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

Three different psychedelics—nitrous oxide, ketamine, and lysergic acid diethylamide—produce a common pattern of brain network changes despite having distinct molecular mechanisms and delivery methods. Each drug reduced connectivity within brain networks and enhanced connectivity between networks. Specifically, all three increased connections between the right temporoparietal junction and bilateral intraparietal sulcus, and between the precuneus and left intraparietal sulcus. These regions lie within the posterior cortical "hot zone," an area thought to mediate the qualitative aspects of experience. The findings identify a biologically plausible candidate for the subjective effects of both classical and non-classical psychedelics.

Study at a glance

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.