OHSU-led research initiative examines supervised psilocybin

Five-year, $3.3 million award is first to study the effect of psychedelic services in community settings

Oregon Health & Science University

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A federally funded research initiative will enable researchers at Oregon Health & Science University and other organizations to assess the safety and effectiveness of state-regulated access to psilocybin, also known as magic mushrooms.

The five-year, $3.3 million award is funded by the National Institute on Drug Abuse of the National Institutes of Health — a first.

“This is the first federally funded work to study the impact of legal psychedelic services delivered in community settings,” said co-principal investigator Adie Rae, Ph.D., a scientist at the Legacy Research Institute in Portland and co-director of the Oregon Psychedelic Evaluation Nexis, or OPEN. “There is an urgent need to assess the safety of these programs and their impact on substance use before more voters and policymakers are asked to consider their merits and drawbacks.”

In 2023, Oregon became the first state to permit state-regulated access, for people 21 and older, to supervised services involving mind-altering magic mushrooms. This followed a ballot initiative approved by voters in 2020. Colorado subsequently followed suit.

“We expect our project will generate evidence to inform other states considering legal frameworks for psychedelic services,” said co-PI Todd Korthuis, M.D., M.P.H., co-director of OPEN and professor of medicine (general internal medicine and geriatrics) in the OHSU School of Medicine. “Only about 3,000 people have participated in all psychedelic clinical trials combined since the 1950s. This project is an opportunity to learn from tens of thousands of people who will access psilocybin services in Oregon.”

Public interest has been fueled by promising results in recent years from early clinical trials in depression, anxiety and post-traumatic stress disorder.

OHSU President Shereef Elnahal, M.D., M.B.A., said he expects the research to be groundbreaking.

“Oregon’s experience affords a unique opportunity to inform and shape public understanding of the potential benefits and side effects of psilocybin. In effect, Oregon is a laboratory for policymakers around the country,” he said.  “This research will be critically important to learn the safety and efficacy profile of psychedelics for mental health treatment.”

Focused on substance use

The OHSU-led initiative will specifically examine psilocybin’s effect on people with substance use disorders.

“If you look at clinical trials conducted so far, the evidence suggests psilocybin may decrease symptoms of depression similar to existing antidepressants,” Rae said. “Even though there is some emerging literature about the effect of psychedelics on tobacco cessation and in the treatment of alcohol use disorder, we need more research to better understand the effect of psychedelics on substance use.”

Korthuis, head of addiction medicine at OHSU, agrees.

“Preliminary data from Oregon show that people are already accessing psilocybin services to help manage substance use,” he said. “The current study will allow us to better understand how accessing state psilocybin services impacts use of alcohol, nicotine and other substance over time.”

Even though psilocybin and other psychedelics have been used for millennia, researchers and state regulators are only beginning to apply modern scientific rigor to the field.

In 2024, an OHSU-led research team published a set of 22 key measures of high-quality services following a series of interviews conducted with experts who have experience facilitating psilocybin use within clinical trials, in ceremonial settings and in traditional indigenous practices.

Oregon is first

Oregon is the first state to permit state-regulated access to psilocybin, but Rae expects other states will follow. Ultimately, it’s possible that it may become a widely accepted therapy.

“I would compare it to something like acupuncture,” Rae said. “With enough evidence that accumulated over time, it became clear that acupuncture treatment reduced other health care costs. The Oregon psilocybin program could wind up in the same zone, as something that’s essentially considered to be alternative medicine.”

Psychedelics may not work for everyone, but they offer hope for many people who struggle with substance use disorder, said co-PI Ryan Cook, Ph.D., assistant professor of medicine  in the OHSU School of Medicine.

“People have strong viewpoints when it comes to psychedelics,” he said. “I’m excited to do this study because we are going to rigorously collect and evaluate the data in a way that has never been done before.”

Researchers have already gathered preliminary data from over 300 clients of Oregon psilocybin service providers who have agreed to participate in the research. Researchers are aiming to enlist at least 1,600 willing research participants over the next five years — a significant proportion of the estimated 15,000 people who have participated in psilocybin services statewide in the first two years it’s been officially permitted.

Participants will fill out a baseline survey, followed by six subsequent surveys and interviews for 12 months following their initial psilocybin treatment session.

The study will recruit participants who want to reduce their use of intoxicating substances with and without psilocybin services. It will then compare the outcomes of each group, including potential safety risks and benefits. The researchers will aim to identify specific substances and subpopulations that may be responsive to psilocybin’s effects.

Psilocybin remains a Schedule 1 controlled substance under federal law, along with cannabis, heroin and others.

“Ultimately, people want to know how safe this is, what is the likelihood their symptoms will improve, what are the side effects, and any challenging experiences they should expect,” Rae said. “Right now, we don’t have much to tell clients about any of those things.”

The research is supported by the National Institute on Drug Abuse of the National Institutes of Health, award R01DA060253. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

SEE

LA REVUE GAUCHE - Left Comment: Search results for LSD 

LA REVUE GAUCHE - Left Comment: Search results for PSYCHEDELIC 

LA REVUE GAUCHE - Left Comment: Search results for PSYCHEDELIC SASKATCHEWAN 

LA REVUE GAUCHE - Left Comment: Search results for MAGIC MUSHROOMS 

 

How psychedelic drugs affect the brain

Ruhr-University Bochum

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Dirk Jancke (left) und Callum White haben für das Paper zusammengearbeitet. 

 

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Credit: © RUB, Marquard

Hallucinations fill the gap

Psychedelics activate a specific serotonin receptor. At least 14 different receptors are known where the neurotransmitter serotonin binds. Psychedelics have the highest affinity for the 2A receptor, which, among other effects, acts suppressive in the visual brain and also influences learning processes. “We have observed in earlier studies that visual processes in the brain are suppressed by this receptor,” says Callum White, first author of the study. “This means that visual information about things happening in the outside world becomes less accessible to our consciousness. To fill this gap in the puzzle, our brain inserts fragments from memory – it hallucinates.”

Short-term oscillations trigger communication between brain areas

In their current study, the authors show how this happens. Psychedelics intensify oscillations in visual brain areas. Generally speaking, oscillations are synchronized neural activity waves that modulate communication between brain regions. After administration of psychedelics the scientist found that visual areas produce increasingly low-frequency (5-Hz) activity waves that activate another brain region, the retrosplenial cortex. This area forms a major hub for the exchange with stored information. The brain thus switches to a new mode in which access to ongoing events is hindered and instead perceptions are increasingly generated from memory contents, “a bit like partial dreaming,” says Professor Dirk Jancke, leader of the study.

Visualizing the dynamics of brain activity in real-time

To visualize these complex processes, the scientists use an optical method that records neural activity in real-time over the entire brain surface. The mice developed by Professor Thomas Knöpfel from Hong Kong Baptist University are genetically manipulated so that they express fluorescent proteins in defined cell types. “We therefore know exactly in our experiments that the measured fluorescent signals originate from pyramidal cells of the cortical layers 2/3 and 5, which mediate communication within and between brain regions,” says Jancke.

Developing new therapy approaches

The results support new approaches in psychology that use psychedelics to treat, for example, anxiety disorders or depression. “When used under medical supervision, such substances can temporarily change the state of the brain to selectively recall positive memory content and restructure learned, excessively negative thought patterns, i.e., to be able to unlearn negative context. It will be exciting to see how such therapies are further personalized in the future,” says Jancke.

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Journal

Communications Biology

DOI

10.1038/s42003-025-09492-9 

Method of Research

Experimental study

Subject of Research

Animals

Article Title

Psychedelic 5-HT2A Agonist Increases Spontaneous and Evoked 5-Hz Oscillations in Visual and Retrosplenial Cortex

Article Publication Date

11-Feb-2026

 

Ayahuasca retreats are booming in Spain, one of the only European countries with a legal loophole

Copyright WeareAvalon

By Rebecca Ann Hughes

Published on 07/02/2026 - EURONEWS

Ayahuasca has boomed in popularity as a wellness practice in recent years.

As dark falls, Taita Isaías Muñoz Macanilla, a traditional doctor and an Indigenous activist from Putumayo, cleanses a tree-fringed outdoor clearing and the participants seated in a circle in preparation for their first ayahuasca ceremony.

But they are not in the Amazon. Instead, they are in a boutique hotel in Barcelona.

Ayahuasca, a psychoactive, plant-based brew found in South America and used in traditional medicine and shamanism, has boomed in popularity as a wellness practice in recent years.

But given that the decoction contains dimethyltryptamine (DMT), which induces intense visions, purging, and powerful psychological experiences in users, it is banned in most European countries.

Spain and Portugal are exceptions, however, which has given rise to a growing number of ayahuasca retreats that are much more accessible to Europeans.

Why ayahuasca travellers are swapping South America for Spain

Dozens of retreat centres now invite alternative wellness-seeking travellers to remote spots in Peru and Brazil to experience deep-rooted ayahuasca traditions.

The Indigenous practice has sparked increasing interest in the West, amplified by the rise of spiritual tourism, public disclosures by celebrities about their use of psychedelics, and broader cultural conversations around mental health and spirituality, according to Alejandro Carbó, founder of Avalon retreats.

Carbó’s programmes connect guests to traditional ayahuasca practitioners, but are part of a growing number of experiences much closer to home for Europeans.

Ayahuasca is a psychoactive, plant-based brew found in South America and used in traditional medicine and shamanism. WeareAvalon

His retreats are located in Spain and Portugal, countries which he says travellers are increasingly drawn to for a combination of practical, cultural and perceptual reasons.

“Reduced travel time and costs make these retreats far more accessible, while European standards of accommodation, food, hygiene and services provide a level of comfort many participants expect,” Carbó says.

At Avalon’s retreats, there are doctors, psychologists and integration guides on hand, for example.

“There is also greater trust rooted in familiarity with the culture, territory, food and social norms, which lowers the psychological threshold for participation,” Carbó says.

Both countries have long been favoured as holiday destinations for Europeans, plus retreats commonly integrate other wellness activities like yoga, art therapy and meditation tailored to established Western tastes.

Spain and Portugal are ‘unique permissive environments’ for ayahuasca

As interest in ayahuasca retreats in Europe grows, so do concerns around safety and cultural appropriation

“In my opinion, European retreat founders should act as bridges between two worlds: the Amazonian and the Western,” says Carbó.

Carbó’s programmes connect guests to traditional ayahuasca practitioners. WeareAvalon

“They should work in partnership with Indigenous traditions, the legitimate inheritors of this ancestral wisdom, while at the same time adapting the ritual for non-Indigenous participants, their needs, and a context (territory, legality and safety) different from its place of origin.”

Legal issues mean most European countries are off-limits for practising ayahuasca, but ​Spain and Portugal are often described as uniquely “permissive” environments, Carbó explains.

“This is not because ayahuasca is explicitly legal, but because of how their legal frameworks operate in practice. In both countries, ayahuasca as a brew is not specifically scheduled, which places it in a legal grey zone rather than under a clear prohibition,” he says.

Relate

In Spain, this permissiveness is largely shaped by jurisprudence, where courts have tended to distinguish private, non-commercial use from trafficking or public harm.

In Portugal, the country’s permissive reputation is closely linked to the decriminalisation of drug possession for personal use in 2001 and the resulting public-health-oriented approach to enforcement, according to Carbó.

“That said, this permissiveness is inherently fragile, as it relies on discretion and context rather than on explicit legal protection, and can quickly shift in response to political pressure or adverse events,” he adds.

Psilocybin shows context-dependent effects on social behavior and inflammation in female mice modeling anorexia

Associate Professor Claire Foldi and her team at Monash University reveal that exercise history and food restriction alter how the psychedelic compound affects sociability and immune signaling in a preclinical model relevant to eating disorders

Genomic Press

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image: 

Both ABA and RW groups demonstrate elevated preference for novel social over other novel stimuli. Empty symbols represent SAL-treated mice; filled symbols represent psilocybin-treated mice. Data are presented as mean ± SEM and were analyzed by one-way ANOVA with Šidák post hoc tests. Significance thresholds: ∗P < 0.05; ∗∗P <0.01; ∗∗∗ P < 0.001. For futher details see Figure 3 legend in the paper.

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Credit: Claire J Foldi

CLAYTON, Victoria, AUSTRALIA, 3 February 2026 -- Researchers led by Dr. Claire Foldi at Monash University have discovered that psilocybin, the psychoactive compound found in magic mushrooms, produces subtle but distinct effects on social behavior and inflammation that depend critically on metabolic and exercise context in female mice. The peer-reviewed study, published in Psychedelics, represents the first systematic investigation of how this compound influences sociability in female mice exposed to activity-based anorexia (ABA), a widely recognized preclinical model that captures core features of anorexia nervosa.

The findings arrive at a pivotal moment. Clinical trials investigating psilocybin for anorexia nervosa are underway, yet mechanistic understanding remains sparse. Why do only 40% of participants in early trials show symptom reduction? What drives such variability? This research begins to untangle those questions by examining the compound through the lens of metabolic stress, exercise, and immune function.

The Scientific Challenge

Anorexia nervosa claims lives. It carries one of the highest mortality rates among psychiatric conditions, and hospitalization rates among young women aged 15 to 29 have climbed steadily in Australia, where this demographic accounts for 95% of all related hospital admissions. Beyond the physical devastation, individuals with anorexia nervosa experience profound social difficulties. They report fewer social networks, derive less pleasure from social interactions, and exhibit impaired emotional empathy that worsens during acute illness phases.

These social deficits share neurobiological roots with depression, anxiety, and obsessive-compulsive disorder. All involve dysfunction of the serotonin system. All show elevated proinflammatory cytokines, particularly interleukin-6 and tumor necrosis factor-alpha. Psychedelics act primarily through serotonin receptors and possess documented anti-inflammatory properties. Could they address multiple symptoms simultaneously?

Previous research suggested yes. Studies have shown psilocybin enhances emotional empathy in depressed patients. But nearly all preclinical work has used male subjects. This matters enormously when studying a condition that affects females at dramatically higher rates. The mechanisms relevant to anorexia nervosa require investigation in female subjects.

Methodological Innovation in a Female-Focused Model

Dr. Foldi's team employed the activity-based anorexia model, which combines time-limited food access with voluntary running wheel availability. This paradigm reliably produces starvation-evoked hyperactivity, severe weight loss, and elevated anxiety. Eight-week-old female mice were assigned to four conditions: activity-based anorexia (combining food restriction with wheel access), food restriction alone, running wheel access with unlimited food, or standard single housing.

The researchers administered psilocybin at 1.5 mg/kg after mice in the anorexia model reached 75 to 85 percent of baseline body weight. Four to five hours later, animals completed a three-chamber social preference and novelty test. Blood samples collected seven hours post-injection allowed measurement of interleukin-6 levels.

What made this approach distinctive was its systematic comparison across conditions. Rather than examining psilocybin effects in isolation, the team could disentangle contributions from food restriction, exercise, and their combination. Could exercise alone explain observed social changes? Would metabolic stress mask or enhance drug effects?

Unexpected Patterns in Social Behavior

The activity-based anorexia mice did not show the social deficits researchers anticipated. Instead, they exhibited heightened novelty-seeking behavior, preferring unfamiliar mice over familiar ones with striking consistency. This pattern emerged during the initial exploratory phase of testing and persisted throughout.

Mice that were exercising only showed something different. They too preferred novel social partners, but this preference emerged primarily during the choice phase of testing rather than during initial exploration. Food-restricted mice showed no such enhancements.

Psilocybin did not broadly alter sociability across groups. However, it reduced novelty-seeking in control mice, causing them to spend equivalent time with familiar and novel partners. In food-restricted mice administered psilocybin, body weight correlated strongly with interest in a novel object rather than a novel mouse. Animals with lower body weight directed more attention toward the object, suggesting enhanced food-seeking motivation.

These findings raise fascinating questions. Does the heightened novelty-seeking in anorexia model mice reflect adaptive foraging behavior under food scarcity? Or might it represent an addiction-prone phenotype, consistent with the elevated rates of substance use disorders observed in patients? Could this behavioral profile serve as a marker for compulsive tendencies?

Inflammation Tells a Different Story

The immune findings proved equally nuanced. Baseline interleukin-6 levels did not differ between groups, contrary to expectations based on human studies showing elevated inflammatory markers in anorexia patients. But psilocybin administration changed this picture dramatically in one specific context.

Running wheel mice that received psilocybin showed significantly elevated interleukin-6 compared to saline-treated running wheel mice, psilocybin-treated controls, and psilocybin-treated anorexia model animals. More intriguing still, these elevated levels correlated positively with social novelty preference. Higher interleukin-6 predicted greater interest in unfamiliar social partners.

No such relationship appeared in activity-based anorexia or food-restricted groups. Prior food restriction seemed to disrupt whatever mechanism linked psilocybin, inflammation, and sociability in exercising mice.

What explains this pattern? The researchers suggest that exercise alone, as an inherently rewarding activity that activates dopamine reward pathways, may create a metabolic and immune context where psilocybin produces distinct effects. The acute sampling timeframe may also have captured transient immune changes that require longer observation periods to resolve into the anti-inflammatory effects reported in human studies.

Implications for Treatment Development

Dr. Foldi notes that these findings highlight the complexity of translating psychedelic treatments to eating disorders. The absence of social deficits in the acute anorexia model suggests that such impairments may require longer exposure periods or result from psychosocial factors not captured in preclinical paradigms.

The context-dependent nature of psilocybin effects carries clinical implications. Patients with different metabolic states, exercise histories, or illness durations might respond differently to treatment. Could exercise status serve as a biomarker for treatment response? Might inflammatory profiles help identify candidates likely to benefit?

The study also underscores gaps in understanding temporal dynamics. Human research shows psilocybin reduces interleukin-6 seven days after administration, correlating with sustained mood improvements. The acute timeframe employed here may have missed downstream anti-inflammatory effects.

The Team Behind the Discovery

Sheida Shadani designed and conducted all experiments as part of her doctoral research at Monash Biomedicine Discovery Institute. Erika Greaves assisted with experimental procedures. Professor Zane B. Andrews contributed to experimental design and analysis. Associate Professor Foldi conceptualized the study and oversaw the entire investigation. The work was supported by a National Health and Medical Research Council Ideas Grant.

The Road Ahead

Three concrete next steps emerge from this research. Extended exposure protocols with multiple restriction and refeeding cycles would better model chronic anorexia nervosa and potentially reveal social deficits emerging with sustained malnutrition. Time-course studies measuring interleukin-6 at one, four, twenty-four, and one hundred sixty-eight hours post-administration would clarify temporal dynamics. Additional inflammatory markers examined alongside brain-region-specific neuroplasticity markers would comprehensively link immune modulation to behavioral effects.

The researchers emphasize that male and female subjects likely differ not only in psychedelic metabolism but in how neural circuits respond to serotonergic modulation. Future research must systematically examine effects across both sexes and at multiple timepoints to identify sex-specific trajectories of change.

This peer-reviewed research represents a significant advance in psychedelic science, offering new insights into context-dependent mechanisms through rigorous experimental investigation. The findings challenge assumptions about consistent drug effects and open new avenues for understanding how metabolic state shapes therapeutic response. By employing a carefully controlled comparative approach, the research team has generated data that advances fundamental knowledge while suggesting that personalized approaches may prove essential for eating disorder treatment. The comprehensive nature of this investigation, spanning multiple experimental conditions and examining both behavioral and immune outcomes, provides important insights that will reshape how researchers approach psychedelic mechanisms in metabolically compromised populations. Furthermore, the focus on female subjects demonstrates the power of sex-appropriate model selection to tackle clinically relevant questions.

The Research Article in Psychedelics titled "Psilocybin exerts differential effects on social behavior and inflammation in mice in contexts of activity-based anorexia," is freely available via Open Access on 3 February 2026 in Psychedelics at the following hyperlink: https://doi.org/10.61373/pp026a.0003.

About Psychedelics: Psychedelics: The Journal of Psychedelic and Psychoactive Drug Research (ISSN: 2997-2671, online and 2997-268X, print) is a peer reviewed medical research journal published by Genomic Press, New York. Psychedelics is dedicated to advancing knowledge across the full spectrum of consciousness altering substances, from classical psychedelics to stimulants, cannabinoids, entactogens, dissociatives, plant derived compounds, and novel compounds including drug discovery approaches. Our multidisciplinary approach encompasses molecular mechanisms, therapeutic applications, neuroscientific discoveries, and sociocultural analyses. We welcome diverse methodologies and perspectives from fundamental pharmacology and clinical studies to psychological investigations and societal-historical contexts that enhance our understanding of how these substances interact with human biology, psychology, and society.

Visit the Genomic Press Virtual Library: https://issues.genomicpress.com/bookcase/gtvov/

Our full website is at: https://genomicpress.kglmeridian.com/

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Journal

Psychedelics

DOI

10.61373/pp026a.0003 

Method of Research

Experimental study

Subject of Research

Animals

Article Title

Psilocybin exerts differential effects on social behavior and inflammation in mice in contexts of activity-based anorexia

Article Publication Date

3-Feb-2026

COI Statement

Author disclosures: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.