A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity.
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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 function of DMT may extend central nervous activity and involve a more universal role in cellular protective mechanisms such as neuroprotection, neuroregeneration, and immunity.
“In a previous paper (Frecska et al., 2013) we concluded that the function of DMT may extend central nervous activity and involve a more universal role in cellular protective mechanisms.”
From The therapeutic potentials of Ayahuasca: possible effects against various diseases of civilization (2016) · cites this paper as Frecska et al., 2013
Human clinical studies showed that ayahuasca can alter the number and distribution of blood immune cells in a way that can increase the antiviral and anti-tumor immunity of the consumer.
“Human clinical studies showed that ayahuasca can alter the number and distribution of blood immune cells in a way that can increase the antiviral and anti-tumor immunity of the consumer (reviewed in Frecska et al., 2013).”
From The therapeutic potentials of Ayahuasca: possible effects against various diseases of civilization (2016) · cites this paper as Frecska et al., 2013
The same plasma DMT level can lead to different intraneuronal concentrations depending on the efficacy of the active DMT-uptake processes into the brain, neurons, and vesicles.
“Moreover, the same plasma DMT level can lead to different intraneuronal concentrations depending on the efficacy of the active DMT-uptake processes into the brain, neurons, and vesicles (reviewed in Frecska et al., 2013).”
From The therapeutic potentials of Ayahuasca: possible effects against various diseases of civilization (2016) · cites this paper as Frecska et al., 2013
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dos Santos, R. G., Osório, F. L., Crippa, J. A. S., Riba, J., Zuardi, A. W., & Hallak, J. E. C. (2016) · Therapeutic Advances in Psychopharmacology · doi:10.1177/2045125316638008 · Cited by 306 · see citing works
Neuropharmacology of N,N-dimethyltryptamine
Carbonaro, T. M., & Gatch, M. B. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.04.016 · Cited by 268 · see citing works
“As previously mentioned, it has been hypothesized that high, local concentrations of DMT can occur within neurons (Frecska et al., 2013) and potentially widely produced in peripheral organs, especially in the lungs.”
BackgroundInfluentialThe therapeutic potentials of Ayahuasca: possible effects against various diseases of civilization
Frecska, E., Bokor, P., & Winkelman, M. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00035 · Cited by 242 · see citing works
“By analyzing the binocular rivalry under the effect of the brew, conclusions were drawn that ayahuasca influences hemispheric dominance (Frecska et al., 2003) and gamma oscillations (Frecska et al., 2004).”
BackgroundSelf-citationPsychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms
Inserra, A., De Gregorio, D., & Gobbi, G. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000056 · Cited by 232 · see citing works
Clinical applications of hallucinogens: a review
Garcia-Romeu, A., Kersgaard, B., & Addy, P. H. (2016) · Experimental and Clinical Psychopharmacology · doi:10.1037/pha0000084 · Cited by 201 · see citing works
“Many suggestions have been put forth regarding DMTs physiological role in the body, though there is no widely accepted consensus (Burchett & Hicks, 2006; Callaway, 1988; Frecska et al., 2013; Jacob & Presti, 2005; Su et al., 2009).”
BackgroundSzabo, A., Kovacs, A., Frecska, E., & Rajnavolgyi, E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106533 · Cited by 191 · see citing works
“Hallucinogen indole alkaloids are widespread in nature and abundant in plants, which are used in preparation of sacramental psychoactive decoctions such as yage and ayahuasca [12].”
BackgroundSelf-citationHamill, J., Hallak, J. E. C., Dursun, S. M., & Baker, G. B. (2018) · Current Neuropharmacology · doi:10.2174/1570159x16666180125095902 · Cited by 182 · see citing works
Barker, S. A. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00536 · Cited by 177 · see citing works
“Like any neurotransmitter, uptake and storage can allow a reservoir of DMT to remain stored in vesicles, ready for release, and provide a mechanism for protecting and concentrating the compound (Frecska et al., 2013).”
BackgroundInfluentialAyahuasca, dimethyltryptamine, and psychosis: a systematic review of human studies
SANTOS, R. G. D., Bouso, J. C., & Hallak, J. E. C. (2017) · Therapeutic Advances in Psychopharmacology · doi:10.1177/2045125316689030 · Cited by 168 · see citing works
Potential applications for sigma receptor ligands in cancer diagnosis and therapy
van Waarde, A., Rybczynska, A. A., Ramakrishnan, N. K., Ishiwata, K., Elsinga, P. H., & Dierckx, R. (2014) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2014.08.022 · Cited by 156 · see citing works
“, of malignant prostate and lung cancers) and inmt was identified as a candidate gene in the prevention of cancer progression [7].”
BackgroundPsychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities
Szabo, A. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00358 · Cited by 150 · see citing works
“Until now, very little has been known about the function of DMT in cellular and general physiological processes, and the emphasis of research mostly aimed the understanding of its psychedelic properties (103).”
BackgroundShort term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT
Dakic, V., Minardi Nascimento, J., Costa Sartore, R., Maciel, R. D. M., de Araujo, D. B., Ribeiro, S., Martins-de-Souza, D., & Rehen, S. K. (2017) · Scientific Reports · doi:10.1038/s41598-017-12779-5 · Cited by 134 · see citing works
Morales-Garcia, J. A., Calleja-Conde, J., Lopez-Moreno, J. A., Alonso-Gil, S., Sanz-SanCristobal, M., Riba, J., & Perez-Castillo, A. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-01011-0 · Cited by 138 · see citing works
The Role of Sigma-1 Receptor, an Intracellular Chaperone in Neurodegenerative Diseases
Penke, B., Fülöp, L., Szűcs, M., & Frecska, E. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170529104323 · Cited by 132 · see citing works
“If the Sig-1R mitigates ER stress [71], promotes neuronal survival against oxidative stress [70], and regulates immune processes [168], one may attribute the same role to DMT [169].”
BackgroundSelf-citationSzabo, A., Kovacs, A., Riba, J., Djurovic, S., Rajnavolgyi, E., & Frecska, E. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00423 · Cited by 121 · see citing works
“It is in agreement with recent findings showing alterations in phenotypic similarities between primary tissue and iPSC-derived cortical neurons by the analysis of transcriptomic changes in several typical neural marker genes (Handel et al., 2016).”
ResultSelf-citationBrito-da-Costa, A. M., Dias-da-Silva, D., Gomes, N. G. M., Dinis-Oliveira, R. J., & Madureira-Carvalho, Á. (2020) · Pharmaceuticals · doi:10.3390/ph13110334 · Cited by 117 · see citing works
“These consist, on one hand, of the inhibition of pro-inflammatory cytokines (IL-1β, IL-6, TNFα) production, and on the other of the enhanced release of anti-inflammatory cytokine IL-10 [204].”
BackgroundAcute biphasic effects of ayahuasca.
Schenberg, E. E., Alexandre, J. F. M., Filev, R., Cravo, A. M., Sato, J. R., Muthukumaraswamy, S. D., Yonamine, M., Waguespack, M., Lomnicka, I., Barker, S. A., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0137202 · Cited by 111 · see citing works
“DMT is then actively transported into the brain through an active threestep mechanism [18].”
BackgroundThe involvement of the sigma-1 receptor in neurodegeneration and neurorestoration
Ruscher, K., & Wieloch, T. W. (2014) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2014.11.011 · Cited by 107 · see citing works
Martial, C., Cassol, H., Charland‐Verville, V., Pallavicini, C., Sanz, C., Zamberlán, F., Vivot, R. M., Erowid, F., Erowid, E., Laureys, S., et al. (2019) · Consciousness and Cognition · doi:10.1016/j.concog.2019.01.011 · Cited by 102 · see citing works
Inserra, A. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00330 · Cited by 91 · see citing works
“SIGMAR1 is a transmembrane protein with neuroprotective, neurotrophic, and immunomodulatory properties found in high concentrations in limbic areas of the human brain and in immune cells (Ishikawa et al., 2007; Fujimoto et al., 2012; Frecska et al., 2013; Szabo et al., 2014).”
BackgroundNardai, S., László, M., Szabó, A., Alpár, A., Hanics, J., Zahola, P., Merkely, B., Frecska, E., & Nagy, Z. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113245 · Cited by 94 · see citing works
Self-citationAssociations between lifetime classic psychedelic use and markers of physical health
Simonsson, O., Sexton, J. D., & Hendricks, P. S. (2021) · Journal of Psychopharmacology · doi:10.1177/0269881121996863 · Cited by 74 · see citing works
“…Germann, 2020; Hernandez et al., 2018); immunomodulatory and antiinflammatory effects of relevance to physical health (Flanagan and Nichols, 2018; Frecska et al., 2013, 2016; Szabo, 2015, 2019; Szabo et al., 2014; Thompson and Szabo, 2020; Tourino et al., 2013; Winkelman and Sessa, 2019); and…”
BackgroundSzabó, Í., Varga, V. É., Dvorácskó, S., Farkas, A. E., Körmöczi, T., Berkecz, R., Kecskés, S., Menyhárt, Á., Frank, R., Hantosi, D., et al. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108612 · Cited by 72 · see citing works
Self-citationPsychedelics as a novel approach to treating autoimmune conditions
Thompson, C., & Szabó, A. (2020) · Immunology Letters · doi:10.1016/j.imlet.2020.10.001 · Cited by 71 · see citing works
<i>N,N</i> -dimethyltryptamine and the pineal gland: Separating fact from myth
Nichols, D. E. (2018) · Journal of Psychopharmacology · doi:10.1177/0269881117736919 · Cited by 69 · see citing works
Hassan, Z., Bosch, O. G., Singh, D., Narayanan, S., Kasinather, B. V., Seifritz, E., Kornhuber, J., Quednow, B. B., & Müller, C. P. (2017) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2017.00152 · Cited by 63 · see citing works
Barker, S. A. (2022) · Psychopharmacology · doi:10.1007/s00213-022-06065-0 · Cited by 58 · see citing works
SANTOS, R. G. D., & Hallak, J. E. C. (2019) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2019.04.053 · Cited by 56 · see citing works
Chu, U. B., Vorperian, S. K., Satyshur, K. A., Eickstaedt, K., Cozzi, N. V., Mavlyutov, T. A., Hajipour, A. R., & Ruoho, A. E. (2014) · Biochemistry · doi:10.1021/bi500175p · Cited by 54 · see citing works
NPS: Medical Consequences Associated with Their Intake
Schifano, F., Orsolini, L., Papanti, D., & Corkery, J. (2016) · Current topics in behavioral neurosciences · doi:10.1007/7854_2016_15 · Cited by 52 · see citing works
Exploring DMT: Endogenous role and therapeutic potential
Schimmelpfennig, J., & Jankowiak-Siuda, K. (2025) · Neuropharmacology · doi:10.1016/j.neuropharm.2025.110314 · Cited by 54 · see citing works
Lin, J., Sun‐Waterhouse, D., & Cui, C. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1934813 · Cited by 49 · see citing works
“DMT can influence immune function strongly (Ahern 2011), and likely modulate innate and adaptive inflammatory responses of human monocyte-derived dendritic cells via the sigma-1 receptor (Sig-1R) (Frecska et al. 2013; Szabo et al. 2014).”
BackgroundAyahuasca's therapeutic potential: What we know – and what not
Maia, L. O., Daldegan‐Bueno, D., Wießner, I., de Araújo, D. B., & Tófoli, L. F. (2022) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2022.10.008 · Cited by 47 · see citing works
The Bright Side of Psychedelics: Latest Advances and Challenges in Neuropharmacology
Mastinu, A., Anyanwu, M., Carone, M., Abate, G., Bonini, S. A., Peron, G., Tirelli, E., Pucci, M., Ribaudo, G., Oselladore, E., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021329 · Cited by 49 · see citing works
“As a matter of fact, in the last decade DMT has been investigated for its neuroprotective effects, which are thought to be mediated by binding with the sigma-1 receptor [145].”
BackgroundDimethyltryptamine (DMT): a biochemical Swiss Army knife in neuroinflammation and neuroprotection?
Szabó, A., & Frecska, E. (2016) · Neural Regeneration Research · doi:10.4103/1673-5374.179041 · Cited by 44 · see citing works
“The neuroregenerative potential of DMT through the Sig-1R has been suggested earlier as multiple biochemical and physiological mechanisms exist, which facilitate the transportation and binding of DMT to the Sig-1R in the mammalian brain (Frecska et al., 2013).”
Self-citationKelley, D. P., Venable, K., Destouni, A., Billac, G., Ebenezer, P., Stadler, K., Nichols, C., Barker, S., & Francis, J. (2022) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00660 · Cited by 42 · see citing works
N,N‐dimethyltryptamine and Amazonian ayahuasca plant medicine
James, E., Keppler, J., Robertshaw, T. L., & Sessa, B. (2022) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.2835 · Cited by 43 · see citing works
“DMT could have an immunoregulatory role via sigma‐1 receptor modulation as DMT has been found to inhibit pro‐inflammatory cytokine (IL‐1β, IL‐6, TNFα) production and enhance release of anti‐inflammatory cytokine IL‐10 (Brito‐da‐Costa et al., 2020; Frecska et al., 2013).”
Prasanth, M. I., Malar, D. S., Tencomnao, T., & Brimson, J. M. (2021) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2021.1939681 · Cited by 40 · see citing works
Egger, K., Aicher, H., Cumming, P. D., & Scheidegger, M. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05353-6 · Cited by 36 · see citing works
“Indeed, DMT can enter serotonin neurons via SERT, and then accumulate in synaptic vesicles as a substrate for the vesicular monoamine transporter 2 (VMAT2) [104].”
BackgroundSigma-1 receptors and animal studies centered on pain and analgesia
Davis, M. P. (2015) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2015.1051961 · Cited by 35 · see citing works
“1 Background Neurosteroids and dimethyltryptamine (DMT) are naturally occurring sigma-1 ligands produced in neurons [129,130].”
BackgroundBarman, R., Bora, P. K., Saikia, J., Kemprai, P., Saikia, S. P., Haldar, S., & Banik, D. (2021) · Phytotherapy Research · doi:10.1002/ptr.7098 · Cited by 35 · see citing works
“…drug addiction, PTSD, ASD, cancer, pain and others (Jossang et al., 1991; Takeda, Ikeda, Ohba, & Kondo, 1995; Winkelman, 2001; Zucchi et al., 2006; Frecska et al., 2013; Pavlovska et al., 2015; Tupper, Wood, Yensen, & Johnson, 2015; Gallimore & Strassman, 2016; Carlini & Maia, 2017; Reiche et…”
Borbély, E., Varga, V. É., Szögi, T., Schuster, I., Bozsó, Z., Penke, B., & Fülöp, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052514 · Cited by 34 · see citing works
Significance of mammalian N, N-dimethyltryptamine (DMT): A 60-year-old debate
Jiménez, J. H., & Bouso, J. C. (2022) · Journal of Psychopharmacology · doi:10.1177/02698811221104054 · Cited by 37 · see citing works
“It has been proposed that DMT is a neurotransmitter, a neuromodulator and a neurohormone (Barker, 2018; Christian et al., 1976), and that it serves a protective function in peripheral tissues (Frecska et al., 2013; Szabo, 2015).”
BackgroundInfluentialRossi, G. N., Guerra, L. T. L., Baker, G. B., Dursun, S. M., Bouso, J. C., Hallak, J. E. C., & SANTOS, R. G. D. (2022) · Biomolecules · doi:10.3390/biom12111618 · Cited by 33 · see citing works
“The proposed mechanism and investigations that support it are evidence of DMT’s role as an important cellular messenger, since there is a considerable physiological effort and prioritization to transport, accumulate, and store it within the CNS [89].”
BackgroundInfluentialDean, J. G. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00232 · Cited by 37 · see citing works
“…of the lost transcription factors associated with inheriting the A allele, is linked to immune/inflammatory responses (Iwakoshi et al., 2003) and cellular endoplasmic reticulum stress response (Yoshida et al., 2006)—two functions recently proposed for DMT (Frecska et al., 2013; Szabo et al., 2016).”
BackgroundThe evolution of N, N-Dimethyltryptamine: from metabolic pathways to brain connectivity
Gupta, S., Bhatnagar, R. K., Gupta, D., Maharaj Kumari, K., & Chopra, A. (2025) · Psychopharmacology · doi:10.1007/s00213-025-06777-z · Cited by 30 · see citing works
“However, the functional role of this molecule, which shares the same precursor (tryptophan) as serotonin, is still unclear due to low endogenous levels and rapid degradation that hinder accurate detection (Frecska et al. 2013; Cameron and Olson 2018).”
InfluentialAyahuasca and cancer treatment
Schenberg, E. E. (2013) · SAGE Open Medicine · doi:10.1177/2050312113508389 · Cited by 30 · see citing works
A Comprehensive Review of the Current Status of the Cellular Neurobiology of Psychedelics
Banushi, B., & Polito, V. (2023) · Biology · doi:10.3390/biology12111380 · Cited by 25 · see citing works
The potential of psychedelics for the treatment of Alzheimer's disease and related dementias
Winkelman, M., Szabó, A., & Frecska, E. (2023) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2023.07.003 · Cited by 27 · see citing works
“Various serotonergic tryptamines modulate Sig-1R receptors in both the central nervous system and in peripheral tissues and cell types, including immune cells ( Frecska et al., 2013 ; Szabo, 2015 ).”
BackgroundSelf-citationEpigenetic Mechanisms of Rapid-Acting Antidepressants
Inserra, A., Campanale, A., Rezai, T., Romualdi, P., & Rubino, T. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-03055-y · Cited by 27 · see citing works
“…1) it is actively transported across the blood-brain barrier, 2) acts as a 5-HT transporter substrate on the neuronal plasma membrane, and 3) it is internalized by neuronal cells, and stored into synaptic vesicles by the neuronal vesicle monoamine transporter 2 for up to 1 week [204 – 206].”
BackgroundRisk assessment of dietary exposure to tryptamine for the Austrian population
Wüst, N., Rauscher‐Gabernig, E., Steinwider, J., Bauer, F., & Paulsen, P. (2016) · Food Additives & Contaminants Part A · doi:10.1080/19440049.2016.1269207 · Cited by 24 · see citing works
“The physiological role of endogenous DMT in humans is largely unknown (Su et al. 2009; Barker et al. 2012; Frecska et al. 2013).”
BackgroundN,N-dimethyltryptamine Prevents Renal Ischemia-Reperfusion Injury in a Rat Model
Nemes, B., Pető, K., Németh, N., Mester, A., Magyar, Z. É., Ghanem, S., Sógor, V., Tánczos, B., Deák, Á., Kállay, M., et al. (2019) · Transplantation Proceedings · doi:10.1016/j.transproceed.2019.04.005 · Cited by 22 · see citing works
Self-citationGlavonic, E., Mitić, M., & Adžić, M. (2022) · Journal of Neuroscience Research · doi:10.1002/jnr.25017 · Cited by 21 · see citing works
“…with regard to its suitability for clinical use, there have been no consistent reports of DMT's toxic effects or severe cognitive deficits even in long- term users (Bouso et al., 2013; Carbonaro & Gatch, 2016), and Frecska et al. (2013) even outlined DMT's potential neuroprotective effects.”
BackgroundAyahuasca and Dimethyltryptamine Adverse Events and Toxicity Analysis: A Systematic Thematic Review
White, E., Kennedy, T., Ruffell, S., Perkins, D., & Sarris, J. J. (2024) · International Journal of Toxicology · doi:10.1177/10915818241230916 · Cited by 21 · see citing works
“18 19 – 24 A further set of potential pathways associated with aya-huasca relates to the harmala alkaloids, containing harmine, harmaline, and tetrahydroharmine.”
BackgroundLaszlo, M. J., Vigh, J. P., Kocsis, A. E., Porkoláb, G., Hoyk, Z., Polgár, T. F., Walter, F. R., Szabó, A., Djurovic, S., Merkely, B. P., et al. (2025) · Science Advances · doi:10.1126/sciadv.adx5958 · Cited by 18 · see citing works
Self-citationEffects of psychedelics on neurogenesis and broader neuroplasticity: a systematic review
da Cruz, R. V. L., Leão, R. N., & Moulin, T. C. (2024) · Molecular Medicine · doi:10.1186/s10020-024-01013-4 · Cited by 18 · see citing works
“…(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 · see citing works
Mind over matter: the microbial mindscapes of psychedelics and the gut-brain axis
Caspani, G., Ruffell, S., Tsang, W., Netzband, N., Rohani-Shukla, C., Swann, J. R., & Jefferies, W. A. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107338 · Cited by 18 · see citing works
“…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].”
Vorobyeva, N. S., & Kozlova, A. A. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.927984 · Cited by 19 · see citing works
“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).”
BackgroundAyahuasca: what mental health professionals need to know
SANTOS, R. G. D., Bouso, J. C., & Hallak, J. E. C. (2017) · Archives of Clinical Psychiatry (São Paulo) · doi:10.1590/0101-60830000000130 · Cited by 16 · see citing works
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 · see citing works
“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).”
BackgroundPsychedelic 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 · see citing works
“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.”
BackgroundAyahuasca 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 · see citing works
Brimson, J. M., Prasanth, M. I., Isidoro, C., Sukprasansap, M., & Tencomnao, T. (2021) · Nutrition and Healthy Aging · doi:10.3233/nha-200108 · Cited by 13 · see citing works
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 12 · see citing works
Kubicskó, K., & Farkas, Ö. (2020) · Organic & Biomolecular Chemistry · doi:10.1039/d0ob01118e · Cited by 12 · see citing works
The Therapeutic Potential of Ayahuasca
Coe, M. A., & McKenna, D. J. (2016) · Springer eBooks · doi:10.1007/978-3-319-42307-4_7 · Cited by 12 · see citing works
Self-citationChaves, C., SANTOS, R. G. D., Dursun, S. M., Tusconi, M., Carta, M. G., Brietzke, E. M., & Hallak, J. E. C. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1485337 · Cited by 11 · see citing works
Vargas-Pérez, H., Grieder, T. E., & van der Kooy, D. (2022) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2022.2033889 · Cited by 10 · see citing works
“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).”
BackgroundBarman, R., Bora, P. K., Saikia, J., Konwar, P., Sarkar, A., Kemprai, P., Saikia, S. P., Haldar, S., Slater, R. J., & Banik, D. (2023) · Phytochemistry · doi:10.1016/j.phytochem.2023.113928 · Cited by 9 · see citing works
Mu, H., Ye, L., & Wang, B. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116361 · Cited by 8 · see citing works
Sousa, D. D. N., Azevedo, M. D. A., dos Santos, M. L., Borges, T. K. D. S., de Oliveira, D. M., & Caldas, E. D. (2025) · Metabolic Brain Disease · doi:10.1007/s11011-025-01650-6 · Cited by 8 · see citing works
“…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
Kéri, S. (2022) · Life · doi:10.3390/life12111707 · Cited by 7 · see citing works
“Sigma receptors, previously considered opioid receptors, are abundant cell surface proteins with multiple actions on neuronal and peripheral tissue functions [76].”
BackgroundTyagi, R., Saraf, T. S., & Canal, C. E. (2023) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.3c00137 · Cited by 7 · see citing works
López‐Arnau, R., Camarasa, J., Carbó, M., Nadal‐Gratacós, N., Puigseslloses, P., Espinosa‐Velasco, M., Urquizu, E., Escubedo, E., & Pubill, D. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.990405 · Cited by 6 · see citing works
The immunomodulatory effects of psychedelics in Alzheimer’s disease-related dementia
Hosseini, A. M., Khaleghzadeh‐Ahangar, H., & Rahimi, A. (2024) · Neuroscience · doi:10.1016/j.neuroscience.2024.11.062 · Cited by 4 · see citing works
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“29 Evidence also suggests prevention against ischaemia/reperfusion lesion in the eye and kidney cells.”
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- 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
- Venue
- Journal of Neural Transmission
- Published
- 2013-04-26
- Volume
- 120
- Issue
- 9
- Pages
- 1295-1303
- ISSN
- 0300-9564 (ISSN-L)
- 1435-1463
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 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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