Ayahuasca

What it is

Ayahuasca is a brew of two kinds of plant. One is the stem of a vine, Banisteriopsis caapi, which contains alkaloids called beta-carbolines. The other is usually the leaf of a shrub, Psychotria viridis, which contains N,N-dimethyltryptamine, better known as DMT, a classic psychedelic whose main effects come from activating the serotonin receptor called 5-HT2A. The plants and the preparation differ from one maker to the next [4] [29], not every brew contains a DMT plant [41], and Brazilian communities recognise many folk types of the vine [44].

Swallowed alone, DMT is broken down in the gut and liver by monoamine oxidase (MAO). The beta-carbolines block that enzyme reversibly, and in a human trial that blockade was enough to let DMT reach the brain while blood levels of harmine stayed very low [2]. Whether the compounds act additively or synergistically is unclear [39], and the degree of MAO inhibition in people has not been established [41]. Because MAO also helps clear serotonin, this affects how the body handles other drugs.

Metanoia studies natural psychedelics for personal growth in healthy adults, so this page sorts the evidence by who was studied.

What is known

The short version. Controlled experiments in healthy volunteers are few and small, and they mostly measured the hours after drinking. Long-term users often show no sign of harm among those who stayed in the study, but cannot show what ayahuasca caused. Reports of lasting change in healthy people come from uncontrolled studies, with mixed results. The one randomized trial of a lasting effect was in patients with depression, and a reanalysis shows its effect size depends heavily on the placebo comparison.

Controlled experiments in healthy volunteers

Six healthy men who had used the brew before took part in a single-blind crossover trial with a placebo and three ascending dose levels. Five rated it pleasant and satisfactory. The sixth had an intensely dysphoric reaction at the middle level, with transient disorientation and anxiety, and withdrew [1]. In 18 volunteers with prior psychedelic experience, diastolic blood pressure rose by 9 mm Hg at the higher of two dose levels, with no significant rise in systolic pressure or heart rate [2]. In 10 healthy volunteers, prolactin rose only with ayahuasca, and cortisol rose with both it and d-amphetamine but more with ayahuasca, which the authors called moderately sympathomimetic [3].

A randomized, double-blind, placebo-controlled trial in 50 healthy volunteers found altered perception, mystical-type experiences, visual discontinuous thinking and lower global alpha activity on EEG [13]. A placebo-controlled crossover trial in 28 healthy men (36 enrolled) tested isolated alkaloids, harmine as a cheek tablet and DMT as a nasal spray, so it does not model drinking the brew. Embarrassment fell against placebo when participants heard recordings of their own singing (p = 0.001), harmine alone showed no significant effect, the combination did not differ significantly from harmine alone, the drug-by-condition interaction was not significant (p = .072), and the analysis plan was not fixed in advance. Raters also scored the recordings as better under the combination, which may reflect a positivity bias, and the effect cannot be attributed to DMT specifically [14]. An open-label phase 1 study of pure harmine in 25 healthy volunteers, with no placebo, found no full hallucinations and no change in blood pressure or heart rate. Vomiting was the limiting effect, and diarrhoea occurred in none, which the authors attribute to other alkaloids in the brew. The low-tyramine diet was precautionary, and no interaction with food or medicines was tested [43].

Only the abstract of the 50-volunteer trial was available, so its effect sizes are not reported. None of these experiments followed participants beyond a few days or measured outcomes that personal-growth claims depend on.

People who use it regularly

In a Spanish-led study of members of two Brazilian ayahuasca churches, Santo Daime and Barquinha, 127 regular users with at least 15 years of use and 115 controls were assessed twice, 8 to 12 months apart. At baseline users scored lower on all nine measures of psychiatric symptoms, did better on several attention and executive-function tests, and scored higher on spirituality, purpose in life and wellbeing. At follow-up, with 78 users and 68 controls returning, most differences held, but the differences in depression and bodily symptoms were no longer significant, and the purpose-in-life difference was not reproduced. Users also scored lower on Self-Directedness, which is not favourable, and the authors suggest an emphasis on community and that such differences may follow from the use. They found no psychological maladjustment or cognitive impairment, and name two limits: the groups were not matched on baseline IQ, and people who had a bad time may have stopped drinking and left the study [5].

Smaller studies carry the same limits. Thirty members of the União do Vegetal (UDV), a Brazilian religious group, had lower depression and confusion scores than 27 matched controls (small effect sizes) but also more past alcohol intoxication and cannabis use [6], and long-term Santo Daime members scored lower on panic-like and hopelessness measures after drinking, with anxiety unchanged [8]. Of 32 American Santo Daime members found physically healthy, 19 met criteria for a lifetime psychiatric disorder and 24 had substance abuse or dependence, and the authors warned against extrapolating to other people who use hallucinogens [7]. None of these is a sample of healthy adults in Metanoia's sense.

Imaging findings are preliminary. In 22 regular users and 22 matched controls (16 women and 6 men in each group), users had a thinner posterior cingulate cortex, a node of the default mode network, but a thicker anterior cingulate and precentral gyrus, at a threshold (p < 0.002) not corrected for multiple comparisons. No difference appeared on a general psychiatric symptom scale, users did better on some working-memory and task-switching tests, and the authors state that causation cannot be established [9]. In 19 long-term users and 19 non-users, all men, users had higher resilience scores (43.9 against 39.1, p = 0.01), with no difference in anxiety, depression or mood. A classifier separated the groups from brain scans with 75 percent overall accuracy, but only 65 percent in the users alone, not significant (p = 0.10), and predicting resilience from the scans was weak. The authors read the patterns as plasticity without showing it, and the journal grades the level of evidence 4 [10]. Both studies are cross-sectional and small.

One ceremony, followed over weeks

Two observational studies with no control group followed ceremony attendees. Of 57 attendees in the Netherlands and Colombia, only 31 (about 54 percent) completed the four-week online follow-up. Depression and stress ratings fell the day after and at four weeks. Convergent thinking was close to significant the next day (p = .09) and significant at four weeks (p = .003), while divergent thinking and anxiety did not change, and gains in life satisfaction and mindfulness were not significant at four weeks. Some attendees reported diagnoses such as depression or anxiety [11]. In a second sample from retreats in the Netherlands, 43 completed the baseline assessment and only 20 and 19 returned, so the number answering each measure ranged from 8 to 27. Cognitive empathy, life satisfaction and decentering rose for up to a week (empathy in only 12 people at one week), explicit empathy did not change, and of the divergent-thinking measures only the ratio of originality to fluency fell. At two of the four sites the brew was made from Mimosa hostilis and Peganum harmala rather than the classic pair, and the retreat leaders were not clinically trained to screen for mental disorders [12]. Without a placebo group, expectation cannot be separated from the drug.

The clinical trial, and why its size is disputed

The one clinical result is a double-blind, placebo-controlled trial in 29 patients with treatment-resistant depression, all taking benzodiazepines, all given one batch of brew from a single church. The primary outcome, the Hamilton depression score at day seven, was lower with ayahuasca (p = 0.019, between-group effect size 0.98), with a response rate of 57 percent against 20 percent. Remission, 43 percent against 13 percent, was not significant (p = 0.07). On the secondary MADRS scale the effect size was 1.49 and the response rate 64 percent against 27 percent at day seven, but response rates did not differ significantly on days one and two. Vomiting occurred in 57 percent on ayahuasca and none on placebo, which makes blinding hard to keep [15]. A 2024 network meta-analysis found placebo response lower in psychedelic trials than in antidepressant trials, a gap the authors tied to unsuccessful blinding. In its main analysis only high-dose psilocybin still beat placebo clearly, and ayahuasca did not. In a sensitivity analysis limited to major depressive disorder ayahuasca also exceeded the antidepressant-trial placebo, but narrowly (credible interval 0.02 to 10.61 Hamilton points), resting on a single trial of 29 patients, with healthy volunteers excluded [16].

Safety in healthy adults

This section describes findings, not guidance. Nothing below supports treating ayahuasca as safe in general, and the reassuring findings come mostly from supervised or ritual settings.

The largest dataset is an online survey of 10,836 people from more than 50 countries (2017 to 2019). Acute physical effects, mostly nausea and vomiting, were reported by 5,742 of 8,216 respondents (69.9 percent), and 132 of 5,775 (2.3 percent) said they needed medical attention afterwards. Seizure-like events were reported by 1.3 percent, by self-report and without neurological confirmation. Mental health difficulties in the following weeks or months were reported by 4,341 of 7,839 (55.4 percent), though about 88 percent of those people saw them as part of a positive process of growth and about 12 percent needed professional support. The sample is self-selected and not healthy (13 percent reported a diagnosed anxiety disorder and 19 percent depression), so the percentages describe who answered and not the risk to a typical person, and differences between settings may reflect who chooses each setting [17].

A systematic thematic review of 78 articles concluded that ayahuasca and DMT have an acceptable safety profile in healthy volunteers but with narrow safety margins, with serious adverse effects rarely reported. The authors judged that the literature did not suit a PRISMA-style review and advised avoiding the brew in pregnancy and in people with certain psychiatric conditions. They reported high-dose animal effects that cause miscarriage (abortifacient) and harm fetal development (teratogenic), and possible toxicity of isolated harmala alkaloids with certain co-administered medicines, while cautioning against reading such animal data as predictive of human use of plant preparations. Human evidence on pregnancy and breastfeeding is anecdotal, and there are no data in older adults or children [18]. A separate systematic review, mostly of case reports, found psychotic episodes after ayahuasca or DMT rare. Several cases involved a personal or family history of psychosis or mania, or other drug use, but some did not, and the authors concluded that screening reduces the chance of such reactions. Most incidence figures come from the UDV in series gathered by authors who were members, a possible conflict of interest, and the denominators are unexplained (about 25,000 doses in one estimate and about 250,000 in the Supreme Court record). Two authors also work with ICEERS, an ethnobotanical education organisation [23].

Interactions with serotonin-acting drugs are the most discussed specific hazard, and the evidence behind them is thin. Serotonin syndrome is a state of excess serotonin activity that in severe cases brings muscle rigidity and respiratory failure. In 1998 two researchers warned that the MAO-inhibiting alkaloids combined with SSRI antidepressants might produce it [24]. That warning rests on a single case report, described by two later reviews: a 36-year-old man taking fluoxetine developed symptoms of serotonin toxicity about an hour after drinking the brew and recovered within about four hours, without treatment and without lasting harm [19] [20]. The original article was not accessible in full. One review urges caution when the brew's MAO inhibitors meet SSRIs and SNRIs and found only this case among 36 reports from 52 studies [19]. The other, a scoping review of 19 studies, attributes the case to those inhibitors and calls ayahuasca with SSRIs and MAO inhibitors a critical gap in knowledge. It found antidepressants with classic psychedelics generally tolerable, but that comes largely from psilocybin and LSD and cannot be assumed for a brew that itself inhibits MAO [20]. A 2026 modelling study predicted that fluoxetine and paroxetine would raise harmine exposure about 1.2 to 1.3 times (a weak interaction) and DMT exposure about 2.1 times (moderate). The authors say these increases may be clinically relevant but that no firm conclusion about serotonin toxicity can be drawn, because no established relationship links brain DMT levels to toxic effects. It is a simulation and not a clinical trial [21].

A case report describes severe serotonin syndrome with respiratory failure in a 46-year-old man after three days of drinking ayahuasca, followed by over-the-counter cough and allergy medicines containing dextromethorphan and diphenhydramine. It is one case, the timing and amounts of the medicines came from the patient, nothing was measured in blood or urine, the Hunter criteria could not be applied, and a urine screen was positive for benzodiazepines without explanation. The suggestion that the risk lasts for days is a hypothesis and not a measurement [25]. The thematic review above searched only to 2023 and found no confirmed case of serotonin syndrome linked to ayahuasca [18].

A review of fatalities lists three earlier deaths after DMT use: one after a herbal tonic, one after a shaman-led ceremony in the UK (inquest verdict inconclusive), and one after an ayahuasca ceremony in Colombia, recorded as poisoning by ayahuasca and hyoscine (scopolamine). It added two UK deaths, in 2022 and 2023, that were not ceremony or ayahuasca cases but involved DMT with several other substances. The 2022 findings included cocaine toxicity, and the coroner discussed serotonin syndrome as a possibility. In 2023 a 58-year-old man on venlafaxine and mirtazapine had DMT and harmala alkaloids in his blood, a packet of seeds possibly of Syrian rue was found, and the coroner recorded a hypertensive crisis and serotonin syndrome, together with drug toxicity. The authors conclude that deaths from DMT are rare, that other substances were involved in every case, and that risk rises with serotonergic drugs or MAO inhibitors [22]. US poison control centres took calls about 538 cases coded as ayahuasca exposure between 2005 and 2015: 7 percent had a major effect, 28 were intubated, 12 had seizures and three died, two reported indirectly. No toxicology confirmed ayahuasca or ruled out other substances, and there is no denominator, so the data show that severe outcomes occur and cannot give a rate [40].

Advice about tyramine-rich foods such as aged cheese and red wine comes from irreversible MAO inhibitors, which can cause a hypertensive crisis, and has not been tested directly in ayahuasca. A 2021 survey of 614 UDV members says the proposed contraindications are based on conventional MAO inhibitors [38]. Reversible, selective MAO-A inhibitors interact less strongly with tyramine [39], but less strongly is not the same as not at all. In the survey, 25 members reported taking antidepressants, with no significant difference in adverse effects, but the group was too small to analyse drug by drug, members on classic MAO inhibitors or tricyclics were not included, and the authors call safety alongside specific drugs a challenge. They judge the church's own screening largely sufficient and say the findings should not guide people new to ayahuasca [38].

The interaction question is therefore important and unsettled, and weak evidence is not evidence of safety. The SSRI warning rests on one case report, the food advice is borrowed from other MAO inhibitors, and the only group study of antidepressant users was small. The mechanism is real, serotonin syndrome can be severe, and the reviews urge caution because no controlled study of the combination exists.

At least three of the studies above enrolled only men [1] [10] [14], and several abstracts do not state sex, so this page cannot say how many women the controlled work included. People on serotonin-acting medicines and pregnant or breastfeeding women are excluded from healthy-volunteer designs or are not described in the abstracts read. One case report describes rhabdomyolysis (severe muscle breakdown) and kidney injury in a previously healthy 38-year-old man found about a day after an ayahuasca retreat. He said he was repeatedly struck with thin branches and was dehydrated after a long journey. The authors give a Naranjo causality score of 6 but cannot show ayahuasca alone caused the injury, probably multifactorial. He recovered fully with supportive care and without dialysis [26].

Legal status

These entries are checked against primary texts and dated. A point that rests on a news notice instead of the primary text is marked not verified. Nothing here is a permission or legal advice. Only the United States and Brazil are covered, because other jurisdictions were not verified to the same standard.

United States, federal law

Checked 4 October 2026. DMT is listed in Schedule I of the Controlled Substances Act at 21 CFR 1308.11(d)(19) for any preparation containing it, and the text does not name Banisteriopsis caapi or Psychotria viridis. The eCFR text read was current as of 1 October 2026. A September 2026 rule adding diphenidine to Schedule I does not concern DMT, and no change to the DMT listing was found. In 2006 the Supreme Court proceeded on the basis that DMT, and preparations containing it, are in Schedule I [30] [32].

Religious exemptions in the United States

Gonzales v. O Centro Espírita Beneficente União do Vegetal, 546 U.S. 418, was decided on 21 February 2006. The UDV, a Christian Spiritist church with about 130 American members, takes communion with hoasca, a tea made from the same two plants. Chief Justice Roberts wrote the opinion. The Court held that the Religious Freedom Restoration Act (RFRA) required the government to show a compelling interest in applying the Controlled Substances Act to this particular use, and that at the preliminary-injunction stage it had not done so. The government had pointed to health risks, including psychosis, heart-rhythm problems and drug interactions, and the district court had found the evidence evenly balanced. The Court held that the 1971 UN Convention on Psychotropic Substances covers hoasca as a preparation but left open whether it allows exceptions, and the case went back for further proceedings [30]. The decision did not remove DMT from Schedule I or make ayahuasca legal in general.

DEA guidance, version 2 dated 20 November 2020 (the version found on 4 October 2026, later versions not checked), explains how a religious group asks for an exemption. No banned activity is allowed until the petition is granted and the group has a DEA registration. The petition is signed under penalty of perjury, and a petitioner who does not answer a DEA request within 60 days is treated as having withdrawn. The guidance is an interim measure without the force of law [31].

Outcomes have varied. On 18 March 2009 a federal district court in Oregon ruled after trial that RFRA required allowing members of two Santo Daime churches, about 80 active Oregon members in all, to import and drink their tea, subject to reasonable restrictions, and stated that judgment and a permanent injunction would be entered. The text read is the court's findings and conclusions, not the injunction itself, and the findings describe the churches' screening questionnaire and its list of medicines to avoid [33]. A different church petitioned DEA on 21 August 2017, and DEA denied it on 16 April 2021, finding no sincerely held beliefs or religious exercise shown and compelling interests in public safety and preventing diversion. The Eleventh Circuit dismissed the church's petition for review as untimely on 27 February 2024, in an unpublished opinion that did not decide the religious-freedom question [34]. On 21 June 2024 the D.C. Circuit held that an ayahuasca church lacked standing for a RFRA claim against the IRS's refusal of 501(c)(3) status, without prejudice, and rejected its tax-exemption claim because it had not shown an exemption from the Controlled Substances Act, adding that the 2006 decision did not make ayahuasca use automatically lawful for any religious group [35]. Exemptions are decided group by group. A peer-reviewed article reports a 2010 settlement between the American UDV branch and DEA, but only its abstract was read, the agreement was not seen, and its terms were not verified [45]. The present registration status of any particular group was not verified.

Brazil

Checked 4 October 2026. Brazil's national drug council, CONAD, recognized the legitimacy of religious use of ayahuasca through a process that began in 1985, and in September 1987 removed the plants and the brew from its lists of proscribed substances. Resolution No. 1 of 25 January 2010 published the final report of a later working group, approved by the council in December 2006. It restricts use to religious rituals and says that use outside a religious setting is not recognised as legitimate and that any practice using ayahuasca only for therapeutic purposes should be prohibited until its efficacy is shown in studies at academic research centres. It recites a position of the UN International Narcotics Control Board that neither the drink nor its plants are under international control [36]. The prosecutors' notice says DMT is prohibited by Brazil's health regulator, Anvisa, and the recommendation to Anvisa cites Portaria SVS/MS 344/1998, which was not opened (not verified against the primary text) [37].

On 4 September 2026 federal prosecutors in Acre recommended that CONAD and Anvisa open two-year working groups to revise the rules, including moving DMT toward an administrative rather than a criminal regime. The 30-day reply period ended around the date of this review, and whether either body replied was not checked. The text of the recommendation to CONAD was not opened [37].

History and tradition

The material in this section is tradition and recorded belief, graded 4. It describes what people say and do. It is not evidence about what the brew does to a person.

A review describes ayahuasca as part of Indigenous Amazonian ethnomedicine and shamanism and of mestizo folk medicine in the northwest Amazon [29]. The best-known Brazilian churches that use it are modern, and the 1961 founding date given for the UDV appears in the Oregon court's findings without a cited source [33] and was not verified elsewhere. A ritual bundle about 1,000 years old (905 to 1170 CE) from a cave in southwest Bolivia held harmine and DMT together, but the authors say it does not prove use of the brew in its modern form, because DMT can come from other plants [42]. Tradition records no safety data, practice varies by group and region, and this page does not describe ceremonies or take a position on practices that belong to those communities.

What is not known

No controlled study reviewed here has measured lasting change in healthy adults on outcomes such as creativity, empathy, resilience or mindfulness. The few uncontrolled studies that touch these show mostly short-lived changes, with no way to separate drug, ceremony, expectation and the decision to attend [11] [12].

Several other questions are open. The brew's composition varies by maker, so a result with one preparation may not transfer to another, and four batches in one observational study differed about 4.8-fold in DMT and 2.6-fold in harmine [11]. In a healthy-volunteer trial of LSD (45 enrolled, 43 analysed), blood BDNF did not change although motor learning improved the next day. Every participant identified the LSD, so blinding failed, the authors do not attribute the learning gain to plasticity, and blood BDNF mostly does not come from the brain [28]. Finally, an international Delphi panel of 89 experts from 17 countries (62 completing round four) produced 30 items for reporting the setting of a session in psychedelic clinical trials in 2025. These are reporting guidelines and not a finding about what shapes outcomes, the authors say the work centred on clinical trials, and the items have not been tested against outcomes in healthy people [27].

What Metanoia asks

Metanoia has not run a study on ayahuasca, does not provide it or direct anyone toward it, and has not yet built its measurement work for this substance. It asks two research questions. The first is which of the 30 setting items predict outcomes in a healthy person seeking growth rather than symptom relief, and Metanoia's context standard is intended to line up with that guideline. The second is what a screening and safety framework for interactions would look like for a healthy-adult research population, since the existing literature is clinical or religious and the modelling work is new.

By discipline, the questions are these. Genetics asks how variation in MAO enzymes might shape individual response, and the 2026 modelling study notes that CYP2D6, an enzyme that clears harmine, differs 50 to 60 times in activity between people [21]. Chemistry asks for the full alkaloid profile across preparations and plant sources [44]. Neuroscience asks about acute and next-day effects measured with markers more reliable than a blood test. Cultivation asks where the plant material in published studies came from. Therapy asks what screening and context records a growth-oriented design would need. Sex and gender differences have no dedicated data reviewed yet.

Where Metanoia's research reaches human data, it is built on four record-keeping standards covering what the material was, what exposure occurred, the surrounding context and the outcome, together with an outcome measure still in development that addresses the twelve dimensions of human potential: creativity, problem-solving, emotional resilience, social connection, self-awareness, empathy, well-being, perception, learning and memory, mindfulness, nature connectedness and leadership.

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