The evolution of N, N-Dimethyltryptamine: from metabolic pathways to brain connectivity

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.

Keywords: Cognition; Endogenous DMT; Exogenous DMT; Global neural network; Neurotransmitter; Psychedelic.