Default Mode Network Modulation by Psychedelics: A Systematic Review
This systematic review shows that classical psychedelics (LSD, psilocybin, ayahuasca) consistently cause acute disruption of resting-state connectivity within the Default Mode Network and increase cross-network functional connectivity, but it remains unclear how central DMN modulation is to their therapeutic effects. The article synthesises existing evidence and highlights gaps to guide future mechanistic research.
Authors
- David Nutt
- Christopher Timmermann
- Nathalia Galvão-Coelho
Published
Abstract
Psychedelics are a unique class of drug that commonly produce vivid hallucinations as well as profound psychological and mystical experiences. A grouping of interconnected brain regions characterized 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, attention deficit hyperactive disorder, schizophrenia, and obsessive-compulsive disorder. To date, several studies have investigated how psychedelics modulate this network, but no comprehensive review, to our knowledge, has critically evaluated how major classical psychedelic agents—lysergic acid diethylamide, 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 in such a way as to elucidate the neurocognitive mechanisms of psychedelics.
Research Summary of 'Default Mode Network Modulation by Psychedelics: A Systematic Review'
Introduction
Gattuso and colleagues set out the background that classical psychedelics (notably LSD, psilocybin and ayahuasca/DMT-containing preparations) act primarily at serotonin 5-HT2A receptors and produce profound alterations of consciousness, including changes in self-experience. They describe the Default Mode Network (DMN) — a set of midline and lateral brain regions including the medial prefrontal cortex, posterior cingulate cortex/precuneus and angular gyrus — as a canonical resting-state network implicated in self-referencing, mind-wandering and several neuropsychiatric disorders. Previous neuroimaging work has linked altered DMN functional connectivity (FC) to clinical conditions such as depression, anxiety, PTSD, ADHD and Alzheimer’s disease, and individual measures such as ego dissolution and mystical-type experiences have been correlated with changes in DMN measures during psychedelic states. The review aims to fill a gap in the literature by systematically evaluating human clinical studies that assess how classical psychedelics modulate the DMN, and whether DMN changes relate to therapeutic effects. Specifically, the authors sought to: critically evaluate effects of classical psychedelics on the DMN; assess evidence linking DMN modulation to psychotherapeutic outcomes; identify limitations in the current literature; and outline directions for DMN-focused psychedelic research and potential clinical applications. The review focused on LSD, psilocybin, DMT, mescaline and ayahuasca and searched the literature through April 2022.
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Gattuso, J. J., Perkins, D., Ruffell, S., Lawrence, A. J., Hoyer, D., Jacobson, L. H., Timmermann, C., Castle, D., Rossell, S. L., Downey, L. A., Pagni, B. A., Galvão-Coelho, N. L., Nutt, D., & Sarris, J. (2023). Default Mode Network Modulation by Psychedelics: A Systematic Review. International Journal of Neuropsychopharmacology, 26(3), 155-188. https://doi.org/10.1093/ijnp/pyac074
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