Journal of Psychopharmacology
August 1, 2022
Javier Hidalgo Jiménez, José Carlos Bouso
34 citations
DMT, a potent psychedelic naturally produced by many plants and animals including humans, may play significant roles in mammalian physiology. This review integrates historical and recent evidence to address ongoing debates about DMT's relevance. Arguments dismissing endogenous DMT are often based on obsolete data or misleading assumptions. Evidence strongly suggests DMT functions as a neurotransmitter, neuromodulator, hormone, and immunomodulator, and is important in pregnancy and development. Key experiments are proposed to definitively determine DMT's specific physiological roles.
Brain Network and Modulation
July 1, 2023
Javier Hidalgo Jiménez
2 citations
DMT is a naturally occurring psychedelic with potent subjective effects and preliminary evidence for antidepressive, anxiolytic, and antiaddictive properties. Its effects arise from neuromodulation of glutamatergic, monoaminergic, and cholinergic systems, causing acute shifts in brain networks including visual, auditive, and default-mode networks. Top-down cognitive processing becomes restricted while bottom-up processing is enhanced. DMT also induces neuroplasticity via sigma 1 receptor, BDNF, TrkB, and 5-HT2A, which may underlie therapeutic benefits. This review updates the neuromodulatory mechanisms of DMT, covering molecular targets, changes in cortical function and structure, neuroplasticity, and therapeutic relevance and risks.
bioRxiv (Cold Spring Harbor Laboratory)
March 23, 2026
Marco Taddei-Tardon, Lidia Medina-Rodríguez, Jessica L. Maltman et al.
Serotonergic psychedelics, including tryptamines, phenethylamines, and ergolines, promote structural and transcriptional changes in neurons through an integrated signaling network involving the 5-HT2A receptor and TrkB. Using a neural stem cell-derived model, the study shows that TrkB silencing blocks dendritogenesis induced by psychedelics, ketamine, and TrkB agonists, while 5-HT2A silencing selectively impairs psychedelic-induced plasticity. Most compounds increase synaptogenesis and immediate-early gene expression, though psilocin and the phenethylamines DOI and Ariadne show ligand-specific differences. Lactate production, dependent on 5-HT2A and both Gq/11 and Gi/o protein signaling, also occurs. These results establish a platform for dissecting psychedelic action.