Canonical and Non-Canonical Psychedelic Drugs Induce Common Network Changes in Human Cortex

AO_SCPLOWBSTRACTC_SCPLOWThe neurobiology of the psychedelic experience is not fully elucidated. Identifying common brain network changes induced by both canonical (i.e., acting at the 5-HT2 receptor) and non-canonical psychedelics would provide mechanistic insight into state-specific characteristics. We analyzed whole-brain functional connectivity based on resting-state fMRI data in humans, acquired before and during the administration of nitrous oxide, ketamine, and lysergic acid diethylamide. We report that, despite distinct molecular mechanisms and modes of delivery, all three psychedelics reduced within-network functional connectivity and enhanced between-network functional connectivity. More specifically, all drugs tested increased connectivity between right temporoparietal junction and bilateral intraparietal sulcus as well as between precuneus and left intraparietal sulcus. These regions fall within the posterior cortical "hot zone," posited to mediate the content of consciousness. Thus, both canonical and non-canonical psychedelics modulate networks within an area of known relevance for conscious experience, identifying a biologically plausible candidate for their subjective effects.