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.
Patients with chronic cluster headache (CCH) suffer from poor sleep, which may affect brain microstructure and waste clearance. In 11 CCH patients, subjective sleep quality—measured by the Pittsburgh Sleep Quality Index—improved one week after three doses of psilocybin (0.14 mg/kg) given one week apart, with a mean PSQI change of -2.50 points. Before treatment, CCH patients had poorer sleep and differences in brain microstructure and water diffusivity compared to 24 healthy controls, primarily in grey matter. Psilocybin intervention was not associated with statistically significant changes in brain microstructure or water diffusivity on average, though most patients showed lower white matter diffusivity and neurite volume. Subjective sleep quality showed borderline significant correlations of moderate effect size with brain microstructure and water diffusivity.