2026-08-07 — Opened (ben-steer)

• Opened as a dedicated child thread of mh-evidence-watch, seeded from the EBP therapy-science research crawl. Compass Pathways’ NDA target is also logged to upcoming.yaml as compass-psilocybin-nda, due 2026-12-31. (EBP therapy-science crawl, 2026-08-07) ⟨steer 2026-08-07⟩

2026-07 — FDA finalizes the trial-design rules the MDMA rejection demanded

• FDA finalized new psychedelic trial-design guidance requiring active placebos, blinding questionnaires, expectancy controls, and paired placebo-controlled/no-placebo dose-response designs — the whole psychedelic field must now build around these standards. Whether they were actually applied to the already-completed pivotal Compass trials, or whether approval is outrunning the fix, is not yet publicly resolved. (Tech Times) ⟨steer 2026-08-07⟩

2026-04 — Executive order + National Priority Vouchers compress FDA review to 1-2 months

• A presidential executive order directed agencies to accelerate psychedelic drug review, and FDA issued “National Priority Vouchers” to Compass Pathways (psilocybin/treatment-resistant depression), Usona Institute (psilocybin/MDD), and Transcend Therapeutics (methylone/PTSD) — compressing review time from the usual 10-12 months to 1-2. Compass is targeting an NDA in Q4 2026, with FDA Commissioner Marty Makary publicly floating an approval decision by late 2026. (Medical Daily) ⟨steer 2026-08-07⟩
• Transcend’s actual Phase 3 trial didn’t start enrolling until the same month it received its voucher. EMPOWER-1 (TSND-201/methylone for PTSD, n=300) began enrolling April 2026 — the regulatory fast lane opened before the trial meant to justify it produced a single result; primary completion isn’t expected until December 2027. (ClinicalTrials.gov NCT07456696) (wave: mh-q03) ⟨daily 2026-08-07⟩

2026 — Neuromodulation’s SAINT/SNT gets a real confirmatory trial, four years after clearance

• A proper sham-controlled RCT (Kratter et al., World Psychiatry) replicated SAINT/SNT’s effect — 50.0% remission active vs. 20.8% sham (p=0.035) — four years after the single 30-patient trial that underpinned FDA 510(k) clearance and nationwide commercial rollout. The effect is far more modest than the “80-90%” figure that circulated off the original small trial, but it’s the one somatic bet in this set where evidence has actually caught up to deployment — the counter-case to psilocybin’s chronology problem below. (PubMed PMID 41536095) (wave: mh-q03) ⟨daily 2026-08-07⟩

2026-02 — COMPASS Pathways’ second Phase 3 trial (COMP006) hits its primary endpoint

• COMP360 (psilocybin) hit its primary endpoint in a second Phase 3 trial for treatment-resistant depression, following the June 2025 result below — industry-reported by Compass and not yet independently peer-reviewed as of this crawl. Source URL for this specific release was truncated in the underlying research crawl (Compass investor-relations press release, exact link not captured). ⟨steer 2026-08-07⟩

2025-06 — COMPASS Pathways’ first Phase 3 trial (COMP005) shows a −3.6 MADRS advantage

• COMP360’s first Phase 3 trial (n=258, 25mg dose vs. placebo) delivered a statistically robust −3.6-point MADRS advantage over placebo (p<0.001), with 39% of high-dose responders reaching ≥25% MADRS reduction, rapid (next-day) onset, and durability out to 26 weeks — industry-reported, not yet independently peer-reviewed. Source URL for this specific release was truncated in the underlying research crawl (Compass investor-relations press release, exact link not captured). ⟨steer 2026-08-07⟩

2024-08 — FDA rejects MDMA-assisted therapy: the wall the whole field is now building around

• FDA issued a Complete Response Letter to Lykos Therapeutics for MDMA-assisted therapy for PTSD after its advisory committee voted 2-9 against efficacy and 1-10 against benefit outweighing risk, citing functional unblinding and cardiovascular safety concerns. The CRL wasn’t publicly released until September 2025. FDA didn’t just reject one drug — it used the episode to eventually write the new trial-design rules logged above (July 2026). (MAPS) ⟨steer 2026-08-07⟩

2023-01 — Compass’s two pivotal Phase 3 trials fully enroll before FDA’s guidance fix even existed in draft

• COMP005 started dosing January 19, 2023, and COMP006 started February 14, 2023 — both months before FDA’s first draft psychedelic-trial guidance (June 2023), and years before the final version (July 2026) requiring active-placebo/expectancy-questionnaire designs. The trials could not have built in a fix that didn’t exist yet. Only COMP006’s low-dose 1mg arm partially matches the guidance’s recommended active-comparator design; Compass’s own CMO, Guy Goodwin, says COMP005’s placebo-controlled arm exists mainly to characterize safety, not efficacy — “the less we peek, the better.” Neither trial registered a formal blinding-integrity outcome measure. (ClinicalTrials.gov NCT05624268, NCT05711940) (wave: mh-q03) ⟨daily 2026-08-07⟩

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