{"title":"The evolution of N, N-Dimethyltryptamine: from metabolic pathways to brain connectivity.","authors":"Swanti Gupta, Raj K Bhatnagar, Dinesh Gupta, Maharaj Kumari K, Amla Chopra","doi":"10.1007/s00213-025-06777-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Rationale: </strong>N, N-Dimethyltryptamine (DMT), a potent serotonergic psychedelic, bridges ancient wisdom and modern science. The mechanisms underlying its powerful psychedelic effects and out-of-body experiences continue to intrigue scientists. The functional role of DMT remains ambiguous. This paper explores the endogenous presence of DMT in the human body and its diverse neuroregulatory functions, which influence hierarchical brain connectivity, and the mechanisms driving its psychedelic effects.</p><p><strong>Objective: </strong>This paper aims to analyze DMT-receptor binding, its effects on neuronal modulation, brain oscillations, and connectivity, and its influence on hallucinations, out-of-body experiences, and cognitive functions.</p><p><strong>Results: </strong>DMT administration induces significant changes in brain wave dynamics, including reduced alpha power, increased delta power, and heightened Lempel-Ziv complexity, reflecting enhanced neural signal diversity. Functional neuroimaging studies reveal that DMT enhances global functional connectivity (GFC), particularly in transmodal association cortices such as the salience network, frontoparietal network, and default mode network, correlating with ego dissolution. The receptor density-dependent effects of DMT were mapped to brain regions rich in serotonin 5-HT2A receptors, supporting its role in modulating consciousness and neuroplasticity.</p><p><strong>Conclusion: </strong>This integrated analysis provides insights into the profound effects of DMT on human cognition, and consciousness, and its role in enhancing natural well-being. As we uncover the endogenous functions of DMT, it becomes clear that the study of its biology reveals a complex interplay between brain chemistry and consciousness.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00213-025-06777-z","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Rationale: N, N-Dimethyltryptamine (DMT), a potent serotonergic psychedelic, bridges ancient wisdom and modern science. The mechanisms underlying its powerful psychedelic effects and out-of-body experiences continue to intrigue scientists. The functional role of DMT remains ambiguous. This paper explores the endogenous presence of DMT in the human body and its diverse neuroregulatory functions, which influence hierarchical brain connectivity, and the mechanisms driving its psychedelic effects.
Objective: This paper aims to analyze DMT-receptor binding, its effects on neuronal modulation, brain oscillations, and connectivity, and its influence on hallucinations, out-of-body experiences, and cognitive functions.
Results: DMT administration induces significant changes in brain wave dynamics, including reduced alpha power, increased delta power, and heightened Lempel-Ziv complexity, reflecting enhanced neural signal diversity. Functional neuroimaging studies reveal that DMT enhances global functional connectivity (GFC), particularly in transmodal association cortices such as the salience network, frontoparietal network, and default mode network, correlating with ego dissolution. The receptor density-dependent effects of DMT were mapped to brain regions rich in serotonin 5-HT2A receptors, supporting its role in modulating consciousness and neuroplasticity.
Conclusion: This integrated analysis provides insights into the profound effects of DMT on human cognition, and consciousness, and its role in enhancing natural well-being. As we uncover the endogenous functions of DMT, it becomes clear that the study of its biology reveals a complex interplay between brain chemistry and consciousness.
期刊介绍:
Official Journal of the European Behavioural Pharmacology Society (EBPS)
Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields:
Human Psychopharmacology: Experimental
This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered.
Human Psychopharmacology: Clinical and Translational
This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects.
Preclinical psychopharmacology: Behavioral and Neural
This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels.
Preclinical Psychopharmacology: Translational
This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways.
Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic
This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.