Twenty-four healthy subjects underwent a double-blind, randomized, placebo-controlled, counterbalanced, crossover study to examine the time-dependent effects of psilocybin on functional connectivity in the brain. Resting-state functional connectivity was quantified through a data-driven method known as global brain connectivity (GBC). Subjects received a placebo and 0.2 mg/kg of psilocybin on different test days and underwent magnetic resonance imaging at 20 minutes, 40 minutes and 70 minutes after administration. Psilocybin increased sensory brain-wide connectivity while reducing associative connectivity. Baseline global connectivity was associated with the strength of psilocybin-induced changes in functional connectivity. In a time-dependent manner, psilocybin-induced changes correlated with the spatial gene expression patterns of the 5-HT2A and 5-HT1A receptors.