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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.

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.

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.

Latest monthly recap: June 2026 →

1,580 articles · 342 from the last two years · 2,919,753 participants across 453 studies reporting sample size

Common study designs

review 232 qualitative study 91 systematic review 89 observational cohort 55 theoretical or philosophical paper 227

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-Sancristóbal 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.

Beyond Enthusiasm: Ayahuasca and the Future of Depression Research.

Braz J Psychiatry July 7, 2026 Alberto Souza Sá Filho, James Oluwagbamigbe Fajemiroye, Antonio Egidio Nardi et al.

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.

Registered Clinical Trials of Ayahuasca and DMT: A Scoping Review.

Clinical pharmacology and therapeutics July 1, 2026 Tijana Stojanovic, Kent W Nilsson, Robert Fredriksson et al.

The clinical trial landscape for ayahuasca and DMT expanded rapidly after 2020-2021, dominated by early-stage development. Most trials are phase I, primarily sponsored by academic or hospital institutions, and focus on DMT-only administration. Eligibility criteria are conservative, enrolling medically and psychiatrically healthy adults with extensive cardiovascular and psychiatric exclusions. Primary outcomes prioritize acute safety, physiological monitoring, and characterization of subjective altered-states, while disorder-specific symptom endpoints are less common. Publications from depression-focused trials provide preliminary evidence of potential clinical effects, but the field remains constrained by a limited number of indication-specific programs beyond depression.

Single Ayahuasca administration attenuates alcohol relapse and associated behavioral, neurochemical, and oxidative alterations in rats

Progress in Neuro-psychopharmacology and Biological Psychiatry July 1, 2026 Guilherme Lodetti, Rafael Mariano de Bitencourt, Antonio Inserra et al.

A single dose of Ayahuasca reduced relapse-like alcohol drinking in alcohol-dependent rats, with effects varying by sex and alcohol concentration. It also lessened anxiety- and depression-like behaviors caused by alcohol withdrawal, increased dopamine in the striatum of both male and female rats, and restored serotonin levels in the cortex primarily in males. Ayahuasca partially reversed alcohol-related drops in brain-derived neurotrophic factor and reduced markers of oxidative stress in the frontal cortex, hippocampus, and striatum. However, antioxidant enzyme activities were not consistently altered, and some neurochemical and oxidative stress measures showed only partial normalization. The findings suggest Ayahuasca modulates multiple neurobiological pathways disrupted by chronic alcohol exposure, with region- and sex-dependent effects.

DMT und Ayahuasca / DMT and Ayahuasca

Zenodo (CERN European Organization for Nuclear Research) July 1, 2026 Schüller Thomas

DMT is the fourth classical psychedelic in a series and has five distinguishing features: oral inactivity without an MAO inhibitor; ultra-short duration (minutes) when smoked or injected; ayahuasca as a plant combination (DMT source plus β-carboline MAOI); endogenous occurrence in mammals; and the unique religious legal ruling Gonzales v. O Centro (2006). Chemically, DMT is a tryptamine (like psilocybin and LSD), contrasting with the phenethylamine mescaline. This bilingual full work provides a transdisciplinary scientific overview of DMT and ayahuasca across eight disciplines, with explicit labeling of levels of certainty (confirmed / probable / open).

EXPANSÃO GLOBAL DA AYAHUASCA E SAÚDE MENTAL

Interações - cultura e comunidade June 23, 2026 Leonardo Tondato Mello, Kemily Bakri Ottoni, Janaína Liz Aquino

The global expansion of ayahuasca carries both creative and destructive potential for mental health, depending on the historical and social context of Indigenous peoples' exclusion and marginalization since the colonial period. Ongoing studies of ayahuasca's therapeutic effects indicate that proper management and interdisciplinary collaboration between ancestral knowledge and Western psychology/psychiatry are essential. The article concludes that a fair and respectful exchange with Indigenous knowledge is necessary to avoid predatory appropriation.

Global pressure on ayahuasca threatens Amazonian plants and knowledge systems

June 23, 2026 Carlos Minuano

Benki Piyãko, an Ashaninka leader in the Brazilian state of Acre, warns that the Amazon rainforest, which he calls one of the world's largest pharmacies, is being destroyed. This statement highlights multiple threats to the Amazon and underscores a growing debate about ayahuasca, an Indigenous psychedelic beverage considered a forest medicine.

Koshering Psychedelics: Ayahuasca in the Ultra-Orthodox (Haredi) Jewish World

June 21, 2026 Jonathan David, Aviva Berkovich-Ohana, Yair Dor-Ziderman et al. preprint

Ayahuasca use among ultra-Orthodox (Haredi) Jews is adapted to Jewish contexts, with ceremonies modified to fit religious norms. Motivations for use are primarily therapeutic. Acute experiences include Jewish and Jewish mystical visionary content. Longer-term effects include strengthened belief, connection to Judaism, and changes in religious practice. Religious tensions arise from ayahuasca's perceived foreignness, concerns about idolatry, mixed-gender participation, and competing authority structures. Strategies to address these tensions include medicalization, making the set, setting, and experience religiously permissible ("koshering"), and framing ceremonies as liminal spaces. The findings highlight psychedelics' contextual flexibility and diffusion into understudied populations.

Brain-body integromics of the ayahuasca experience.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie June 1, 2026 Francisco Madrid-Gambin, Pablo Mallaroni, Noemí Haro et al.

The psychedelic state induced by ayahuasca arises from coordinated, system-level interactions between peripheral metabolism and brain network dynamics, rather than isolated neurochemical events. In 20 experienced ceremonial users, the subjective dimensions of oceanic boundlessness, visionary restructuralization, and auditory alterations covaried with circulating DMT and β-carbolines, shifts in lipid, amino acid, and energy metabolism, and reconfiguration of dorsal attention and default mode network connectivity. Shared features across these experiences were most strongly linked to endocannabinoid-related N-acylethanolamines, acylglycerols, and ceramides, extending beyond canonical serotonergic models to downstream lipid-signaling and metabolic processes. The findings offer translational insight into metabolic pathways that may modulate brain function and subjective response.

An exploratory persistent-homology analysis of resting-state fMRI functional connectivity under Ayahuasca

Chaos Solitons & Fractals May 30, 2026 Tales Ramos Monteiro Dos Santos, Draulio B Araujo, Helcio Felippe et al.

Psychedelic states can help researchers understand how the brain reorganizes at a large scale. In nine people scanned before and after taking ayahuasca, topological data analysis of resting-state fMRI connectivity showed a nominal decrease in persistent entropy of H2 features—a measure of higher-dimensional topological structure—that did not survive correction for multiple comparisons and was not reproduced with signed correlations. Exploratory analyses of signal complexity found descriptive but non-significant increases. These preliminary, hypothesis-generating results highlight persistent homology as a potential framework for studying psychedelic-related brain changes, but replication in larger placebo-controlled studies is needed.

Clinical trials

All Ayahuasca trials →