For individuals grappling with mental health challenges like PTSD, anxiety, and depression, finding a path forward can often seem daunting, especially when traditional treatments have provided little relief.
Psilocybin, the psychoactive compound found in certain mushrooms, was long stigmatized as an illicit substance.
However, recent outcomes from the first state-regulated psilocybin program in the U.S. indicate that this drug might offer hope beyond the boundaries of clinical trials.
From November 2024 to June 2026, a team from Oregon Health & Science University monitored 346 participants in the program. They discovered that within the first three months after taking psilocybin, participants reported notable improvements in mental health, well-being, and life satisfaction.
One month after the dose, 92.2 percent of participants described the experience as beneficial, with their mental health symptoms showing significant reduction on average.
“This paper is going to be cited for decades,” comments neuroscientist Adrianne R. Wilson-Poe of the Legacy Research Institute and co-director of the Open Psychedelic Evaluation Nexus (OPEN).
“This is the first large-scale study to monitor the safety and mental health symptoms of real people in the real world.”
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Mental illness affects tens of millions of Americans, many of whom find standard treatments lacking or inaccessible. In 2024, around 23 percent of U.S. adults reported experiencing mental illness symptoms in the previous year; yet only half received any form of treatment.
This has prompted researchers to explore alternative solutions like psilocybin. Over the past decade, clinical trials have increasingly suggested that psilocybin may alleviate symptoms of mental illness, particularly in cases where other treatments have failed.
However, clinical trials are conducted in highly controlled environments.
The Oregon study represents a fundamentally different approach.
The program began welcoming clients in mid-2023. Instead of using pre-selected participants, synthetic psilocybin, and continuous therapeutic support, it allows any adult over 21 to participate for any reason, uses mushroom-derived products, and does not require facilitators to have clinical training.
The researchers sought to understand what happens when psilocybin is offered to the general public outside the confines of a clinical trial.
OPEN involved 346 clients from 24 licensed service centers in Oregon to evaluate the program’s outcomes and safety.
Each participant received a supervised psilocybin dose averaging 31.9 milligrams, though individual doses ranged from 2 to 50 milligrams. Participants engaged in preparation beforehand, took psilocybin under facilitator supervision, and could attend follow-up integration sessions.
Surveys assessed changes in symptoms and life satisfaction before the dose and at various intervals up to three months later.
The findings were remarkable.
After three months, the percentage of participants with moderate-to-severe PTSD symptoms decreased from 48 percent to 16.8 percent. Moderate-to-severe anxiety dropped from 45.1 percent to 13.2 percent, and moderate-to-severe depression fell from 42.2 percent to 16.5 percent.
Conversely, life satisfaction improved from 63 percent to 82.3 percent among those surveyed.
However, there were some adverse outcomes. Four people—1.2 percent of the cohort—experienced serious behavioral reactions necessitating medical attention.
One participant became violent and required hospitalization. Another reported an emergency room visit due to worsening anxiety and depression, with suicidal thoughts. A third experienced a similar hospital visit and mental health decline. The fourth faced severe anxiety and insomnia needing medication, along with worsening depression and suicidal thoughts over three months.
All four were inexperienced with psychedelics and had pre-existing symptoms of depression, anxiety, and/or PTSD. They also received doses ranging from 25 to 50 milligrams.
Researchers suggest that a lack of psychedelic experience, greater psychological vulnerability, and higher doses might heighten the risk of severe reactions, although the small number of cases makes it difficult to establish a definitive link.
Several limitations exist. Since this is a real-world study, causation cannot be definitively attributed to psilocybin.
There was no control group; participation was voluntary; and only about 5 percent of Oregon’s psilocybin users during the study participated in OPEN. Additionally, most participants were white and relatively affluent.
Nonetheless, Oregon’s initiative is significantly larger than this study alone suggests.
Since 2023, over 20,000 people have accessed regulated psilocybin services in Oregon, a figure more than six times larger than the total number of participants in clinical trials involving classic psychedelics since 1951.
Related: Huge Psilocybin Dose Has Incredible Effect on Elderly Dementia Patient
According to Todd Korthuis of Oregon Health & Science University and his team, the study indicates that the benefits observed in controlled clinical trials might extend to real-world settings, though the few severe reactions highlight that psilocybin is not without risk.
Psilocybin may not be suitable for everyone, and individuals considering its use should discuss potential risks with a medical professional, especially if they have existing health conditions or medications that might interact with it.
Yet, the results provide promising initial evidence that utilizing psilocybin outside the traditional medical framework does not necessarily diminish its potential benefits.
“Just because something isn’t a medical model doesn’t mean you can’t have mental health benefits,” Korthuis states.
The study findings have been published in JAMA Network Open.
This article was fact-checked by Fiona MacDonald and edited by Fiona MacDonald. While we pride ourselves on our process, we are only human. If you spot a mistake, please let us know.
