PloS one
January 1, 2014
Attila Szabo, Attila Kovacs, Ede Frecska et al.
191 citations
The sigma-1 receptor, a protein found in the central nervous system and immune cells, can be activated by the psychedelic compounds N,N-dimethyltryptamine (NN-DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) to dampen inflammatory responses in human immune cells. When human dendritic cells were exposed to inflammatory triggers along with these compounds, production of pro-inflammatory cytokines IL-1β, IL-6, TNFα, and chemokine IL-8 decreased, while the anti-inflammatory cytokine IL-10 increased. The compounds also reduced the cells' ability to activate inflammatory T-cells. This suggests dimethyltryptamines may act as endogenous regulators of inflammation and immune balance, pointing toward potential treatments for autoimmune and chronic inflammatory conditions.
Frontiers in Immunology
July 14, 2015
Attila Szabo
153 citations
Classical psychedelics, including DMT, 5-MeO-DMT, LSD, and others, modulate immune responses by altering signaling pathways involved in inflammation, cellular proliferation, and survival. These substances activate NF-κB and mitogen-activated protein kinases, and their effects are mediated through serotonin and sigma-1 receptors, which also play roles in immunological processes. The review discusses the immunomodulatory potential of these compounds from a molecular immunology and pharmacology perspective, focusing on the interaction between serotonin and sigma-1 receptors and their cross-talk with pattern-recognition receptor signaling. It suggests novel approaches for treating chronic inflammatory diseases such as atherosclerosis, rheumatoid arthritis, multiple sclerosis, schizophrenia, depression, and Alzheimer's disease, aiming to reframe psychedelics as potential therapeutic agents rather than solely as drugs of abuse.
Neural Regeneration Research
January 1, 2016
Attila Szabo, Ede Frecska
42 citations
Inflammation in the brain, driven by microglia and pattern recognition receptors like Toll-like receptors, is linked to neuropsychiatric illnesses such as schizophrenia, depression, and Alzheimer's disease. The orphan receptor sigma-1 (Sig-1R) and serotonin receptors (5-HTRs), both G protein-coupled receptors, modulate immune responses by controlling NF-κB and MAPK pathways, influencing cytokine release. The endogenous tryptamine N,N-dimethyltryptamine (DMT) acts on both Sig-1R and 5-HTRs, suppressing inflammation by blocking cytokine release from dendritic cells and inhibiting Th1 and Th17 T cell activation. DMT's regulation of NF-κB and MAPKs via G proteins suggests potential as a therapeutic for chronic inflammatory and autoimmune diseases, though its hallucinogenic properties remain a challenge. Selective Sig-1R agonists promote neuroprotection and regeneration.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
November 1, 2023
Michael James Winkelman, Attila Szabo, Ede Frecska
26 citations
Serotonergic psychedelics show potential for treating Alzheimer's disease by promoting neuroplasticity and counteracting brain atrophy. Classic psychedelics modulate glutamatergic neurotransmission, stimulate synaptic and network remodeling, and up-regulate neurotrophic factors that support neuronal survival. Muscimol reduces Aβ-induced neurotoxicity, and Sigma-1 receptor agonists protect against Aβ toxicity. Psychedelics activate mTOR pathways in brain regions that atrophy in Alzheimer's, induce structural and functional neural plasticity, increase neurogenesis, and rewire pathological neurocircuitry. These effects enhance brain functional connectivity and address multiple degenerative mechanisms, warranting immediate investigation of psychedelics as treatments for Alzheimer's patients.
Comprehensive psychoneuroendocrinology
February 1, 2023
Daniel Rødbro Burmester, Martin Korsbak Madsen, Attila Szabo et al.
24 citations
A single dose of psilocybin did not significantly change peripheral biomarkers of inflammation—high-sensitivity C-reactive protein (hsCRP), tumor-necrosis-factor (TNF), and soluble urokinase plasminogen activator receptor (suPAR)—in 16 healthy individuals one day after administration. All effect sizes were small (Cohen's d ≤ 0.31) and p-values were ≥ 0.23. These findings do not support that a single dose of psilocybin reduces inflammation in healthy people, though future studies should examine additional markers and clinical populations where effects may be more detectable.
International review of neurobiology
January 1, 2025
Ede Frecska, Attila Kovács, Attila Szabo
2 citations
DMT, an endogenous agonist of the sigma-1 receptor (Sig-1R) in addition to its serotonin receptor actions, shows therapeutic potential for neuroprotection against ischemia-reperfusion injury (IRI) and neurodegenerative disorders. Sigma-1 receptors are highly expressed in the brain and spinal cord and are implicated in central nervous system disorders. Previous theoretical and experimental work suggests targeting sigma and serotonin receptors via DMT may treat conditions like stroke, global brain ischemia, Alzheimer's disease, and amyotrophic lateral sclerosis. The paper reviews Sig-1R's role in cellular bioenergetics related to IRI and summarizes preclinical DMT studies that mitigated IRI and related neuropathologies. DMT's effect may involve universal cellular protective mechanisms, positioning it as a model molecule for developing treatments for neurodegenerative disorders.
Journal of Psychedelic Studies
September 8, 2025
Malin Vedøy Uthaug, Giancarlo Allocca, Martha Havenith et al.
1 citation
The paper introduces the concept of 'bodyset'—the state of the body, including both body and brain—as a vital element in preparing for psychedelic experiences, expanding the traditional 'set and setting' framework. Through a literature review, it argues that the body likely matters for wellbeing, peak performance, and peak experiences. Comprehensive multidisciplinary research, especially on biomarkers, is needed to clarify the role of bodyset in psychedelic experiences and therapy outcomes. The authors suggest that considering physical state alongside psychological and environmental factors may enhance understanding of psychedelic effects and inform other treatments like breathwork.
bioRxiv (Cold Spring Harbor Laboratory)
April 12, 2026
Ibrahim A. Akkouh, Jordi Requena Osete, N. W. Steen et al.
Activating GABA-A receptors with muscimol, a non-classic psychedelic, suppresses inflammatory signaling and promotes neuroplasticity in human cortical spheroids and astrocytes derived from patients with schizophrenia. Inflammatory stimulation triggered interferon-responsive gene programs, with astrocytes acting as key mediators. Muscimol reduced proinflammatory cytokine secretion, attenuated interferon signaling, and upregulated neuroplasticity-related genes such as NTRK2 and ELK1. It also restored impaired glutamate uptake in schizophrenia-derived astrocytes. These effects depended on GABA-A receptor activation. Proteomic analyses of spheroids and human brain tissue confirmed baseline dysregulation of GABAergic and neurotrophin signaling in schizophrenia, supporting the therapeutic potential of targeting astrocyte GABAergic signaling to restore neural homeostasis.
Journal of behavioral addictions
February 3, 2026
Atanas Tannous, Zsolt Demetrovics, Bhavya Chhabra et al.
Mindfulness-based interventions (MBIs) consistently reduce gambling frequency and cravings while improving psychological outcomes. When combined with cognitive behavioral therapy, MBIs produce significant declines in problem gambling behavior. Psychological distress and cravings also decrease notably across different intervention types. However, it remains unclear how much of these effects come from mindfulness-specific mechanisms. The evidence comes from 12 studies, including five randomized controlled trials, but small sample sizes and methodological limitations mean more robust research is needed.