Default Mode Network Modulation by Psychedelics: A Systematic Review

This review (2022) covers the effects of psychedelics on the Default Mode Network (DMN). There is an acute disruption within the DMN and increased functional connectivity between resting-state networks. Though changes in the DMN correlate with well-being outcomes, it’s still too early to say what causal role the DMN has in this.


“Psychedelics are a unique class of drug which commonly produce vivid hallucinations as well as profound psychological and mystical experiences. A grouping of interconnected brain regions characterised by increased temporal coherence at rest have been termed the ‘Default Mode Network’ (DMN). The DMN has been the focus of numerous studies assessing its role in self-referencing, mind wandering and autobiographical memories. Altered connectivity in the DMN has been associated with a range of neuropsychiatric conditions such as depression, anxiety, post-traumatic stress disorder (PTSD), attention deficit hyperactive disorder (ADHD), schizophrenia and obsessive-compulsive disorder (OCD). To date, a number of studies have investigated how psychedelics modulate this network, but no comprehensive review has critically evaluated how major classical psychedelic agents – Lysergic Acid Diethylamide (LSD), psilocybin, and ayahuasca – modulate the DMN. Here we present a systematic review of the knowledge base. Across psychedelics there is consistent acute disruption in resting state connectivity within the DMN and increased functional connectivity between canonical resting-state networks. Various models have been proposed to explain the cognitive mechanisms of psychedelics and in one model DMN modulation is a central axiom. Although the DMN is consistently implicated in psychedelic studies, it is unclear how central the DMN is to the therapeutic potential of classical psychedelic agents. This article aims to provide the field with a comprehensive overview that can propel future research forward in such a way that the neurocognitive mechanisms of psychedelics can be further elucidated.”

Authors: James J. Gattuso, Daniel Perkins, Simon Ruffell, Andrew J. Lawrence, Daniel Hoyer, Laura H. Jacobson, Christopher Timmermann, David Castle, Susan L. Rossell, Luke A. Downey, Broc A. Pagni, Nicole L. Galvão-Coelho, David J. Nutt & Jerome Sarris

Summary of Default Mode Network Modulation by Psychedelics


Psychedelics are a class of hallucinogenic agents that affect the sense of self, sensory perception, and emotions. They are suggested to illuminate hidden terrains of the human psyche. Neuroimaging studies have shown that the Default Mode Network (DMN) is activated above baseline when an individual is at rest and that this activity is anti-correlated and orthogonal to task-dependent brain networks such as the Salience Network (SLN).

Altered FC within the DMN has been correlated with various psychometric components and clinical questionnaires, which may have downstream therapeutic effects. Altered FC within the DMN has also been implicated in neuropsychiatric and neurodegenerative conditions.

Study details

Topics studied

Study characteristics
Literature Review


Authors associated with this publication with profiles on Blossom

David Nutt
David John Nutt is a great advocate for looking at drugs and their harm objectively and scientifically. This got him dismissed as ACMD (Advisory Council on the Misuse of Drugs) chairman.

Chris Timmermann
Chris Timmerman is a postdoc at Imperial College London. His research is mostly focussed on DMT.

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