Mindscape Collective is now The Consciousness Library. Same library, new name. You may need to sign in again. About the change
Skip to content

5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine)

A fast-acting tryptamine from Bufo alvarius secretion and synthetic sources, studied for treatment-resistant depression and for the whole-dose mystical experiences it reliably occasions.

State of the evidence

Synthesized

Synthesized from 6 studies in the library · AI-generated, grounded in the abstracts below

Found by searching the library for 5-MeO-DMT, 5-methoxy-N, N-dimethyltryptamine, 5-MeO, bufo alvarius, incilius alvarius, then ranked by relevance.

Research on 5-MeO-DMT is limited but suggests that a single inhalation in naturalistic settings is associated with sustained improvements in life satisfaction, mindfulness, and reduced psychopathological symptoms. In vitro evidence indicates that 5-MeO-DMT, like DMT, can modulate inflammatory responses via the sigma-1 receptor. However, a fatal intoxication case highlights potential risks, especially when combined with MAO inhibitors like harmaline, which can increase exposure and risk of serotonin toxicity. Overall, the evidence is preliminary, based on small or single studies, and lacks controlled clinical trials.

Evidence by study

Direction is which way each study's own result points, not our rating of the study. Synthesized from the 6 strongest of 25 matching studies in the library.

What the directions mean
Supports:
the study found the intervention worked, or its hypothesis held.
Opposes:
it found the opposite, no benefit or a harm.
No effect:
no significant difference either way.
Mixed:
effects in both directions within the same study.
Unclear:
the abstract does not report a direction.

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

observational study

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

in vitro study

Concurrent use of harmaline with 5-MeO-DMT reduces deamination metabolism, increasing exposure to both the parent drug and its active metabolite bufotenine, which may lead to serotonin toxicity.

review

The cause of death was hallucinogenic amine intoxication from herbal extracts containing beta-carbolines and hallucinogenic tryptamines, including 5-MeO-DMT.

case study Sample size: 1

Three indole alkaloids with psychedelic activity—DMT, bufotenine, and 5-MeO-DMT—have been detected as endogenous substances in human body fluids, but past methods have limitations that newer findings may overcome.

systematic review

Recent patent applications disclose selective 5-HT2A receptor activators, precision aerosol delivery technologies for psychedelic compounds, and structured 5-MeO-DMT treatment regimens for depression, indicating a convergence toward scalable and safer neuropsychiatric therapies.

review

Points of agreement

  • 5-MeO-DMT and DMT share similar serotonergic mechanisms and immunomodulatory effects via sigma-1 receptors.
  • Both compounds have been detected endogenously in humans.
  • There is interest in developing 5-MeO-DMT-based therapies for psychiatric conditions.

Conflicts

  • One observational study reports positive effects on well-being, while a case study documents a fatal intoxication, highlighting a potential risk-benefit conflict.
  • The review on endogenous detection notes methodological limitations, while other studies assume endogenous roles without definitive proof.

Gaps

  • No randomized controlled trials on 5-MeO-DMT in humans.
  • Durability of effects beyond a single inhalation is not established.
  • Safety profile, especially regarding serotonin toxicity and cardiovascular effects, is poorly characterized.
  • Dose-response relationships and optimal dosing regimens are unknown.
  • Effects in clinical populations (e.g., depression, anxiety) have not been studied in controlled settings.
Browse these studies in the library
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is 5-MeO-DMT, up to 25 in all. The most-cited set anchors the established evidence, and the recent set surfaces work that is too new to have gathered citations yet.

A study qualifies only when 5-MeO-DMT or a known alias appears in its title or keywords, so broad reviews that mention it only in passing are left out. Each study is read from its abstract, strongest evidence first, and the summary reports the direction of the results along with any conflicts and gaps.

1,073 articles · 324 from the last two years · 793,422 participants across 288 studies reporting sample size

Common study designs

review 176 experimental study 187 observational study 38 observational cohort 40 theoretical or philosophical paper 48

Therapeutic properties of ayahuasca component N,N-Dimethyltryptamine in a pre-clinical model of Parkinson's disease.

Experimental Neurology September 1, 2026 Javier Calleja‐conde, Víctor Echeverry‐alzate, Marina Sanz-Sancristóbal et al.

In a preclinical model of Parkinson's disease, the compound N,N-dimethyltryptamine (DMT), the main psychoactive ingredient in ayahuasca, reduced neuroinflammation and preserved neurons in the nigrostriatal pathway. Treated animals also showed improvements in behavior. These results suggest DMT may have disease-modifying potential for Parkinson's disease, a progressive neurodegenerative disorder marked by loss of dopaminergic neurons and chronic inflammation, for which current treatments only relieve symptoms.

ProliferativeEffects of the Psychedelic N,N-Dimethyltryptamine(DMT) in Human Neural Stem Cells

Figshare July 10, 2026 José Alexandre Salerno, Elizabeth R. Dominguez, Karina Karmirian et al.

A brief 24-hour exposure to the serotonergic psychedelic DMT increases proliferation of human neural stem cells derived from induced pluripotent stem cells. The effect was concentration-dependent, with half-maximal effect at 59.7 nM. DMT treatment also altered trophic gene expression, decreasing neurotrophin-3 while increasing nerve growth factor and brain-derived neurotrophic factor (BDNF) transcripts and intracellular BDNF protein. After DMT was removed, the primed stem cells formed larger neurospheres, with progenitor and early neuronal marker composition matching controls by day 10. These findings demonstrate that brief DMT exposure engages proliferative and neurotrophin-associated responses in human neural stem cells at concentrations consistent with those reported for DMT-induced plasticity in other systems.

Advancing Next-Generation Psychedelic Therapeutics through Selective 5-HT2A Activation, Precision Aerosol Delivery, and Optimized 5-MeO-DMT Treatment Paradigms

ACS Medicinal Chemistry Letters July 10, 2026 Anna C. Renner, Robert B. Kargbo

The psychedelic therapeutics field is moving beyond classical hallucinogens to integrated treatment platforms that combine optimized pharmacology, drug delivery, and clinical implementation. Recent patent applications describe selective 5-HT2A receptor activators, precision aerosol delivery technologies for psychedelic compounds, and structured 5-MeO-DMT treatment regimens for depression. These innovations represent a convergence toward scalable, safer, and clinically practical neuropsychiatric therapies that may reshape the future of serotonergic medicine.

Proliferative Effects of the Psychedelic N,N-Dimethyltryptamine (DMT) in Human Neural Stem Cells.

ACS Chemical Neuroscience July 9, 2026 José Alexandre Salerno, Elizabeth R. Dominguez, Karina Karmirian et al.

Brief exposure to the psychedelic N,N-dimethyltryptamine (DMT) increases proliferation of human neural stem cells derived from induced pluripotent stem cells. A 24-hour DMT treatment boosted cell division in a concentration-dependent way, with half-maximal effect at 59.7 nM, and raised levels of G1 cell-cycle regulators. DMT also altered expression of trophic genes, decreasing neurotrophin-3 while increasing nerve growth factor and brain-derived neurotrophic factor (BDNF) transcripts and intracellular BDNF protein. After DMT was removed, treated stem cells formed larger neurospheres, with progenitor and early neuron markers matching controls by day 10. The findings indicate DMT can engage proliferative and neurotrophin-related responses in human neural stem cells at concentrations linked to plasticity in other systems.

Reconstituting a two-step pathway for N,N-dimethyltryptamine (DMT) biosynthesis in bacteria

Metabolic Engineering Communications July 1, 2026 Lucas Henrique Junges, Flávia Lada Degaut Pontes, Francisco J. Teles Mota et al.

A two-step bacterial pathway converting L-tryptophan to the psychoactive alkaloid N,N-dimethyltryptamine (DMT) was reconstructed in Escherichia coli. The pathway combined a tryptophan decarboxylase from Ruminococcus gnavus and a methyltransferase from the cane toad Rhinella marina. Methionine supplementation increased DMT levels 2.8-fold, indicating that methylation capacity is a key constraint. In shake-flask cultures, a co-expression strain produced 103 mg/L DMT after 48 hours in complex medium. Using a tryptophan-enriched supernatant from Corynebacterium glutamicum enabled de novo DMT formation at 16 mg/L in defined medium. The findings identify methyltransferase capacity as a target for yield improvements.

N,N-dimethyltryptamine elicits antidepressant and anxiolytic effects in helpless mice: a comparative study with S-ketamine.

Neuropharmacology July 1, 2026 Anne Nathalia De Sousa-Silva, Clarissa de Almeida Moura, Carina Ioná De Oliveira Torres et al. 1 citation

In helpless mice, the psychedelic compound N,N-dimethyltryptamine (DMT) produced rapid and long-lasting antidepressant effects comparable to the fast-acting antidepressant S-ketamine. DMT at 10 mg/kg reversed escape deficits and reduced immobility in several behavioral tests, with effects lasting up to 8 days, whereas S-ketamine's effects lasted up to 30 hours. DMT also showed anxiolytic-like effects, reversing stress-induced hypolocomotion and increasing open-arm exploration, while S-ketamine did not. Neither drug altered behavior in the novelty-suppressed feeding test. These findings suggest DMT has transdiagnostic therapeutic potential for stress-related disorders.

The Architecture of Ego Dissolution: A Mechanical-First Evaluation of N,N-Dimethyltryptamine at the Sigma-1 and 5-HT2A Interfaces

Zenodo (CERN European Organization for Nuclear Research) June 24, 2026 Enkhamgalan Nasanjargal

The text provided is a fragment consisting only of a period, which is insufficient to describe any study, argument, or finding. It cannot be summarized.

A Critical Evaluation of the Hypothesis that N,N-Dimethyltryptamine Maintains Neuroplasticity

Zenodo (CERN European Organization for Nuclear Research) June 24, 2026 Ramiro Solis

The brain's ability to rewire itself declines with age, but why remains unclear. This paper examines whether the compound N,N-dimethyltryptamine (DMT) helps maintain neuroplasticity, and whether its decline contributes to age-related loss of cognitive flexibility. DMT promotes synaptic growth and neurogenesis in animals, and levels are reportedly highest during development. However, evidence is mixed: one study finds DMT concentrations comparable to serotonin, while another finds it undetectable in rat brain. DMT's affinity for the sigma-1 receptor is three orders of magnitude higher than physiological concentrations, and a key finding about intracellular 5-HT2A receptor binding has not been replicated. The paper does not claim the hypothesis is established, but proposes a research program to test whether DMT depletion causes lost plasticity or is incidental.

Impact of CYP2D6 Polymorphisms on the Pharmacokinetics of N,N-Dimethyltryptamine and Harmine via PBPK Modeling and Simulation

Future Pharmacology June 23, 2026 Gabriella de Souza Gomes Ribeiro, Pieter Annaert, Frederico Severino Martins et al.

CYP2D6 genetic variants substantially alter the body's exposure to the psychedelic brew ayahuasca's active compounds, N,N-dimethyltryptamine (DMT) and harmine (HRM). Using physiologically based pharmacokinetic modeling, poor metabolizers showed 53.3% higher area under the curve (AUC) and 40.5% higher peak concentration (Cmax) for DMT, with similar but smaller increases for HRM; ultra-rapid metabolizers showed reduced exposure to both. These results indicate that CYP2D6 polymorphisms contribute to interindividual variability in ayahuasca pharmacokinetics, with potential clinical implications.

Clinical trials

All 5-MeO-DMT trials →