One dose rewired their brains a month later

Psilocybin Causes Lasting White Matter Changes in Drug-Naive Adults

• A Nature Communications study (UCSF/Imperial College London; n=28 entirely psychedelic-naive healthy adults) produced the first evidence of anatomical brain changes from a single psilocybin dose in humans: diffusion tensor imaging at one month showed decreased axial diffusivity in prefrontal-subcortical white matter tracts (prefrontal cortex–striatum and prefrontal cortex–thalamus) at 25 mg. The 1 mg comparator produced no detectable changes.

• Acute EEG brain entropy (Lempel-Ziv complexity) at 1–2 hours post-dose predicted next-day psychological insight, which in turn mediated improved psychological well-being at one month. Cognitive flexibility (extradimensional set-shifting) also improved at one month; decreased network modularity negatively correlated with well-being gains.

---

Ketamine Reduces Suicidal Ideation Within 4 Hours; NIH Funds First Psychedelic Trial for Adults 65+

• A JAMA Psychiatry meta-analysis (26 placebo-controlled RCTs, n=1,166) found IV ketamine produced significant reductions in suicidal ideation as early as 4 hours post-infusion (SMD ~0.7), with ketamine patients having fewer suicidal thoughts than approximately 75% of the placebo group at 24 hours. Response advantages did not persist beyond one week and most participants required repeated infusions; bipolar depression showed worse outcomes than unipolar. Expert commentary via Science Media Centre noted the findings support France's ANSM IV ketamine authorization for suicidal crisis (reported April 16) and challenge NICE's UK rejection.

• The NIH launched the $21M INSPIRE Network, the first federally funded psychedelic clinical research program dedicated to adults 65 and older (NIA/NCCIH; UC Anschutz lead; NYU, UCSF, Emory, Dana-Farber/Harvard, and U Nebraska as sites; 5-year initiative). Phase 1 (years 1–2) assesses psilocybin and LSD safety in healthy adults 65–85 for cardiac, cognitive, and delirium risks; Phase 2 runs two multi-site RCTs — psilocybin plus pain reprocessing therapy for chronic low back pain and LSD-assisted therapy for cancer-related bone pain — with Emory Phase 1 enrollment beginning May 2026.

---

COMPASS Leads Approval Race; CNPV Process and Trial Standards Under Scrutiny

• A Medscape survey of leading psychiatrists finds COMPASS Pathways' COMP360 most likely to reach market first, citing its 2018 Breakthrough designation and two completed Phase 3 readouts. Usona's Phase 3 (UAspire/MDD) has an expected completion of January 2027 — potentially too late for a 2026 CNPV-accelerated review; Transcend's methylone Phase 3 (PTSD) is expected to complete late 2027. FDA Commissioner Makary has publicly targeted late summer or fall 2026 for first approval decisions.

• Fierce Biotech reports COMPASS was initially denied a CNPV by the White House before ultimately receiving one (CNPV awards reported in the April 30 issue), raising questions about political filtering of what HHS describes as career FDA scientist selections. Medical ethicist Holly Fernandez Lynch (Penn) called the program "completely absurd and really terrifying"; Rep. Jacob Auchincloss characterized it as "an illegal, unauthorized program." The FDA's concurrent rejections of Disc Medicine's bitopertin and Lykos's MDMA are cited as evidence of continued regulatory independence.

• Reps. Jack Bergman (R-MI) and Lou Correa (D-CA) led 30 bipartisan colleagues in a May 6 letter to FDA Commissioner Makary requesting written responses on: standards for mitigating functional unblinding and expectancy effects in trials; psychedelic-field expertise on review panels; timeline for finalizing the FDA's June 2023 psychedelic trial guidance; and how Special Protocol Assessments communicate concerns beyond primary endpoints. The letter explicitly cites the Lykos MDMA Complete Response Letter as evidence of unclear regulatory expectations.

• WPR profiles Usona Institute post-CNPV: UW-Madison pharmacology director Paul Hutson warns that distribution logistics remain entirely unresolved — which pharmacies can carry Schedule I compounds, how physicians will screen eligible patients, and how insurers will cover six-to-eight-hour supervised sessions requiring multiple trained monitors.

---

State Legislation: Tennessee, Connecticut, Maryland Advance

• Tennessee passed the HOPE Act (Helping Open Pathways to Effective Treatment), authorizing state participation in FDA-approved ibogaine clinical trials primarily targeting veterans with PTSD and opioid use disorder; the state plans to solicit university proposals later this year. Tennessee joins Texas and Arizona among states with active ibogaine research legislation.

• Connecticut's House passed SB 191 by 122–27 on May 6, completing both chambers and sending the bill to Gov. Ned Lamont. (The Senate passed 35–0 in March, as reported in the April 10 issue.) The bill expands Yale's psilocybin/MDMA pilot to all adults 18+, removes the DEA-approval sunset clause, and makes the program eligible for federal EO matching funds; Yale researchers reported no serious adverse events to date.

• Maryland Gov. Wes Moore signed two bills: one extending the state Psychedelics Task Force through December 2027 and directing it to develop a multi-pathway access framework (supervised medical access → deprioritization → commercial sales), explicitly recommending against waiting for FDA approval before state action; and a second creating a state fund for cost-free psilocybin, MDMA, and ketamine for military veterans with PTSD and TBI.

• Ohio lawmakers heard testimony May 6 on state funding for ibogaine research for addiction treatment and PTSD; no vote is scheduled.