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

N.L. Mason*, K.P.C. Kuypers, F. Müller, J. Reckweg, D.H.Y. Tse, S.W. Toennes, N.R.P.W. Hutten, J.F.A. Jansen, P. Stiers, A. Feilding, J.G. Ramaekers

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

46 Citations (Web of Science)

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.

Original languageEnglish
Pages (from-to)2003-2011
Number of pages9
JournalNeuropsychopharmacology
Volume45
Issue number12
Early online date23 May 2020
DOIs
Publication statusPublished - Nov 2020

Keywords

  • POSITRON-EMISSION-TOMOGRAPHY
  • MYSTICAL-TYPE EXPERIENCES
  • V PYRAMIDAL CELLS
  • PREFRONTAL CORTEX
  • 5-HT2A RECEPTORS
  • DEFAULT-MODE
  • IN-VIVO
  • METABOLIC HYPERFRONTALITY
  • HEALTHY HUMANS
  • SEROTONIN

Cite this