Psilocybin exerts differential effects on social behavior and inflammation in mice in contexts of activity-based anorexia
This study challenges assumptions that psilocybin broadly enhances social engagement in an anorexia model instead, its effects on social preference and novelty depend strongly on metabolic and exercise status
“Psychedelics, particularly psilocybin, have shown therapeutic potential across several psychiatric conditions, including depression, anxiety, obsessive-compulsive disorder, and anorexia nervosa (AN).
These disorders often share social deficits that may be effectively alleviated by psychedelics considering their use has been linked with emotional empathy and enhanced social cognition. However, the mechanisms through which psychedelics alter social behavior are unclear, and mechanistic studies in animal models have largely focused on male subjects.
This is problematic for understanding the therapeutic effects relevant for disorders that predominantly affect females, such as AN. Here, we used the activity-based anorexia (ABA) mouse model to characterize their social behavior compared to mice exposed to food restriction (FR), running wheels (RW) or standard housing (Controls) in female mice. Together with these metabolic stressors, we also investigated the effects of psilocybin on the circulating proinflammatory cytokine interleukin-6 (IL-6), which is implicated in AN and is suppressed by psychedelics. Psilocybin did not alter sociability in ABA, RW, or FR mice but increased preference for social familiarity (reduced novelty-seeking) in Controls.
Novelty-seeking behavior was elevated in both ABA and RW groups, although with distinct social patterns. Psilocybin elevated IL-6 levels in RW mice, which was positively correlated with preference for novelty. No such relationships were found in ABA or FR groups.
These findings reveal subtle, context-dependent effects of psilocybin on social behavior and inflammation in female mice, advancing our understanding of how ABA and exercise influence social behavior and inflammatory signaling. They underscore the need to clarify the temporal, neuroplastic, and immune-related mechanisms of psilocybin across sexes and disease models.”
Notes
Psilocybin’s impact on social behavior in this mouse model was context-dependent rather than universally pro-social.
Metabolic and exercise states shaped both behavioural and immune responses, illustrating that biological context matters when interpreting psilocybin’s effects.
The study advances understanding of how psychedelics might work in conditions involving metabolic stress or social dysfunction and underscores the need for careful modeling and interpretation in translational research.
Shadani S, Greaves E, Andrews ZB, Foldi CJ. Psilocybin exerts differential effects on social behavior and inflammation in mice in contexts of activity-based anorexia. Psychedelics. Published online 03 February 2026. doi:10.61373/pp026a.0003. Read Paper
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