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.
At concentrations that produce psychedelic effects, nitrous oxide reduces the functional differentiation—the distinctness of activity patterns—within frontoparietal and somatomotor cortical networks. This suggests that the gas alters brain network organization, potentially contributing to its consciousness-altering properties. The finding points to a neural mechanism underlying the non-ordinary state induced by nitrous oxide, involving reduced specialization of key brain regions.
Subanesthetic nitrous oxide (N2O) alters visual experience by reconfiguring large-scale brain networks rather than changing early visual processing. In a placebo-controlled fMRI study with 13 healthy adults, participants viewed a flashing checkerboard and rated visual intensity and unpleasantness. Increased unpleasantness under N2O was linked to reduced connectivity between the right anterior insula and the anterior cingulate cortex and lateral occipital cortex. Network analyses revealed reduced modularity and a collapse of hierarchical organization, with sensorimotor connectivity redistributed toward salience and associative networks. These findings suggest that altered visual experience under N2O arises from disrupted salience integration and increased cross-network communication.