Psilocybin, a novel therapeutic, is metabolized to psilocin, which alters brain function by engaging serotonin receptors. In fifteen healthy individuals, a psychoactive dose (0.2-0.3 mg/kg) reduced the integrity and segregation of brain networks, including the default mode network, while increasing connectivity between networks like the executive control and dorsal attention networks. These changes correlated with plasma psilocin levels and subjective drug intensity. The findings link psilocin's time course to shifts in brain functional architecture and subjective experience, offering insight into the neurobiological mechanisms of psychedelic effects and consciousness.
Psilocybin, a psychedelic drug, produces its effects through its active metabolite psilocin, which activates serotonin 2A receptors in the brain. In fifteen healthy individuals given a moderate oral dose (0.2–0.3 mg/kg), higher plasma psilocin levels and stronger subjective drug intensity correlated with reduced integrity and segregation of brain networks, particularly the default mode network, and with increased connectivity between networks such as the executive control and dorsal attention networks. These changes in functional brain architecture tracked the time course and magnitude of the psychedelic experience, linking network desegregation to altered consciousness.