Cited by 109Pharmacological Receptor Mechanisms and EffectsPsychedelics and Drug StudiesTryptophan and brain disorders

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A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity.

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Frecska, Ede, Szabo, Attila, Winkelman, Michael J., Luna, Luis E., McKenna, Dennis J.·2013·Journal of Neural Transmission

DOI 10.1007/s00702-013-1024-y

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Abstract

N,N-dimethyltryptamine (DMT) is classified as a naturally occurring serotonergic hallucinogen of plant origin. It has also been found in animal tissues and regarded as an endogenous trace amine transmitter. The vast majority of research on DMT has targeted its psychotropic/psychedelic properties with less focus on its effects beyond the nervous system. The recent discovery that DMT is an endogenous ligand of the sigma-1 receptor may shed light on yet undiscovered physiological mechanisms of DMT activity and reveal some of its putative biological functions. A three-step active uptake process of DMT from peripheral sources to neurons underscores a presumed physiological significance of this endogenous hallucinogen. In this paper, we overview the literature on the effects of sigma-1 receptor ligands on cellular bioenergetics, the role of serotonin, and serotoninergic analogues in immunoregulation and the data regarding gene expression of the DMT synthesizing enzyme indolethylamine-N-methyltransferase in carcinogenesis. We conclude that the function of DMT may extend central nervous activity and involve a more universal role in cellular protective mechanisms. Suggestions are offered for future directions of indole alkaloid research in the general medical field. We provide converging evidence that while DMT is a substance which produces powerful psychedelic experiences, it is better understood not as a hallucinogenic drug of abuse, but rather an agent of significant adaptive mechanisms that can also serve as a promising tool in the development of future medical therapies.

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The Structure of Scientific Revolutions
Kuhn, T. S., & Schlegel, R. (1963) · Physics Today · doi:10.1063/1.3050879 · Cited by 35,538
The Structure of Scientific Revolutions.
Böhm, D., & Kühn, T. (1964) · The Philosophical Quarterly · doi:10.2307/2217783 · Cited by 9,193
Control of inositol 1,4,5-trisphosphate-induced Ca2+ release by cytosolic Ca2+
Bootman, M. D., Missiaen, L., Parys, J. B., SMEDT, H. D., & Casteels, R. (1995) · Biochemical Journal · doi:10.1042/bj3060445 · Cited by 5,131
Sigma-1 Receptor Chaperones at the ER- Mitochondrion Interface Regulate Ca2+ Signaling and Cell Survival
Hayashi, T., & Su, T.-P. (2007) · Cell · doi:10.1016/j.cell.2007.08.036 · Cited by 1,826
Neuropsychopharmacology
Bunney, W. E., Hippius, H., Laakmann, G., & Schmauß, M. (1990) · Springer eBooks · doi:10.1007/978-3-642-74034-3 · Cited by 1,523
Hallucinogens
Nichols, D. E. (2004) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2003.11.002 · Cited by 1,211
Immunomodulatory functions of type I interferons
González-Navajas, J. M., Lee, J., David, M., & Raz, E. (2012) · Nature reviews. Immunology · doi:10.1038/nri3133 · Cited by 1,030
A proposal for the classification of sigma binding sites
Quirion, R., Bowen, W. D., Itzhak, Y., Junien, J., Musacchio, J. M., Rothman, R. B., Su, T., Tam, S. W., & Taylor, D. P. (1992) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(92)90030-a · Cited by 754
The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator
Fontanilla, D., Johannessen, M., Hajipour, A. R., Cozzi, N. V., Jackson, M. B., & Ruoho, A. E. (2009) · Science · doi:10.1126/science.1166127 · Cited by 535
Serotonin and Lysergic Acid Diethylamide Binding in Rat Brain Membranes: Relationship to Postsynaptic Serotonin Receptors
Bennett, J. P., & Snyder, S. H. (1976) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)10753-0 · Cited by 509

Show all 95 references

Research works printed but not linked: 3

Beaton JM, Christian ST (1977) Stress induced changes in whole brain indolealkylamine levels in the rat: using gas liquid chromatography-mass spectrometry. Abstr Soc Neurosci 4:1322
Cozzi NV, Mavlyutov TA, Thompson MA, Ruoho AE (2011) Indolethylamine-N-methyltransferase expression in primate nervous tissue. Abstr Soc Neurosci 37:840.19
Luna LE (2011) Indigenous and mestizo use of ayahuasca: an overview. In: Dos Santos RG (ed) The ethnopharmacology of ayahuasca. Transworld Research Network, Kerala, pp 1–21

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Self-citation
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da Cruz, R. V. L., Leão, R. N., & Moulin, T. C. (2024) · Molecular Medicine · doi:10.1186/s10020-024-01013-4 · Cited by 19
“…(R.-J. Liu et al., 2013; Zhou & Song, 2001), neurogenesis (García-Cabrerizo & García-Fuster, 2016; Lima da Cruz, Moulin, Petiz, & Leão, 2018; F. Liu et al., 2017), and oxidative stress reduction (Frecska, Bokor, & Winkelman, 2016; Frecska, Szabo, Winkelman, Luna, & McKenna, 2013; Szabo, 2015).”
Immunological Effects of Ayahuasca in Humans
SANTOS, R. G. D. (2014) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2014.960113 · Cited by 18
Mind over matter: the microbial mindscapes of psychedelics and the gut-brain axis
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“…D1 and D2 [151], while DMT and 5-MeO-DMT, in addition to various serotonergic and dopaminergic receptor subtypes, also bind a number of ionotropic and metabotropic glutamate receptors, acetylcholine, Trace-Amine-Associated Receptors (TAAR), and the opioid-like receptor sigma-1 (Sig1R) [182,62,63].”
Three Naturally-Occurring Psychedelics and Their Significance in the Treatment of Mental Health Disorders
Vorobyeva, N. S., & Kozlova, A. A. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.927984 · Cited by 20
“Additionally, DMT can increase the levels of secreted interferon-β and interferon-γ in cultured human natural killer cells and that could be mediated by the sigma-1 receptor (Frecska et al., 2013).”
Background
Ayahuasca: what mental health professionals need to know
dos Santos, R. D., Bouso, J., & Hallak, J. (2017) · Archives of Clinical Psychiatry (São Paulo) · doi:10.1590/0101-60830000000130 · Cited by 12
Characterization of pulmonary sigma receptors by radioligand binding
Lever, J. R., Litton, T. P., & Fergason-Cantrell, E. A. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.05.026 · Cited by 16
“Interestingly, evidence points to the hallucinogen N,N-dimethyltryptamine as an endogenous sigma1 receptor agonist that is synthesized, in large measure, by the lung enzyme indolethylamine-N-methyltransferase (Fontanilla et al., 2009; Frecska et al., 2013; Chu et al., 2015).”
Background
Psychedelic Therapy: A Primer for Primary Care Clinicians—N,N-Dimethyltryptamine and Ayahuasca
Shinozuka, K., Tabaac, B. J., Arenas, A., Beutler, B. D., Cherian, K. N., Evans, V. D., Fasano, C., & Muir, O. S. (2024) · American Journal of Therapeutics · doi:10.1097/mjt.0000000000001725 · Cited by 15
“30,32,33 Proper measurement of endogenous DMT is difficult because of the small concentration of DMT in the human body, 23 DMT ’ s rapid breakdown by MAO, 34 and the traditional use of whole-brain homogenate samples in experiments that may dilute local peaks in DMT concentration.”
Background
Ayahuasca and Childhood Trauma: Potential Therapeutic Applications
Perkins, D., & Sarris, J. J. (2021) · Springer eBooks · doi:10.1007/978-3-030-55688-4_6 · Cited by 13
Cleistocalyx nervosum var. paniala seed extracts exhibit sigma-1 antagonist sensitive neuroprotective effects in PC12 cells and protects C. elegans from stress via the SKN-1/NRF-2 pathway
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Microdosing psychedelics as cognitive and emotional enhancers.
Rifkin, B. D., Maraver, M. J., & Colzato, L. S. (2020) · Psychology of Consciousness Theory Research and Practice · doi:10.1037/cns0000213 · Cited by 15
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The Therapeutic Potential of Ayahuasca
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Self-citation
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Neural Plasticity in the Ventral Tegmental Area, Aversive Motivation during Drug Withdrawal and Hallucinogenic Therapy
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“Recently, it has been observed that a key contribution of 5-HT2A agonists could be related to restore normal mitochondrial metabolism trough the action of the sigma-1 receptor (Sig-1 R) (Fontanilla et al. 2009; Frecska et al. 2013; Mavlyutov et al. 2017; Su, Hayashi, and Vaupel 2009).”
Background
Hypothetical biosynthetic pathways of pharmaceutically potential hallucinogenic metabolites in Myristicaceae, mechanistic convergence and co-evolutionary trends in plants and humans
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Detailed resume of S-methyltransferases: Categories, structures, biological functions and research advancements in related pathophysiology and pharmacotherapy
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Immunomodulatory and behavioral effects of ayahuasca and N, N-dimethyltryptamine in a rat model of lipopolysaccharide-induced depression
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“…hypoth - eses suggest that DMT may have additional molecular roles, including the potential involvement of trace amine-associated receptor and sigma-1 receptor (Frecska et al. 2013), which may contribute to its significant anti-inflammatory effects (Riba et al. 2012 ; Rodrigues and Carlini 2006).”
Trauma and Remembering: From Neuronal Circuits to Molecules
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“Sigma receptors, previously considered opioid receptors, are abundant cell surface proteins with multiple actions on neuronal and peripheral tissue functions [76].”
Background
The Psychedelic N , N -Dipropyltryptamine Prevents Seizures in a Mouse Model of Fragile X Syndrome via a Mechanism that Appears Independent of Serotonin and Sigma1 Receptors
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3,4-Methylenedioxy methamphetamine, synthetic cathinones and psychedelics: From recreational to novel psychotherapeutic drugs
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“29 Evidence also suggests prevention against ischaemia/reperfusion lesion in the eye and kidney cells.”
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Self-citation
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Unique biological and physiological properties of endogenous N, N-dimethyltryptamine from the perspective of functioning of the nervous system
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Self-citation
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Miller, C. W. T. (2024) · Psychodynamic Practice · doi:10.1080/14753634.2024.2371787 · Cited by 2
“In life-threatening and near-death states, the body may increase endogenous release of DMT, which has antioxidant properties and may be the body’s attempt to preserve brain function when facing extreme circumstances (Frecska et al., 2013).”
Functional and structural characterization of the human indolethylamine N-methyltransferase through fluorometric, thermal and computational docking analyses
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Rodriguez, V., Villani, A., Sénica, M., Panebianco, C., Pazienza, V., & Preto, A. (2026) · Cancers · doi:10.3390/cancers18030369 · Cited by 1
“…properties. β -carboline alkaloids, including compounds structurally related to THC, are naturally present in various medicinal plants traditionally used in Chinese, Ayurvedic, and South American medicine, including Peganum harmala , Passiflora species, and Banisteriopsis cappi [82–84].”
Plantas de poder: o uso da ayahuasca no Centro de Unificação Rosa Azul (CURA), Pará-Brasil
Mesquita, U. D. O., Lucas, F. C. A., Sarmento, P. S. D. M., & de Moraes, M. R. (2020) · REVER - Revista de Estudos da Religião · doi:10.23925/1677-1222.2020vol20i2a17 · Cited by 1
Pharmahuasca Reduces ROS Production and inflammatory Gene Expression in the Brain in a Model of PTSD: Exploration by RNA SequencingPreprint
Kelley, D. P., Venable, K. E., Billac, G. B., Destouni, A., Ebenezer, P. J., Stadler, K., Nichols, C. D., Barker, S. A., & Francis, J. (2021) · Research Square · doi:10.21203/rs.3.rs-602961/v1 · Cited by 1
Evaluation of Hippocampal Allostatic Load-Associated Factors in Animal Models of Post-Traumatic Stress Disorder: Relevance to Human PTSD
Kelley, D. P. (2022) · Louisiana State University · doi:10.31390/gradschool_dissertations.5761 · Cited by 1
Ação de metabólitos da via das triptaminas em linhagens de melanomas
Coimbra, J. B. (2015) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.9.2015.tde-26102015-093528
Ayahuasca: il vino dell'anima
Ossato, A., Canazza, I., & Marti, M. (2015) · Institutional Research Information System University of Ferrara (University of Ferrara)
Phenomenology and psychosomatics: a Jungian and post-Jungian approach
Szabó, A. (2016)
Determinação de pH ideal para aumento de produtividade no processo de biotransformação de esteróides
Cardoso, J. C. D. S., Leite, C. O., & Giovanni, D. N. S. (2020) · Brazilian Journal of Natural Sciences · doi:10.31415/bjns.v3i1.79
A Critical Appraisal on the Epidemiological Evidence Linking Perinatal Inflammation and Risk of Psychosis
Sanders, L. L. O., Gabler, F., & de Lucena, D. F. (2020) · Progress in inflammation research · doi:10.1007/978-3-030-39335-9_8
Avaliação das possíveis interações entre o canabidiol e a ayahuasca em voluntários saudáveis: um estudo randomizado, duplo-cego e controlado com placebo
Rossi, G. N. (2020) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.17.2020.tde-08022021-150020
O receptor aril de hidrocarbonetos (AhR) em melanomas: associação com mutações BRAF, com a progressão da doença e identificação de ligantes
de Sales, M. C. O. P. (2020) · doi:10.11606/t.9.2020.tde-01072021-144540

Authors: Frecska, E., Szabo, A., Winkelman, M. J., Luna, L. E., & McKenna, D. J.
Affiliations: University of Debrecen (HU)
Arizona State University (US)
University of Minnesota (US)
Corresponding author: Frecska, Ede
ORCID: Frecska, Ede
Winkelman, Michael J.
Venue: Journal of Neural Transmission
Publisher: Springer Science and Business Media LLC
Published: 2013-04-26
Volume: 120
Issue: 9
Pages: 1295-1303
ISSN: 0300-9564 (ISSN-L)
1435-1463
DOI: 10.1007/s00702-013-1024-y
OpenAlex: W2158268739
Cited by: 109
References: 95
Citations by year: 2026: 6 · 2025: 8 · 2024: 13 · 2023: 11 · 2022: 13 · 2021: 8 · 2020: 14 · 2019: 4 · 2018: 4 · 2017: 6 · 2016: 10 · 2015: 6 · 2014: 5 · 2013: 1
FWCI: 0.69
Type: journal article
Language: en
Open access: green
link.springer.com
Licence: other-oa
www.springer.com/tdm (tdm)
Locations: Journal of Neural Transmission (publishedVersion)
PubMed (publishedVersion)
Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion, other-oa)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacological Receptor Mechanisms and Effects
Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords: N,N-dimethyltryptamine, sigma-1 receptor, serotonin, immune regulation, tissue protection, regeneration, cellular bioenergetics, carcinogenesis, indole alkaloids, hallucinogens, drug repurposing
MeSH terms: Sigma-1 Receptor, Animals, Death, N,N-Dimethyltryptamine, Hallucinogens, Heart Arrest, Humans, Methyltransferases, Neoplasms, Receptors, Serotonin, Regeneration, Tissue Distribution, Receptors, sigma, Oxidative Stress, Serotonin Agents

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A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity.

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