Psychedelics disrupt hierarchical cortical propagations in the default mode network of humans and mice.
Proceedings of the National Academy of Sciences of the United States of America June 16, 2026 Adam R Pines, Xue Zhang, John Kochalka et al.
Psychedelic drugs consistently reduce the strength and bottom-up direction of signal flow within the brain's default mode network, according to analyses of four independent datasets spanning humans and mice and three different psychedelic compounds (MDMA, psilocybin, and LSD). This attenuation of cortical propagations is not explained by data quality or previously known effects of psychedelics and is uniquely tied to self-reported outcomes. The findings clarify how psychedelics alter macroscale hierarchical processing in the brain.