LSD flattens the functional hierarchy of the human brain

This placebo-controlled, within-subjects study (n=20) investigated the effects of LSD (75μg) on brain connectivity while listening to music and during resting-state, and found that LSD attenuated brain hierarchical organization reflected in a less differentiated pattern of distributed brain activity.


“Introduction: LSD is a potent serotonergic psychedelic compound. Findings indicate that psychotherapeutic applications of LSD and related psychedelic compounds have value in the treatment of mental health disorders. Deepening our understanding of LSD brain action may shed light on the mechanisms underlying the effectiveness of psychedelic therapy. A recent model hypothesized reduced whole-brain hierarchical organization as a key mechanism underlying the psychedelic state, but this has yet to be directly tested.

Methods: Here, we applied an unsupervised manifold learning technique that is sensitive to cortical hierarchy to pharmacological resting-state fMRI data to assess cortical organization in the LSD state.

Results: Results directly supported our primary hypothesis: The Principal Gradient, describing a hierarchical transition from unimodal to transmodal cortex, was significantly contracted under LSD relative to placebo. Between-condition contrasts revealed that this was primarily driven by a reduction of functional differentiation at both hierarchical extremes – default and frontoparietal networks at the upper end, and somatomotor cortex at the lower. In addition, results pertaining to the visual-somatomotor Second Gradient revealed that LSD reduced the differentiation of visual from auditory/somatomotor and association regions. Significantly, gradient changes tracked state-specific changes in specific dimensions of self-reported LSD experience.

Discussion: These findings support a recent mechanistic model of the psychedelic state that has relevance to therapeutic applications of psychedelics. More fundamentally, these findings provide the first evidence that cortical hierarchical organization can be modulated in a state-dependent manner, highlighting an important relationship between the features of neural topography and ongoing conscious experience.

Authors: Manesh Girna, Leor Roseman, Boris Bernhardt, Jonathan Smallwood, Robin Carhart-Harris & R. Nathan Spreng

Study details

Compounds studied

Topics studied

Study characteristics
Placebo-Controlled Single-Blind Within-Subject



Authors associated with this publication with profiles on Blossom

Leor Roseman
Leor Roseman is a researcher at the Centre for Psychedelic Research, Imperial College London. His work focussed on psilocybin for depression, but is now related to peace-building through psychedelics.

Robin Carhart-Harris
Dr. Robin Carhart-Harris is the Founding Director of the Neuroscape Psychedelics Division at UCSF. Previously he led the Psychedelic group at Imperial College London.

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