Large-scale brain connectivity changes following the administration of lysergic acid diethylamide, d-amphetamine, and 3,4-methylenedioxyamphetamine.

Autor: Avram M; Translational Psychiatry, Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany. mihai.avram@uksh.de.; Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany. mihai.avram@uksh.de., Fortea L; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.; Department of Medicine, University of Barcelona, Institute of Neuroscience, Barcelona, Spain., Wollner L; Translational Psychiatry, Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany., Coenen R; Translational Psychiatry, Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany., Korda A; Translational Psychiatry, Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany.; Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany., Rogg H; Translational Psychiatry, Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany., Holze F; Division of Clinical Pharmacology and Toxicology, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland., Vizeli P; Division of Clinical Pharmacology and Toxicology, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland., Ley L; Division of Clinical Pharmacology and Toxicology, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland., Radua J; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.; Department of Medicine, University of Barcelona, Institute of Neuroscience, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain., Müller F; Department of Psychiatry (UPK), University of Basel, Basel, Switzerland., Liechti ME; Division of Clinical Pharmacology and Toxicology, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland., Borgwardt S; Translational Psychiatry, Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany.; Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2024 Sep 11. Date of Electronic Publication: 2024 Sep 11.
DOI: 10.1038/s41380-024-02734-y
Abstrakt: Psychedelics have recently attracted significant attention for their potential to mitigate symptoms associated with various psychiatric disorders. However, the precise neurobiological mechanisms responsible for these effects remain incompletely understood. A valuable approach to gaining insights into the specific mechanisms of action involves comparing psychedelics with substances that have partially overlapping neurophysiological effects, i.e., modulating the same neurotransmitter systems. Imaging data were obtained from the clinical trial NCT03019822, which explored the acute effects of lysergic acid diethylamide (LSD), d-amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) in 28 healthy volunteers. The clinical trial employed a double-blind, placebo-controlled, crossover design. Herein, various resting-state connectivity measures were examined, including within-network connectivity (integrity), between-network connectivity (segregation), seed-based connectivity of resting-state networks, and global connectivity. Differences between placebo and the active conditions were assessed using repeated-measures ANOVA, followed by post-hoc pairwise t-tests. Changes in voxel-wise seed-based connectivity were correlated with serotonin 2 A receptor density maps. Compared to placebo, all substances reduced integrity in several networks, indicating both common and unique effects. While LSD uniquely reduced integrity in the default-mode network (DMN), the amphetamines, in contrast to our expectations, reduced integrity in more networks than LSD. However, LSD exhibited more pronounced segregation effects, characterized solely by decreases, in contrast to the amphetamines, which also induced increases. Across all substances, seed-based connectivity mostly increased between networks, with LSD demonstrating more pronounced effects than both amphetamines. Finally, while all substances decreased global connectivity in visual areas, compared to placebo, LSD specifically increased global connectivity in the basal ganglia and thalamus. These findings advance our understanding of the distinctive neurobiological effects of psychedelics, prompting further exploration of their therapeutic potential.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: