The federal push accelerating psychedelic research to treat mental illness is being driven more by advocacy and anecdotal momentum than new scientific breakthroughs, Jerry Rosenbaum, MD, founding director of the Boston-based Mass General Brigham Center for the Neuroscience of Psychedelics, told Becker’s.
Earlier in April, President Donald Trump directed federal agencies to accelerate research, regulatory review and access to psychedelic drugs, including ibogaine, psilocybin and methylone, to treat serious mental illness. The FDA has issued national priority vouchers to three companies studying psilocybin for treatment-resistant depression and major depressive disorder as well as methylone for post-traumatic stress disorder. The Advanced Research Projects Agency for Health also launched a $139.4 million behavioral health initiative to develop new therapies, with $50 million to match state investments in psychedelic research.
There has been a resurgence of interest in psychedelic treatment, primarily driven by difficult-to-treat psychiatric conditions as well as potential applications for neurodegeneration and pain.
Dr. Rosenbaum said there has been an expectation that HHS would explore psychedelics due in part to Secretary Robert F. Kennedy Jr.’s past use of the substances.
“It seems like [the investment in psychedelics] was less driven by some new understanding or science, but more lobbying of the president and so forth,” he said. “There’s nothing wrong with the idea of accelerating research and investing in the science, because we need to do more research in this space to be sure that what we hope for is real, and that we understand any residual risks.”
Rather than new clinical breakthroughs, Dr. Rosenbaum pointed to a convergence of advocacy forces — which he said reached a “tipping point” — and testimonials shaping federal action. Individuals who have had positive experiences and benefits from the drugs often become “proselytizers,” feeling compelled to influence others, he said.
Among the most influential voices have been military veterans, whose treatment experiences have helped elevate psychedelics into a bipartisan policy issue. Dr. Rosenbaum said veterans often return from deployment with “invisible wounds of war” such as PTSD, depression and substance use disorder. Many have experienced “profound and relatively enduring benefits” through these treatments.
Despite strong anecdotal support, emerging clinical data presents a more tempered picture. The idea that psychedelics are “psychopatholytics or miracle drugs” has not been reflected in pivotal studies — not because the drugs are ineffective, but potentially due to challenges in study design and patient selection, he said. Recent phase 3 study data suggests efficacy has been more modest.
For example, a Compass Pathways’ phase 3 trial evaluated two doses of its psilocybin therapy (25 milligrams versus 1 milligram) in patients with treatment-resistant depression, measuring changes in symptom severity at week six. The study found statistically significant improvement with the 25 mg dose, with 39% of patients achieving a clinically meaningful response.
As the executive order groups treatments together, Dr. Rosenbaum emphasized critical distinctions for providers, particularly regarding ibogaine.
Ibogaine, a plant-based psychoactive compound, has different mechanisms of action and pharmacological profile compared to classic psychedelics such as psilocybin, he said. Ibogaine works through a “shotgun approach,” interacting with “numerous neurotransmitters in the central nervous system, including components of the acetylcholine, serotonin, dopamine, glutamate and opioid systems.”
Clinical trials of ibogaine include highly screened samples without cardiovascular illness, drug interactions or broader age ranges, meaning participants are more uncomplicated than typical patient populations, Dr. Rosenbaum said.
A 2023 review of 24 studies involving 705 people found reductions in withdrawal symptoms and cravings, but also identified concerns about heart toxicity and risk of death. The report cited at least 27 deaths linked to ibogaine use.
“People are looking to find versions of [ibogaine] that may be able to dial out that property,” he said. “But the current ibogaine has to be given in a situation with cardiac monitoring and the ability to resuscitate somebody who may go into a sudden death event.”
In comparison, psilocin “attaches to and activates receptors for the brain chemical serotonin,” and has a half-life of about three hours, with no detectable drug remaining in the body 24 hours after a single dose. Some psychedelics can last for between two and 12 hours, depending on the drug. A typical ibogaine dose produces an experience lasting 12 to 36 hours, with residual effects that can persist for up to 24 to 72 hours depending on dosage and metabolism.
As adoption expands, safety and patient selection will be key for health systems, Dr. Rosenbaum said.
Individuals have reported bad outcomes from psychedelic use, including feeling “traumatized,” with rare cases of new-onset schizophrenia or other psychotic states. It is unclear whether the drugs cause these conditions or reveal underlying vulnerabilities, he said.
Even when approved, delivering these therapies at scale presents operational challenges. Psychedelic care is often optimized in a comfortable setting where patients can lie down, listen to music and use eye shades, rather than in traditional clinical settings. The scale issue arises if treatment is administered to one patient at a time, requiring hours per patient.
“Given that a drug like Ibogaine requires monitoring for many hours, [psychedelics are] not, at least in the short term, going to be a solution for the huge unmet need in psychiatric care,” Dr. Rosenbaum said. “But it’s the infrastructure to be able to deliver this at scale [that] is going to be a real challenge.”
Looking ahead, Dr. Rosenbaum said he would position psychedelics as additives, working as part of the behavioral health toolkit.
One potential advantage is some patients may respond after one or two administrations, with effects lasting an average of three months, rather than requiring a daily medication with ongoing side effects. However, studies in broader patient populations with psychiatric conditions are still needed, he said.
“A treatment that you can give four times a year would be game changing for quality of life, as they do seem to work in a broad spectrum of [psychiatric] disorders,” Dr. Rosenbaum said.
As psychedelic treatments gain traction, health systems will need to address economic considerations such as space and staffing. Ketamine, another treatment for difficult-to-treat mental illness, followed a gradual rollout that required infrastructure development over time, and psychedelics are expected to face similar challenges, he said.
“What I see going forward is building on this and discovering new drugs from how we understand psychedelics work, but finding new and better versions that are truly novel,” Dr. Rosenbaum said. “That’s the future that I’m invested in.”
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