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Neurometabolic Effects of Psilocybin, 3,4-Methylenedioxyethylamphetamine (MDE) and d-Methamphetamine in Healthy Volunteers A Double-Blind, Placebo-Controlled PET Study with [18F]FDG
Abstract
The neurometabolic effects of the hallucinogen psilocybin (PSI; 0.2 mg/kg), the entactogen 3,4-methylenedioxyethylamphetamine (MDE; 2 mg/kg) and the stimulant d-methamphetamine (METH; 0.2-0.4 mg/kg) and the drugs' interactions with a prefrontal activation task were investigated in a double-blind, placebo-controlled human [F-18]fluorodeoxyglucoseFDG-positron emission tomographicPET study (each group: n = 8). Subjects underwent two scans (control: word repetition; activation word association) within 2-4 weeks. Psilocybin increased rMRGlu in distinct right hemispheric frontotemporal cortical regions, particularly in the anterior cingulate and decreased rMRGlu in the thalamus. Both MDE and METH induced cortical hypometabolism and cerebellar hypermetabolism. In the MDE group, cortical hypometabolism was more pronounced in frontal regions, with the exception of the right anterior cingulate, which tended to be hyperactive. Cognitive activation-related increases in left frontocortical regions were attenuated under all three psychoactive substances, but less so under MDE. Taking into account performance data and subjective reports on task difficulty, these effects may result from different mechanisms across the three groups. Our PSI data are in line with studies on acute schizophrenic patients suggesting frontal overactivity at rest, but diminished capacity to activate prefrontal regions upon cognitive demand. The MDE data support the hypothesis that entactogens constitute a distinct psychoactive substance class, which takes an intermediate position between stimulants and hallucinogens.
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“Next-generation, psychoplastogenic antidepressants also modulate PFC function with both ketamine and psychedelics increasing PFC activation as measured by 18F-FDG PET imaging (113–116).”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [116]
In the citing paper
“Relative to a control group, the treatment provoked 5–10% increases in CMRglc in frontal operculum, anterior cingulate cortex, and inferior temporal cortex, along with 5–10% decreases in the precentral cortex and thalamus in a study by Gouzoulis-Mayfrank et al. [138].”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [138]
In the citing paper
“Whereas Vollenweider et al. [137] reported symmetrical changes in CMRglc, Gouzoulis-Mayfrank et al. [138] saw greater effects in the right hemisphere.”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [138]
In the citing paper
“There was relatively little overlap between the patterns of altered CMRglc in subjects receiving psilocybin (2) versus the non-hallucinogenic indirect serotonin/dopamine agonist methylendioxymetamphetamine (MDMA).”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [138]
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Phenylketonuria with mental retardation and valproate-induced hyperammonemia
Sterpu, D. (2020) · Romanian Journal of Psychiatry & Psychotherapy · doi:10.37897/rjpp.2020.4.5
Lyon, A. (2023) · Oxford University Press eBooks · doi:10.1093/oso/9780198843757.003.0010
Lyon, A. (2023) · Oxford University Press eBooks · doi:10.1093/oso/9780198843757.003.0011
Metadata
- Authors
- Gouzoulis-Mayfrank, E.
- Venue
- Neuropsychopharmacology
- Published
- 1999-06
- Volume
- 20
- Issue
- 6
- Pages
- 565-581
- ISSN
- 0893-133X (ISSN-L)
- OpenAlex
- W2102963347
- Cited by
- 219
- References
- 87
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 10 · 2023: 32 · 2022: 11 · 2021: 16 · 2020: 9 · 2019: 2 · 2018: 11 · 2017: 7 · 2016: 13 · 2015: 5 · 2014: 8 · 2013: 3 · 2012: 5
- FWCI
- 7.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Eberhard Karls Universität Tübingen
- RWTH Aachen University
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- psilocybin, MDMA, hallucinogens, entactogens, stimulants, brain glucose metabolism, 18F-FDG PET, prefrontal cortex, anterior cingulate cortex, thalamus, cerebellar hypermetabolism, cognitive activation, word association task, healthy volunteers
- MeSH terms
- Adult, Cerebellum, Cognition, Double-Blind Method, Female, Glucose, Hallucinogens, Humans, Magnetic Resonance Imaging, Male, Methamphetamine, Middle Aged, Psilocybin, Psychopathology, Radionuclide Imaging, 3,4-Methylenedioxyamphetamine, Adrenergic Agents, Nootropic Agents
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