Psilocybin did not alter sociability in female mice under metabolic stressors—activity-based anorexia, food restriction, or running wheels—but increased preference for social familiarity (reduced novelty-seeking) in control mice. Both activity-based anorexia and running wheel groups showed elevated novelty-seeking behavior, though with distinct social patterns. Psilocybin raised levels of the proinflammatory cytokine interleukin-6 (IL-6) in running wheel mice, and that increase correlated with preference for novelty; no such relationship appeared in the other groups. These context-dependent effects on social behavior and inflammation highlight the need for further research on psilocybin's mechanisms across sexes and disease models.
A single dose of psilocybin did not alter sociability in female mice exposed to activity-based anorexia, food restriction, or exercise, but increased preference for familiarity in control mice. Novelty-seeking behavior rose in both anorexia-model and exercise mice, with distinct social patterns. Psilocybin elevated the inflammatory marker interleukin-6 in exercised mice, which correlated with novelty preference; no such link appeared in other groups. These context-dependent effects on social behavior and inflammation underscore the need to study psilocybin's mechanisms across sexes and disease models.