Federal Health Officials Outline Pre-Approval Roadmap for Psychedelic Medicines at Horizons Forum

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Federal Health Officials Outline Pre-Approval Roadmap for Psychedelic Medicines at Horizons Forum

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By Jack Gorsline

Source: Lucid News

With late-stage psychedelic drug candidates closing in on potential regulatory decisions, federal health officials say the U.S. government is coordinating across multiple agencies to build out clinical, regulatory, and reimbursement infrastructure before the first wave of treatments hits the market.

Speaking on Oct. 15 during the opening day of The Psychedelic Healthcare Forum, co-hosted by Psychedelic Alpha as part of the broader Horizons: Perspectives on Psychedelics conference at The New York Academy of Medicine, representatives from the Department of Health and Human Services (HHS), the Food and Drug Administration (FDA), the Department of Veterans Affairs (VA), and the Advanced Research Projects Agency for Health (ARPA-H) detailed how an April executive order has fundamentally reshaped federal priorities.

According to Psychedelic Alpha founder Josh Hardman, who delivered a "State of the Field" address to kick off the forum, the overarching question facing the psychedelic sector is rapidly pivoting from "if" to "how" these medicines can be delivered safely, effectively, and ethically within the existing U.S. healthcare paradigm. Over the past six years, the field has evolved from fringe, cannabis-adjacent gatherings into high-level policy discussions hosted directly on the FDA’s campus and inside the White House.

As Hardman outlined in his opening remarks, psychedelics now account for at least a third of all Phase 3 trials in psychiatry. Key upcoming New Drug Applications (NDAs) include Compass Pathways’ synthetic psilocybin candidate COMP360 for treatment-resistant depression, which the company expects to submit this quarter, and Resilient Pharmaceuticals’ (formerly Lykos) MDMA candidate for PTSD, which was recently pre-filed with the FDA.

At the same time, compelling clinical data and favorable regulatory winds have driven major pharmaceutical capital into the space, highlighted by Eli Lilly Co.’s $2.8 billion upfront acquisition of AtaiBeckley earlier this year.

Accelerating Timelines Without Lowering Standards

In an opening fireside discussion with Hardman, HHS Deputy General Counsel Matt Zorn, a former litigator who previously sued the DEA and HHS over cannabis and psychedelic policy before taking a government post in May 2025, explained how the April executive order has catalyzed internal action. The directive explicitly mentions the word "psychedelics" seven times, destigmatizing open dialogue across federal departments and placing the drug class at the top of the priority list for political leadership and career civil servants alike.

Still, Zorn stressed that executive branch orders operate strictly within existing statutory frameworks, guiding agencies where discretionary authority exists without lowering scientific thresholds.

“The order doesn’t change any statutory or regulatory standards,” Zorn said. “Just because you may move faster doesn’t mean any agency is applying a different standard than they would apply to any other drug. You apply the same standards, moving on a faster timeline. The title is ‘accelerating’; it’s not changing any of the standards we’re applying”.

What the order has enabled, Zorn noted, is vital pre-approval preparation across the government to ensure agencies do not lag behind prospective FDA approvals. That groundwork includes early planning around Medicare and CPT billing codes through the Centers for Medicare & Medicaid Services (CMS), analyzing points of care, and soliciting broad public input. An FDA public comment window and Part 15 hearing recently drew 609 submissions, with speaking slots heavily favoring non-industry stakeholders. Additionally, the Health Resources and Services Administration (HRSA) is expected to publish a report within the coming weeks following its request for information on healthcare workforce training.

Addressing queries regarding alternative access channels, Zorn noted that while HHS is acting on presidential direction under Section 2(b) of the executive order regarding Right to Try, established expanded access programs have long been available. Hesitancy around expanded access, he contended, usually stems from drug sponsors wanting clean clinical trial cohorts rather than FDA resistance.

Zorn also touched on state-regulated psychedelic frameworks in Oregon, Colorado, and New Mexico, viewing them as valuable sources of short-term real-world data, though he doubted their long-term sustainability over a 10-year horizon given that patients must pay entirely out of pocket rather than relying on insurance coverage for FDA-approved therapies.

Zorn also briefly addressed his own future in government and possible job offers to leave HHS and return to the private sector.

"I've had a [few] things come up, and I'm evaluating my options," Zorn said.

During a subsequent panel moderated by POLITICO Deputy Health Care Editor Erin Schumaker, Andrew Gradison, Senior Advisor at the Veterans Health Administration, pointed to White House leadership as the catalyst for current federal momentum.

“What do I owe the recent momentum to? Maybe not the most popular answer in the great city of New York, but this administration took a stance. The president took a stance on this, and he decided that we were going to go full steam ahead to understand this class of medicines, to continue to build out our research, [and] to enroll more patients in clinical trials. That is a position that no administration had taken for decades. So whether you passionately dislike this president or you love him, on this issue we owe the momentum that we have today to him [having the] intestinal fortitude to take the stand,” Gradison said.

Federal momentum around psychedelic medicine also saw notable progress under former President Joe Biden's administration, which established a historic federal psychedelic task force in 2022.

Unprecedented Interagency Coordination and the VA Rollout

Panelists during the roundtable emphasized an unprecedented level of interagency cooperation following a July 13 memorandum of understanding between HHS and the VA. That partnership features weekly working sessions among the VA, FDA, and ARPA-H; joint efforts with the Substance Abuse and Mental Health Services Administration (SAMHSA) on patient education and clinical guidance.

There is also a formal data-sharing framework under which the VA has already supplied long-term MDMA durability data for PTSD to the FDA; and regular executive communications among VA Secretary Doug Collins, HHS Secretary Robert F. Kennedy Jr., and CMS leadership under Dr. Mehmet Oz. Officials are engaging directly with the Department of Justice and the Drug Enforcement Administration (DEA) to ensure post-approval DEA scheduling, which typically takes two to three months, does not cause unnecessary clinical delays.

Both Zorn and panel participants contrasted this forward-leaning posture with the 2019 approval of the esketamine nasal spray Spravato. At the time, the VA had not engaged in advance cross-agency strategy. The agency received its initial deployment call the day following approval, before rollout efforts across its 53 esketamine centers were disrupted by the COVID-19 pandemic in March 2020.

Across the VA system, the patient need remains vast. Out of 9 million enrolled veterans and 6.4 million active healthcare users, roughly 2.1 million carry diagnoses of PTSD, major depressive disorder, or treatment-resistant depression. Even after filtering through strict clinical trial exclusion criteria for comorbidities and family psychiatric histories, Gradison estimated that around 100,000 veterans would qualify for psychedelic-assisted therapy immediately upon approval.

In preparation, Secretary Collins approved a phased rollout framework three weeks prior to the conference, designating 10 experienced VA medical centers as Phase 1 lead sites. Those 10 facilities formed a formal community of practice in early October, working through infrastructure retrofits, staffing allocations, and resource requirements so the VA can begin administering care immediately if a drug receives commercial approval as early as January or February 2027.

Still, Gradison offered a realistic perspective on initial throughput. Given that psychedelic therapy demands significant staff and clinical resources, he acknowledged that treating even four-digit numbers of veterans in year one will be challenging, though the agency is assessing group delivery models to expand capacity across more sites over time.

Regulatory Workload, Ibogaine Hurdles, and Real-World Risks

At the FDA, Associate Director for Regulatory Science Dr. Valentina Mantua cited rapid expansion in psychedelic clinical research. The agency currently oversees approximately 433 Investigational New Drug (IND) applications, roughly 85% originating from academic institutions and 15% from commercial developers, which outpaces the European Medicines Agency and accounts for one-third of her division's overall review load.

Drawing on past regulatory lessons, such as the agency's decision last year to remove an overly restrictive Risk Evaluation and Mitigation Strategies (REMS) lab-monitoring requirement for the psychiatric medication clozapine because it hindered patient access, Mantua noted the FDA is working to balance oversight and accessibility proactively. Instead of delaying until final review phases, the FDA has already requested REMS proposals from psychedelic drug developers to establish clear prescribing and administration standards. Addressing Resilient’s reported MDMA resubmission without new Phase 3 trials, Mantua explained that the regulatory framework remains clear: sponsors must address the specific safety and efficacy deficiencies detailed in the agency’s initial Complete Response Letter.

Meanwhile, federal efforts to evaluate ibogaine for opioid use disorder face substantial clinical and technical challenges. Dr. Al Bugazia, a former ICU physician and Deputy Director of Proactive Health at ARPA-H, described the ibogaine program as the most complex endeavor of his professional career.

While ARPA-H is funding early-phase trials and consulting directly with Dr. Oz at CMS to ensure future interventions are scalable and reimbursable, ibogaine presents significant cardiotoxicity risks and QTc interval prolongation. Furthermore, the U.S. currently lacks a domestic GMP manufacturer for an ibogaine IND, and the DEA’s annual manufacturing quota remains capped at just over 200 grams.

Both Zorn and Mantua underscored the critical need for rigorous Phase 1 safety studies utilizing well-characterized chemical compounds, with Mantua pointing to an Oct. 5 FDA Request for Information open through November to collect empirical data on early-stage ibogaine protocols. Bugazia also highlighted ARPA-H’s EVIDENT initiative, which seeks to replace legacy 1950s psychiatric evaluation scales with objective biological markers to better identify which depression patients will respond to specific medical compounds.

Despite tangible regulatory progress, officials voiced shared concerns surrounding real-world implementation and public overhype. Bugazia cautioned against repeating the policy errors of the 1960s, emphasizing that psychedelics are not universal cures, carry real potential risks, and must be guided by sound science rather than media narrative or political momentum. Panelists also noted a marked demographic contrast between highly screened clinical trial cohorts, which lean younger, healthier, and female, and real-world clinical populations. Within the VA system, Gradison observed, the typical patient is a 72-year-old male managing alcohol use issues, six to 10 concurrent diagnoses, and more than six prescribed medications.

While Zorn posited that psychedelics may actually demonstrate higher relative efficacy in complex, treatment-resistant patient populations, he anticipated that real-world adverse event rates will exceed those observed in controlled trials. Furthermore, both Hardman and Zorn highlighted a key industry reality: even following FDA approvals, a significant portion of psychedelic use will persist outside formal healthcare channels.

Zorn warned that a primary risk to the field is a sudden surge in unregulated use sparked by the signal of an FDA approval, leading to avoidable adverse events. Mantua and Bugazia similarly raised concerns regarding veterans traveling to offshore clinics in Mexico, citing a lack of safety oversight on frequent or off-protocol use alongside the challenges of replicating retreat model settings within standard U.S. clinical environments.

Concluding his fireside discussion, Zorn advised psychedelic advocates to prioritize pragmatic, incremental progress over ideological perfection to keep regulatory policy moving forward. Gradison echoed those thoughts to close the following panel, while emphasizing that a pragmatic posture represents a daily race against time, as 17 veterans are lost to suicide every single day.

“What keeps me up at night is the balance between moving quickly and moving safely,” Gradison said. “Every single day that we move too slowly is another wasted opportunity to save someone's life, to restore a relationship, to build out a community, to save a father, to save a mother, and to allow them to reintegrate into their community.”