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What fMRI studies say about the nature of the psychedelic effect: a scoping review

Michal Beneš, Tomáš Páleníček, Jiřı́ Horáček

Frontiers in Neuroscience July 1, 2025 DOI: 10.3389/fnins.2025.1606798 via OpenAlex

Summary

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A scoping review of fMRI studies on serotonergic psychedelics (psilocybin, LSD, DMT) identifies unifying themes: de-differentiation centered on the default mode network, complex changes in the thalamus, amygdala, and medial temporal lobe, and the importance of ego dissolution. These findings complement established models of psychedelic action and highlight contrasts with phenomenologically similar states and links to other biological markers.

Study at a glance

Characteristics Scoping review Peer reviewed
Topics Psilocybin Serotonin
Keywords Neuroscience Cognitive psychology Modality human–computer interaction
Citations 4
Key finding fMRI studies of serotonergic psychedelics reveal de-differentiation with the default mode network at its core, complex changes to the thalamus, amygdala, and medial temporal lobe, and the importance of ego dissolution.

Abstract

Research on psychedelic drugs, such as psilocybin, LSD or DMT, is a burgeoning field, with an increasing number of studies showing their promise in treatment of mental disorders as well as examining their mechanism of action. Determining their effect on the brain is crucial from clinical standpoint, but also offers highly promising avenues of advancement in basic neuroscience—functional magnetic resonance imaging (fMRI) is one of the most useful techniques to do so, with a number of newly published studies increasing every year. Here we present a scoping review of existing fMRI studies of serotonergic psychedelics to date, with a focus on finding unifying themes among them, in order to comprehensively grasp current directions within this field. We cluster the existing studies by fMRI modality and find several lines of developing concepts complementing the established models of psychedelic actions on the brain: namely, we describe a general picture of de-differentiation with the default mode network at its core captured by a diverse array of different techniques, complex changes to the thalamus, amygdala and medial temporal lobe structures, and the importance of the phenomenon of ego dissolution. Finally, contrasts to phenomenologically similar states and the successful process of anchoring fMRI findings to other markers are discussed.

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