Classical and non-classical psychedelic drugs induce common network changes in human cortex

Introduction

Dai and colleagues situate their work in the context of incomplete understanding of the neurobiology of the psychedelic experience. They note that classical psychedelics such as LSD primarily act at the serotonergic 5-HT2 receptor, while non-classical drugs such as ketamine and nitrous oxide act at different molecular targets but can produce overlapping phenomenology, increased neurophysiologic complexity, and changes in oscillatory activity and brain state repertoire. Prior to this study there had been no resting-state fMRI characterisation of nitrous oxide at psychedelic concentrations in humans, and it remained unclear whether diverse psychedelics share drug-invariant network-level signatures. The study therefore set out to identify common brain network changes induced by both classical and non-classical psychedelics. Using a primary, prospective fMRI dataset of nitrous oxide administration and secondary analyses of existing ketamine and LSD fMRI datasets, the investigators compared within- and between-network functional connectivity changes associated with each drug. Propofol sedation was included as a non-psychedelic control to help distinguish general state-dependent connectivity changes from psychedelic-specific effects.