This placebo-controlled multimodal [functional MRI-electroencephalography (fMRI-EEG)] human neuroimaging study offers the most comprehensive view of the acute brain action of psychedelics to date. It assessed N,N-Dimethyltryptamine (DMT), a psychedelic that generates immersive altered conscious experience with no diminishment of wakefulness. Global hyperconnectivity, collapsed hierarchical organization and reduced intranetwork integrity, was observed (fMRI) that correlated with decreased alpha power and increased entropy (EEG). Regions with the densest expression of serotonin 2A receptors as determined via independent positron emission tomography (PET) data, were most affected by DMT, and overlapped with regions related to evolved cognitive functions such as language and semantic processing. These results support the notion that psychedelics impact a principal axis of brain organization, and relatedly, the quality of human conscious experience.