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

Abstract

The neurobiology of the psychedelic experience is not fully understood. Identifying common brain network changes induced by both classical (i.e., acting at the 5-HT₂ receptor) and non-classical 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 three drugs 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 qualitative aspects of experience. Thus, both classical and non-classical psychedelics modulate networks within an area of known relevance for consciousness, identifying a biologically plausible candidate for their subjective effects.

Trial registration: ClinicalTrials.gov NCT03435055.

Keywords: Consciousness; Cortex; Functional connectivity; Ketamine; LSD; Nitrous oxide; fMRI.