Psychedelic N,N-Dimethyltryptamine and 5-Methoxy-N,N-Dimethyltryptamine Modulate Innate and Adaptive Inflammatory Responses through the Sigma-1 Receptor of Human Monocyte-Derived Dendritic Cells
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The orphan receptor sigma-1 (sigmar-1) is a transmembrane chaperone protein expressed in both the central nervous system and in immune cells. It has been shown to regulate neuronal differentiation and cell survival, and mediates anti-inflammatory responses and immunosuppression in murine in vivo models. Since the details of these findings have not been elucidated so far, we studied the effects of the endogenous sigmar-1 ligands N,N-dimethyltryptamine (NN-DMT), its derivative 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and the synthetic high affinity sigmar-1 agonist PRE-084 hydrochloride on human primary monocyte-derived dendritic cell (moDCs) activation provoked by LPS, polyI:C or pathogen-derived stimuli to induce inflammatory responses. Co-treatment of moDC with these activators and sigma-1 receptor ligands inhibited the production of pro-inflammatory cytokines IL-1β, IL-6, TNFα and the chemokine IL-8, while increased the secretion of the anti-inflammatory cytokine IL-10. The T-cell activating capacity of moDCs was also inhibited, and dimethyltryptamines used in combination with E. coli or influenza virus as stimulators decreased the differentiation of moDC-induced Th1 and Th17 inflammatory effector T-cells in a sigmar-1 specific manner as confirmed by gene silencing. Here we demonstrate for the first time the immunomodulatory potential of NN-DMT and 5-MeO-DMT on human moDC functions via sigmar-1 that could be harnessed for the pharmacological treatment of autoimmune diseases and chronic inflammatory conditions of the CNS or peripheral tissues. Our findings also point out a new biological role for dimethyltryptamines, which may act as systemic endogenous regulators of inflammation and immune homeostasis through the sigma-1 receptor.
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DMT and 5-MeO-DMT exert potent anti-inflammatory effects through the modulation of innate and adaptive immune processes.
“DMT and 5-MeO-DMT have also been shown to exert potent anti-inflammatory effects through the modulation of innate and adaptive immune processes (Szabo 2015; Szabo et al. 2014).”
From Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment (2020) · cites this paper as Szabo et al. 2014
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- Authors
- Szabo, A., Kovacs, A., Frecska, E., & Rajnavolgyi, E.
- Affiliations
- University of Debrecen (HU)
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-08-29
- Volume
- 9
- Issue
- 8
- Pages
- e106533
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4149582
- OpenAlex
- W2085670677
- Cited by
- 191
- References
- 49
- Citations by year
- 2026: 22 · 2025: 30 · 2024: 24 · 2023: 18 · 2022: 19 · 2021: 23 · 2020: 12 · 2019: 13 · 2018: 13 · 2017: 6 · 2016: 6 · 2015: 3 · 2014: 1
- FWCI
- 2.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion, other-oa)
- Funders
- European Commission (-2012-0001, A/2-11-1-2012-0001, 4.2.4.A/2-11-1-2012-0001)
- Hungarian Scientific Research Fund (A/2-11-1-2012-0001, -2012-0001)
- European Social Fund (A/2–11/1-2012-0001, -2012-0001)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- sigma-1 receptor, N,N-dimethyltryptamine, 5-MeO-DMT, PRE-084, monocyte-derived dendritic cells, immunomodulation, inflammatory cytokines, IL-10, dendritic cell activation, endogenous ligands, autoimmune disease, chronic inflammation
- MeSH terms
- Sigma-1 Receptor, Animals, Cells, Cultured, Dendritic Cells, N,N-Dimethyltryptamine, Gene Expression Regulation, Hallucinogens, Humans, Immunity, Innate, Lipopolysaccharides, Methoxydimethyltryptamines, Monocytes, Morpholines, Receptors, sigma, Mice, Adaptive Immunity
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