Veterans, Microdosing, And Faster Psilocybin Timelines

Key Takeaways for This Month

• A large, Phase 2b, at‑home LSD microdosing trial in major depressive disorder showed no benefit over active placebo on any primary or secondary endpoint, despite a design that was arguably favourable to microdosing advocates.
• ARPA‑H has launched EVIDENT, a $100 million initiative to build objective, regulatory‑grade measures for rapid‑acting mental health treatments, with psychedelics explicitly in scope.
• Compass Pathways has secured a path to rolling FDA review and accelerated readouts for its psilocybin programme, advancing launch preparations by almost a year.
• Australia’s Department of Veterans’ Affairs (DVA) will reimburse MDMA‑ and psilocybin‑assisted psychotherapy for veterans who have failed conventional care, while the US Department of Veterans Affairs is preparing a large Phase 3 psilocybin trial (PIVOT) in treatment‑resistant depression.

Behind those headlines sits a clearer story: regulators are willing to move quickly for high‑quality, high‑intensity interventions in severe illness, but are also insisting on conventional drug‑development standards. Veterans and other high‑need groups are becoming the test bed for early access and reimbursement models. Meanwhile, big pharma and federal innovation agencies are building the measurement and data infrastructure that will shape the second wave of products.

1. LSD Microdosing: A Phase 2b Collapse, Not Just a Speed Bump

What actually happened?

MindBio’s “Microdosing in Depression” Phase 2b trial enrolled 89 people with major depressive disorder into an eight‑week, at‑home regimen of LSD microdoses or active placebo (caffeine). Participants self‑titrated LSD doses between 4 and 20 micrograms twice a week, with intention‑setting and psychoeducation that resemble real‑world microdosing practices.

Topline results, shared by the company showed:

• Both arms improved substantially on MADRS, a standard depression scale, over eight weeks.
• The caffeine group improved more than the LSD group: roughly a 36 percent reduction in MADRS scores versus about 30 percent for LSD.
• The between‑group difference was not statistically significant (p = 0.5469), and LSD failed on all primary and secondary endpoints.

This follows another rigorous RCT from Switzerland in adults with ADHD, where six weeks of LSD microdosing again produced no advantage over placebo, with the placebo group slightly ahead on the primary symptom scale. Together with smaller controlled studies that have failed to show robust mood or cognition benefits at low doses, the pattern is now consistent.

Why this matters more than “one negative trial”

Microdosing has been one of the most commercially hyped psychedelic use cases, often framed as a low‑risk “wellness” intervention that might slip in under the regulatory bar. The MindBio trial was designed in ways that should have favoured a positive signal: at‑home dosing rather than a sterile clinic, self‑titration, psychoeducation that could raise expectancy, and an active stimulant comparator rather than an inert placebo.

If microdosing cannot beat an active control in this kind of ecologically valid setting, the most conservative assumption for regulators and payers is that whatever benefit exists is either small or largely driven by expectancy and non‑specific factors. That aligns with the ADHD trial and with systematic reviews that find little convincing clinical signal from low‑dose psychedelic RCTs to date.

Implications for stakeholders

For clinicians

• There is now no high‑quality evidence base to support LSD microdosing as a treatment for major depressive disorder or ADHD.
• For physicians operating in regulated settings, recommending or informally endorsing microdosing for diagnosed conditions now carries a higher medico‑legal and reputational risk relative to recommending participation in trials of high‑dose or short‑acting psychedelic therapies.

For developers and investors

• Programmes that rely on microdosing as a core depression strategy should be treated as high risk when you run pipeline and portfolio screens.
• Regulatory agencies will expect any future microdosing indication to be supported by at least one large, placebo‑ or active‑controlled Phase 3 trial with rigorous blinding and expectancy management. That puts microdosing on essentially the same evidentiary footing as high‑dose therapies, but with a weaker effect size and less clear mechanistic rationale.

For policy and access pathways

• Jurisdictions that were considering lighter‑touch access regimes for microdosing, based on its perceived safety and anecdotal efficacy, now have little evidence basis for that distinction.
• The results reinforce a trend toward focusing policy energy on high‑intensity, supervised interventions in severe illness, rather than lifestyle‑oriented microdosing frameworks.

2. ARPA‑H’s EVIDENT Program: Measurement is the New Bottleneck

What ARPA‑H is actually funding

ARPA‑H has launched EVIDENT, a mental health “moonshot” with up to $100 million in funding to develop objective measures and predictive tools for rapid‑acting behavioral health treatments. Core features:

• Four technical areas:
  1. Multimodal objective measures (imaging, wearables, physiology, blood biomarkers, psychological and social data).
  2. In‑session mechanisms of change, including detailed analysis of interactions between patient and facilitator or therapist.
  3. Personal response, risk and durability profiles, using predictive modelling to identify responders and patients at higher risk.
  4. Supplemental data and samples from existing Phase 2 and 3 trials, which ARPA‑H will augment with additional measurements.
• The agency explicitly lists “neuroplastogens” as a focus, naming ketamine and psychedelic compounds alongside neuromodulation and digital therapeutics.
• Veterans are singled out as a priority population for strong inclusion across technical areas.

The stated end goal is to deliver “gold‑standard objective measures and a Rapid Response Data Repository to support future research and regulatory acceptance of emerging rapid‑acting therapies.”

Story behind the story

Right now, most psychedelic trials still hinge on subjective rating scales like MADRS or CAPS‑5, plus therapist‑reported observations. That makes it harder for regulators and payers to compare them with standard therapies and to quantify long‑term benefit or harm.

EVIDENT is effectively an attempt to industrialise “precision psychiatry” for fast‑acting interventions. If it succeeds even partially, developers will be able to:

• Embed pre‑validated sensor and biomarker panels into trials instead of inventing their own measurement suites.
• Use common data models and repositories to benchmark their candidate against other rapid‑acting interventions, including different psychedelic molecules.
• Present FDA and other regulators with objective indicators of both response and risk, not just rating scales and qualitative reports.

Because Technical Area 4 is built around existing Phase 2/3 trials, there is a strong incentive for current sponsors to bolt ARPA‑H’s measurement modules onto their ongoing studies. That could include psilocybin, 5‑MeO‑DMT, ibogaine‑like compounds, and even non‑psychedelic rapid‑acting agents.

Implications

For pharma and biotech

• Expect pressure, and opportunity, to align trial designs with EVIDENT’s measurement framework. Early adopters will be better placed when regulators start to treat these measures as standard.
• Companies with strong digital health, biomarker and data‑science capabilities will have an edge in EVIDENT‑style consortia and in negotiations around labelling, REMS and post‑marketing commitments.

For regulators and payers

• EVIDENT is a clear signal that the US federal apparatus wants more objective data on rapid‑acting therapies, including psychedelics. That will eventually strengthen the basis for coverage decisions, risk‑sharing agreements and practice guidelines.
• Veterans’ inclusion as a “strong” priority ties EVIDENT directly to VA and DoD health systems, increasing the odds that early implementation and reimbursement models will be piloted in these populations.

For health systems and clinicians

• Over time, expect more use of wearables, behavioral data and structured therapy‑session metrics in both trials and real‑world psychedelic practice. That may feel intrusive at first, but it will be one of the main levers for shifting these treatments from boutique offerings to scalable, evidence‑tracked services.

3. Compass psilocybin: how fast, and who is close behind?

Where Compass now stands

Compass Pathways announced that, following a “positive” September meeting with FDA, it is bringing forward its commercial launch planning for COMP360 psilocybin in treatment‑resistant depression by roughly nine to twelve months. Key elements:

• FDA has indicated willingness to accept a rolling new drug application (NDA), so Compass can submit manufacturing and non‑clinical modules ahead of the full clinical package.
• Phase 3 timing has tightened:
  • 26‑week data from COMP005 and 9‑week Part A data from the larger COMP006 trial are now expected in Q1 2026.
  • 26‑week Part B data from COMP006 are expected in early Q3 2026.
• Compass has completed enrolment in COMP006 and is already pulling forward commercial infrastructure planning and payer discussions.

Psychedelic Alpha’s modelling, which aligns with standard FDA timelines, suggests that under the old plan, a launch in late 2027 or early 2028 was the base case, assuming priority review and a separate scheduling process of up to 90 days. The new nine-to-twelve-month acceleration, therefore, implies:

• Best‑case scenario:
  • Rolling NDA initiated shortly after Q1 2026 readouts, with final clinical modules added in early Q3 2026.
  • Priority review with a six‑month clock starting near the final module.
  • Scheduling completed in parallel or shortly after.
  • Commercial launch late 2026.
• Base case:
  • Some lag between Q3 2026 data and full NDA acceptance, plus typical review friction.
  • Launch in Q1 or Q2 2027. Kabir Nath has publicly framed “if we get there by the end of next year, that would be fantastic,” while guiding that Q1 2027 is more realistic.

In practical terms, this now positions COMP360 as a potential first‑in‑class, FDA‑approved psychedelic therapy in the United States, ahead of MDMA and well ahead of other classic psychedelics.

How close are the others really?

AtaiBeckley – BPL‑003 (intranasal 5‑MeO‑DMT) for TRD

AtaiBeckley has reported positive results from the open‑label extension of its Phase 2b trial of BPL‑003 in treatment‑resistant depression. A second, 12 mg dose, given eight weeks after the first, produced additional rapid antidepressant effects that were sustained for up to eight weeks. Key points:

• After two active doses, remission and response rates at week 16 were 48 percent and 63 percent respectively, notably higher than after a single dose in the blinded portion.
• The drug has shown good tolerability across doses, with one serious adverse event in the OLE classified as a transient worsening of pre‑existing suicidal ideation, resolving after brief hospitalisation.
• The company has shelved the 12 mg dose for Phase 3 and plans to move forward with an 8 mg regimen, likely exploring single versus two‑dose induction designs.
• AtaiBeckley has Breakthrough Therapy Designation and expects to have its Phase 3 programme underway in Q2 2026, after FDA and EMA meetings.

If you assume two global Phase 3 trials with roughly two‑year timelines from first patient in to last patient out, plus a year for NDA review and scheduling, BPL‑003 looks like a 2029 approval candidate at best. In other words, roughly two to three years behind a successful COMP360 program. The US clinical hold on GH Research’s inhaled 5‑MeO‑DMT, which remains unresolved as of late‑2025, widens AtaiBeckley’s lead in the 5‑MeO class.

Resilient Pharmaceuticals (formerly Lykos) – MDMA‑assisted therapy for PTSD

FDA’s complete response letter on MDMA‑assisted therapy requested at least one additional Phase 3 trial and raised significant questions about data integrity, long‑term safety, abuse potential, and the role of psychotherapy. The subsequent publication of the CRL revealed deeper concerns about under‑reported euphoric adverse events and the reliability of site‑level safety reporting.

The company has since rebranded as Resilient Pharmaceuticals and secured new funding, but it still needs to design and run an additional pivotal trial that satisfies FDA’s demands. Even with an efficient trial:

• Designing the new protocol, negotiating it with FDA and setting up sites is likely to take at least a year.
• A 12–18 month Phase 3, plus data cleaning and NDA resubmission, pushes any realistic approval scenario into the early 2030s.

In practice, MDMA has gone from being the presumed first mover to a second‑wave therapy, and the FDA has made clear that psychedelic candidates will not receive special dispensations on trial conduct or safety reporting.

AbbVie – Bretisilocin (GM‑2505)

AbbVie’s acquisition of Gilgamesh’s short‑acting 5‑HT2A agonist bretisilocin, with $900 million paid upfront and up to $1.2 billion total deal value, is the clearest sign yet that large pharma sees serious commercial potential in rapid‑acting “psychedelic‑adjacent” mechanisms. Bretisilocin is in Phase 2 for major depression; even in the most optimistic scenario, it will trail COMP360 by several years. The relevance here is not so much timeline competition as validation of the modality and increased M&A interest in second‑generation compounds.

Strategic implications

For developers

• The window for “first classic psychedelic to market” now belongs to psilocybin in TRD, provided Compass’ second Phase 3 reads out positively, and no major safety surprises emerge.
• Short‑acting agents like BPL‑003 are likely to define the first competitive wave after COMP360, especially for centres that cannot support all‑day dosing sessions. Those programmes are still multiple years behind and will need to navigate the post‑MDMA regulatory environment.

For payers and providers

• If COMP360 is approved on a timescale aligned with the accelerated plan, health systems will need to be ready to evaluate and potentially implement psilocybin services within 18–24 months, not at the end of the decade.
• Given the relatively low number of high‑volume centres required to drive utilisation (Compass and AtaiBeckley both reference a Spravato‑like model with hundreds rather than thousands of sites), early decisions by large systems and payers will strongly shape access patterns.

For investors

• The regulatory bar has been reaffirmed as “no lower than for other CNS drugs,” but the FDA is clearly willing to use its expedited tools when trials are robust and indications severe. The Compass and AtaiBeckley pathways show that high‑quality datasets still command both regulatory flexibility and M&A attention.

4. Veterans as Early Adopters: Australia and the US VA

Australia’s Department of Veterans’ Affairs steps in

The Australian DVA has committed to funding psychedelic‑assisted psychotherapy for eligible veterans:

• MDMA‑assisted psychotherapy for PTSD, and psilocybin‑assisted psychotherapy for treatment‑resistant depression,
• Only after multiple conventional treatment options have been tried,
• Delivered strictly within intensive psychotherapy programs, including preparation and integration around clinician‑supervised dosing days.

Crucially, DVA is recommending that clinicians use the Australian Interventional Pharmacotherapy and Psychedelic Assisted Psychotherapy Research Registry (AIPPAP‑RR), run by the Australian National University, so that outcomes and safety data from real‑world veterans’ treatment feed into a national dataset.

This decision answers the major question that followed Australia’s 2023 rescheduling of MDMA and psilocybin for limited medical use: even if the drugs are legal to prescribe, who will pay for therapy‑heavy treatment courses that can cost around 20,000 AUD per patient. The DVA commitment, combined with earlier moves by private insurer Medibank to fund MDMA and later psilocybin therapy in specific programs, effectively creates a two‑payer ecosystem for veterans and some civilians.

The US VA’s PIVOT Trial

In parallel, the US Department of Veterans Affairs is preparing PIVOT, a Phase 3 trial in which 240 veterans with treatment‑resistant depression will receive either a lower “comparator” or higher COMP360 psilocybin dose, with the primary outcome at two weeks on MADRS and a range of secondary measures including PTSD scales and side‑effect inventories. The trial is slated to start in mid‑2026 and complete in 2031, across five VA facilities.

This means that, regardless of the exact timing of FDA approval, the VA will have in‑house, veteran‑specific Phase 3 data to guide its own coverage and implementation decisions for psilocybin.

Why veterans are the vanguard

Veterans’ health systems occupy a unique policy position:

• They treat high‑burden populations with elevated rates of PTSD, depression, and suicide.
• They are relatively centralized and can run large pragmatic trials and registries.
• Their decisions are politically visible and can be framed both as fulfillment of obligations to veterans and as cautious innovation.

In Australia, DVA’s willingness to fund psychedelic‑assisted psychotherapy, tied to registry participation and stringent psychotherapy requirements, gives regulators and payers in other countries a live example of how to structure early access without de‑medicalising these treatments.

In the US, VA’s PIVOT trial and likely involvement in ARPA‑H’s EVIDENT program mean that veterans will probably be among the first groups to receive psilocybin in a highly structured, federally funded setting, even if commercial access elsewhere is still ramping up.

Implications

For health systems

• Veterans’ programmes in Australia and the US will generate some of the earliest high‑quality real‑world data on psychedelic treatment pathways, multidisciplinary staffing models, and cost trajectories.
• Other public payers can treat these systems as proving grounds, rather than committing to large‑scale reimbursement themselves from day one.

For clinicians

• Veterans’ mental health providers will need training pipelines, supervision structures, and governance around psychedelic‑assisted care sooner than most other public systems.
• Clinical protocols that prove workable in VA and DVA settings, especially around triage, risk managemen,t and integration, are likely to be influential in subsequent national guidelines.

For policymakers

• Veterans’ programs provide a politically acceptable way to explore novel therapies while keeping clear boundaries around indication, patient selection, and data capture.
• Success or failure in these programmes will either unlock or constrain broader psychedelic policy moves in the late 2020s.

Bringing Home the Psychedelic Policy Insights from November 2025

Taken together, this month’s developments sharpen several trends:

1. The hype‑driven corners of the field are losing ground. Rigorous trials of microdosing, in both depression and ADHD, are not showing efficacy over placebo, while high‑dose or short‑acting treatments in severe illness are where regulatory and payer attention is converging.
2. Regulators are not lowering standards for psychedelics. FDA’s handling of MDMA and its detailed CRL, combined with ARPA‑H’s push for objective measures, show an expectation that psychedelic programmes meet or exceed conventional CNS drug standards, even as the agency uses expedited tools like rolling review when warranted.
3. Governments and large pharma are investing in infrastructure and assets that assume these therapies will become part of mainstream care. DVA reimbursement, VA’s PIVOT trial, EVIDENT and AbbVie’s bretisilocin deal would not exist if decision‑makers saw psychedelics as a passing fad.
4. Timelines are compressing at the front of the queue and stretching at the back. Psilocybin for TRD now plausibly enters the US market in 2027, while MDMA has slid to the early 2030s and second‑generation compounds cluster in the late 2020s and beyond.

For people inside the psychedelic ecosystem, these dynamics are obvious. For busy healthcare leaders, policymakers, and investors who are not immersed in the space, it is easy to misread them.

That is exactly the gap Delphi is set up to close.

• We maintain a live view of regulatory signals, trial designs, and policy experiments across jurisdictions, then translate them into concrete scenarios: who gets approved when, under what conditions, at what likely cost.
• We work with health systems and providers on practical questions: which indications to prioritise, how to structure service lines, and how to integrate new therapies with existing mental health infrastructure.
• We support investors, pharma, and biotech with structured landscape and competitor analyses that are honest about risk, but clear about where value is most likely to accrue.

As psychedelic policy and therapeutics move rapidly from the margins into mainstream health and life sciences strategy, the cost of being a year late or misreading a signal is rising. Delphi’s role is to absorb that complexity and give you clear, decision‑ready insight.