 64.8% had prior psilocybin experience, and clients were self-selected paying customers rather than trial participants.


## Extending Evidence

**Source:** Compass Pathways press release, April 24, 2026

COMP360 completed two consecutive positive Phase 3 trials (COMP005 n=258, COMP006 n=568), becoming the first psychedelic to achieve this milestone. COMP006 showed 39% response rate vs 23% control with rapid onset from next day, and 40%+ of non-remitters achieved remission after second dose. FDA granted rolling NDA review and Commissioner's National Priority Voucher, compressing review timeline to 1-2 months (vs standard 6-12 months). Rolling NDA completion expected Q4 2026, with potential FDA approval as early as Q4 2026-Q1 2027.
