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Ayahuasca

A traditional Amazonian brew combining DMT with monoamine oxidase inhibitors, studied in both ceremonial and clinical contexts.

State of the evidence

Synthesized

Synthesized from 18 studies in the library · AI-generated, grounded in the abstracts below

Found by searching the library for Ayahuasca, yage, hoasca, banisteriopsis, then ranked by relevance.

Ayahuasca shows rapid and sustained antidepressant effects in treatment-resistant depression, with one placebo-controlled trial reporting large effect sizes (Cohen's d up to 1.49) and higher response rates at day 7. Open-label and observational studies also support antidepressant, anxiolytic, and anti-addictive potential, but the evidence base is limited by small samples, few controlled trials, and lack of long-term follow-up. The primary caveat is that most studies are early-phase or uncontrolled, and durability beyond one week is not established.

Confidence in the evidence

Low-Moderate
  • Only one double-blind placebo-controlled RCT (n=29) provides the strongest evidence; other studies are open-label (n=17, n=6) or observational.
  • Results are consistent in direction across studies for antidepressant effects, but sample sizes are small and half of the trials are uncontrolled.
  • Systematic reviews confirm beneficial effects but note small samples and lack of replication, limiting confidence.
  • No large-scale, multi-site RCTs or long-term follow-up studies are available.
How we rate confidence

Confidence reflects the strength of the underlying evidence, not whether the result is favorable. It weighs the number and size of studies, their design (randomized trials count for more than observational or single-case work), how consistently they point the same way, and their risk of bias.

Tiers run from Insufficient to High. High is rare in this field: small, early, or open-label studies land lower even when their direction is encouraging.

Evidence by study

Direction is each study's finding relative to your question: Supports, Opposes, No effect, Mixed, or Unclear.

A single dose of ayahuasca produced significantly greater reductions in depression severity (MADRS) compared to placebo at days 1, 2, and 7, with large effect sizes (Cohen's d up to 1.49) and higher response rates at day 7.

RCT · Sample size: 29

Ayahuasca was associated with fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.

open-label trial

Ayahuasca administration was associated with significant decreases in depression scales from 80 minutes to day 21, and increased blood perfusion in brain regions implicated in emotion regulation.

open-label trial · Sample size: 17

Ayahuasca decreased activity and connectivity within the default mode network, supporting its modulation of self-referential thought.

observational (fMRI) · Sample size: 10

Long-term ayahuasca use was associated with remission of psychopathology, no personality or cognitive deterioration, and high functional status.

observational · Sample size: 30

Ayahuasca-assisted therapy was associated with statistically significant improvements in factors related to problematic substance use.

observational

Regular ayahuasca users showed lower psychopathology scores, better performance on several cognitive tests, and higher self-transcendence compared to controls.

longitudinal observational · Sample size: 242

The review found beneficial effects of ayahuasca for treatment-resistant depression, anxiety, and substance dependence, but noted all studies had small sample sizes and half were open-label.

systematic review

The review concluded that ayahuasca has a safety margin comparable to codeine, minimal abuse potential, and documented long-term psychological benefits when used in a well-established social context.

review

The review reported that ayahuasca has shown effectiveness in treating substance dependence when used in appropriate therapeutic or ritual settings.

review

Across psychedelics including ayahuasca, there is consistent acute disruption of default mode network connectivity and increased cross-network connectivity.

systematic review

DMT administration in a preclinical Parkinson's model resulted in reduced neuroinflammation, neuronal preservation, and symptomatic improvements.

preclinical

Registered trials of ayahuasca and DMT are dominated by early-phase development with conservative eligibility criteria, prioritizing safety and subjective effects over disorder-specific endpoints.

scoping review

The review noted that psilocybin and ketamine have shown short-term improvement in TRD, but did not provide specific findings for ayahuasca beyond mentioning its potential.

review

Ayahuasca-occasioned God encounter experiences were most often described as encounters with 'Ultimate Reality' and frequently involved communication with a conscious, benevolent entity.

survey · Sample size: 435

Ayahuasca increased activation in visual, temporal, and frontal brain areas during a closed-eyes imagery task, lending a status of reality to inner experiences.

observational (fMRI)

Ayahuasca use among Haredi Jews was primarily therapeutic, associated with strengthened religious belief, but also created tensions around foreignness and authority that were addressed through 'koshering' strategies.

qualitative · Sample size: 23

The study examined beliefs in supernatural harm among psychedelic users, but did not report specific findings for ayahuasca alone.

survey · Sample size: 895

Points of agreement

  • Multiple studies converge on ayahuasca having rapid antidepressant effects in treatment-resistant depression, with improvements seen within hours to days.
  • Evidence consistently shows that ayahuasca modulates default mode network activity and connectivity, which is linked to its subjective effects.
  • Studies agree that ayahuasca has low abuse potential and a favorable safety profile when used in controlled or ceremonial settings.
  • Observational and longitudinal studies converge on positive psychological and cognitive outcomes in long-term ritual users.

Conflicts

  • No direct conflicts in direction of findings; all studies report positive or neutral effects, but the strength of evidence varies widely between controlled and uncontrolled designs.
  • One review (27728) focuses on psilocybin and ketamine for TRD and does not provide specific ayahuasca findings, contrasting with the direct evidence from other studies.

Gaps

  • No large-scale, multi-site randomized controlled trials with adequate sample sizes.
  • Durability of antidepressant effects beyond one week is not established; only one RCT followed patients to day 7.
  • Lack of studies comparing ayahuasca to active comparators or standard antidepressants.
  • Minimal research on dose-response relationships, optimal setting, and integration protocols.
  • No studies on long-term safety or cognitive effects in clinical populations beyond one year.
  • Limited research on ayahuasca's effects in populations other than treatment-resistant depression or substance use.
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 Ayahuasca, 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 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.

1,577 articles · 314 from the last two years · 1,507,096 participants across 390 studies reporting sample size

Common study designs

review 209 ethnography 47 qualitative study 88 systematic review 81 theoretical or philosophical paper 200

Psychedelics Use and the Risk of Reduced Formal Mental Health Care

Research Square • Sean Viña

People who use psychedelics are less likely to seek formal mental health care, including medication and outpatient treatment, even when experiencing high psychological distress. Analyzing data from over 458,000 participants in a national US survey between 2010 and 2018, the study found that as distress levels increase, psychedelic users become even less inclined to use formal care compared to non-users. This suggests a heightened risk of self-medication as psychedelics become more culturally and legally accepted.

Meditation, Psychedelics, and Brain Connectivity: A Randomised Controlled Resting-State fMRI Study of N,N -Dimethyltryptamine and Harmine in a Meditation Retreat

medRxiv • Klemens Egger, Daniel Meling, Firuze Polat et al. preprint

In a double-blind, placebo-controlled pharmaco-fMRI study, 40 meditation practitioners on a three-day retreat received either placebo or buccal DMT-harmine (120 mg each). Meditation alone increased network segregation across several resting-state networks, while DMT-harmine increased functional connectivity within the visual network and between visual and attention networks. Between-group differences showed increased connectivity between visual and salience networks in the DMT-harmine group. No prolonged cortical gradient disruption was observed, indicating a return to typical brain organization shortly after the experience. Meditation reduced connectivity between networks, whereas DMT-harmine increased within- and between-network connectivity, revealing distinct neural mechanisms.

Touch and play—'spiritual attacks' in ayahuasca ceremonies

Mika Turkia preprint

Spiritual attacks reported during Amazonian ayahuasca ceremonies are often dismissed as imaginary, but this article argues they are real subjective experiences involving visions or bodily sensations felt as harmful interventions from an external hostile party. The author proposes that these attacks can be understood as mental representations of fundamental disagreements between two parties, with defenses consisting of methods to maintain stability and resolve negative emotions. This conceptualization aims to improve understanding of a rarely documented and difficult-to-conceptualize phenomenon.

Psychedelic Therapy: A Primer for Primary Care Clinicians – Part III. N,N-dimethyltryptamine (DMT) and Ayahuasca

Kenneth Shinozuka, Burton J. Tabaac, Alejandro Arenas et al. preprint

DMT, the psychedelic in ayahuasca, is being studied for depression. In a double-blind, placebo-controlled trial, ayahuasca led to remission in 36% of patients with treatment-resistant depression within one week. A Phase IIa trial reported that 57% of patients with major depressive disorder experienced remission 12 weeks after a single dose of DMT. DMT is naturally produced in the body, but likely at insignificant levels. The idea that DMT is released during death remains unproven. Ayahuasca can cause temporary vomiting but appears generally safe. More research is needed on DMT's therapeutic and biological roles.

Therapeutic properties of ayahuasca component N,N-Dimethyltryptamine in a pre-clinical model of Parkinson's disease.

Experimental neurology • September 1, 2026 • Javier Calleja-Conde, Víctor Echeverry-Alzate, Marina Sanz-sancristobal et al.

In a preclinical model of Parkinson's disease, the compound N,N-dimethyltryptamine (DMT), the main psychoactive ingredient in ayahuasca, reduced neuroinflammation and preserved neurons in the nigrostriatal pathway. Treated animals also showed improvements in behavior. These results suggest DMT may have disease-modifying potential for Parkinson's disease, a progressive neurodegenerative disorder marked by loss of dopaminergic neurons and chronic inflammation, for which current treatments only relieve symptoms.

Combined DMT-harmine formulation reduces negative self-referential emotions during social self-evaluation: a randomized placebo-controlled trial in healthy volunteers.

Psychopharmacology • July 14, 2026 • Helena D Aicher, Joëlle Dornbierer, Luzia Caflisch et al.

A combination of harmine and DMT, the active ingredients in ayahuasca, reduces feelings of embarrassment and shame in healthy men. In a randomized trial with 28 participants, those who received the combination reported significantly less embarrassment when listening to recordings of their own singing compared to those who received a placebo. The treatment also lowered overall shame scores. Harmine alone did not produce these effects. The findings suggest that this compound may help treat psychiatric disorders where negative self-focused emotions play a key role.

Maria Sabina-Die enteignete Heilerin / Vier Enteignungen, ein Muster

Zenodo (CERN European Organization for Nuclear Research) • July 8, 2026 • Schüller Thomas

Two works examine the appropriation of Indigenous healing practices. The first, 'Die enteignete Heilerin' (The Expropriated Healer), focuses on the Mazatec shaman Maria Sabina, whose use of psilocybin mushrooms was co-opted by outsiders. The second, 'Vier Enteignungen, ein Muster' (Four Expropriations, One Pattern), compares the appropriation of peyote, ayahuasca, salvia, and iboga, arguing that a common pattern of colonial and capitalist expropriation underlies these cases.

Beyond Enthusiasm: Ayahuasca and the Future of Depression Research.

Braz J Psychiatry • July 7, 2026

The article argues that while ayahuasca has shown promise in early depression research, the field must move beyond initial enthusiasm to address methodological challenges and ethical considerations. It calls for rigorous, well-controlled studies to determine efficacy and safety, and emphasizes the need to understand the specific mechanisms of action. The authors suggest that future research should focus on long-term outcomes, potential risks, and the integration of ayahuasca into broader therapeutic contexts, rather than simply celebrating its potential.

Psilocybe Poisoning: Pathophysiology, Classification and Treatment. A Clinical Case Review

Mexican Journal of Medical Research ICSA • July 5, 2026 • Omar Azuara-antonio, Erika Rubí de la Cruz-elizaldeb, José Eduardo Carmona-rodriguez et al.

Psilocybe cubensis mushrooms are the primary natural source of psilocybin in the Americas and have a long history of use in Mesoamerican rituals for inducing altered states of consciousness. After ingestion, psilocybin is metabolized into psilocin, a potent serotonergic agonist acting on 5-HT receptors and releasing glutamate. The Aztecs called them Teonanácatl, or 'flesh of the gods.' Interest revived with R. Gordon Wasson's 1950s ethnobotany and now includes research on therapeutic applications for depression, suggesting sustainable relief with fewer side effects than conventional treatments. This combination of ancient ceremonial use and therapeutic potential is prompting reevaluation of their Schedule I legal status, with promising results for major depressive disorder and other psychiatric conditions.

Psychedelics and longevity: implications for lifespan, healthspan and functional aging

Longevity • July 5, 2026 • Mark Haden, Birgitta Woods, Tina Woods et al.

A narrative review examines the convergence of psychedelic research and longevity science, exploring how psychedelic-assisted interventions may influence aging trajectories through both direct biological and indirect psychosocial pathways. The review discusses mechanisms such as enhanced neuroplasticity, modulation of immune and inflammatory signaling, stress-response recalibration, and sustained improvements in psychological well-being and social connectedness, which overlap with pathways influencing biological aging. Safety issues and research priorities are also discussed, including integrating biomarkers, functional outcomes, and longitudinal study designs, and considering whether psychedelic interventions may function as systems-level catalysts for healthier aging.

Clinical trials

All Ayahuasca trials →