Trump's ibogaine order changes everything

Federal Policy: Trump Expected to Sign Ibogaine Research Executive Order

• Trump is expected to sign an executive order directing federal agencies to advance ibogaine research for veterans' PTSD and traumatic brain injury as soon as this week. The EO will not reschedule ibogaine from Schedule I; the stated goal is determining whether the drug is "snake oil or legitimate treatment," with strategies for directing federal funding still being finalized.
• The evidence base for ibogaine remains limited to mostly observational studies and one completed double-blind RCT, with cardiac arrhythmia implicated in at least 27 known deaths across 705 documented cases as the primary unresolved safety concern, per Marijuana Moment's review of the scientific record.

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COMPASS Confirms Q3 2026 Rolling NDA Submission for COMP360

• COMPASS Pathways has aligned with FDA on a rolling NDA submission for COMP360 psilocybin in treatment-resistant depression. COMP006 showed -3.8 MADRS vs. placebo (p<0.001); 26-week follow-up data will be added in early Q3 2026, with the full NDA submission targeted by end of Q3 2026.
• COMPASS launched a US provider training grant program (April 14–May 14) funding up to three organizations to develop pre-approval healthcare provider training, covering psychedelic treatment experience, scalability, and regulatory alignment ahead of a potential commercial launch.

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Functional Unblinding: JAMA Psychiatry Finds Parity with Open-Label Antidepressants

• A 24-trial meta-analysis in JAMA Psychiatry (8 psychedelic, 16 open-label antidepressant; 8,170 patients) found no meaningful efficacy difference between psychedelic therapy and open-label antidepressants when controlling for functional unblinding — the near-universal ability of participants to identify whether they received the active drug (~95–96% accuracy).
• Lead author Balázs Szigeti told PsyPost the findings "do not mean psychedelics are not effective, only that they are not more effective than traditional antidepressants." Key limitations: psychedelic trials recruited more treatment-resistant populations; measurement timelines differed (3 vs. 8 weeks for antidepressants); functional outcomes and side-effect profiles were not compared.
• Three foundational open questions persist for the field, per pharmaphorum: whether the hallucinogenic experience is required for benefit, whether blinding is achievable, and how durable effects actually are. COMPASS's blinding approach — comparing across active dose levels rather than against inert placebo — and an Ohio State study reporting depression remission persisting 5 years post-psilocybin-assisted therapy (small sample) represent current partial answers.

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Ketamine: France Issues Global-First IV Authorization; Esketamine Real-World Safety Data

• France's ANSM issued the world's first national authorization for intravenous racemic ketamine for adult severe suicidal crisis in emergency and inpatient settings, based on the KETACRISIS trial showing significant anti-suicidal effects within 24 hours. The FDA's Spravato REMS prohibits ED administration — the French approval creates regulatory precedent that may pressure the FDA to accept foreign clinical data for acute psychiatric emergencies.
• A Nature Mental Health target trial simulation (n=3,383 matched pairs, TriNetX real-world data) found esketamine associated with lower suicide-related events at days 1–14 (0.77% vs. 3.78%; HR 0.19), lower events through one year (HR 0.63), and lower 2-year all-cause mortality (HR 0.61). The composite suicide outcome was driven primarily by suicidal ideation reduction, not confirmed attempt rates.

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Epidemiology, State Legislation, and Basic Science

• A 2026 RAND study estimates 11 million U.S. adults used psilocybin in the past year (up from ~5 million in 2023); a companion survey of 10,122 Americans found 23% support psilocybin legalization vs. 10% for LSD and 9% for MDMA, with medical-facility delivery as the top-preferred supply model. RAND warns aggressive state reforms — especially if minors gain access — could trigger federal intervention harming clinical research.
• Minnesota's House Veterans and Military Affairs Committee heard testimony on HF 4577, which would establish a supervised psilocybin therapeutic pilot for PTSD and severe depression; a companion decriminalization bill was also heard. Passage this session is considered unlikely.
• New Zealand's Medsafe granted an Auckland GP permission to prescribe psilocybin to terminally ill patients — the first such authorization outside a clinical trial framework reported in a major regulatory jurisdiction.
• A Harvard brain lesion network mapping study in 88 tumor surgery patients identified a bipolar neural circuit for self-transcendence: disruption of the posterior midline cortex increased self-transcendence, consistent with default mode network suppression under psychedelics; cross-validation with ketamine neuroimaging showed overlapping activation patterns.
• Baeocystin, norbaeocystin, and aeruginascin — tryptamines co-occurring naturally in psilocybin mushrooms — may produce stronger and longer-lasting effects than synthetic psilocybin alone in rodent models. Because FDA requires isolated synthetic psilocybin for clinical trials, human data on entourage tryptamines remains essentially nonexistent.
• Scientists have engineered tobacco plants to simultaneously biosynthesize five psychedelic compounds, including psilocybin and DMT, potentially opening a plant-based manufacturing route for pharmaceutical-grade psychedelics at scale.