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
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology November 1, 2020 DOI: 10.1038/s41386-020-0718-8 via PubMed
Summary
AI-generated from the abstractA double-blind, placebo-controlled study using ultra-high field brain imaging found that psilocybin (0.17 mg/kg) caused region-dependent changes in glutamate levels in the human brain. Higher medial prefrontal cortical glutamate was linked to negatively experienced ego dissolution, while lower hippocampal glutamate was linked to positively experienced ego dissolution. These results suggest a neurochemical basis for the therapeutic effects of psychedelics on disorders involving distortions of self-experience, such as depression.
Study at a glance
| Characteristics | Double-blind, placebo-controlled, parallel group design Peer reviewed |
|---|---|
| Population | Human participants |
| Intervention | Psilocybin |
| Dose | 0.17 mg/kg |
| Citations | 261 |
| Key finding | Psilocybin induced region-dependent alterations in glutamate that predicted the valence of ego dissolution experiences. |
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.