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Ayahuasca for depression

Studies whose primary subject is both Ayahuasca 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 Ayahuasca, yage, hoasca, banisteriopsis, Depression, major depressive disorder, then ranked by relevance.

Research on ayahuasca for depression points in a positive direction: a small double-blind placebo-controlled trial in treatment-resistant depression found large reductions in depression severity versus placebo, and open-label, naturalistic, and longitudinal studies report rapid symptom improvements, sometimes lasting weeks to months. Results are broadly consistent across designs, but the evidence base is small, mostly unblinded or observational, and relies heavily on self-report; long-term follow-up suggests symptom reductions may be limited to a few weeks, and larger rigorous trials are needed.

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
Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial 2018 RCT 29 Supports A single dose of ayahuasca produced significantly greater reductions in depression severity than placebo at days 1, 2, and 7, with effect sizes increasing to d=1.49 at day 7.
Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report 2015 observational Supports Ayahuasca showed fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.
Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression 2015 open-label trial 17 Supports A single oral dose of ayahuasca was associated with significant decreases in depression rating scale scores from 80 minutes to day 21, alongside increased blood perfusion in mood-regulating brain regions.
Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis. 2023 systematic review and meta-analysis 14 Supports Psychedelic therapy including ayahuasca was associated with significant reduction of depressive symptoms at 1 day, 1 week, and 3-5 weeks, though results at 6-8 weeks were less conclusive.
Psychological and neuropsychological assessment of regular hoasca users. 2016 cross-sectional study 57 Supports Regular ritual hoasca users showed lower depression and confusion scores than matched controls, without adverse neuropsychological effects.
Cortisol Modulation by Ayahuasca in Patients With Treatment Resistant Depression and Healthy Controls 2018 RCT Supports A single dose of ayahuasca normalized the blunted awakening salivary cortisol response in treatment-resistant depression patients 48 hours after dosing.
Registered clinical studies investigating psychedelic drugs for psychiatric disorders. 2021 review 70 Unclear As of December 2020, 70 registered trials studied psychedelics for psychiatric disorders, with ayahuasca among the less common agents and only 21 studies having published results.
Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial. 2021 open-label trial (secondary analysis) 17 Supports Among individuals with baseline suicidality, a single dose of ayahuasca was associated with rapid and sustained decreases in suicidality over 21 days, with large effect sizes.
Effects of Naturalistic Psychedelic Use on Depression, Anxiety, and Well-Being: Associations With Patterns of Use, Reported Harms, and Transformative Mental States. 2022 cross-sectional survey 2510 Supports Psychedelic use was associated with significant improvements in depressive and anxious symptoms and well-being, with benefits increasing with exposure up to a ceiling, though 13% reported at least one harm.
Ayahuasca use and reported effects on depression and anxiety symptoms: An international cross-sectional study of 11,912 consumers 2021 cross-sectional survey 2011 Supports 78% of participants with depression reported their symptoms were very much improved or completely resolved after ayahuasca, while 2.7% reported worsening.
Pilot Evaluation of a Residential Drug Addiction Treatment Combining Traditional Amazonian Medicine, Ayahuasca and Psychotherapy on Depression and Anxiety 2020 pre-post observational study 31 Supports Integrating ayahuasca and traditional Amazonian medicine with psychotherapy led to significant reductions in anxiety and depression scores from pre- to post-treatment.
Changes in mental health, wellbeing and personality following ayahuasca consumption: Results of a naturalistic longitudinal study. 2022 longitudinal observational study 53 Supports One month after ayahuasca, participants showed significant reductions in depression, anxiety, and stress alongside increases in positive mood and self-efficacy.
Serotonergic psychedelics for depression: What do we know about neurobiological mechanisms of action? 2023 narrative review Supports Argues that serotonergic psychedelics may exert rapid antidepressant effects through 5HT2A agonism, receptor downregulation, BDNF and immune effects, and default mode network disruption.
Acute effects of ayahuasca in a juvenile non-human primate model of depression 2018 RCT (animal) 15 Supports A single dose of ayahuasca reversed hypocortisolemia, reduced stereotypic scratching in males, increased feeding in males, and restored body weight in both sexes.
Long-term effects of ayahuasca in patients with recurrent depression: a 5-year qualitative follow-up 2018 long-term follow-up of an open-label trial 8 Mixed Ayahuasca was well tolerated and most patients rated the experience among the most important of their lives 4-7 years later, but symptom reductions were limited to a few weeks.
Single ayahuasca administration mitigates long-term behavioral and neurochemical effects of early-life stress in rats. 2026 preclinical animal study Supports A single dose of ayahuasca attenuated behavioral and neurochemical changes induced by early-life stress when assessed 15 days later.
Psilocybin and ayahuasca in treatment-resistant depression: clinical evidence, methodological constraints and ethical challenges: a narrative review 2026 narrative review Supports Both psilocybin and ayahuasca show rapid reductions in depressive symptoms in treatment-resistant depression, with psilocybin having more robust evidence for sustained effects; the authors argue trials are limited by strict selection, blinding difficulties, and small samples.
Beyond Enthusiasm: Ayahuasca and the Future of Depression Research. 2026 commentary Unclear Frames psychedelics as a potentially disruptive development in depression treatment, noting many patients still experience partial response, relapse, or treatment resistance.
Psychedelics in treatment-resistant depression: a comprehensive review of mechanisms, clinical evidence, and recommendations. 2026 review Supports Psychedelics including ayahuasca show promise for treatment-resistant depression through neuroplasticity and corticolimbic mechanisms, with rapid and sustained symptom reduction.
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 administration was consistently associated with rapid and significant reductions in suicidal ideation and depressive symptoms.
Psychedelics: Future Therapeutics in Major Depression? 2026 review Supports Argues that typical psychedelics including ayahuasca offer fast-onset, long-lasting antidepressant effects in major depression and treatment-resistant depression.
The therapeutic potential of ayahuasca in depression, generalized anxiety, and substance use disorders: modulation of the depressive burden in a longitudinal study. 2026 longitudinal observational study 280 Supports Ayahuasca combined with psychotherapeutic support was associated with significant reductions in depressive symptoms sustained for up to 180 days, though individual responses varied.
Immunomodulatory and behavioral effects of ayahuasca and N, N-dimethyltryptamine in a rat model of lipopolysaccharide-induced depression. 2025 RCT (animal) 126 Supports Ayahuasca and DMT reduced pro-inflammatory cytokine levels and altered behavior in LPS-induced depressive rats.
Long-Term Mental Health and Wellbeing Outcomes Associated with Naturalistic Ayahuasca Consumption. 2025 prospective cohort study 66 Supports Ayahuasca use was associated with persisting improvements in mental health and wellbeing up to 12 months, with the largest symptom reductions in individuals diagnosed with depressive or anxiety disorders.
Ayahuasca partially preserves striatal integrity in juvenile non-human primates exposed to chronic stress: evidence from stereological evaluation. 2025 controlled experiment (animal) 6 Supports Ayahuasca prevented the reduction in striatal neuronal volume caused by chronic social isolation in marmosets.

Points of agreement

  • A single ayahuasca dose is repeatedly associated with rapid reductions in depression severity, from hours to days after dosing.
  • The only double-blind placebo-controlled trial in treatment-resistant depression found significantly greater improvement than placebo, with large effect sizes.
  • Open-label, naturalistic, and longitudinal studies consistently report symptom improvements, often largest in people with depressive or anxiety diagnoses.
  • Several studies report reductions in suicidality or suicidal ideation alongside depressive symptoms.
  • Animal models show behavioral and neurochemical changes consistent with antidepressant-like effects.
  • Proposed mechanisms converge on serotonergic 5HT2A action, neuroplasticity/BDNF, cortisol modulation, and default mode network changes.

Conflicts

  • Long-term follow-up found symptom reductions limited to a few weeks, whereas some naturalistic cohorts report improvements persisting up to 6-12 months.
  • Reviews note psilocybin has more robust evidence for sustained effects than ayahuasca, while other reviews group them as similarly promising.
  • Survey data show a minority report worsening symptoms or harms, in contrast to the predominantly positive trial and cohort findings.

Gaps

  • Very small samples in controlled trials and open-label studies; few replications.
  • Blinding is difficult with psychedelics, and participant expectations are high.
  • Long-term durability beyond a few weeks to months is unclear and inconsistently measured.
  • Trials exclude patients with comorbidities, high suicide risk, or polypharmacy, limiting generalizability.
  • Dose, ceremony context, and psychotherapy/adjunct support vary widely across studies.
  • Most evidence is observational or self-report; large rigorous randomized trials are lacking.
Browse these studies in the library

Common questions

What does the research agree on about ayahuasca for depression?
  • A single ayahuasca dose is repeatedly associated with rapid reductions in depression severity, from hours to days after dosing.
  • The only double-blind placebo-controlled trial in treatment-resistant depression found significantly greater improvement than placebo, with large effect sizes.
  • Open-label, naturalistic, and longitudinal studies consistently report symptom improvements, often largest in people with depressive or anxiety diagnoses.
  • Several studies report reductions in suicidality or suicidal ideation alongside depressive symptoms.
  • Animal models show behavioral and neurochemical changes consistent with antidepressant-like effects.
  • Proposed mechanisms converge on serotonergic 5HT2A action, neuroplasticity/BDNF, cortisol modulation, and default mode network changes.
Where do studies on ayahuasca for depression conflict?
  • Long-term follow-up found symptom reductions limited to a few weeks, whereas some naturalistic cohorts report improvements persisting up to 6-12 months.
  • Reviews note psilocybin has more robust evidence for sustained effects than ayahuasca, while other reviews group them as similarly promising.
  • Survey data show a minority report worsening symptoms or harms, in contrast to the predominantly positive trial and cohort findings.
What is still unknown about ayahuasca for depression?
  • Very small samples in controlled trials and open-label studies; few replications.
  • Blinding is difficult with psychedelics, and participant expectations are high.
  • Long-term durability beyond a few weeks to months is unclear and inconsistently measured.
  • Trials exclude patients with comorbidities, high suicide risk, or polypharmacy, limiting generalizability.
  • Dose, ceremony context, and psychotherapy/adjunct support vary widely across studies.
  • Most evidence is observational or self-report; large rigorous randomized trials are lacking.
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is Ayahuasca 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 Ayahuasca 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

46 articles · 11 from the last two years · 5,567 participants across 28 studies reporting sample size

Common study designs

review 8 case study 3 systematic review 3 cross-sectional survey 2 randomized controlled trial 4

Research volume by year

Compare topics →

46 studies whose primary subject is ayahuasca for depression since 2013

Studies about ayahuasca for depression per year, 2013 to 2026, peaking at 9 in 2023 Bar chart: one bar per year, taller where more studies were published that year. 0 5 10 2015 2020 2025
2026 is partial
Show the numbers
Studies about ayahuasca for depression per year, 2013 to 2026, peaking at 9 in 2023
Year Studies
2013 1
2014 0
2015 2
2016 1
2017 1
2018 6
2019 0
2020 1
2021 7
2022 5
2023 9
2024 2
2025 4
2026 7

Research

Synthesize the evidence →

Single ayahuasca administration mitigates long-term behavioral and neurochemical effects of early-life stress in rats.

Journal of Neural Transmission September 19, 2026 Guilherme Lodetti, Henrique Redivo, Amanda Gomes Teixeira et al.

Pharmacotherapy for depression is commonly prescribed, yet fewer than half of patients achieve remission with a single treatment. Many also experience intolerable side effects, highlighting the need for new treatment approaches. Classic psychedelics interact with the serotonin (5-HT) receptor class and are therefore strongly involved in the treatment of psychiatric illnesses such as depression,...

DOI: 10.1007/s00702-026-03287-w (opens in new tab) Full text (opens in new tab) Anxiety Depression Serotonin Bdnf +2

Psilocybin and ayahuasca in treatment-resistant depression: clinical evidence, methodological constraints and ethical challenges: a narrative review

Frontiers in Psychiatry September 15, 2026 Serena Chiara Civardi, Filippo Besana, Federico Durbano et al.

Background Treatment-resistant depression (TRD) is a major clinical challenge, with many patients failing to respond to conventional antidepressants. Psychedelic compounds such as psilocybin and ayahuasca have recently gained attention as potential rapid-acting therapies. Beyond their neurobiological effects, methodological, ethical, and real-world applicability concerns are critical for...

DOI: 10.3389/fpsyt.2026.1858319 (opens in new tab)

Beyond Enthusiasm: Ayahuasca and the Future of Depression Research.

Revista Brasileira de Psiquiatria July 7, 2026 Alberto Souza Sá Filho, James Oluwagbamigbe Fajemiroye, Antonio Egidio Nardi et al.

Few topics in contemporary psychiatry generate as much fascination, hope, and discomfort as the therapeutic use of psychedelics.For some, they represent a long-awaited disruption in the treatment of depression, a field in which many patients still experience partial response, relapse, or treatment resistance despite decades of

DOI: 10.47626/1516-4446-2026-5035 (opens in new tab)

Psychedelics in treatment-resistant depression: a comprehensive review of mechanisms, clinical evidence, and recommendations.

Neuropsychiatrie June 30, 2026 Cielo A Estela-Fernandez, Reem Mohamed Yousif Elsheikh, Dal Bianco Beatrice et al.

Major depressive disorder (MDD) is a heterogeneous, debilitating disorder. A distinct subgroup within the MDD spectrum is identified to have treatment-resistant depression (TRD). There is an impetus to find alternative treatments for TRD to reduce disease burden and improve quality of life. Psychedelics have been used in the treatment of various psychiatric disorders since the 1950s, with...

DOI: 10.1007/s40211-026-00584-4 (opens in new tab) Full text (opens in new tab) Ayahuasca Depression Ketamine Psilocybin +2

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

The therapeutic potential of ayahuasca in depression, generalized anxiety, and substance use disorders: modulation of the depressive burden in a longitudinal study.

Frontiers in Psychiatry 2026 Gláucio Silva Camargos, Geraldo Magela De Faria Júnior, Marcelo Lourenço et al.

This longitudinal observational study evaluated changes in depressive symptoms associated with ritualistic ayahuasca use in patients diagnosed with depressive disorders, as well as depressive burden in individuals with anxiety and substance use disorders. The research was conducted with 280 adults treated at clinics in the northwestern region of the state of São Paulo, under the jurisdiction of...

DOI: 10.3389/fpsyt.2026.1726909 (opens in new tab) Full text (opens in new tab) Ayahuasca Mental disorders Psychedelics Psychotherapy +1

Psychedelics: Future Therapeutics in Major Depression?

Advances in experimental medicine and biology 2026 Berend Olivier, Jocelien D A Olivier

Major depressive disorder (MDD), including treatment-resistant depression (TRD), is a highly prevalent psychiatric disorder. MDD is associated with severe suffering, burden and large economical costs. Although various conventional antidepressant treatments are available, a large portion of depressed people does not or not adequately respond to the first-line treatments (mostly SSRIs and SNRIs)...

DOI: 10.1007/978-981-95-6872-7_25 (opens in new tab) Full text (opens in new tab) Ayahuasca Ketamine Major depressive disorder Psilocybin +11

Immunomodulatory and behavioral effects of ayahuasca and N, N-dimethyltryptamine in a rat model of lipopolysaccharide-induced depression.

Metabolic Brain Disease June 11, 2025 Daniel do Nascimento Sousa, Monique de Azevedo, Maria Lucília Santos et al. 5 citations

Ayahuasca (Aya) is an Amazonian beverage traditionally used as medicine by Indigenous people in South America to treat various illnesses and have shown a potential to treat depression. This study aimed to investigate the antidepressant effects of fluoxetine, Aya and N, N dimethyl tryptamine (DMT), a component of the beverage, focusing on the modulation of inflammatory serum cytokine profiles...

DOI: 10.1007/s11011-025-01650-6 (opens in new tab) Full text (opens in new tab) Ayahuasca DMT Behavior Lps-induced depressive rats +10

Long-Term Mental Health and Wellbeing Outcomes Associated with Naturalistic Ayahuasca Consumption.

Journal of Psychoactive Drugs February 20, 2025 Broc A. Pagni, Andreas Halman, Jerome Sarris et al. 7 citations

The durability of ayahuasca's effects on mental health and the influence of clinical diagnoses on therapeutic response is unclear. Adults with no prior exposure to ayahuasca (n = 66) participating in neo-shamanic ayahuasca ceremonies completed questionnaires at baseline, 7 days, and 1, 6, and 12 months. Mixed models were used to characterize temporal trajectories in mental health, alcohol and...

DOI: 10.1080/02791072.2025.2465800 (opens in new tab) Full text (opens in new tab) DMT Anxiety Depression Addiction +10

Gut-Mind Interactions in Psychedelic Healing: A Case Study Assessing the Effects of Huachuma and Ayahuasca on the Mind and Microbiome.

Journal of Restorative Medicine 2025 Payton Follestad, Patricia Filbin, Brice Thompson et al.

Psychedelic plant medicines such as Ayahuasca and Huachuma (San Pedro cactus) are gaining scientific attention for their potential to improve mental health. However, the interplay between these traditional medicines, the gut microbiome, and mental health outcomes remains underexplored. The main objectives of this study are to investigate the effects of Ayahuasca and Huachuma ceremonies on the...

DOI: 10.14200/jrm.2025.0006 (opens in new tab) Full text (opens in new tab) Ayahuasca Depression Huachuma San pedro +3

Clinical trials

All ayahuasca for depression trials →