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 September 21, 2026

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.

The research generally points toward ayahuasca reducing depressive symptoms, with the strongest single piece of evidence being a small randomized placebo-controlled trial in treatment-resistant depression that found large between-group effects (Cohen's d up to 1.49 at day 7). Open-label, observational, and survey studies consistently report rapid symptom reductions, but these designs cannot rule out expectancy and selection effects, and the one long-term follow-up found symptom reductions lasted only a few weeks. Overall the evidence is promising but limited by very small samples, few controlled trials, and uncertain durability.

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 between-group effect sizes increasing from d=0.84 to d=1.49.
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, along with increased blood perfusion in mood-regulating brain regions.
Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis. 2023	systematic review with 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, but 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, with no 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 were investigating psychedelics for psychiatric disorders, with ayahuasca representing a small fraction 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 (Hedges' g = 1.31-1.75).
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	Mixed	Psychedelic use was associated with significant improvements in depressive and anxious symptoms and increased well-being, with benefits increasing with exposure up to a ceiling, but 13% of participants reported at least one harm from use.
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, stress, and substance use, 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	Serotonergic psychedelics may exert rapid antidepressant effects through 5HT2A receptor agonism, receptor downregulation, effects on BDNF and immune responses, and disruption of the default mode network.
Acute effects of ayahuasca in a juvenile non-human primate model of depression 2018	RCT	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 in a juvenile marmoset model of depression.
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 but symptom reductions were limited to a few weeks, although most patients rated the experience among the most important of their lives 4 to 7 years later.
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 anxiety- and depressive-like behaviors and neurochemical changes in maternally deprived rats 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		Mixed	Both psilocybin and ayahuasca show rapid reductions in depressive symptoms in treatment-resistant depression, with psilocybin having more robust evidence for sustained effects, but trials are constrained by strict selection criteria, blinding difficulties, small samples, and ethical gaps.
Beyond Enthusiasm: Ayahuasca and the Future of Depression Research. 2026	theoretical		Unclear	Argues that ayahuasca research for depression requires more rigorous methodology and caution before drawing conclusions about efficacy.
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 mechanisms such as neuroplasticity and corticolimbic enhancement, 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 studies, ayahuasca administration was consistently associated with rapid and significant reductions in suicidal ideation and depressive symptoms in patients with depressive disorders.
Psychedelics: Future Therapeutics in Major Depression? 2026	review		Supports	Typical and atypical psychedelics, including ayahuasca, offer fast-onset and lasting antidepressant effects in major depressive disorder 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	126	Supports	Ayahuasca and DMT reduced pro-inflammatory cytokine levels and altered behavior in LPS-induced depressive rats, indicating potential for treating inflammation-related aspects of depression.
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	6	Supports	Ayahuasca prevented the reduction in striatal neuronal volume caused by chronic social isolation in marmosets.

Points of agreement

Across controlled, open-label, observational, and survey designs, ayahuasca is repeatedly associated with reductions in depressive symptoms.
Effects are described as rapid, often within hours to days of a single dose.
Several studies report benefits persisting for weeks to months, with the largest reductions in people who had depression or anxiety diagnoses.
Multiple reviews attribute the antidepressant action to serotonergic, neuroplastic, and anti-inflammatory mechanisms.

Conflicts

The single long-term follow-up found symptom reductions limited to a few weeks, whereas some observational studies report improvements sustained up to 6-12 months.
One narrative review states psilocybin has more robust evidence for sustained effects than ayahuasca, while other reviews group them as similarly promising.
A theoretical paper argues for caution about efficacy claims, contrasting with the generally positive conclusions of most empirical and review studies.

Gaps

Very few randomized placebo-controlled trials of ayahuasca specifically; most evidence comes from open-label or observational designs.
Small sample sizes throughout, limiting statistical power and generalizability.
Blinding is difficult with psychedelics, and expectancy effects are rarely controlled.
Durability beyond a few weeks is unclear, with conflicting findings.
Dosing regimens (single vs repeated) and optimal therapeutic context are not established.
Populations studied are narrow: mostly treatment-resistant or recurrent depression, with little on comorbidities, high suicide risk, or polypharmacy.

Browse these studies in the library

Common questions

What does the research agree on about ayahuasca for depression?

Across controlled, open-label, observational, and survey designs, ayahuasca is repeatedly associated with reductions in depressive symptoms.
Effects are described as rapid, often within hours to days of a single dose.
Several studies report benefits persisting for weeks to months, with the largest reductions in people who had depression or anxiety diagnoses.
Multiple reviews attribute the antidepressant action to serotonergic, neuroplastic, and anti-inflammatory mechanisms.

Where do studies on ayahuasca for depression conflict?

The single long-term follow-up found symptom reductions limited to a few weeks, whereas some observational studies report improvements sustained up to 6-12 months.
One narrative review states psilocybin has more robust evidence for sustained effects than ayahuasca, while other reviews group them as similarly promising.
A theoretical paper argues for caution about efficacy claims, contrasting with the generally positive conclusions of most empirical and review studies.

What is still unknown about ayahuasca for depression?

Very few randomized placebo-controlled trials of ayahuasca specifically; most evidence comes from open-label or observational designs.
Small sample sizes throughout, limiting statistical power and generalizability.
Blinding is difficult with psychedelics, and expectancy effects are rarely controlled.
Durability beyond a few weeks is unclear, with conflicting findings.
Dosing regimens (single vs repeated) and optimal therapeutic context are not established.
Populations studied are narrow: mostly treatment-resistant or recurrent depression, with little on comorbidities, high suicide risk, or polypharmacy.

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 randomized controlled trial 4 theoretical or philosophical paper 2

Research volume by year

Compare topics →

46 studies whose primary subject is ayahuasca for depression since 2013

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 (Vienna, Austria : 1996) 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 Full text 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

Beyond Enthusiasm: Ayahuasca and the Future of Depression Research.

Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999) 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

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

Neuropsychiatrie : Klinik, Diagnostik, Therapie und Rehabilitation : Organ der Gesellschaft Osterreichischer Nervenarzte und Psychiater 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 Full text 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 Full text 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 Full text 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 Full text 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 Full text 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 Full text 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 Full text Ayahuasca Depression Huachuma San pedro +3

Clinical trials

Ayahuasca and Esketamine for Major Depression (opens in new tab)

Completed Phase 2 22 participants University of Sao Paulo
Antidepressant Effects of Ayahuasca: a Randomized Placebo Controlled Trial in Treatment Resistant Depression (opens in new tab)

Completed Phase 1/2 35 participants Universidade Federal do Rio Grande do Norte

All ayahuasca for depression trials →