Issue 1 — May 11, 2026
A decade after the first modern psilocybin trial, the second decade begins under a different political and regulatory frame. Eight events.
Welcome to the first issue of Entheon Intelligence.
Ten years ago this spring, Robin Carhart-Harris and colleagues at Imperial College London published the first modern clinical trial of psilocybin for treatment-resistant depression — an open-label feasibility study in twenty patients, sponsored by the Beckley Foundation and the Medical Research Council, conducted under a UK Home Office Schedule One license. The 2016 Lancet Psychiatry paper reported clinically significant reductions in depressive symptoms at three weeks and again at three months in a population for whom existing antidepressants had failed. It was a small study with no control arm. It was also the event that opened the second wave of academic psychedelic research after a forty-year regulatory freeze.
The decade since has been characterized by three overlapping movements: an academic research program led from Imperial, Johns Hopkins, NYU, and UCSF; a commercial buildout led by Compass Pathways, MAPS-spinout Lykos, atai, GH Research, Cybin, and others; and a policy track played out in state legislatures, ballot measures, and FDA advisory committees.
The arc was not linear. The FDA granted Breakthrough Therapy designation to MDMA-assisted therapy for PTSD and to psilocybin for major depressive disorder. Capital flowed in. Then, in August 2024, the FDA issued a Complete Response Letter rejecting Lykos’s MDMA-PTSD application despite two positive Phase 3 trials, citing concerns about functional unblinding, durability of effect, and clinical-site oversight. Lykos restructured, capital pulled back, and several sponsors paused or redirected programs. Compass shifted its lead indication from major depressive disorder to PTSD. Cybin’s partner Helus walked away from intravenous DMT after a positive Phase 2a readout in Nature Medicine. The post-Lykos period, through most of 2025, was a regulatory winter under a system that had been built to accept Phase 3 randomized trials as the proof bar and was now applying retroactive standards to a category that had progressed through agency-sanctioned protocols.
On April 18, 2026, President Trump signed Executive Order Accelerating Medical Treatments for Serious Mental Illness. The order directs the FDA Commissioner to issue National Priority Vouchers to psychedelic drugs with Breakthrough Therapy designation. It allocates $50 million in ARPA-H funding for federal-state collaboration on psychedelic research, modeled on Texas’s $100 million ibogaine program. It expands Right to Try pathways to investigational psychedelic compounds including ibogaine. It directs the DEA to establish a pathway for rescheduling FDA-approved psychedelics post-approval. And it requires HHS, FDA, and the VA to sign data-sharing memoranda for clinical trials in veteran populations.
Within three weeks, the FDA issued priority review vouchers to Compass Pathways and Usona Institute for their psilocybin programs and to Otsuka for methylone, and cleared DemeRx’s noribogaine to begin the first U.S. ibogaine-derivative trial.
The executive order does not change the FDA’s proof bar. It does not legalize any compound. It does not guarantee approvals. What it changes is the political and institutional posture that determined how slowly approvals could move — and that change is worth tracking with caution rather than celebration. The same regulatory system that rejected Lykos in 2024 is now being asked to accelerate decisions on compounds with thinner safety records. Priority review vouchers reduce review timelines; they do not generate new evidence. The order’s expansion of Right to Try access to ibogaine — a compound linked to at least thirty deaths in the medical literature due to documented cardiotoxicity, and previously discontinued from NIH-funded research for exactly that reason — creates a real tension between political ambition and patient safety that the order’s text does not resolve. Legal scholars at Harvard’s Petrie-Flom Center have noted that an executive can request but not compel DEA rescheduling, that the order is silent on religious-use frameworks, and that the precedent of presidential prioritization of specific drug categories cuts both ways depending on who holds the office.
This is the frame Entheon Intelligence is being launched into.
What the executive action stands to enable, if implementation matches the order’s text, is real: faster FDA review for breakthrough-designated psychedelic compounds, federal matching dollars that may unlock state programs in legislatures that had been on the fence, structured veteran-population trials with VA data infrastructure, and a credible post-approval DEA rescheduling pathway. What it does not enable — and what no executive order can enable — is the substitution of political enthusiasm for clinical evidence. The MDMA-PTSD program’s collapse happened despite Breakthrough Therapy designation and Special Protocol Assessment agreement. The work of generating durable, well-blinded, well-reported clinical evidence remains where it has always been: with sponsors and academic groups, on the timelines that good evidence actually takes.
This publication exists to track that work. Each Monday, Entheon Intelligence will surface the events that matter from public records — clinical trial registrations and updates on ClinicalTrials.gov, regulatory actions in the Federal Register and from the DEA’s diversion control program, public-company filings with the SEC, and state and federal legislation tracked through LegiScan. The editorial scope is intentionally narrow: psychedelic medicine and the regulatory, capital, and policy environment around it. The editorial posture is intentionally non-advocacy. Readers should expect facts, sources, and importance ranking — not advocacy, not hype, not prescription about what should happen next.
This week’s eight events show the new frame already taking shape: a multi-country Phase 2 academic trial in palliative depression (PsyPal), Compass Pathways’ Phase 2b/3 PTSD registration, continued state-level policy advancement in Illinois, and three new academic Phase 2 registrations covering MDD, group-format clinician dosing, and veteran PTSD.
The decade-long second wave of psychedelic research enters its second decade in a meaningfully different regulatory environment. What that allows, and what gets done with what it allows, is the work this publication will track week by week.
Top Stories
PsyPal Phase 2 psilocybin trial enrolls across Europe for palliative depression
May 8, 2026 · ClinicalTrials.gov · importance 4
PsyPal (NCT06782724), a Phase 2 randomized controlled trial sponsored by University Medical Center Groningen, is enrolling 108 patients with COPD, ALS, MS, or atypical Parkinson disease who have comorbid major depression. The trial compares two escalating doses of psilocybin (15mg, then 25mg) versus low-dose control (1mg) across sites in the Netherlands, Denmark, Czechia, and Portugal. Primary endpoint is depressive symptom reduction (MADRS) at 56 days post-second dose; secondary endpoints include end-of-life anxiety, demoralization, quality of life, and biomarkers (EEG, blood-based). Study began July 2025 with estimated completion January 2028.
Editor's note: The patient-selection choice — psilocybin in actively dying or progressively ill cohorts — is unusual in psychedelic trials and runs against the industry sponsor preference for healthier MDD populations. The multi-country academic consortium structure (Netherlands, Denmark, Czechia, Portugal under a single coordinated protocol) is also notable as an alternative to the single-sponsor commercial model that has dominated the space.
Companies: University Medical Center Groningen, HumanKindLabs, University of Copenhagen, CTC Clinical Trial Consultants AB, and 14 others
Compounds: psilocybin
Indications: major depressive disorder, depression, end-of-life anxiety, demoralization, treatment-resistant depression
Source: ClinicalTrials.gov (NCT06782724)
Compass registers Phase 2b/3 COMP360 PTSD trial (COMP202)
May 6, 2026 · ClinicalTrials.gov · importance 4
Compass Pathways registered NCT07570654 (Redefine/COMP202), a Phase 2b/3 randomized, double-blind, controlled trial of COMP360 psilocybin in 300 participants with post-traumatic stress disorder. The trial will compare 1 mg (active comparator), 10 mg, and 25 mg doses, with primary endpoint CAPS-5 total severity score change from baseline to week 8. Enrollment is estimated to begin September 2026 with primary completion in November 2028.
Companies: Compass Pathways
Compounds: psilocybin
Indications: PTSD
Source: ClinicalTrials.gov (NCT07570654)
Illinois SB 2772 passes Senate; psilocybin board bill advanced
May 7, 2026 · LegiScan · importance 3
Illinois SB 2772, sponsored by Sen. Rachel Ventura and co-sponsored by 12 additional Democratic senators, passed the Illinois Senate 41-13 on May 7, 2026. The bill establishes a Psilocybin Advisory Board to evaluate the medical efficacy of psilocybin and other psychedelic substances and recommend Medicaid coverage policies. The bill received committee approval in March and underwent three floor amendments before passage.
Compounds: psilocybin
Source: LegiScan (SB2772)
CAMH psilocybin-risperidone trial completes; proof-of-concept readout pending
May 7, 2026 · ClinicalTrials.gov · importance 3
A Phase 2 proof-of-concept trial (NCT05710237) evaluating whether psilocybin’s antidepressant effects depend on its psychedelic properties has completed enrollment of 41 participants with treatment-resistant depression at Centre for Addiction and Mental Health in Toronto. The three-arm, quadruple-blind study compared psilocybin 25 mg plus risperidone 1 mg, psilocybin 25 mg plus placebo, and risperidone 1 mg plus placebo, with primary endpoints of feasibility and safety. The trial started July 2023 and completed April 14, 2026; results have not yet been posted.
Companies: Centre for Addiction and Mental Health
Compounds: psilocybin, risperidone
Indications: treatment-resistant depression
Source: ClinicalTrials.gov (NCT05710237)
Sunstone registers Phase 2 MDMA trial in veterans with PTSD
May 6, 2026 · ClinicalTrials.gov · importance 3
Sunstone Medical registered NCT07569159, a Phase 2, open-label study of 120 mg oral MDMA followed by 60 mg supplemental dose in conjunction with therapy for adult veterans with PTSD. The study will enroll an estimated 52 participants across individual and group therapy arms, with primary endpoints on safety/tolerability and suicidal ideation (C-SSRS), and secondary endpoints on PTSD symptom severity (CAPS-5, PCL-5) and functional impairment. The trial is scheduled to begin May 2026 with primary completion estimated April 2027.
Companies: Sunstone Medical
Compounds: MDMA
Indications: PTSD
Source: ClinicalTrials.gov (NCT07569159)
Trial Completion
USC epigenetics substudy on MDMA-assisted PTSD therapy completed
May 4, 2026 · ClinicalTrials.gov · importance 3
A Phase 3 substudy examining epigenetic changes in MDMA-assisted psychotherapy for PTSD has completed enrollment and data collection. The study, led by Rael Cahn at USC in collaboration with the Multidisciplinary Association for Psychedelic Studies (MAPS), enrolled 45 participants and measured DNA methylation changes in glucocorticoid receptor and stress-related genes (NR3C1, FKBP5, BDNF) before and after treatment over approximately 4 months. Results were posted May 4, 2026, and the trial began in November 2018 with primary completion in November 2023.
Companies: Multidisciplinary Association for Psychedelic Studies
Compounds: MDMA
Indications: PTSD
Source: ClinicalTrials.gov (NCT06189027)
Trial Registration
UCLA registers Phase 2 psilocybin-assisted CBT trial for major depression
May 4, 2026 · ClinicalTrials.gov · importance 3
UCLA Semel Institute registered a Phase 2 trial (NCT07566104) evaluating psilocybin as an adjunct to group cognitive-behavioral therapy for major depressive disorder. The open-label study will enroll 30 adults aged 21–60 with current major depressive symptoms, administering 10 mg then 25 mg psilocybin orally one month apart alongside 12 sessions of group PA-CBT. Primary endpoints are treatment acceptability, participant retention, and change in Hamilton Depression Rating Scale scores over 7 months; enrollment begins January 2027 with completion estimated December 2028.
Companies: University of California, Los Angeles
Compounds: psilocybin
Indications: major depressive disorder
Source: ClinicalTrials.gov (NCT07566104)
UW registers Phase 2 psilocybin group retreat trial for healthcare clinicians
May 4, 2026 · ClinicalTrials.gov · importance 3
University of Washington registered NCT07565909, a Phase 2 sequential dose-escalation study of psilocybin therapy for 72 healthcare clinicians (physicians, nurses, nurse practitioners, physician assistants) aged 25–70 with moderate depression and loss of meaning in their work. The trial will test three preparation dose levels (7, 4, and 2 sessions) across 9 group retreats of 8 participants each, with primary endpoints on safety and feasibility and estimated completion in July 2028. The study targets clinical burnout and loss of meaning in healthcare workers using a group retreat format rather than individual dosing.
Companies: University of Washington
Compounds: psilocybin
Indications: depression, anxiety
Source: ClinicalTrials.gov (NCT07565909)