Psychedelics in neuroinflammation: Mechanisms and therapeutic potential

Authors

Junia Lara de Deus, Department of Anesthesiology and Critical Care Medicine, George Washington University, Washington, DC, USA; Department of Oral and Basic Biology Ribeirão Preto, Dental School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Juliana Marino Maia, Department of Medicine, Federal University of Juiz de Fora, Governador Valadares,MG, Brazil.
Renato Nery Soriano, Division of Physiology and Biophysics, Department of Basic Life Sciences, Federal University of Juiz de Fora, Governador Valadares, MG, Brazil.
Mateus R. Amorim, Department of Anesthesiology and Critical Care Medicine, George Washington University, Washington, DC, USA; Program of Physiology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Luiz G. Branco, Department of Oral and Basic Biology Ribeirão Preto, Dental School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil; Program of Physiology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: branco@forp.usp.br.

Document Type

Journal Article

Publication Date

1-30-2025

Journal

Progress in neuro-psychopharmacology & biological psychiatry

DOI

10.1016/j.pnpbp.2025.111278

Keywords

Astrocytes; Macrophages; Microglia; Neurodegenerative diseases; Serotonin system

Abstract

Neuroinflammation is a critical factor in the pathogenesis of various neurodegenerative and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, and major depressive disorder. Psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), and dimethyltryptamine (DMT), have demonstrated promising therapeutic effects on neuroinflammation, primarily through interactions with serotonin (5-HT) receptors, particularly the 5-HT2A receptor. Activation of these receptors by psychedelics modulates the production of pro-inflammatory cytokines, regulates microglial activity, and shifts the balance between neurotoxic and neuroprotective metabolites. Additionally, psychedelics affect critical signaling pathways, including the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), and mechanistic target of rapamycin (mTOR) pathways, promoting neuroplasticity and exerting anti-inflammatory effects. Beyond the serotonergic system, other neurotransmitter systems-including the glutamatergic, dopaminergic, noradrenergic, gamma-aminobutyric acid (GABAergic), and cholinergic systems-also play significant roles in mediating the effects of psychedelics. This review examines the intricate mechanisms by which psychedelics modulate neuroinflammation and underscores their potential as innovative therapeutic agents for treating neuroinflammatory and neuropsychiatric disorders.

APA Citation

de Deus, Junia Lara; Maia, Juliana Marino; Soriano, Renato Nery; Amorim, Mateus R.; and Branco, Luiz G., "Psychedelics in neuroinflammation: Mechanisms and therapeutic potential" (2025). GW Authored Works. Paper 6299.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/6299

Department

Anesthesiology and Critical Care Medicine