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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 8 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 it can produce sustained improvements in life satisfaction, mindfulness, and psychopathological symptoms after a single naturalistic inhalation, and it may have immunomodulatory and neuroplastic effects. However, evidence is largely observational, preclinical, or theoretical, with no controlled clinical trials in patient populations, and safety concerns include potential serotonin toxicity when combined with MAO inhibitors and a rare fatal intoxication. Overall, findings are promising but preliminary, with significant gaps in dose-response, long-term durability, and clinical efficacy.

Evidence by study

Direction is which way each study's own result points, not our rating of the study. All 25 matching studies were reviewed; the 8 that directly address the question are shown here.

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-methoxy-N,N-dimethyltryptamine (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. 2019
Supports

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

observational

Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. 2014
Supports

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

Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. 2010
Unclear

The review summarizes that 5-MeO-DMT is metabolized by MAO-A and CYP2D6, and concurrent use with harmaline reduces deamination, increasing exposure to the parent drug and active metabolite bufotenine, potentially leading to serotonin toxicity.

review

A fatal intoxication following the ingestion of 5-methoxy-N,N-dimethyltryptamine in an ayahuasca preparation. 2005
Opposes

A fatal intoxication following ingestion of an ayahuasca preparation containing 5-MeO-DMT was attributed to hallucinogenic amine intoxication, with high blood levels of 5-MeO-DMT and other tryptamines.

case study Sample size: 1

A dominant frontoparietal beta oscillatory brain state in the days after psilocybin and 5-MeO-DMT 2026
Supports

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

observational cohort Sample size: 42

Preclinical Comparison of DMT and 5-MeO-DMT Reveals Behavioral Dissociation, Distinct TrkB Activation and Differential Plasticity Profiles 2026
Mixed

DMT and 5-MeO-DMT produced distinct acute profiles (bell-shaped vs. monotonic head-twitch response), and hallucinogenic-like activity could be pharmacologically dissociated from therapeutic-like behavioral and plasticity outcomes.

preclinical

5-MeO-DMT induces NEIL3-independent acute cell proliferation in the adult dentate gyrus 2026
Supports

A single dose of 5-MeO-DMT increased acute cell proliferation in the dentate gyrus of both wild-type and Neil3 knockout mice, with knockout mice showing significantly more proliferation, indicating NEIL3 is not required for the acute response.

experimental

Advancing Next-Generation Psychedelic Therapeutics through Selective 5-HT2A Activation, Precision Aerosol Delivery, and Optimized 5-MeO-DMT Treatment Paradigms 2026
Supports

The review argues that recent patent applications disclose selective 5-HT2A receptor activators, precision aerosol delivery technologies, 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 shows potential for positive effects on well-being and neuroplasticity in observational and preclinical studies.
  • 5-MeO-DMT has immunomodulatory effects via sigma-1 receptor in vitro.
  • Recent research emphasizes the need for optimized delivery and treatment paradigms for 5-MeO-DMT.

Conflicts

  • One case study reports a fatal intoxication, while other studies suggest limited adverse effects at typical doses.
  • Preclinical findings show distinct acute profiles between DMT and 5-MeO-DMT, but the therapeutic relevance of these differences is debated.

Gaps

  • No randomized controlled trials of 5-MeO-DMT in clinical populations were provided.
  • Long-term durability of effects beyond a few weeks is not established.
  • Dose-response relationships and optimal dosing regimens are not well characterized.
  • Safety data are limited, especially regarding interactions with MAO inhibitors and potential toxicity.
  • The role of endogenous 5-MeO-DMT and its physiological functions remain unclear.
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.

Ask your own question in the Research Synthesis Tool

Latest monthly recap: July 2026 →

1,065 articles · 321 from the last two years · 792,579 participants across 287 studies reporting sample size

Common study designs

review 180 experimental study 191 observational study 38 observational cohort 42 theoretical or philosophical paper 53

Research

Synthesize the evidence → Search all →

Safety, pharmacokinetics, and pharmacodynamics of intravenously administered deuterated N,N-dimethyltryptamine (CYB004) in healthy volunteers.

Journal of psychopharmacology (Oxford, England) September 3, 2026 Katelijne V. van der Heijden, Gabriël E. Jacobs, Ellen James et al.

Serotonergic psychedelics, such as N,N-dimethyltryptamine (DMT), have shown therapeutic potential in various psychiatric disorders. However, DMT demonstrates pharmacokinetic (PK) variability and a short half-life. This exploratory study investigated the PK, pharmacodynamic (PD), and safety profile of CYB004, a deuterated DMT analogue, following intravenous administration in healthy volunteers....

DOI: 10.1177/02698811261478616 (opens in new tab) Full text (opens in new tab) DMT Deuteration Pharmacodynamics Pharmacokinetics +1

A dominant frontoparietal beta oscillatory brain state in the days after psilocybin and 5-MeO-DMT

bioRxiv (Cold Spring Harbor Laboratory) August 27, 2026 Chloe L. West, Bradley Baker, Annabel Duran et al. preprint

Abstract Background Serotonergic psychedelics show promise for treating psychiatric disorders, with symptom improvements lasting for weeks after a single dose. Clarifying the neural basis of these effects would benefit from an identification of empirical biomarkers of such lasting shifts in brain function. Resting state EEG offers a rapid (<5 minute), low-cost window into functional brain...

DOI: 10.64898/2026.08.23.746502 (opens in new tab) Full text (opens in new tab)

Preclinical Comparison of DMT and 5-MeO-DMT Reveals Behavioral Dissociation, Distinct TrkB Activation and Differential Plasticity Profiles

bioRxiv (Cold Spring Harbor Laboratory) August 12, 2026 Orr Shahar, Alexander Botvinnik, Masha Chaykin et al. preprint

Abstract N, N-dimethyltryptamine (DMT) and 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) are structurally related tryptamine psychedelics with emerging therapeutic potential, yet their comparative acute pharmacology and longer-term neuroplastic effects remain incompletely defined. Here we show that DMT produces a bell-shaped dose–response curve in the mouse head-twitch response (HTR) assay,...

DOI: 10.64898/2026.08.06.743248 (opens in new tab)

5-MeO-DMT induces NEIL3-independent acute cell proliferation in the adult dentate gyrus

Molecular Brain July 24, 2026 Rafael V. Lima da Cruz, Richardson N. Leão, Thiago C. Moulin

Abstract Adult dentate gyrus neurogenesis and cell proliferation are regulated by multiple physiological inputs, including experience-dependent signals that have been linked to the DNA glycosylase NEIL3. Whether NEIL3 also gates psychedelic-induced proliferation is unknown. Here we tested the effect of a single dose of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT), a serotonergic agonist with...

DOI: 10.1186/s13041-026-01337-8 (opens in new tab)

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

High Resolution Image Download MS PowerPoint Slide The psychedelic therapeutics field continues to evolve beyond classical hallucinogens toward integrated treatment platforms that combine optimized pharmacology, drug delivery, and clinical implementation. Recent patent applications disclose selective 5-HT2A receptor activators, precision aerosol delivery technologies for psychedelic compounds,...

DOI: 10.1021/acsmedchemlett.6c00364 (opens in new tab) Aerosol Precision medicine Nanotechnology

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.

The serotonergic psychedelic N,N-dimethyltryptamine (DMT) produces rapid antidepressant effects in preclinical and early clinical studies. Therapeutic benefits have been linked to sustained neural plasticity, including adult neurogenesis in rodents. Whether brief DMT exposure engages proliferative responses in human neural stem cells (NSCs) remains unresolved. Using human iPSC-derived NSCs, we...

DOI: 10.1021/acschemneuro.6c00209 (opens in new tab) Full text (opens in new tab) Bdnf N,N-Dimethyltryptamine DMT Cell cycle Neurosphere

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.

N,N-dimethyltryptamine (DMT) is a bioactive indole alkaloid that could greatly benefit from scalable, fermentation-based production for research and pharmaceutical applications. In this study, we reconstructed a two-step bacterial pathway converting L-tryptophan to DMT via tryptamine. This involved combining a pyridoxal 5'-phosphate (PLP)-dependent tryptophan decarboxylase from the bacterium...

DOI: 10.1016/j.mec.2026.e00286 (opens in new tab) Tryptamine Corynebacterium glutamicum Tryptophan Escherichia coli +14

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

N,N-dimethyltryptamine (DMT) is an naturally occurring indoleamine with hallucinogenic and antidepressant effects in humans. Here, we compared the effects of DMT and S-ketamine, a fast-acting antidepressant, in helpless mice. To induce helplessness, male single and group-housed mice were exposed to inescapable footshock stress; only helpless animals were subsequently treated with S-ketamine 10...

DOI: 10.1016/j.neuropharm.2026.110947 (opens in new tab) Full text (opens in new tab) Anxiety Depression Animal models Mouse +2

Clinical trials

All 5-MeO-DMT trials →