Methods: We therefore conducted a double-blind, randomized, counterbalanced, cross-over study during which 23 healthy human participants received placebo and 0.2 mg/kg of psilocybin p.o. on two different test days. Participants underwent MRI scanning at three time points between administration and peak effects: 20 mins, 40 mins, and 70 mins after administration. We quantified resting-state functional connectivity via a data-driven global brain connectivity method and compared it to cortical gene expression maps.
Results: Psilocybin reduced associative, but concurrently increased sensory brain-wide connectivity. This pattern emerged over time from administration to peak-effects. Furthermore, we show that baseline connectivity is associated with the extent of Psilocybin-induced changes in functional connectivity. Lastly, Psilocybin-induced changes correlated time-dependently with spatial gene expression patterns of the 5-HTR2A and 5-HTR1A.
Conclusion: Together, these results suggest that the integration of sensory and the dis-integration of associative regions may underlie the psychedelic state and pinpoint the critical role of the serotonin 2A and 1A receptor systems. Furthermore, baseline connectivity may represent a predictive marker of the magnitude of changes induced by psilocybin and may therefore contribute to a personalized medicine approach within the potential framework of psychedelic treatment.