A single 1 mg/kg dose of psilocybin durably restored social novelty investigation in male SAPAP3 knockout mice and engaged prefrontal, hippocampal circuitry.

In a preclinical study in Molecular Psychiatry, psilocybin increased c-Fos activation in the medial prefrontal cortex and hippocampus across genotypes. In male SAPAP3 knockout mice, infralimbic cortex activation correlated most strongly with improved social recognition, suggesting domain-specific effects on social cognition in compulsive-like disorders.