The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers

Psychedelic drugs like psilocybin and MDMA perturb consciousness in distinct ways, offering a tool to study brain mechanisms underlying conscious states. In placebo-controlled studies, psilocybin increased resting-state functional connectivity between brain networks, making them less differentiated, while decreasing connectivity between visual and sensorimotor networks. MDMA produced less marked changes in between-network connectivity, suggesting that the extensive network alterations under psilocybin may be unique to classic psychedelics and relate to their profound effects on consciousness. This analytical approach could help characterize other altered conscious states.

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Abstract

Perturbing a system and observing the consequences is a classic scientific strategy for understanding a phenomenon. Psychedelic drugs perturb consciousness in a marked and novel way and thus are powerful tools for studying its mechanisms. In the present analysis, we measured changes in resting-state functional connectivity (RSFC) between a standard template of different independent components analysis (ICA)-derived resting state networks (RSNs) under the influence of two different psychoactive drugs, the stimulant/psychedelic hybrid, MDMA, and the classic psychedelic, psilocybin. Both were given in placebo-controlled designs and produced marked subjective effects, although reports of more profound changes in consciousness were given after psilocybin. Between-network RSFC was generally increased under psilocybin, implying that networks become less differentiated from each other in the psychedelic state. Decreased RSFC between visual and sensorimotor RSNs was also observed. MDMA had a notably less marked effect on between-network RSFC, implying that the extensive changes observed under psilocybin may be exclusive to classic psychedelic drugs and related to their especially profound effects on consciousness. The novel analytical approach applied here may be applied to other altered states of consciousness to improve our characterization of different conscious states and ultimately advance our understanding of the brain mechanisms underlying them.