Psilocybin and psilocin regulate microglial immunomodulation and support neuroplasticity via serotonergic and AhR signaling.
International immunopharmacology June 26, 2025 Salma Laabi, Claire LeMmon, Callie Vogel et al. 15 citations
Psilocybin and its active metabolite psilocin suppress the pro-inflammatory cytokine TNF-α and increase levels of the neuroplasticity marker BDNF in activated microglia. These effects are mediated through 5-HT2A, 5-HT2B, 5-HT7, and TrkB signaling. AhR activation is required for psilocin-induced BDNF upregulation but not for TNF-α suppression. IL-10 levels remain unchanged under normal conditions but rise when serotonergic, TrkB, or AhR signaling is blocked, indicating a compensatory anti-inflammatory shift. The compounds promote a microglial phenotype that reduces inflammation and supports neuroplasticity via distinct receptor-specific pathways.