New research suggests magic mushrooms may influence metabolism far beyond the brain
For years, the idea of psychedelics treating obesity has sounded… unconventional, to say the least. These compounds are best known for altering consciousness, reshaping perception, and catalyzing psychological insight — not regulating blood sugar or repairing fatty livers.
But a growing body of research is quietly expanding that narrative. While earlier theories focused on psychedelics “rewiring” compulsive eating behaviors in the brain, new preclinical findings suggest psilocybin may also work outside the mind entirely, acting directly on metabolic organs like the liver, muscle, and pancreas.
Together, these findings point to a surprising possibility. Psilocybin’s therapeutic potential may extend well beyond mental health, into the realm of obesity, type 2 diabetes, and metabolic disease.
Obesity Is More Than Calories In, Calories Out
Obesity is a complex, chronic condition marked by excessive fat accumulation and metabolic dysfunction. While diet, physical activity, genetics, and environment all play key roles, researchers increasingly recognize that obesity isn’t a single disease — it’s a constellation of biological and behavioral patterns.
For some people, overeating resembles addictive behavior. Highly palatable foods can hijack the brain’s reward system, driving compulsive consumption despite negative consequences. In these cases, food cues trigger powerful cravings that are difficult to override, even with strong motivation.
Researchers have used tools like the Yale Food Addiction Scale to identify individuals whose eating patterns closely resemble substance-use disorders. The implication? Treatments that work for addiction might also help certain forms of obesity.
The Early Psychedelic Hypothesis: Changing the Brain
This idea formed the basis of a recent review published in the Journal of Eating Disorders. In it, researchers from the University of Oxford explored whether psychedelics could offer a novel therapeutic pathway for obesity linked to compulsive eating.
Classic psychedelics like psilocybin, LSD, and ayahuasca primarily act on serotonin receptors (especially the 5-HT2A-receptor) which plays a central role in perception, cognition, and emotional processing. These compounds are also known to promote neuroplasticitet, the brain’s ability to form new connections and revise deeply ingrained habits.
In addiction studies, psychedelics have been shown to enhance the effects of psychotherapy, helping people loosen rigid behavioral patterns and make lasting changes. One prominent framework, the REBUS model (Afslappede overbevisninger under psykedelika), suggests that psychedelics temporarily soften entrenched mental predictions. This creates a window where new behaviors can take root.
Applied to eating behavior, this could mean weakening the automatic link between food cues and consumption. Thus allowing individuals to relate to food in a more flexible, intentional way.
A New Twist: Psilocybin Without the Psychedelic Effect
While this brain-based theory is compelling, a new preclinical study adds an unexpected layer to the story.
Published in Pharmacological Research, researchers from two Italian universities, along with collaborators across Europe and the United States, investigated whether very low doses of psilocybin could improve metabolic health — without producing psychedelic effects.
In the study, mice were fed a high-fat, high-sugar diet to induce obesity, type 2 diabetes, and metabolic dysfunction–associated steatotic liver disease (MASLD). The mice then received a chronic microdose of psilocybin — 0.05 mg per kilogram of body weight — over 12 weeks.
The results were striking.
Compared to untreated mice, those receiving psilocybin showed:
- Reduced weight gain
- Improved insulin sensitivity
- Normalized blood glucose levels
- Regression of fatty liver disease
Crucially, these changes occurred without reduced food intake og without detectable effects on the central nervous system.
What’s Happening in the Liver?
To understand how this was possible, researchers conducted molecular and tissue-level analyses. They found that psilocybin:
- Reduced the buildup of harmful “toxic” fats in the liver
- Restored insulin signaling pathways
- Improved liver structure and metabolic markers
“These data challenge the idea that the therapeutic potential of psilocybin is necessarily linked to the psychedelic experience,” said Sara De Martin, corresponding author of the study and professor of pharmaceutical sciences at the University of Padua.
“At chronic low doses, psilocybin acts as a peripheral modulator of metabolism, particularly at the liver level, through a distinct serotonergic pathway.”
Using human tissue cells, the team examined the role of three serotonin receptors: 5-HT2A, 5-HT2B, and 5-HT2C. The findings revealed that the metabolic benefits were ikke mediated by the 5-HT2A receptor — the one responsible for psychedelic effects.
Instead, the key mechanism involved blocking the 5-HT2B receptor. This is highly expressed in the liver and involved in metabolic regulation, cardiac development, and tissue growth.
Beyond Fat Loss: Muscle, Hormones, and the Pancreas
The benefits didn’t stop at the liver.
Mice treated with psilocybin also showed:
- Improved muscle strength and function
- Increased sensitivity to leptin, a hormone that regulates energy balance and metabolism
- Signs of repair in pancreatic beta cells, which produce insulin and are often damaged in type 2 diabetes
“In summary, we demonstrated that the 5-HT2BR-mediated beneficial metabolic effects induced by non-psychedelic psilocybin are correlated to a remodelling of the hepatic lipidome and accompanied by preservation of muscular strength and function in mice,” skrev forfatterne.
“These effects taken all together point to psilocybin as a potential muscle-sparing, CNS- and cardio-safe drug candidate for the treatment of MASLD, obesity and type 2 diabetes mellitus.”
What Does This Mean for Humans?
It’s important to be clear: these findings are preclinical. The results come from animal models, not human trials. Much more research is needed before psilocybin could be considered a metabolic treatment.
Still, the implications are significant.
Rather than acting solely through mindset shifts or appetite suppression, psilocybin may influence core metabolic processes directly. This offers a fundamentally different approach to treating obesity and related diseases.
If future studies confirm these effects in humans, psilocybin could one day complement existing strategies like lifestyle interventions, psychotherapy, and metabolic medications — potentially helping people who haven’t responded to conventional treatments.
A Broader View of Psychedelic Medicine
Taken together, this research suggests a broader truth: psychedelics may not fit neatly into the box we’ve placed them in.
They are not just tools for consciousness exploration or mental health. They are biologically active compounds that interact with systems throughout the body — from the brain and gut to the liver, muscle, and immune pathways.
As obesity and metabolic disease continue to rise globally, solutions may need to be just as complex as the conditions themselves. Psychedelics, it seems, may have more to offer than we once imagined.
