The first psychedelic-based treatments for depression and posttraumatic stress disorder (PTSD) could be approved as early as this fall, as a new FDA pathway accelerates review for particular drugs that are already backed by late-stage clinical data. 

The FDA awarded three compounds National Priority Vouchers in the wake of a White House executive order seeking to accelerate development of psychedelics for psychiatric disorders. 

The executive order also directed the US Drug Enforcement Administration to conduct a quick review of psychedelics that have completed phase 3 research, in anticipation that they could be moved from Schedule 1 to Schedule 2 or 3 upon FDA approval.

In addition, the order led to the awarding of an investigational new drug application for DemeRx’s DMX-1001, a form of the psychedelic ibogaine, for alcohol use disorder.

Of the three compounds given priority vouchers, Compass Pathways’ COMP360 (a synthetic psilocybin) for treatment-resistant depression is furthest along. Both the nonprofit Usona Institute’s psilocybin for major depressive disorder and Transcend Therapeutics’s TSND-201 (methylone, a synthetic drug similar to MDMA) for PTSD are also on a fast track. 

FDA Commissioner Marty Makary, MD said in an interview he expected the agency to issue a decision by the late summer or fall, and that the agency would direct that the therapies be given in a “supervised clinical setting.”

Unanswered Questions 

Psychiatrists said all three compounds have great potential but also raise questions about how they will be administered, cost, reimbursement, long-term safety, and durability of effect.

“There’s no way the FDA is going to allow this to be taken home without supervision,” said Roger McIntyre, MD, professor of psychiatry and pharmacology at the University of Toronto. 

McIntyre told Medscape Medical News the FDA will probably require one or two health care professionals to be on site during administration, and that the agency would institute a Risk Evaluation and Management Strategy for the compounds. 

“There are legitimate safety concerns and there are very profound non-ordinary effects that people have when they take psychedelics,” he said, adding that the “trips” can “be quite unpleasant and quite distressing.” 

The administration of these compounds “must be under medical supervision,” agreed Charles Nemeroff, MD, PhD, Matthew P. Nemeroff Endowed Chair, Department of Psychiatry & Behavioral Sciences, University of Texas at Austin Dell Medical School. 

Nemeroff, a member of the American Psychiatric Association’s research council, said participants in trials of psychedelics have experienced intense, raw emotions that can lead to hypertension and other cardiac effects.

He told Medscape Medical News that efforts to speed psychedelics into use was “really exciting.” It’s possible they are “an absolute game changer for psychiatry,” he said. But the drugs “are not panaceas,” said Nemeroff, who is also co-director of the Charmaine & Gordon McGill Center for Psychedelic Research & Therapy at Dell Medical School.

Paraphrasing psychedelics pioneer Timothy Leary, he said the compounds’ utility is dictated by “set and setting.” It’s still unclear which patients will most benefit and under what circumstances, said Nemeroff.

Both Nemeroff and McIntyre agree that trial data submitted to the FDA will be just the first step in getting these answers.

What Is a Priority Voucher? 

The FDA has already been looking at data from Compass, Usona, and Transcend, as part of the typical approval process. But that process can take years, sometimes up to a decade. With an eye on telescoping reviews, the FDA began the Commissioner’s National Priority Voucher (CNPV) program in June 2025. 

The program cuts review time to 1-2 months for therapies considered breakthroughs or those that address unmet medical needs or urgent emerging threats, are potentially more affordable, or can reduce dependence on foreign supply chains.

The agency granted the first vouchers in October. In December, the FDA approved the first, for the antibiotic Augmentin XR. 

FDA has since issued nine more vouchers and six additional approvals, including for orforglipron (Foundayo, an oral GLP-1 receptor agonist), the first new molecular entity, and Otarmeni (lunsotogene parvec-cwha), a gene therapy for a type of hearing loss.

A CNPV Council, is made up of FDA officials, chooses which drugs receive vouchers, guided by a manual. Agency staff conduct the reviews in accordance with FDA statutes.

Compass May Be the First to Market 

Psilocybin has been studied for decades, producing evidence that “it can be effective in some patients with depression,” said Nemeroff. 

He and McIntyre agreed that Compass’ COMP360, which received FDA’s breakthrough designation in 2018, is most likely to come to market first.

The Compass trials “look to me like adequate, well controlled and rigorous studies,” said McIntyre, adding he thought results were promising and demonstrated safety as well. 

The data looks both statistically and clinically significant, said Nemeroff, who expects the company to submit a full approval application “this summer.” UT Austin was a COMP360 study sites, although Nemeroff was not a primary investigator. 

In a phase 2b double-blind trial of 233 patients with treatment-resistant depression, a single 25-mg dose of COMP360 plus psychological support was associated with a statistically significant reduction in symptoms after 3 weeks (P < .001) that lasted for up to 12 weeks.

Two pivotal randomized, double-blind phase 3 trials — COMP005 and COMP006 — are underway. One is evaluating safety and efficacy of a single 25-mg dose; the second is assessing the same outcomes with two doses. 

Positive topline results from COMP005 showed a statistically significant (P < .001) and clinically meaningful reduction in symptom severity on the Montgomery-Asberg Depression Rating Scale. 

COMP006 has enrolled 572 patients at 116 locations. Compass had expected to complete the trial later this year and then seek FDA approval. The voucher program may have accelerated that timeline.

Compass is also preparing for a rollout. It has cemented agreements with multiple clinical organizations that could administer the therapy, including Radial, Greenbrook Mental Wellness Centers, Hackensack Meridian Health, Reliant Medical Group, Journey Clinical, Mindful Health Solutions, and HealthPort.

Madison, Wisconsin-based Usona Institute may have a big hill to climb. The nonprofit has not publicly stated whether it has agreements with clinics to administer its compound if it is approved.

McIntyre and Nemeroff both noted that the company’s compound has been studied only in depression, not treatment-resistant depression, and that it has conducted just a single phase 2 trial.

That randomized, double-blind study showed a significant reduction in symptoms after a single 25-mg dose. Usona’s phase 3 trial, UAspire, has enrolled 238 patients and is due to be completed in January 2027.

“I would certainly want to see a replication of their study,” said McIntyre, noting that major depression is different from treatment-resistant depression. He said that multiple alternative therapies exist for MDD, he said.

New Hope for PTSD 

Both McIntyre and Nemeroff said that PTSD represents a seriously unmet medical need, given that it’s been more than two decades since a new therapy was approved. 

In 2024 the FDA declined to approve a formulation of MDMA for PTSD, stating that it had concerns about trial conduct and that it had not seen evidence of efficacy. The agency directed the sponsor (Lykos Therapeutics, now Resilient Pharmaceuticals) to conduct more studies, but the decision disappointed patient advocates.

Transcend’s TSND-201 (methylone, an analog of MDMA), increases the release of serotonin, norepinephrine, and dopamine, but does not act on the serotonin 5-HT2A receptor, which means it does not lead to hallucinogenic effects. 

The FDA designated TSND-201 a breakthrough therapy in 2025, based on results from a randomized, placebo-controlled phase 2 trial, IMPACT-1. Participants received oral TSND-201 or placebo once a week for four weeks and were followed for an additional six weeks. 

Each dosing session lasted 8 hours. Those receiving TSND-201 had rapid and statistically significant, greater improvement in Clinician-Administered PTSD Scales for DSM-5 (CAPS-5) scores compared to the placebo group. 

Those preliminary data look “very, very good,” said McIntyre.

The compound is promising enough that in March, Japanese company Otsuka Pharmaceutical announced that it would buy Transcend Therapeutics.

Transcend has just begun enrolling patients in a phase 3 study, is expected to be completed in late 2027.

McIntyre reported that he has received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, 

Pfizer, Otsuka, Takeda, Neurocrine, Neurawell, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eli Lilly, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, AbbVie, Bristol Myers Squibb Teva, Adhere Tech, GH Research, Autobahn Theapeutics, and Atai Life Sciences. 

Nemeroff reported that he is supported by the National Institutes of Health, the National Institute of Mental Health, the Texas Child Mental Health Consortium, and the National Institute of Alcohol Abuse and Alcoholism. He is a consultant for Abbott Laboratories, Engrail Therapeutics, Clexio Biosciences LTD, Sero (previously Galen Mental Health LLC), Senseye Inc, Precisement Health, Autobahn Therapeutics Inc, EMA Wellness, Denovo Biopharma LLC, Alvogen, Acadia Pharmaceuticals, Inc, Reunion Neuroscience, Kivira Health, Inc, Wave Neuroscience, Patient Square Capital LP, Invisalert Solutions Inc., Bluecarta Inc., Incannex Healthcare Inc., Supernus, Concierge Clinical Trials Inc., Otsuka, Sensorium, Sirtsei Pharmaceuticals Inc, and Neurocrine Biosciences, LLC. Nemeroff owns the following patents: Method and devices for transdermal delivery of lithium (US 6,375,990B1), Method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay (US 7,148,027B2), Compounds, Compositions, Methods of Synthesis, and 

Methods of Treatment (CRF Receptor Binding Ligand) (US 8,551, 996 B2). He also reported that he owns stock in Corcept Therapeutics Company, EMA Wellness, Precisement Health, Relmada Therapeutics Inc, Signant Health, Galen Mental Health LLC, Kivira Health, Inc., Denovo Biopharma LLC, Headlamp Health Inc. Bluecarta Inc, and Senseye Inc. 

Alicia Ault is a Saint Petersburg, Florida-based freelance journalist whose work has appeared in many health and science publications, including Smithsonian.com. You can find her on X @aliciaault and on Bluesky @aliciaault.bsky.social.