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DMT for depression

Studies whose primary subject is both DMT and Depression, with an evidence synthesis read across the most-cited and most recent of them.

State of the evidence

Synthesized

Synthesized from 25 studies in the library · AI-generated, grounded in the abstracts below

Found by searching the library for DMT, dimethyltryptamine, N,N-DMT, Depression, major depressive disorder, MDD, then ranked by relevance.

Direct clinical evidence on DMT for depression is early-stage and comes from small, mostly open-label trials, but it consistently points toward rapid antidepressant effects: single-day inhaled or intravenous DMT produced large drops in depression scores within a day and response/remission in a majority of treatment-resistant patients, with some benefit persisting to a week or a month. Related compounds (5-MeO-DMT, ayahuasca) show similar rapid effects in small trials and surveys, and animal work supports antidepressant-like actions. The main caveats are very small samples, lack of placebo control or blinding in the depression trials, and limited data on durability beyond weeks to months.

Evidence by study

Direction is which way each study's own result points, not our rating of the study.

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
Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression 2018 experimental animal study Supports DMT reduced immobility in the forced swim test and facilitated extinction of cued fear memory, indicating antidepressant- and anxiolytic-like effects despite initial anxiogenic responses.
Exploratory study of the dose-related safety, tolerability, and efficacy of dimethyltryptamine (DMT) in healthy volunteers and major depressive disorder. 2022 open-label dose-escalation phase 1 trial 10 Supports HAMD-17 scores fell significantly the day after 0.3 mg/kg IV DMT (mean difference -4.5 points, Hedge's g = 0.75), with transient blood pressure, heart rate and anxiety increases resolving within 20-30 minutes.
5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety. 2019 cross-sectional survey 362 Supports Among respondents with prior depression diagnoses, 80% reported improvement after 5-MeO-DMT, and improvement was associated with greater mystical experience intensity and spiritual significance.
Registered clinical studies investigating psychedelic drugs for psychiatric disorders. 2021 review of registered trials 70 Unclear Only a small fraction of registered psychedelic trials involved DMT or 5-MeO-DMT (each about 1.4%), both targeting MDD, and only 21 of 70 registered studies had published results.
A phase 1/2 trial to assess safety and efficacy of a vaporized 5-methoxy-N,N-dimethyltryptamine formulation (GH001) in patients with treatment-resistant depression 2023 phase 1/2 clinical trial 16 Supports Inhaled 5-MeO-DMT (GH001) was well tolerated and produced 87.5% remission at day 7 with individualized dosing, with remissions observed from day 1 and a mean MADRS reduction of -24.4 (-76%).
Rapid and sustained antidepressant effects of vaporized N,N-dimethyltryptamine: a phase 2a clinical trial in treatment-resistant depression. 2025 open-label trial 14 Supports Inhaled DMT (15 mg and 60 mg) was safe and produced a mean 21.14-point MADRS reduction by day 7 (p < 0.001) with an 85.71% response rate.
Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate) in healthy participants. 2024 double-blind placebo-controlled dose-escalation trial 44 Supports Intranasal 5-MeO-DMT was well tolerated up to 12 mg with rapid absorption and dose-proportional exposure, and 60% had a complete mystical experience at 10-12 mg; depression outcomes were not assessed.
Role of Psychedelics in Treatment-Resistant Depression. 2023 review Mixed Evidence for classic psychedelics including ayahuasca/DMT in treatment-resistant depression is limited but early studies show promising results, and the field may be subject to a hype bubble.
Psilocybin and Other Classic Psychedelics in Depression. 2024 review Supports 5-HT2A-targeting psychedelics such as psilocybin and DMT, coupled with psychological support, can produce rapid mood improvement in depression lasting for months, likely via mechanisms distinct from classical antidepressants.
Lysergic Acid Diethylamide, Psilocybin and Dimethyltryptamine in Depression Treatment: A Systematic Review 2021 systematic review 10 Supports Most included studies showed significant correlation between psilocybin and DMT use and reduced depression symptom intensity, though further observations are required.
Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression 2025 review Supports Early small trials show short 15-30 minute interventions with 5-MeO-DMT and DMT are safe and can induce marked depression improvement within 24 hours that sustains at least one week, with long-term efficacy data scarce.
Ayahuasca for the Treatment of Depression. 2022 review Supports Open and randomized placebo-controlled ayahuasca trials show significant and rapid antidepressant effects starting as early as one day after intervention.
A Physician’s Attempt to Self-Medicate Bipolar Depression with N,N-Dimethyltryptamine (DMT) 2017 case study 1 Opposes Chronic self-administered DMT augmented with phenelzine in a physician with bipolar depression resulted in mania and psychosis.
The current state of ayahuasca research in animal models: A systematic review. 2023 systematic review of animal studies 32 Supports Ayahuasca was safe at ceremonial-comparable doses and showed antidepressant effects and reduced reward from ethanol and amphetamines in animal models, while anxiety outcomes were inconclusive.
The Antidepressant Effects of Vaporized N,N-Dimethyltryptamine: An Open-Label Pilot Trial in Treatment-Resistant Depression. 2025 open-label clinical trial 6 Supports Vaporized DMT (15 mg then 60 mg) produced significant MADRS and PHQ-9 reductions from day 1 to month 1, with 83.33% responding by day 7 and 66.67% maintaining response at one month.
Beyond symptom reduction: DMT improves anxiety, life satisfaction, and quality of life in healthy volunteers and patients with depression 2026 open-label clinical trials 41 Supports Inhaled DMT with psychological support reduced state anxiety up to one day, increased life satisfaction in healthy volunteers up to 14 days, and produced sustained quality-of-life improvements in patients over 12 months.
N,N-dimethyltryptamine elicits antidepressant and anxiolytic effects in helpless mice: a comparative study with S-ketamine. 2026 animal study Supports DMT was as effective as S-ketamine in reversing escape deficits and preventing stress-induced anhedonia, and reduced immobility for up to 8 days, longer than S-ketamine's 30 hours.
Treatment of major depressive disorder and treatment resistant depression with 5-MeO-DMT: Impact of 25 years of non-traditional public scientific communication and education on clinical development and commercialization 2026 review Supports Argues that 25 years of informal and underground 5-MeO-DMT use has generated substantial but underrecognized knowledge of depressive symptom relief, and that communication gaps hinder integration into mainstream psychiatry.
Ayahuasca Therapy: Possible Reduction of Suicidal Ideation in Treatment-Resistant Depression - A Systematic Review. 2026 systematic review 5 Supports Across five methodologically heterogeneous studies, ayahuasca was consistently associated with rapid and significant reductions in suicidal ideation and depressive symptoms.
A phase 2 uncontrolled, open-label study of intranasal BPL-003 (5-methoxy- N,N -dimethyltryptamine) in patients with treatment-resistant depression 2026 phase 2 open-label clinical trial Supports A single dose of intranasal 5-MeO-DMT (BPL-003) produced a rapid and sustained reduction in MADRS score over 12 weeks, warranting larger controlled trials.
5-Methoxy-N,N-Dimethyltryptamine: Functional Safety Pharmacology and Video-EEG Assessment of a Short-Acting Serotonergic Psychedelic in Beagle Canines. 2026 preclinical animal study 11 No effect Intranasal 5-MeO-DMT produced dose-dependent serotonergic behavioral signs but no seizures or epileptiform EEG activity at any dose; depression efficacy was not assessed.
Single-dose DMT reverses anhedonia and cognitive deficits via restoration of neurogenesis in a stress-induced depression model. 2026 preclinical animal study Supports A single 30 mg/kg dose of DMT reversed depressive-like behavior and cognitive deficits and increased adult-born granule cell integration, outperforming chronic fluoxetine in most domains.
Safety and tolerability of multiple sublingual microdoses of 5-MeO-DMT in adults with moderate symptoms of depression and/or anxiety: a randomized, double-blind, placebo-controlled study. 2025 randomized double-blind placebo-controlled trial No effect Repeated sub-psychedelic sublingual 5-MeO-DMT doses were safe and well tolerated with dose-dependent brain modulation but no full psychedelic effects; antidepressant efficacy was not reported.
Optimized Parenteral and Intranasal Formulations of Tryptamine Psychedelics for Rapid-Acting Antidepressant Therapy. 2025 review Supports Argues that parenteral and intranasal DMT and 5-MeO-DMT formulations overcome bioavailability and metabolism limits, enabling rapid-onset, short-duration therapeutic effects for treatment-resistant depression.
Immunomodulatory and behavioral effects of ayahuasca and N, N-dimethyltryptamine in a rat model of lipopolysaccharide-induced depression. 2025 randomized controlled animal trial 126 Supports Ayahuasca and DMT reduced pro-inflammatory cytokine levels and altered behavior in LPS-induced depressive rats, suggesting potential for inflammation-related depression.

Points of agreement

  • Small open-label human trials of inhaled or intravenous DMT report rapid, large reductions in depression scores, often within a day, with response and remission in a majority of treatment-resistant patients.
  • 5-MeO-DMT and ayahuasca (which contains DMT) show similarly rapid antidepressant signals in small trials, surveys and reviews.
  • Animal studies consistently show DMT produces antidepressant-like behavioral effects, sometimes lasting days and comparable to or longer than ketamine.
  • Reviews agree the human evidence base is early, small and preliminary, and call for larger controlled trials.
  • Short-acting tryptamines are described as safe and well tolerated in the studied doses, with transient cardiovascular and anxiety effects.

Conflicts

  • One case report describes mania and psychosis from chronic self-administered DMT with a MAOI in bipolar depression, contrasting with the generally favorable safety reported in trials.
  • Some reviews caution about a possible hype bubble and limited evidence, while trial reports and other reviews emphasize marked efficacy.
  • Rodent work notes initial anxiogenic responses to DMT even as longer-term effects are anxiolytic.

Gaps

  • Most depression trials are open-label and uncontrolled, so placebo and expectancy effects are not excluded.
  • Samples are very small (single digits to low tens), limiting precision and generalizability.
  • Durability beyond one week to a few months is largely unestablished, and long-term efficacy data are scarce.
  • Optimal dose, dosing schedule, route and the necessity of psychological support are unresolved.
  • Little evidence in bipolar depression, and safety data on combining DMT with MAOIs are limited to a single case.
  • Blinding is difficult with psychedelics, and few randomized placebo-controlled depression trials of DMT exist.
Browse these studies in the library

Common questions

What does the research agree on about DMT for depression?
  • Small open-label human trials of inhaled or intravenous DMT report rapid, large reductions in depression scores, often within a day, with response and remission in a majority of treatment-resistant patients.
  • 5-MeO-DMT and ayahuasca (which contains DMT) show similarly rapid antidepressant signals in small trials, surveys and reviews.
  • Animal studies consistently show DMT produces antidepressant-like behavioral effects, sometimes lasting days and comparable to or longer than ketamine.
  • Reviews agree the human evidence base is early, small and preliminary, and call for larger controlled trials.
  • Short-acting tryptamines are described as safe and well tolerated in the studied doses, with transient cardiovascular and anxiety effects.
Where do studies on DMT for depression conflict?
  • One case report describes mania and psychosis from chronic self-administered DMT with a MAOI in bipolar depression, contrasting with the generally favorable safety reported in trials.
  • Some reviews caution about a possible hype bubble and limited evidence, while trial reports and other reviews emphasize marked efficacy.
  • Rodent work notes initial anxiogenic responses to DMT even as longer-term effects are anxiolytic.
What is still unknown about DMT for depression?
  • Most depression trials are open-label and uncontrolled, so placebo and expectancy effects are not excluded.
  • Samples are very small (single digits to low tens), limiting precision and generalizability.
  • Durability beyond one week to a few months is largely unestablished, and long-term efficacy data are scarce.
  • Optimal dose, dosing schedule, route and the necessity of psychological support are unresolved.
  • Little evidence in bipolar depression, and safety data on combining DMT with MAOIs are limited to a single case.
  • Blinding is difficult with psychedelics, and few randomized placebo-controlled depression trials of DMT exist.
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is DMT for depression, 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 DMT for depression 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

37 articles · 17 from the last two years · 843 participants across 17 studies reporting sample size

Common study designs

review 9 case study 2 systematic review 4 randomized controlled trial 2 theoretical or philosophical paper 2

Research volume by year

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37 studies whose primary subject is DMT for depression since 2017

Studies about DMT for depression per year, 2017 to 2026, peaking at 9 in 2025 Bar chart: one bar per year, taller where more studies were published that year. 0 5 10 2020 2025
2026 is partial
Show the numbers
Studies about DMT for depression per year, 2017 to 2026, peaking at 9 in 2025
Year Studies
2017 1
2018 2
2019 1
2020 0
2021 3
2022 2
2023 8
2024 3
2025 9
2026 8

Research

Synthesize the evidence →

From Toad Venom to Drug Development: The Clinical Pharmacology of Mebufotenin (5-MeO-DMT) in Treatment-Resistant Depression.

CNS Drugs November 4, 2026 Robert Likić, Igor Radanović, Deni Rkman et al.

Treatment-resistant depression affects about one-third of patients with major depressive disorder and remains a major unmet need. Mebufotenin (5-methoxy-N,N-dimethyltryptamine; 5-MeO-DMT), the principal psychoactive constituent of Incilius alvarius parotoid secretion and of several Amazonian plants, is a pharmacologically atypical serotonergic psychedelic in clinical development for this...

DOI: 10.1007/s40263-026-01346-0 (opens in new tab) Full text (opens in new tab)

Beyond symptom reduction: DMT improves anxiety, life satisfaction, and quality of life in healthy volunteers and patients with depression

Journal of Psychopharmacology July 8, 2026 Raynara Bolcont, Fernanda Palhano-Fontes, Handersson Barros et al.

BACKGROUND: -dimethyltryptamine (DMT); however, long-term effects, including broader well-being dimensions, are sparsely explored across populations. AIMS: Investigating whether DMT produces sustained improvements in anxiety, life satisfaction, and quality of life, in both healthy individuals and patients with treatment-resistant depression (TRD). METHODS: In 2 open-label clinical trials, 27...

DOI: 10.1177/02698811261465005 (opens in new tab) Anxiety Life satisfaction Depression economics Optimism +8

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

Treatment of major depressive disorder and treatment resistant depression with 5-MeO-DMT: Impact of 25 years of non-traditional public scientific communication and education on clinical development and commercialization

Psychedelics April 25, 2026 Juliet Meccia, David Casimir, Sisi Li et al.

Over the past 25 years, the use of 5-MeO-DMT in informal and underground settings has contributed a substantial, yet underrecognized, body of knowledge relating to the efficacy of 5-MeO-DMT in alleviating depressive symptoms. Traditional models of drug development, typically characterized by structured trials and regulatory milestones, rarely consider findings from these alternative routes. The...

DOI: 10.1016/j.psyche.2026.100019 (opens in new tab) Major depressive disorder Mainstream Commercialization Grassroots +8

Ayahuasca Therapy: Possible Reduction of Suicidal Ideation in Treatment-Resistant Depression - A Systematic Review.

Journal of Psychoactive Drugs April 23, 2026 Brayan Jonas Mano-Sousa, Maria Clara Gama Fontes, Ana Clara Anacleto Gonçalves et al.

Suicide, particularly in treatment-resistant depression (TRD), remains a pressing global health issue, with over 700,000 annual deaths. Existing treatments often have limited efficacy and delayed onset, creating a need for rapid-acting interventions. Ayahuasca, a traditional Amazonian psychedelic, has shown potential for rapidly reducing suicidal ideation. Our systematic review evaluated the...

DOI: 10.1080/02791072.2026.2661580 (opens in new tab) Full text (opens in new tab) DMT Ayahuasca Neuroplasticity Psychedelic therapy +2

A phase 2 uncontrolled, open-label study of intranasal BPL-003 (5-methoxy- N,N -dimethyltryptamine) in patients with treatment-resistant depression

Journal of Psychopharmacology February 27, 2026 Claire T. Roberts, Mathieu Seynaeve, Anna O. Ermakova et al.

Results confirmed the safety profile of BPL-003 in a TRD population. A rapid and sustained reduction in MADRS score was observed over 12 weeks, suggesting BPL-003 could be beneficial in TRD, warranting investigation in larger controlled trials.

DOI: 10.1177/02698811261420087 (opens in new tab) Treatment-resistant depression Major depressive disorder Depression economics Nasal administration +5

5-Methoxy-N,N-Dimethyltryptamine: Functional Safety Pharmacology and Video-EEG Assessment of a Short-Acting Serotonergic Psychedelic in Beagle Canines.

International journal of toxicology January 31, 2026 Amir Lotfi, Samantha Sparapani, Mylène Pouliot et al.

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a serotonin receptor agonist, in clinical development for the treatment of major depression and other psychiatric disorders. A critical safety concern for serotonergic compounds is their potential to induce seizures, as a severe manifestation of serotonin toxicity. The objective of this study was to evaluate the seizure liability of 5-MeO-DMT in a...

DOI: 10.1177/10915818261419429 (opens in new tab) Full text (opens in new tab) Depression Serotonin Cns safety pharmacology EEG +3

Single-dose DMT reverses anhedonia and cognitive deficits via restoration of neurogenesis in a stress-induced depression model.

Translational Psychiatry January 29, 2026 Rafael V Lima Da Cruz, Rêmullo B. G. De Miranda Costa, Gabriel M. De Queiroz et al. 2 citations

Major depressive disorder (MDD) remains a leading cause of disability worldwide, with current treatments limited by delayed onset and low efficacy. The serotonergic psychedelic N,N-dimethyltryptamine (DMT) has shown rapid antidepressant effects in early clinical studies, yet its mechanisms and efficacy remain poorly characterized in established models of depression. Here, we evaluated the...

DOI: 10.1038/s41398-026-03852-7 (opens in new tab) Full text (opens in new tab)

Safety and tolerability of multiple sublingual microdoses of 5-MeO-DMT in adults with moderate symptoms of depression and/or anxiety: a randomized, double-blind, placebo-controlled study.

Neuropsychopharmacology July 15, 2025 Maria Beatriz Bistue Millón, Laura Noguera, Diana Bruno et al. 4 citations

This Phase I clinical trial is the first to rigorously evaluate the safety, tolerability, and pharmacokinetics of a novel sublingual formulation of 5-MeO-DMT, administered at sub-psychedelic doses to adults with moderate to high levels of anxiety and/or depression, without formal psychiatric diagnosis or ongoing treatment. Using a double-blind, placebo-controlled design, participants received a...

DOI: 10.1038/s41386-025-02167-3 (opens in new tab) Full text (opens in new tab) 5-MEO-DMT Mental health therapy Clinical trials Drug safety

Optimized Parenteral and Intranasal Formulations of Tryptamine Psychedelics for Rapid-Acting Antidepressant Therapy.

ACS Medicinal Chemistry Letters June 12, 2025 Robert B. Kargbo 1 citation

Innovative formulations of N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) enable parenteral and intranasal delivery, respectively. These delivery systems overcome limitations of poor bioavailability and rapid metabolism, offering rapid-onset, short-duration therapeutic effects. The compositions support controlled psychedelic interventions for psychiatric...

DOI: 10.1021/acsmedchemlett.5c00265 (opens in new tab) Full text (opens in new tab) 5-MEO-DMT Treatment-resistant depression Entheogenic treatment Hallucinogen-assisted therapy +9

Clinical trials

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