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5-MeO-DMT research: what the evidence shows

(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 11 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.

Direct human research on 5-MeO-DMT is thin but points in a positive direction: a small observational cohort found that a single inhaled dose was followed by improved life satisfaction, mindfulness, and reduced depression, anxiety, and stress that persisted to four weeks, and a systematic review reports rapid antidepressant effects, including a Phase 2b trial of an inhalable formulation meeting its primary endpoint in treatment-resistant depression. Preclinical work in rodents supports rapid antidepressant-like and anxiolytic effects, with dependence on both 5-HT1A and 5-HT2A receptors and on administration context. The main caveats are small samples, mostly uncontrolled or observational human designs, short follow-up, and a documented fatal case involving 5-MeO-DMT with MAO inhibitors.

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 11 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.
Study Design Sample size Direction Finding
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 observational cohort 42 Supports A single inhalation was followed by significant increases in satisfaction with life and convergent thinking at 24 hours persisting at four weeks, increased mindfulness at four weeks, and decreased depression, anxiety, and stress reaching significance at four weeks, with greater ego dissolution associated with better outcomes.
Pharmacological, clinical, and translational evidence for N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, and zalsupindole: a systematic review. 2026 systematic review Supports Across 51 publications, clinical evidence was most developed for depression, with 5-MeO-DMT associated with rapid reductions in depressive symptoms and an inhalable formulation meeting its primary endpoint in a Phase 2b treatment-resistant depression trial, while evidence for other conditions remained preliminary.
Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. 2010 review Opposes Concurrent use of harmaline with 5-MeO-DMT reduces its deamination metabolism, increasing exposure to the parent drug and its active metabolite bufotenine and potentially producing hyperserotonergic effects or serotonin toxicity.
A fatal intoxication following the ingestion of 5-methoxy-N,N-dimethyltryptamine in an ayahuasca preparation. 2005 case study 1 Opposes A fatal intoxication was attributed to hallucinogenic amine intoxication after ingestion of an ayahuasca preparation containing 5-MeO-DMT along with beta-carbolines and other tryptamines.
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 in vitro study Supports 5-MeO-DMT inhibited production of pro-inflammatory cytokines, increased anti-inflammatory IL-10, and reduced T-cell activating capacity of dendritic cells via the sigma-1 receptor.
A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines in humans: 1955-2010. 2012 systematic review Unclear Reports that 5-MeO-DMT has been detected as an endogenous substance in human body fluids, while noting methodological limitations of past detection studies.
515. Influence of the context of administration on 5-MeO-DMT-promoted antidepressant-like effects and neuroplasticity 2026 preclinical experimental study Mixed 5-MeO-DMT at 0.5 mg/kg produced antidepressant-like effects in neutral or positive settings but not in a negative setting, which instead promoted anxiogenic-like responses, with positive setting linked to perineuronal net degradation around hippocampal parvalbumin interneurons.
188. A single high-dose acute injection of 5-MeO-DMT reverses stress-induced anhedonia in rats 2026 preclinical experimental study Supports A single 10 mg/kg dose of 5-MeO-DMT reversed stress-induced anhedonia and normalized REM sleep reductions, while vehicle-treated stressed rats remained anhedonic.
805. Rapid Antidepressant-Like Effects of 5-MeO-DMT Require Both 5-HT 1A and 5-HT 2A Receptors 2026 preclinical randomized controlled trial Supports 5-MeO-DMT at 10 mg/kg produced rapid antidepressant-like effects in the forced swim test that were blocked by both 5-HT1A and 5-HT2A antagonism but not by 5-HT7 or sigma antagonists, dissociating head twitch from antidepressant-like efficacy.
Exploratory Insights into 5-MeO-DMT Experiences on Reddit: A Thematic Analysis 2026 qualitative study 120 Supports Users described introspective, cathartic, and spiritually unifying experiences often viewed as transformative, with individualized dosing, a distinct tolerance profile, and emphasis on preparation, supportive settings, integration, and harm reduction.
Adverse Health Outcomes of Psilocybin, LSD, MDMA, Ibogaine, and 5-MeO-DMT 2026 cross-sectional survey Unclear Describes self-reported health outcomes attributed to recent use of several psychedelics including 5-MeO-DMT, without specific outcomes or effect sizes reported in the available text.

Points of agreement

  • Human observational and systematic-review evidence points toward rapid reductions in depressive symptoms after 5-MeO-DMT
  • Rodent studies consistently show rapid antidepressant-like and anxiolytic behavioral effects
  • Effects appear to depend on serotonergic receptor activity, with both 5-HT1A and 5-HT2A implicated
  • Non-drug factors such as setting, preparation, and integration are repeatedly emphasized

Conflicts

  • Rodent work finds antidepressant-like effects can occur alongside anxiogenic responses depending on dose and context, whereas human reports emphasize predominantly positive outcomes
  • Preclinical data suggest head twitch (a hallucinogen-typical response) can be dissociated from antidepressant efficacy, leaving unclear whether psychedelic intensity is required

Gaps

  • Human evidence rests largely on small, uncontrolled observational samples with only four-week follow-up
  • Blinding and placebo control in human 5-MeO-DMT trials are limited
  • Dose-response relationships in humans are not established
  • Long-term durability and safety data are lacking
  • Interactions with MAO inhibitors and serotonergic drugs carry documented toxicity risk
  • Populations studied are narrow, and clinical evidence for conditions other than depression remains preliminary
Browse these studies in the library

Common questions

What does the research agree on about 5-MeO-DMT?
  • Human observational and systematic-review evidence points toward rapid reductions in depressive symptoms after 5-MeO-DMT
  • Rodent studies consistently show rapid antidepressant-like and anxiolytic behavioral effects
  • Effects appear to depend on serotonergic receptor activity, with both 5-HT1A and 5-HT2A implicated
  • Non-drug factors such as setting, preparation, and integration are repeatedly emphasized
Where do studies on 5-MeO-DMT conflict?
  • Rodent work finds antidepressant-like effects can occur alongside anxiogenic responses depending on dose and context, whereas human reports emphasize predominantly positive outcomes
  • Preclinical data suggest head twitch (a hallucinogen-typical response) can be dissociated from antidepressant efficacy, leaving unclear whether psychedelic intensity is required
What is still unknown about 5-MeO-DMT?
  • Human evidence rests largely on small, uncontrolled observational samples with only four-week follow-up
  • Blinding and placebo control in human 5-MeO-DMT trials are limited
  • Dose-response relationships in humans are not established
  • Long-term durability and safety data are lacking
  • Interactions with MAO inhibitors and serotonergic drugs carry documented toxicity risk
  • Populations studied are narrow, and clinical evidence for conditions other than depression remains preliminary
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.

The full method, including what a person does and does not review, is on the methods page.

Ask your own question in the Research Synthesis Tool

Latest monthly recap: September 2026 →

1,095 articles · 311 from the last two years · 800,177 participants across 289 studies reporting sample size

Common study designs

review 180 experimental study 185 observational study 35 observational cohort 36 theoretical or philosophical paper 51

Research volume by year

Compare topics →

292 studies whose primary subject is 5-MeO-DMT since 2002

Studies about 5-MeO-DMT per year, 2002 to 2026, peaking at 54 in 2025 Bar chart: one bar per year, taller where more studies were published that year. 0 30 60 2005 2010 2015 2020 2025
2026 is partial
Show the numbers
Studies about 5-MeO-DMT per year, 2002 to 2026, peaking at 54 in 2025
Year Studies
2002 1
2003 0
2004 1
2005 3
2006 7
2007 3
2008 5
2009 6
2010 2
2011 7
2012 6
2013 6
2014 7
2015 4
2016 8
2017 6
2018 9
2019 12
2020 13
2021 10
2022 13
2023 28
2024 33
2025 54
2026 48

Research

Synthesize the evidence → Search all →

Analytical characterization of novel psychoactive substances and adulterants: ortho-methyl fentanyl, N,N-dimethyltryptamine, and medetomidine

TUScholarShare October 19, 2026 Sara E Walton

Forensic toxicology relies heavily on foundational analytical chemistry techniques for the identification and characterization of drugs and toxins, and this work specifically focused on novel psychoactive substances (NPS). NPS are drugs that have newly emerged on the illicit or recreational drug market for use that circumvents legislation (i.e., “legal highs”) and cause significant risk to drug...

DOI: 10.34944/22br-ry12 (opens in new tab)

Pharmacological, clinical, and translational evidence for N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, and zalsupindole: a systematic review.

Progress in neuro-psychopharmacology & biological psychiatry October 6, 2026 Chad Collyer, Gia Han Le, Maryam Hassan et al.

Short-acting tryptamine psychedelics are emerging as candidate psychiatric therapeutics with pharmacological profiles that may offer practical advantages over longer-acting psychedelics. N,N-dimethyltryptamine (N,N-DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) differ in pharmacokinetic, receptor, and phenomenological properties, while zalsupindole is a putatively non-hallucinogenic...

DOI: 10.1016/j.pnpbp.2026.111966 (opens in new tab) Full text (opens in new tab) 5-MEO-DMT N,N-DMT Pharmacodynamics Pharmacokinetics +1

Adverse Health Outcomes of Psilocybin, LSD, MDMA, Ibogaine, and 5-MeO-DMT

JAMA Network Open September 29, 2026 Otto Simonsson, Melissa Bradley, Joshua Curtis Black et al.

This cross-sectional study describes health outcomes attributed to recent use of psilocybin, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), ibogaine, and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a nationally representative survey of US adults.

DOI: 10.1001/jamanetworkopen.2026.36756 (opens in new tab)

Spiral brain dynamics track the temporal unfolding of subjective intensity during the N,N-dimethyltryptamine experience

bioRxiv (Cold Spring Harbor Laboratory) September 28, 2026 Gabriela Sawicka, Marian Martínez-Marín, Christopher Timmermann et al. preprint

Psychedelic compounds such as N,N-dimethyltryptamine (DMT) induce rapid and profound changes in conscious experience, requiring neuroimaging measures that capture how brain dynamics evolve across space and time. Emerging evidence suggests that rotational (vortex-like) dynamics may contribute to the coordination of large-scale neural activity. Here, we introduce two vorticity-based metrics;...

DOI: 10.64898/2026.09.22.753116 (opens in new tab)

N,N-Dimethyltryptamine and harmine formulation alters transient EEG topography sequences near the peak of the psychedelic state

Journal of Psychopharmacology September 22, 2026 Maria Niedernhuber, Dila Suay, Bigna Lenggenhager et al.

BACKGROUND: Psychoactive serotonin 5-HT2A receptor agonists are potent modulators of awareness. Influential theories propose that psychedelics alter whole-brain dynamics by increasing neural signal diversity and dynamic flexibility. Beyond temporal variability, it is an open question whether psychedelics impact the characteristics of transient neural state sequences themselves. AIMS: Our goal...

DOI: 10.1177/02698811261481062 (opens in new tab)

Toxicokinetics and analytical toxicology of four N, N-dimethyltryptamine derivatives studied in human in vitro systems and in vivo by means of zebrafish embryos.

Archives of Toxicology September 21, 2026 Gloria Daziani, Lea Wagmann, Matthias D. Kroesen et al.

N,N-Dimethyltryptamine (DMT) is a naturally occurring substituted tryptamine used as a psychedelic drug for ritual purposes by various cultures. Derivatives were already found on the drug of abuse market, such as N1-tert-butoxycarbonyl-N,N-dimethyltryptamine (DMT-Boc). The aim of the current study was to investigate the toxicokinetics of DMT-Boc and three related DMT derivatives, by name...

DOI: 10.1007/s00204-026-04552-3 (opens in new tab) Full text (opens in new tab) Metabolism New psychoactive substances Toxicokinetics Tryptamines

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

The International Journal of Neuropsychopharmacology September 9, 2026 B Richardson, S Socolow, Martha López-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

The International Journal of Neuropsychopharmacology September 9, 2026 S Socolow, B Richardson, Sofia 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

The 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)

Clinical trials

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