It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
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.
Tuesday, February 03, 2026
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
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.
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.
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.
Friday, January 09, 2026
Creating hallucination-free, psychedelic-like molecules by shining light on life’s basic building blocks
Discovery could lead to new drugs for psychiatric disorders
UC Davis researchers have developed a new method that uses light to transform amino acids — the building blocks of proteins — into molecules that are similar in structure to psychedelics and mimic their interaction with the brain. Like psychedelics, these molecules activate the brain’s serotonin 5-HT2A receptors, which promote cortical neuron growth, and could be candidates to treat a host of brain disorders, such as depression, substance-use disorder and PTSD. However, they don’t trigger hallmark hallucinogenic behavior in animal models.
The research was recently published in the Journal of the American Chemical Society.
“The question that we were trying to answer was, ‘Is there whole new class of drugs in this field that hasn’t been discovered?” said study author Joseph Beckett, a Ph.D. student working with Professor Mark Mascal, UC Davis Department of Chemistry, and an affiliate of the UC Davis Institute for Psychedelics and Neurotherapeutics (IPN). “The answer in the end was, ‘Yes.’”
The research opens the door to a streamlined and environmentally friendly drug discovery platform for new serotonin-effecting drugs that confer the benefits of psychedelics without significantly distorting perception.
“In medicinal chemistry, it’s very typical to take an existing scaffold and make modifications that just tweak the pharmacology a little bit one way or another,” said study author Trey Brasher, also a Ph.D. student in the Mascal Lab and an affiliate of IPN. “But especially in the psychedelic field, completely new scaffolds are incredibly rare. And this is the discovery of a brand-new therapeutic scaffold.”
Discovering a new therapeutic scaffold
The researchers created a library of potentially therapeutic molecules by coupling various amino acids with tryptamine, a metabolite of the essential amino acid tryptophan. They then irradiated these molecules with ultraviolet light to transform them into new compounds of medicinal value.
Computer simulations were used to test the binding affinity of 100 of these compounds at the 5-HT2A receptor.
Five candidates were selected for further lab testing to determine efficacy and potency. Efficacies of the selected compounds ranged from 61% to 93%, with the latter representing a full agonist — a compound capable of producing the maximum biological response from the 5-HT2A system.
The team labeled the full agonist in the group as D5. They expected that administering the compound to mouse models would induce head twitch responses, a hallmark of hallucinogenic-like behaviors.
However, that wasn’t the case. Despite fully activating the same receptor as psychedelics, D5 didn’t induce head twitch responses.
“Laboratory and computational studies showed that these molecules can partially or fully activate serotonin signaling pathways linked to both brain plasticity and hallucinations, while experiments in mice demonstrated suppression of psychedelic-like responses rather than their induction,” Beckett and Brasher said.
Next steps: why no hallucinations?
The team plans to conduct follow-up studies to better understand if other serotonin receptors in the brain modulate or suppress the hallucinogenic-like effects of D5.
“We determined that the scaffold itself possesses a range of activity,” Brasher said. “But now it’s about elucidating that activity and understanding why D5 and similar molecules are non-hallucinogenic when they’re full agonists.”
Additional authors on the paper include Mark Mascal and Lena E. H. Svanholm, of UC Davis; Marc Bazin, Ryan Buzdygon and Steve Nguyen, of HepatoChem Inc.; John D. McCorvy, Allison A. Clark and Serena S. Schalk, of the Medical College of Wisconsin; and Adam L. Halberstadt and Bruna Cuccurazza, of UC San Diego.
The research reported on here was funded by grants from the National Institutes of Health and Source Research Foundation.
Microdosing involves ingesting small amounts of a psychedelic substance, commonly psilocybin mushrooms or lysergic acid diethylamide (LSD).
“Most doses vary from one-tenth to one-twentieth of a recreational dose,” Dr. St. Pierre says. “Typical practices alternate varying proportions of non-dosing days to limit the rapid tolerance that can develop with so-called classic psychedelics such as psilocybin and LSD. Anecdotal reports suggest that this may also be intended to leverage residual effects that could carry over to non-dosing days.”
While interest in microdosing has grown rapidly, she notes that scientific research has only emerged over the past 15 years. This means popular use has outpaced the scientific support to back it up.
Using data from the Microdose.me project, the world’s largest international daily diary study of real-world microdosing, Dr. St. Pierre says the findings show people tend to feel more connected, creative, focused and productive on days they microdose, as well as increased wellbeing and contemplation. However, these effects didn’t appear to persist on non-dosing days.
“Microdosing appears to lift mood and mental functioning on the days it’s practiced, but not necessarily beyond that,” she adds. “These findings help clarify when and how microdosing effects are felt.”
More than 1,435 microdosers from 49 countries participated in the study. Each morning, participants were asked if they had microdosed and rated how they felt across variables such as connectedness, contemplation, creativity, focus, productiveness and wellbeing.
The research team also examined whether these day-level effects varied across factors such as gender, mental-health history, the substance being microdosed, and whether participants had previously taken larger doses of psychedelics.
Dr. St. Pierre explains that the results were consistent across nearly all groups.
“The only meaningful difference we observed was among people with a history of taking larger psychedelic doses, who showed slightly higher microdosing-day increases in creativity,” she says.
This pattern aligns with emerging evidence that full-dose psychedelic experiences may enhance creativity. One interpretation, Dr. St. Pierre notes, is that microdosing could “reactivate” or build upon these prior effects, though this idea remains speculative.
“We need future research designed specifically to test whether microdosing can amplify or extend the impacts of larger-dose psychedelic experiences,” she adds.
Overall, the study adds daily-level precision to a growing body of research suggesting microdosing may enhance wellbeing and cognitive performance—although in a short-term, day-specific way. While the results are an extension of earlier work, Dr. St. Pierre says this remains an observational study and further research is needed to separate expectation effects from genuine pharmacological changes.
Daily self-assessment within a regimen of microdosing indicates enhanced psychological functioning on microdosing days relative to non-microdosing days
