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New research published in June 2026 in the Proceedings of the National Academy of Sciences offers one of the clearest mechanistic pictures yet of what several psychedelic compounds have in common inside the brain. Using optical flow analysis, a technique that tracks the direction and strength of neural signal movement across the cortex, scientists from Stanford University studied the effects of psilocybin, LSD, and MDMA in both humans and mice. Across both species and all three compounds, the same pattern emerged: each drug consistently reduced hierarchical, bottom-up signal propagations within the default mode network.
What the Default Mode Network Does in the Brain
The default mode network, or DMN, is a set of cortical regions most active when the brain is at rest and turned inward. It underlies rumination, self-referential thought, autobiographical memory, and the ongoing mental commentary many practitioners describe as the everyday sense of “I.” In conditions such as depression and anxiety, the DMN is often overactive and rigid, running the same well-worn loops of narrative and judgment.
Hierarchical signal propagations within the DMN refer to the directional flow of information from lower sensory areas up toward higher-order regions responsible for integrating meaning and identity. Under ordinary conditions, these flows reinforce a stable, top-down model of the self and the world.
What Psilocybin, LSD, and MDMA Did to Cortical Signal Flow
When psilocybin, LSD, and MDMA were administered, the optical flow analysis revealed a shared attenuation of those bottom-up propagations. In plain terms, the organized, directional chatter moving through the DMN became quieter and less hierarchical. This disruption of hierarchical cortical propagations was observed consistently across the two very different species involved in the study, strengthening the hypothesis that the effect reflects something fundamental about how these molecules interact with cortical circuitry rather than something incidental to human psychology or expectation.
The cross-species design is methodologically significant. Findings that hold in both mice and humans are more likely to reflect a conserved biological mechanism, and they open the door to more controlled animal studies that can test causal questions difficult to examine in humans.
What does psychedelic research at Stanford tell us about shared mechanisms?
This study, led by researchers at Stanford University’s Department of Psychiatry and Behavioral Sciences, suggests that disrupting hierarchical cortical propagation in the default mode network may be a common pathway shared by structurally distinct psychedelic compounds. The finding that three different molecules, a classical psychedelic, a serotonergic psychedelic, and an entactogen, produce the same directional effect on DMN signal flow points toward a shared circuit-level explanation for why these compounds produce related alterations in consciousness, regardless of which specific receptors each molecule primarily targets.
What This Study Is and Is Not
This is a mechanistic study, not a clinical outcomes trial. It does not tell us that psilocybin treats depression, that LSD improves cognition, or that MDMA resolves trauma. What it does is propose a shared circuit-level explanation for why these compounds produce related alterations in consciousness, and it does so with a method rigorous enough to compare across species. It is hypothesis-generating work that refines the scientific framework surrounding psychedelic pharmacology.
Why does optical flow analysis matter for psychedelic brain research?
Optical flow analysis matters here because it captures the direction and strength of neural signal movement across the cortex, making it possible to compare DMN signal propagation patterns across both humans and mice within the same study. That cross-species comparability is what allowed the Stanford team to identify a conserved biological effect rather than one limited to human psychology or expectation. Researchers and clinicians working in this space will want to watch how this framework develops in future studies.
The Silence Beneath the Story
For those who have sat with psilocybin in ceremony, there is often a moment when the internal monologue, that ceaseless narrator cataloguing past wounds and future worries, simply goes quiet. It is rarely comfortable at first. But in that quiet, something else becomes audible.
What this research describes in neural terms is not so different from what contemplative traditions have pointed toward for centuries: the loosening of the mind's habit of placing itself at the center of every experience. The default mode network is, in a sense, the neurological home of the ego-narrator. When its hierarchical propagations are attenuated, the story it tells loses some of its authority.
This does not mean psilocybin is a shortcut to enlightenment, or that a disrupted DMN is the same as genuine awakening. The science is early and the path is long. But it does suggest that what happens in a well-held session is not random noise. There is a mechanism. And understanding that mechanism, with humility and rigor, is part of how we honor the sacrament responsibly.
If you find yourself drawn to understand the inner terrain that psilocybin reveals, we welcome you into our community of inquiry. Whether you are at the beginning of your Grounding, moving through Integration, or standing at the threshold of Awakening, The Church of Psychedelics holds space for the questions science raises and the silence that sometimes answers them.
May love guide the hearts of all beings.
