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Ayahuasca and antidepressants: what has been measured

People ask what is known about ayahuasca for someone who takes an antidepressant. This card sets out what published sources report, what they do not show and what was not located. It gives no instruction on starting, continuing or stopping a prescribed medicine, and a decision about a medicine belongs with the person who prescribed it.

Published Information current to 7 November 2026Review due by 5 February 2027

Read this first. This page is education, not instructions to use. Metanoia does not supply any substance. In the United States, most of the substances discussed here are Schedule I under federal law (21 CFR 1308.11). State programs such as Oregon's and Colorado's operate under state law only, and federal law still applies. Legal status differs between countries, and none of this is legal advice. Nothing here is medical advice, and nothing here gives or recommends a dose. People who host, supply or take part in sessions involving controlled substances can face criminal liability under federal and state law. This page does not advise on that. “Healthy adults” means people with no diagnosed psychiatric or major medical condition, the population Metanoia studies. This page reports what published sources say about work done outside supervised programs, and it takes no position on the legality of any setting, practice or person.
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The short answer

What do published sources report about ayahuasca taken by people who also take antidepressant medicines?

Searches on 7 November 2026 did not locate a controlled study in people. What exists is one computer simulation, one survey, case reports (the original of the oldest was not read) and reviews. They show what has been measured and do not show how risky or how safe the combination is. It gives no instruction on starting, continuing or stopping a prescribed medicine, and a decision about a medicine belongs with the person who prescribed it.

What was found

Figures are as reported, not a recommendation. This marking applies to every amount, length of time and percentage in this section.

Most sources below describe people with a diagnosis or a medicine, or a model, or one person. None measures healthy adults taking both.

  • Mechanism. The sources describe harmala alkaloids in the brew as blocking the enzyme monoamine oxidase A, and some antidepressants as raising serotonin or slowing the breakdown of those alkaloids. Sources 1, 5, level 1
  • Simulation. A 2026 model, checked against six healthy volunteers who took no medicine, simulated fluoxetine or paroxetine taken daily. It predicted DMT exposure about 2.1 to 2.2 times higher and harmine about 1.2 to 1.3 times higher, which the authors class as a moderate interaction for DMT and a weak one for harmine. They also write that the simulations may indicate clinically relevant rises in harmine exposure and moderate rises in DMT exposure, potentially raising the risk of serotonergic effects, and that a conclusion about the risk of serotonin toxicity cannot be drawn, because no link between brain DMT levels and toxic effects is established. Source 1, level 1
  • Survey. In a 2019 online survey of 614 respondents, almost all members of one Brazilian ayahuasca church, 25 took antidepressants. In the 25 who took antidepressants, adverse effects after a ceremony did not differ significantly from the others, a comparison too small to show that no difference exists. Persistent adverse psychological effects were reported by 36% of them and 20% of the others (p = 0.055, a trend the authors did not call significant). The sample was self-selected and mostly long-time users. The authors identified no conventional MAOI or tricyclic antidepressant users, and two participants did not say which antidepressant they took. Source 2, level 1
  • Case reports. Reviews describe a 1998 report of a man on fluoxetine who had tremor, sweating, vomiting and confusion after ayahuasca, which the reviews describe as gone within about four hours. Metanoia has not read the original, and the reviews word it differently, as symptoms resembling serotonin toxicity in one and as a possible interaction-induced serotonin syndrome in another. Sources 3, 4, level 1
  • A 2026 report describes severe serotonin syndrome in a man after ayahuasca and an over-the-counter cough product. No antidepressant was involved, the interval between the last ayahuasca and the product is not stated in the case description, and the authors infer the cause from timing and pharmacology. Source 5, level 1
  • A review also mentions a 2012 report of serotonin toxicity in a person taking fluoxetine and quetiapine who used harmal, a plant that contains the same kind of alkaloid. Metanoia has not read the original. Source 3, level 1
  • A 2024 review found no clear or confirmed ayahuasca serotonin-syndrome case in the literature it searched, with searches ending in July 2023, before the 2026 case above was published. Source 6, level 1
  • Retreat practice. Of 49 retreat organizations interviewed, 43 required or recommended stopping certain medicine groups beforehand and 33 required it. The stated lengths varied widely, from 1 day to over 6 weeks, and the study did not test whether any length matters. These figures cover all substances, and 30 of 48 organizations offered ayahuasca. The study's authors write that abrupt discontinuation of antidepressants carries known withdrawal risks, and ask for clear guidance. Source 7, level 1
  • Research protocol. One registered ayahuasca trial in treatment-resistant depression planned a medicine washout before dosing, with a length set for that trial's participants. The record's results section was posted on 6 April 2025. It reports that 35 people started and 29 completed, and it gives depression-scale scores and adverse events for the two groups, which this card does not summarise. It does not report whether or how the washout was carried out. The washout text in the record is the original plan, and it does not apply to anyone else. Source 8, level 1

What is not known?

“Not located” means that the searches Metanoia ran on 7 November 2026 did not return it. They covered PubMed, Europe PMC and ClinicalTrials.gov. Embase, PsycINFO and Google Scholar were not searched. More searching could change the picture.

  • A controlled study in people. Not located.
  • How often serious reactions occur. None of the sources gives a rate.
  • Whether outcomes differ in people taking both. Not located beyond the small survey above.
  • How long the enzyme blockade lasts after several days of use. The authors of the 2026 case report call for studies of this.
  • Other medicine classes. One 2026 case report involved an over-the-counter cough product, and a review mentions a 2012 report with fluoxetine, quetiapine and harmal. Metanoia did not search by medicine class, so this list is not complete.
  • Whether any of this applies to healthy adults. The combination itself was measured only in people taking a medicine, in one survey and case reports.

What this card does not say

  • It does not say the combination is safe or unsafe, or that anyone should take ayahuasca.
  • Reports of combining substances and of multi-day sequences are on the card about combining substances and multi-day sequences.
  • It does not say that stopping a medicine is safe or unsafe, or that any washout length reported by retreats or planned in a trial is right, needed or enough.
  • It does not rate how risky, how safe or how worthwhile anything is. A small amount of evidence is not a small risk.

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Where does this come from?

Grade key: 1 = peer-reviewed publication, official document or primary record. 2 = reliable secondary source. 3 = grey source (community, social media, organization pages). 4 = traditional or ethnographic source. A grade names the type of source, and the design and limits are given in the text. “Full text” means Metanoia read the body of the paper in full on the date given, and any part not read is named. A source read only in part carries no claim on this card. Sources described in the text as found and not read carry no claim and are not listed.

Searches: PubMed, Europe PMC and ClinicalTrials.gov on 7 November 2026. Embase, PsycINFO and Google Scholar were not searched. Review due by 5 February 2027. A new controlled or registered study, or a new case series, reopens the “not located” lines.

  1. Ribeiro GSG et al. Predicting drug-drug interactions between ayahuasca alkaloids and SSRIs using physiologically based pharmacokinetic modeling. Front Mol Biosci 2026, 13:1768402. DOI 10.3389/fmolb.2026.1768402 PMID 41788629. Grade 1. Computer simulation, six volunteers. Full text read 7 November 2026 (supplement not read).
  2. Durante I et al. Risk assessment of ayahuasca use in a religious context: self-reported risk factors and adverse effects. Braz J Psychiatry 2021, 43:362-369. DOI 10.1590/1516-4446-2020-0913 PMID 33146343. Grade 1. Cross-sectional online survey, self-report. Full text read 7 November 2026 (tables not rendered).
  3. Halman A et al. Drug-drug interactions involving classic psychedelics: A systematic review. J Psychopharmacol 2024, 38:3-18. DOI 10.1177/02698811231211219 PMID 37982394. Grade 1. Systematic review. Full text read 7 November 2026 (LSD and psilocybin tables and supplement not read).
  4. Tap SC et al. Concomitant use of antidepressants and classic psychedelics: A scoping review. J Psychopharmacol 2025, 39:1072-1088. DOI 10.1177/02698811251368360 PMID 40937732. Grade 1. Scoping review. Full text read 7 November 2026 (appendix not read).
  5. Pack S et al. Severe Serotonin Syndrome With Acute Respiratory Failure Following Ayahuasca and Dextromethorphan Use: A Case Report. Cureus 2026, 18(8):e114211. DOI 10.7759/cureus.114211 PMID 42713547. Grade 1. Case report, one person. Full text read 7 November 2026.
  6. White E et al. Ayahuasca and Dimethyltryptamine Adverse Events and Toxicity Analysis: A Systematic Thematic Review. Int J Toxicol 2024, 43:327-339. DOI 10.1177/10915818241230916 PMID 38363085. Grade 1. Systematic thematic review, searches to July 2023. Full text read 7 November 2026 (supplement not read).
  7. McGuire AL et al. Reported Safety Practices of Publicly Advertised Psychedelic Retreats. JAMA Netw Open 2026, 9:e2552505. DOI 10.1001/jamanetworkopen.2025.52505 PMID 41499117. Grade 1. Interviews with organizations, self-report. Full text read 7 November 2026 (appendix not read). The paper does not test links between practices and outcomes.
  8. ClinicalTrials.gov NCT02914769, Antidepressant Effects of Ayahuasca: a Randomized Placebo Controlled Trial in Treatment Resistant Depression. Registry record. Grade 1 (a registry record: the washout text is the registered plan, and the results section posted on 6 April 2025 is the investigators' own report, not peer reviewed). Full record including the results section read 8 November 2026 (the reference list was not read in full).