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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 →

1,104 articles · 332 from the last two years · 792,934 participants across 295 studies reporting sample size

Common study designs

review 182 experimental study 191 observational study 40 observational cohort 42 theoretical or philosophical paper 56

Research

Synthesize the evidence → Search all →

805. Rapid Antidepressant-Like Effects of 5-MeO-DMT Require Both 5-HT 1A and 5-HT 2A Receptors

International Journal of Neuropsychopharmacology September 9, 2026 B Richardson, S Socolow, M Lopez-Canul et al.

Abstract Background Recent clinical trials show that 5-MeO-DMT produces rapid antidepressant effects, yet the receptor mechanisms underlying these outcomes remain incompletely defined. Although 5-MeO-DMT is a high-affinity agonist at multiple serotonergic receptors, the relative contribution of 5-HT1A and 5-HT2A receptor signaling to its antidepressant-like actions has not been causally...

DOI: 10.1093/ijnp/pyag040.131 (opens in new tab)

188. A single high-dose acute injection of 5-MeO-DMT reverses stress-induced anhedonia in rats

International Journal of Neuropsychopharmacology September 9, 2026 S Socolow, B Richardson, S Nasini et al.

Abstract Background Major depression (MD) is a prevalent and debilitating disorder, characterized by anhedonia, persistent low mood, and learned helplessness, affecting up to 21% of adults over a lifetime. Chronic stress is a major environmental contributor to MD, and preclinical models of chronic mild stress (CMS) allow investigation of its behavioral and neurobiological consequences....

DOI: 10.1093/ijnp/pyag040.189 (opens in new tab)

515. Influence of the context of administration on 5-MeO-DMT-promoted antidepressant-like effects and neuroplasticity

International Journal of Neuropsychopharmacology September 9, 2026 Romain Hacquet, P Pantiya, G Gotti et al.

Abstract Background Psychedelics such as psilocybin have demonstrated rapid and sustained antidepressant effects in humans, particularly when administered in carefully designed therapeutic environments (Borkel et al., 2024; Carhart-Harris et al., 2021). DMT and 5-MeO-DMT, distinguished by their brief duration of psychedelic effects, have also shown encouraging preliminary outcomes in depressive...

DOI: 10.1093/ijnp/pyag040.084 (opens in new tab)

Exploratory Insights into 5-MeO-DMT Experiences on Reddit: A Thematic Analysis

Journal of Psychoactive Drugs September 7, 2026 Damian Swieczkowski, Aleksander Kwaśny, Wiesław Jerzy Cubała

This qualitative study examines self-reported experiences with 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) shared on Reddit to explore subjective reports, contextual influences, and perceived effects. A total of 120 posts from 24 discussion threads were purposively selected and thematically analyzed using an inductive, constructivist approach. The analysis resulted in 48 codes, which were...

DOI: 10.1080/02791072.2026.2727030 (opens in new tab)

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

The Role of Nutrition in Psychedelics Clinical Trials: Key Considerations and Recommendations for 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)

Nutritional Psychiatry September 1, 2026 Agnieszka Mechlińska, Aleksander Kwaśny, Michał Pastuszak et al.

ABSTRACT Psychedelic compounds exhibit diverse pharmacological and clinical effects, underscoring the need for further research and the development of clear guidelines to support their safe and effective clinical use. Growing interest in psychedelics has also increased attention toward the relationship between nutrition, dietary habits, and psychiatric disorders. This narrative review presents...

DOI: 10.1016/j.nupsyc.2026.100036 (opens in new tab)

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

Clinical trials

All 5-MeO-DMT trials →