ArticleFrontiers in neuroscience2016
The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells.
Article in Frontiers in neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics.Frontiers in psychiatry · 2021Pooled it
- Proliferative Effects of the Psychedelic N,N-Dimethyltryptamine (DMT) in Human Neural Stem Cells.ACS chemical neuroscience · 2026Article
- Cortical spreading depolarizations in stroke: Mechanisms, neuroprotective interventions, and monitoring techniques.GeroScience · 2026Review
- Ischemia-Induced Neurodegeneration in Glaucoma: Mechanistic Insights and Translational Opportunities for Psychoplastogen-Based Therapies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Dimethyltryptamine and harmine, components of ayahuasca, prevented cocaine-induced apoptosis in SH-SY5Y human neuroblastoma cells.Archives of toxicology · 2026Article
- Combined Neuroprotective Effects of N,N-Dimethyltryptamine and Ventral Root Reimplantation Following Spinal Root Avulsion in Rats.Journal of neurochemistry · 2026Article
- Review
- Hypoxia, Psychedelics, and Terminal Lucidity: A Perspective on Neuroplasticity and Neuropsychiatric Disorders.ACS pharmacology & translational science · 2025Review
- Could R-Ketamine and Wolfram Syndrome Inform Understanding of Depression and Suicidality? A Sigma-1 Receptor-Based Perspective.Human psychopharmacology · 2025Review
- Exploring End-of-Life Experiences and Consciousness through the Lens of Psychedelics.ACS pharmacology & translational science · 2025Article
- The sigma-1 receptor-TAMM41 axis modulates neuroinflammation and attenuates memory impairment during the latent period of epileptogenesis.Animal models and experimental medicine · 2025Article
- Psychedelics meet human brain organoids: insights into proteomics and potential for Alzheimer's disease treatment.Frontiers in dementia · 2025Review
- Potential molecular pathways and therapeutic implications of rapid-acting antidepressants on myelin biology: a scoping review.Frontiers in neuroscience · 2025Review
- An encounter with death: a comparative thematic and content analysis of naturalistic DMT experiences and the near-death experience.Frontiers in psychology · 2025Article
- The intersection of near-death experiences (NDEs) and traumatic brain injury (TBI): neurobiological, phenomenological, and creative implications.Frontiers in human neuroscience · 2025Article
- Network medicine informed multiomics integration identifies drug targets and repurposable medicines for Amyotrophic Lateral Sclerosis.NPJ systems biology and applications · 2024Article
- Review
- N, N-Dimethyltryptamine, a natural hallucinogen, ameliorates Alzheimer's disease by restoring neuronal Sigma-1 receptor-mediated endoplasmic reticulum-mitochondria crosstalk.Alzheimer's research & therapy · 2024Article
- Network medicine informed multi-omics integration identifies drug targets and repurposable medicines for Amyotrophic Lateral Sclerosis.bioRxiv : the preprint server for biology · 2024Article
- Psychedelics for acquired brain injury: a review of molecular mechanisms and therapeutic potential.Molecular psychiatry · 2024Review
Corrections and comments
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Authors and funding
6 authors.
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Abstract
N,N-dimethyltryptamine (DMT) is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R), an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER) and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins. Due to this function, the activation of Sig-1R can mitigate the outcome of hypoxia or oxidative stress. In this paper, we aimed to test the hypothesis that DMT plays a neuroprotective role in the brain by activating the Sig-1R. We tested whether DMT can mitigate hypoxic stress in in vitro cultured human cortical neurons (derived from induced pluripotent stem cells, iPSCs), monocyte-derived macrophages (moMACs), and dendritic cells (moDCs). Results showed that DMT robustly increases the survival of these cell types in severe hypoxia (0.5% O2) through the Sig-1R. Furthermore, this phenomenon is associated with the decreased expression and function of the alpha subunit of the hypoxia-inducible factor 1 (HIF-1) suggesting that DMT-mediated Sig-1R activation may alleviate hypoxia-induced cellular stress and increase survival in a HIF-1-independent manner. Our results reveal a novel and important role of DMT in human cellular physiology. We postulate that this compound may be endogenously generated in situations of stress, ameliorating the adverse effects of hypoxic/ischemic insult to the brain.
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