Psychedelics in neuroinflammation: Mechanisms and therapeutic potential
Júnia L. de Deus, Juliana Marino Maia, Renato Nery Soriano, Mateus R. Amorim, Luiz G.s. Branco
Progress in Neuro-psychopharmacology and Biological Psychiatry January 31, 2025 DOI: 10.1016/j.pnpbp.2025.111278 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Keywords | Neuroinflammation |
| Citations | 27 |
| Key findings | Psychedelics modulate neuroinflammation through serotonin 5-HT2A receptor activation and other pathways, suggesting therapeutic potential for neurodegenerative and psychiatric disorders. |
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.