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Cited by 258Psychedelics and Drug StudiesNeurotransmitter Receptor Influence on BehaviorParanormal Experiences and Beliefs

Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin

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Mason, N. L., Kuypers, K. P. C., Müller, F., Reckweg, J., Tse, D. H. Y., Toennes, S. W., Hutten, N. R. P. W., Jansen, J. F. A. +3 more·2020·Neuropsychopharmacology
DOI 10.1038/s41386-020-0718-8PMC PMC7547711
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Abstract

There is growing interest in the therapeutic utility of psychedelic substances, like psilocybin, for disorders characterized by distortions of the self-experience, like depression. Accumulating preclinical evidence emphasizes the role of the glutamate system in the acute action of the drug on brain and behavior; however this has never been tested in humans. Following a double-blind, placebo-controlled, parallel group design, we utilized an ultra-high field multimodal brain imaging approach and demonstrated that psilocybin (0.17 mg/kg) induced region-dependent alterations in glutamate, which predicted distortions in the subjective experience of one’s self (ego dissolution). Whereas higher levels of medial prefrontal cortical glutamate were associated with negatively experienced ego dissolution, lower levels in hippocampal glutamate were associated with positively experienced ego dissolution. Such findings provide further insights into the underlying neurobiological mechanisms of the psychedelic, as well as the baseline, state. Importantly, they may also provide a neurochemical basis for therapeutic effects as witnessed in ongoing clinical trials.

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  • In ego dissolution states, individuals may more readily engage with their cognitive beliefs and emotional states with enhanced detachment and decentration, potentially leading to therapeutic outcomes.

    “Consequently, in this state, individuals may more readily engage with their cognitive beliefs and emotional states with enhanced detachment and decentration, potentially leading to therapeutic outcomes [42, 43].”

    From Mindfulness meditation and psychedelics: potential synergies and commonalities (2023) · cites this paper as [42]

    The Discussion reports that the degree of ego dissolution has been found to correlate with long-term clinical outcomes and increased well-being. It does not say that ego dissolution helps individuals engage with beliefs or emotions through detachment or decentration, so the proposed pathway to therapeutic outcomes is unsupported. (LLM, conf=0.85)

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  • The potential of classic psychedelics to alter glutamate in the human cortex, albeit in a region-dependent manner, has been demonstrated.

    “The potential of classic psychedelics to alter glutamate in the human cortex, albeit in a region-dependent manner, has been demonstrated (92).”

    From Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics. (2021) · cites this paper as [92]

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Authors
Mason, N. L., Kuypers, K. P. C., Müller, F., Reckweg, J., Tse, D. H. Y., Toennes, S. W., Hutten, N. R. P. W., Jansen, J. F. A., Stiers, P., Feilding, A., & Ramaekers, J. G.
Affiliations
  • Maastricht University (NL)
  • University of Basel (CH)
  • Goethe University Frankfurt (DE)
  • Maastricht University Medical Centre (NL)
  • Beckley Foundation (GB)
Corresponding author
  • Mason, N. L.
  • Ramaekers, J. G.
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2020-05-23
Volume
45
Issue
12
Pages
2003-2011
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/s41386-020-0718-8
PMC
PMC7547711
OpenAlex
W3027590463
Cited by
258
References
102
Citations by year
2026: 36 · 2025: 41 · 2024: 40 · 2023: 62 · 2022: 42 · 2021: 32 · 2020: 5
FWCI
14.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuropsychopharmacology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (submittedVersion, cc-by)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
Funders
Beckley Foundation
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Social Sciences › Psychology › Social Psychology › Paranormal Experiences and Beliefs
Keywords
psilocybin, glutamate, ego dissolution, self-experience, medial prefrontal cortex, hippocampus, subjective experience, psychedelics, depression, ultra-high field MRI
MeSH terms
Ego, Hallucinogens, Humans, Psilocybin, Solubility, Glutamic Acid

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