Psilocybin's Surprising Effects on Social Behavior and Gut Health: New Research Findings

This article explores the emerging scientific evidence that connects psilocybin use to changes in social behavior and the gut microbiome, and what these findings could mean for the future of mental health treatment. 

Synopsis 

Recent research is uncovering a surprising and complex relationship between psilocybin (the active compound in "magic mushrooms"), our social interactions, and the trillions of microbes living in our gut. Studies are beginning to show that psilocybin can increase feelings of sociability and connection, while also altering the composition of the gut microbiome. This article will delve into the science behind this gut-brain connection, exploring how psilocybin might influence our social lives through its effects on our internal ecosystem, and what this could mean for treating conditions like social anxiety and depression.

The Gut-Brain Axis: A New Frontier in Mental Health

For decades, the brain has been seen as the sole command center for our thoughts, emotions, and behaviors. However, a growing field of research is revealing a much more intricate picture: a powerful, bidirectional communication highway between the gut and the brain, known as the microbiota-gut-brain (MGB) axis. This complex network involves the central nervous system, the enteric nervous system (the "second brain" in our gut), and the vast community of microorganisms, including bacteria, fungi, and viruses, that reside in our digestive tract.

These microbes are not just passive residents; they play a crucial role in our health, influencing everything from our immune system and metabolism to our mood and behavior. They produce a wide array of neuroactive compounds, including serotonin and dopamine, which are essential for regulating our emotions. In fact, it's estimated that up to 95% of the body's serotonin is produced in the gut. When the delicate balance of this internal ecosystem is disrupted—a state known as dysbiosis—it can have a significant impact on our mental well-being, contributing to conditions like anxiety, depression, and even social behavior disorders.

Psilocybin's Influence on Sociability and the Gut

This is where psychedelic research enters the picture in a fascinating way. A 2025 study published in Neuropharmacology by Gattuso et al. provided compelling evidence that chronic psilocybin administration in mice increased their sociability and significantly altered their gut microbiome. The researchers observed that the mice became more willing to interact with other mice after receiving psilocybin, a finding that has significant implications for understanding how this compound might be used to treat social anxiety and other related conditions. The study also found that psilocybin treatment led to changes in the abundance of specific gut bacteria, suggesting a direct link between the psychedelic's effects and the MGB axis.

Interestingly, the study also used a preclinical model of obsessive-compulsive disorder (OCD) and found that psilocybin did not have the same pro-social effects in these mice. This suggests that the effects of psilocybin on sociability may be dependent on the baseline state of the individual, a finding that underscores the importance of personalized medicine in the context of psychedelic therapy.

A Deeper Dive into the "Psilocybiome"

The idea that psychedelics could interact with the gut microbiome is so compelling that researchers have even coined a term for it: the "psilocybiome." A comprehensive 2022 review in the International Journal of Clinical and Health Psychology by Kelly et al. explored the potential interactions between psychedelic therapy and the MGB axis. The authors proposed that the gut microbiome could play a role in all three phases of psychedelic therapy: preparation, administration, and integration.

During the preparation phase, the state of an individual's gut microbiome could potentially influence their response to psychedelic therapy. It's conceivable that interventions aimed at improving gut health, such as dietary changes or probiotics, could be used to "prime" an individual for a more positive therapeutic outcome. During the administration phase, the gut microbiome could influence how psilocybin is metabolized, leading to variations in the intensity and duration of the psychedelic experience. And in the integration phase, the long-term changes in behavior and lifestyle that often follow psychedelic therapy could, in turn, lead to lasting changes in the gut microbiome, creating a positive feedback loop that supports sustained mental well-being.

The Serotonin Connection

At the heart of this gut-brain-psychedelic connection is serotonin, a neurotransmitter that plays a crucial role in regulating mood, social behavior, and a host of other physiological processes. Psilocybin's primary psychoactive effects are mediated by its interaction with serotonin receptors in the brain, particularly the 5-HT2A receptor. However, as mentioned earlier, the vast majority of the body's serotonin is produced in the gut, where it is influenced by the gut microbiome. This raises the intriguing possibility that psilocybin's effects on the brain are not just a result of its direct action on cortical receptors, but are also modulated by its influence on the gut and the serotonin signaling that originates there.

The Future of Psychedelic Therapy: A Holistic Approach

The emerging research on the "psilocybiome" points towards a more holistic and systems-based approach to psychedelic therapy. It suggests that to fully understand and optimize the therapeutic potential of these powerful compounds, we need to look beyond the brain and consider the intricate web of connections that link our minds, our bodies, and the microbial world within us.

While this field of research is still in its infancy, the initial findings are incredibly exciting. They open up new avenues for exploring how we can use psychedelic therapy to treat a wide range of mental health conditions, and they highlight the importance of considering the whole person—mind, body, and microbiome—in the journey towards healing and well-being. As we continue to unravel the mysteries of the gut-brain axis and its interaction with psychedelics, we may discover new and even more effective ways to harness the therapeutic power of these ancient medicines.

References

1.Gattuso, J. J., et al. (2025). Chronic psilocybin administration increases sociability and alters the gut microbiome in male wild-type mice but not in a preclinical model of obsessive-compulsive disorder. Neuropharmacology, 264, 109501. https://doi.org/10.1016/j.neuropharm.2025.109501

2.Kelly, J. R., Clarke, G., Harkin, A., Corr, S. C., Galvin, S., Pradeep, V., Cryan, J. F., O'Keane, V., & Dinan, T. G. (2022). Seeking the Psilocybiome: Psychedelics meet the microbiota-gut-brain axis. International Journal of Clinical and Health Psychology, 23(2), 100349. https://doi.org/10.1016/j.ijchp.2022.100349

Disclaimer: Psychedelic Assisted Psychotherapy has not been approved by any regulatory agencies in the United States, and the safety and efficacy are still not formally established at the time of this writing.