DMT (N,N-Dimethyltryptamine)

DMT bound to sigma-1 receptors and inhibited voltage-gated sodium channels, and induced hypermobility in wild-type but not sigma-1 knockout mice, indicating DMT is an endogenous sigma-1 receptor agonist.

experimental study

Intravenous DMT produced dose-dependent hallucinogenic effects—including vivid visual imagery and dissociative states—that began almost immediately, peaked at 90-120 seconds, and resolved by 30 minutes.

double-blind, saline placebo-controlled, randomized study Sample size: 12

Compared with placebo, DMT markedly reduced alpha and beta oscillatory power and increased signal diversity, with delta and theta activity correlating with the peak of subjective visual experience.

observational cohort Sample size: 13

Potencies of hallucinogens in the mouse head-twitch response assay strongly correlated with reported hallucinogenic potencies in humans (r=0.9448) and with drug discrimination ED50 values in rats, supporting translational relevance.

experimental study with dose-response experiments

The review concludes that DMT has limited neurotoxicity and adverse effects except for intense cardiovascular effects when given intravenously in large doses, and may be useful for treating anxiety and psychosis.

review

DMT produced dose-dependent subjective effects with no tolerance after repeated doses, and pindolol pre-treatment increased psychological responses, suggesting 5-HT1A buffering of 5-HT2-mediated effects.

dose-response study, tolerance study, pre-treatment study

God encounter experiences, whether nondrug or psychedelic-occasioned, shared striking similarities and were rated as among the most personally meaningful and spiritually significant lifetime experiences.

cross-sectional survey Sample size: 4285

Ayahuasca used in religious ceremonies has a safety margin comparable to codeine, mescaline, or methadone, with minimal dependence potential and risk of sustained psychological disturbance.

systematic review

DMT administration produced significant increases in near-death experience phenomenology compared to placebo, with significant overlap with features of actual NDEs.

within-subjects placebo-controlled study Sample size: 13

DMT robustly increased global functional connectivity, disintegrated and desegregated brain networks, and compressed the principal cortical gradient, predominantly affecting transmodal association cortex.

within-subjects, placebo-controlled design Sample size: 20

A single inhalation of vapor from dried toad secretion containing 5-MeO-DMT in a naturalistic setting was related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms.

observational study

DMT and (S)-ketamine produced distinct symptom profiles: DMT modeled positive symptoms of schizophrenia, while (S)-ketamine modeled negative symptoms, attention deficits, and catatonia-like features.

double-blind crossover study Sample size: 9

NN-DMT and 5-MeO-DMT inhibited pro-inflammatory cytokine production and T-cell activation in human dendritic cells via the sigma-1 receptor, demonstrating immunomodulatory potential.

in vitro study

Chlorpromazine inhibited hyperactivity and hyperpyrexia caused by L-tryptophan or 5-MeODMT after monoamine oxidase inhibition, likely by receptor competition or physiological antagonism.

experimental study

The review synthesizes evidence for DMT's biosynthesis, metabolism, detection, and potential neurotransmitter role, and proposes future research to clarify its natural function in the brain.

review

CYB004, a deuterated DMT analogue, produced psychedelic effects comparable to DMT at similar plasma concentrations but with a two-fold longer half-life, extending effects to ~40–60 minutes, with acceptable safety at clinically relevant exposures.

randomized controlled trial

DMT produced mild to moderate psychedelic effects at plasma concentrations around 35 ng/mL, with no differences between smokers and non-smokers despite higher plasma levels in smokers; adverse effects were mild to moderate and self-limiting.

randomized controlled trial (single-ascending dose part) and open-label single-sequence two-period escalating dose study

Challenging experiences across DMT, psilocybin, MDMA, and ketamine converged substantially but showed substance-specific features, with more severe acute challenges under DMT and ketamine.

thesis with codebook thematic analysis and exploratory comparative analysis Sample size: 146

A right frontoparietal beta synchrony state was dominant after both typical and atypical psychedelic use, correlating with days since use; a globally distributed theta state was prominent after typical psychedelics but less frequent after atypical use.

observational cohort Sample size: 42

Argues that DMT is an enduring mystery with therapeutic promise and philosophical significance, noting that its biological function and the mechanisms behind its subjective effects remain unresolved.

theoretical or philosophical paper

DMT and 5-MeO-DMT produce distinct acute profiles (bell-shaped vs. monotonic HTR), and their hallucinogenic-like activity can be pharmacologically dissociated from therapeutic-like behavioral and plasticity outcomes.

preclinical study

DMT directly suppressed LPS-induced microglial activation, promoted a homeostatic morphology, and reduced phagocytic activity in rat microglia, with tissue-level neuroprotection depending on serotonergic signaling.

laboratory study

Participant and therapist accounts suggest that a single dose of 5-MeO-DMT, when embedded in relapse-prevention CBT, can support meaningful shifts in self-appraisal, emotional regulation, and behavioral patterns associated with alcohol consumption.

qualitative study (embedded in open-label phase 2a trial) Sample size: 10

5-MeO-DMT increased acute BrdU labeling in both wild-type and Neil3 knockout mice, with knockout mice showing significantly more BrdU-positive cells than wild-type mice after treatment, indicating NEIL3 is not required for the acute proliferative response.

experimental study

Computational analysis proposes that pristine C20 and beryllium-doped C20 strongly adsorb DMT via non-covalent interactions, with BeC19 showing the largest energy gap reduction and charge transfer, suggesting potential as sensors for DMT.

computational study