Liana of the Dead: What the Research Shows About Ayahuasca for Depression

Editor’s note (October 2026): Jason Lupoi’s 2020 article is reproduced below as he wrote it, with a few bracketed notes. After it, a new section sets out what the research on ayahuasca and depression amounts to now: the one placebo-controlled trial, the open-label studies and surveys, what we know about safety and drug interactions, the separate line of trials using DMT alone, and the legal position. For the rest of the series, see our pages on psilocybin, ketamine and MDMA.

Decoctions of the Banisteriopsis caapi vine, the Psychotria viridis shrub, both native to South America, produce the murky liquor called ayahuasca, aka yage. Ayahuasca offers a natural, bewitching option for treating depression.^[1-3] Like other psychedelics we’ve explored such as ketamine, psilocybin, or an upcoming discussion on ibogaine, what’s remarkable about the medicinal aspects of these psychedelic molecules is that they work fast. [Editor: the ibogaine discussion is now our ibogaine page.] Clinical trials have demonstrated this for ayahuasca with study participants reporting significant antidepressant effects after just one day.^[1-3] After one session, where participants consumed 120-200 mL (approximately 4-7 ounces) of an ayahuasca decoction (2.2 mL/kg body weight), beneficent aftereffects survived for 3 weeks.^[1,2] [Editor: the three-week figures come from the two open-label studies, which had no control group; the one placebo-controlled trial, reference 3, followed patients for seven days.] The decoction contained approximately 0.8 mg/mL of N,N-dimethyltryptamine or DMT.

Ayahuasca has articulated its medicinal prowess, and the scientists who have bothered to study the plant appreciate this. The riddle they currently seek to solve is how this all works. A 2020 study sought these answers^[4], but to understand their method, we must first dive into the salience and default mode networks.

Says Lucina Q. Uddin in Salience Network of the Human Brain, “The salience network is a collection of regions of the brain that select which stimuli are deserving of our attention.”^[5] The default mode network (DMN) regards a large portion of our brains that activates when we turn our minds inward to wander and daydream, not focused on the outside world.^[6] The DMN turns on when we reflect on our pasts or contemplate our futures. It’s thought to be the foundation of the self, what makes you you in your own mind.

The salience network modulates our ability to switch between the DMN (e.g., daydreaming) and the central executive network which involves our thinking about tasks at hand and achieving a defined goal via problem solving and our working memory (focusing).^[7] Interestingly, salience network abnormalities are associated with mental health issues like post-traumatic stress disorder, anxiety, and schizophrenia, and neurodegenerative diseases like Alzheimer’s.^[8] Similar conditions have been implicated with disruptions in proper DMN function.

Back to the study…

The researchers utilized functional magnetic resonance imaging to create images of study participants’ brains before and 24 hours after ayahuasca ingestion.^[4] The batch contained 0.36 mg/kg of N,N-DMT in a 1 ml/kg dose of ayahuasca. The Hallucinogenic Rating Scale (HRS) was used to assess the psychedelic experiences of the participants, considering intensity (strength of experience), somesthesia (somatic effects including interoception, visceral, and tactile effects), affect (comfort, emotional, and affective changes), perception (visual, auditory, gustatory, and olfactory effects), cognition (changes in thoughts), and volition (subject’s capacity to willfully interact with his/her ‘self’). All six metrics were significantly increased following ayahuasca ingestion. [Editor: compared with placebo, in 43 healthy volunteers; the volition difference did not survive correction for multiple comparisons.]

Additionally, the study found salience network connectivity increases related to altered levels of somesthesia. Reductions in DMN connectivity related to modified volition. The study found no differences between the primary sensory brain networks (the five senses) in participants who ingested ayahuasca versus those given a placebo. The researchers concluded that ayahuasca has lasting effects on processes that reference the self and that help us understand and feel what’s going on inside our bodies. Although the study utilized healthy individuals, the results point to a “sustained… dampening” on the connectivity of brain systems involved in self-referential processes associated with trademark symptoms of depression.^[4] [Editor: the authors describe these findings as preliminary, citing low statistical power.]

What does the research on ayahuasca and depression show now?

Six years on, the shape of the evidence is clearer, and smaller than the enthusiasm around it. There is one randomized, placebo-controlled trial of ayahuasca in depression; two partly overlapping open-label reports; biomarker and imaging analyses drawn from those trials; and large surveys of people who drink ayahuasca in ceremonies. A 2026 review of the treatment-resistant depression literature described the ayahuasca evidence as limited and preliminary, with little follow-up beyond three or four weeks.^[9]

The trial that matters most is reference 3. In 29 people with treatment-resistant depression, a single dose of ayahuasca outperformed a placebo designed to cause mild stomach upset, as the brew does. At one week, 57 percent responded against 20 percent on placebo on the trial’s primary scale, the HAM-D, and 64 against 27 percent on the MADRS; remission on the MADRS ran 36 percent against 7 percent, a difference that just missed statistical significance.^[3] The authors were candid about the limits: one dose, seven days of follow-up, a high placebo response, permitted benzodiazepine use, and a sample that was mostly female, Brazilian and low-income.^[3] It has not been repeated at scale. The large surveys are encouraging, but a survey of people who chose to drink ayahuasca and chose to answer cannot tell us what it would do for anyone else.^[11]

How does the brew work?

Ayahuasca is a pharmacological partnership. Psychotria viridis supplies DMT, a short-acting psychedelic. Swallowed without an MAO inhibitor, DMT is generally inactive at customary doses because monoamine oxidase A in the gut and liver rapidly breaks it down before enough reaches the brain. The Banisteriopsis caapi vine supplies beta-carbolines, chiefly harmine and harmaline, which reversibly block that enzyme and let DMT through; a third, tetrahydroharmine, also inhibits serotonin reuptake.^[13] That enzyme blockade is what makes the brew work, and it is also the source of its most serious interaction risk.

What about DMT on its own?

A separate line of research gives purified DMT by injection, without the vine. In a phase 2a trial published in February 2026, 34 adults with moderate to severe depression who had not responded to at least two treatments received either a 10-minute intravenous infusion of DMT or placebo, with psychological support. Depression scores fell 7.4 points more on DMT than on placebo at two weeks, with benefits reported up to three months in an open-label extension and no treatment-related serious adverse events.^[12] That is encouraging for DMT as a drug. It says little about ayahuasca, which adds the MAO-inhibiting vine and the variability of a plant brew. For more on DMT itself, see DMT: molecular messiah and our analysis of recurring themes in DMT experiences.

How safe is ayahuasca?

Vomiting is common: 57 percent of patients receiving ayahuasca vomited in the placebo-controlled trial, against none on placebo, and 71 percent had nausea.^[3] In the Global Ayahuasca Survey of 10,836 people from more than 50 countries, 69.9 percent reported acute physical effects, mostly vomiting, and 2.3 percent needed medical attention afterward. More than half, 55.9 percent, reported mental health effects in the weeks or months that followed; most described them as part of a positive process, but about 12 percent sought professional help. Anxiety disorders and physical health conditions predicted mental health adverse effects, and drinking without supervision predicted physical ones.^[14]

The interaction that matters for anyone with depression is with antidepressants. Because the vine’s beta-carbolines inhibit monoamine oxidase A, combining ayahuasca with SSRIs or other serotonergic drugs may increase the risk of serotonin toxicity. The warning rests largely on pharmacology and case reports rather than controlled interaction studies, but the potential consequences can be serious.^[15] No one taking an antidepressant should stop or start one around an ayahuasca ceremony without their prescriber; stopping suddenly carries its own risks. Retreats that do not ask about medications are a warning sign.

Deaths after ayahuasca ceremonies are reported in the press every year. A 2023 review of 58 media-linked deaths between 2010 and 2022 by ICEERS, a nonprofit that supports the traditional and religious use of ayahuasca, found that only 34 involved confirmed ayahuasca use in the preceding hours and that none of nine public autopsies attributed death to ayahuasca itself; tobacco preparations, scopolamine-containing plants, synthetic 5-MeO-DMT, heart conditions, drowning and lapses in supervision accounted for several.^[16] That is an advocacy organization’s reading of press reports, not a peer-reviewed surveillance study. Its practical conclusion holds either way: setting, screening and supervision materially affect the risk. Our piece on the Setting Questionnaire for the ayahuasca experience looks at how researchers measure that.

Is ayahuasca legal?

It depends on where you are and who is drinking it. In the United States, DMT is a Schedule I controlled substance. In 2006 the Supreme Court ruled unanimously, under the Religious Freedom Restoration Act, that the government had not shown a compelling interest in barring the União do Vegetal church’s sacramental use of hoasca tea, as the church calls ayahuasca.^[17] That protection belongs to qualifying religious practice; it does not make ayahuasca legal for retreats, therapy or personal use. In Brazil, a 2010 resolution of the national drug policy council permits religious use and bars commercial sale, tourism, advertising and therapeutic use.^[18] Elsewhere the law ranges from tolerated to prohibited, and it changes; check local law before relying on anything you read about it.

What is still missing?

A second placebo-controlled trial in depression, larger than 29 people, with follow-up measured in months rather than days. A placebo that blinds better than one that only imitates the nausea. Studies that exclude or carefully control benzodiazepine use, and studies outside one country. Standardized brews, since alkaloid content differs widely: 0.36 mg of DMT per milliliter in one trial’s batch, 0.8 mg in another’s.^[2,3] And a clear, tested account of who should not drink it; for now, anyone on antidepressants, with a heart condition, or at risk of psychosis or mania needs specialist medical advice first. The single-dose, fast-acting signal Lupoi described in 2020 is real and worth testing properly. Six years later, it still has not been.

References

1. de Lima Osório F, Sanches RF, Macedo LR, et al. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report. Brazilian Journal of Psychiatry. 2015;37(1):13–20.
2. Sanches RF, de Lima Osório F, dos Santos RG, et al. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a SPECT study. Journal of Clinical Psychopharmacology. 2016;36(1):77–81.
3. Palhano-Fontes F, Barreto D, Onias H, et al. Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychological Medicine. 2019;49(4):655–663.
4. Pasquini L, Palhano-Fontes F, Araujo DB. Subacute effects of the psychedelic ayahuasca on the salience and default mode networks. Journal of Psychopharmacology. 2020;34(6):623–635.
5. Uddin LQ. Salience Network of the Human Brain. London: Academic Press; 2017.
6. Andrews-Hanna JR. The brain’s default network and its adaptive role in internal mentation. The Neuroscientist. 2012;18(3):251–270.
7. Uddin LQ, Yeo BTT, Spreng RN. Towards a universal taxonomy of macro-scale functional human brain networks. Brain Topography. 2019;32(6):926–942.
8. Menon V. Salience network. In: Toga AW, ed. Brain Mapping: An Encyclopedic Reference. Vol 2. Academic Press; 2015:597–611.
9. Civardi SC, Besana F, Durbano F, et al. Psilocybin and ayahuasca in treatment-resistant depression: clinical evidence, methodological constraints and ethical challenges: a narrative review. Frontiers in Psychiatry. 2026;17.
10. Galvão-Coelho NL, de Menezes Galvão AC, de Almeida RN, et al. Changes in inflammatory biomarkers are related to the antidepressant effects of ayahuasca. Journal of Psychopharmacology. 2020;34(10):1125–1133.
11. Sarris J, Perkins D, Cribb L, et al. Ayahuasca use and reported effects on depression and anxiety symptoms: an international cross-sectional study of 11,912 consumers. Journal of Affective Disorders Reports. 2021;4:100098.
12. Erritzoe D, et al. A short-acting psychedelic intervention for major depressive disorder: a phase IIa randomized placebo-controlled trial. Nature Medicine. Published online February 16, 2026.
13. Brito-da-Costa AM, Dias-da-Silva D, Gomes NGM, et al. Toxicokinetics and toxicodynamics of ayahuasca alkaloids N,N-dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine: clinical and forensic impact. Pharmaceuticals. 2020;13(11):334.
14. Bouso JC, Andión Ó, Sarris JJ, et al. Adverse effects of ayahuasca: results from the Global Ayahuasca Survey. PLOS Global Public Health. 2022;2(11):e0000438.
15. Callaway JC, Grob CS. Ayahuasca preparations and serotonin reuptake inhibitors: a potential combination for severe adverse interactions. Journal of Psychoactive Drugs. 1998;30(4):367–369.
16. Suárez Álvarez C. Examining deaths associated with ayahuasca. ICEERS; August 21, 2023.
17. Gonzales v. O Centro Espírita Beneficente União do Vegetal, 546 U.S. 418 (2006).
18. Labate BC, Feeney K. Ayahuasca and the process of regulation in Brazil and internationally: implications and challenges. International Journal of Drug Policy. 2012;23:154–161.

Originally published December 18, 2020 (updated March 16, 2022). Jason Lupoi’s text is reproduced as written; bracketed notes and everything after his final paragraph were added in October 2026.

Featured image: ayahuasca vine (Banisteriopsis caapi), Takiwasi Center botanical garden, by François Delonnay, via Wikimedia Commons, licensed under CC BY-SA 4.0; cropped and resized; Second Image: Sydtomcat, CC BY-SA 4.0, via Wikimedia Commons.