Drug: Ayahuasca

What It Is

Ayahuasca is a brew made from two Amazonian plants, drunk in ceremonies that run for several hours. Indigenous groups across the western Amazon have used it for generations in healing and spiritual practice, and in the twentieth century two Brazilian churches, the Uniao do Vegetal and Santo Daime, built formal religious traditions around it that have since spread to North America and Europe. Its recent draw for psychiatry is narrow and specific: a possible fast-acting effect on depression that has resisted standard drugs.

The brew combines two kinds of plant that do nothing much on their own by mouth, and everything in combination.

The Two Plants, and Why Both Are Needed

1The leaf: DMT

The leaves of Psychotria viridis contain N,N-dimethyltryptamine, or DMT, a short-acting psychedelic that acts on the serotonin 5-HT2A receptor, the same receptor central to psilocybin and LSD. Swallowed on its own, DMT is broken down in the gut and liver by an enzyme called monoamine oxidase before it can reach the brain, so it has almost no effect by mouth.

2The vine: the MAO inhibitors

The vine Banisteriopsis caapi contains harmine, harmaline, and tetrahydroharmine, a group of compounds called harmala alkaloids that block monoamine oxidase. With that enzyme inhibited, the DMT survives digestion and becomes active by mouth. This is the whole reason the brew works, and it is also the source of its most serious danger.

3The combined effect

The result is a psychedelic experience lasting roughly four to six hours, usually with intense nausea and vomiting that the tradition treats as part of the process and calls the purge. The monoamine-oxidase inhibition does not switch off when the visions do; it is an active drug interaction for as long as the alkaloids are in the body.

What It Does

The evidence is graded claim by claim in the research section below, and the plain summary is that it is thin. The strongest single piece is one randomized placebo-controlled trial in about 29 people with treatment-resistant depression. A single dose lowered depression scores more than placebo at one, two, and seven days, and by day seven 64 percent of the ayahuasca group had responded against 27 percent on placebo, with the gap between the groups widening over the week. That is a real controlled signal, and it is small: one site, one dose, fewer than thirty people, and no follow-up beyond three weeks.

Around it sit two open-label studies from the same research group, one in six patients and one in seventeen, that reported large drops in depression scores lasting up to three weeks. These had no control group, so expectation and the intense shared experience cannot be separated from the drug, and the authors said so. A systematic review that pooled the small clinical trials of ayahuasca alongside psilocybin and LSD reached the same measured conclusion: the results are promising and the evidence base is a handful of small studies.

The largest numbers come from surveys of people who already drink ayahuasca in ceremony, some running to thousands of respondents across dozens of countries, and they report associations between ceremonial use and better mood and wellbeing. These describe people who chose to keep drinking and answered a questionnaire about it, so they show a pattern shaped by who volunteers, not proof that the brew caused the change.

Two limits weigh across all of it. The experience is unmistakable, so almost no one in a trial is truly blind to whether they drank ayahuasca or placebo, and expectation is difficult to separate from effect. And the setting is not incidental: nearly all of this happens in a prepared ceremony with support, which is part of what is being measured.

The Research & Studies

Everything here is based on the research we have collected and checked, sorted into groups and ordered with the strongest evidence first. Click any claim to open the studies behind it.

Mood & stress

A single ayahuasca dose eased treatment-resistant depression more than placebo, with 64% responding at seven days versus 27%Emerging

In plain terms

In the one small randomized trial, a single dose of ayahuasca eased hard-to-treat depression more than a placebo drink, and by seven days about two-thirds of the ayahuasca group had responded against about a quarter on placebo.

In detail

This parallel-arm, double-blind trial randomized 29 patients with treatment-resistant depression to a single dose of ayahuasca or a placebo drink designed to mimic its taste and mild effects. Depression was measured with MADRS and the Hamilton scale at baseline and 1, 2, and 7 days after dosing. Ayahuasca separated from placebo at every time point, and the gap widened over the week. It is the first controlled trial of a psychedelic in treatment-resistant depression, and it is very small, single-site, single-dose, and followed patients for only three weeks.

The study · 1

Palhano-Fontes et al., rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial · Psychol Med 2019;49:655-663

In small open-label studies without a control group, a single ayahuasca dose was followed by large drops in depression scores lasting up to three weeksPreliminary

In plain terms

In two small studies where everyone knew they were getting ayahuasca, depression scores dropped sharply within a day and stayed lower for about three weeks, but with no comparison group these results cannot separate the drug from expectation.

In detail

The 2015 report enrolled six volunteers with a current depressive episode in an inpatient unit; the 2016 SPECT study enrolled 17 patients with recurrent depression. Both were open-label, so participants knew they received ayahuasca and there was no placebo or waiting-list arm. The authors described the findings as preliminary and called for randomized, double-blind replication, which the 2019 trial then attempted.

The studies · 2

Osorio et al., antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report · Braz J Psychiatry 2015;37:13-20

Sanches et al., antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a SPECT study · J Clin Psychopharmacol 2016;36:77-81

A systematic review found the clinical evidence for ayahuasca in depression and anxiety is a small number of early-stage trialsPreliminary · mixed

In plain terms

Reviewers who gathered every clinical trial of ayahuasca and related psychedelics over 25 years found only a handful of small, mostly uncontrolled studies, so the promising results rest on a thin base.

In detail

The review pooled clinical trials of ayahuasca alongside psilocybin and LSD and graded the overall body of work as encouraging but preliminary, limited by small samples, few randomized designs, and the difficulty of blinding. It is included here to place the ayahuasca-specific results in context rather than to add a separate efficacy claim.

The study · 1

Dos Santos et al., antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and LSD: a systematic review of clinical trials published in the last 25 years · Ther Adv Psychopharmacol 2016;6:193-213

Large surveys of ceremonial ayahuasca drinkers report associations between use and better mental health and wellbeingPreliminary

In plain terms

In large surveys, people who drink ayahuasca in ceremony tend to report better mood and wellbeing, but these are people who chose to keep drinking, so the result shows a pattern rather than proof it helped.

In detail

The survey captured detailed information on ceremony characteristics, support practices, and motivations across a large international sample of people who use ayahuasca in traditional, neo-shamanic, and syncretic-church settings. It is one of the largest datasets on ceremonial use and underlines how much the setting shapes reported outcomes, which is also what makes it hard to isolate the brew itself.

The study · 1

Perkins et al., influence of context and setting on the mental health and wellbeing outcomes of ayahuasca drinkers: results of a large international survey · Front Pharmacol 2021;12:623979

How It Works

The proposed mechanism is the same one studied for the classic psychedelics. DMT activates the serotonin 5-HT2A receptor, which appears to increase the flexibility of activity across the cortex and loosen the fixed, self-focused patterns of thought that run through depression. In the open-label SPECT study, brain blood flow rose in the nucleus accumbens, insula, and subgenual area, regions tied to mood, after dosing. The idea behind the ceremony is that a person can revisit difficult memories and feelings from a different vantage point while supported, and that the shift can outlast the drug.

None of that is settled for ayahuasca specifically. The controlled evidence is one small trial, the mechanism work is early, and the effect on the brain is described rather than proven to cause the mood change. What is not in doubt is the pharmacology of the interaction the brew depends on, because monoamine-oxidase inhibition is a well-characterized and hazardous drug action.

Where the Law Stands

DMT is a Schedule I controlled substance in the United States, the most restricted category, and ayahuasca as a preparation falls under the same classification. The exception is religious use: the Supreme Court ruled in 2006 that the Uniao do Vegetal could use the brew as a sacrament under the Religious Freedom Restoration Act, and Santo Daime congregations have won similar protection. Outside those recognized exemptions its use is illegal under federal law. In most other countries the brew is either controlled or investigational, reachable only in research settings or specific religious contexts. Nothing here is a route to obtaining it; it is a description of where the law currently stands.

The Chinese Medicine View

Chinese medicine has a long-standing frame for altered states of mind, and it leans toward caution. The Heart is said to house the Shen, the spirit or consciousness, and clear thought, steady emotion, and settled sleep are read as signs of a rooted Shen. A mind flooded, disoriented, or thrown into fear is described as a disturbance of the Shen, and the classical tradition treats such disturbance as something to calm and anchor. The bias of the medicine is toward grounding: settling the Shen, harmonizing the Heart and Liver, and rooting a scattered mind back in the body through stillness, breath, and regular life.

Read through that frame, a brew that produces hours of visions, fear, and heavy vomiting is not a neutral thing. It could be seen as forcefully stirring the Shen, which the tradition would approach with great care, and least of all in someone already depleted, agitated, or unsettled. The heavy vomiting itself reads as a strong draining of Stomach and Spleen Qi, taxing for a weak or deficient person. This is an interpretation offered in the tradition's own language, not a verdict, and not a claim that Chinese medicine anticipated any modern finding. The wider preventive tradition of Yang Sheng, nourishing life, would place the emphasis on grounding practices first: stillness, breath, sleep, and a settled daily rhythm.

Combining ayahuasca with an SSRI or SNRI antidepressant, another MAO inhibitor, or another serotonergic drug can push serotonin to dangerous, sometimes life-threatening levels, and this is the interaction that has harmed people.

Cautions For This Practice

Everything to be aware of is here, in one place. This practice suits most healthy people; a few situations call for real care.

Ayahuasca's MAO-inhibiting alkaloids can combine with serotonergic drugs to cause serotonin syndrome

Monoamine-oxidase inhibition is a well-characterized and hazardous drug action, and it is the mechanism the brew depends on for oral activity. The same inhibition that keeps DMT active also removes a major route for clearing serotonin, so serotonergic drugs stack on top of it. This interaction, not the psychedelic experience itself, is the risk most likely to cause serious physical harm.Callaway & Grob, ayahuasca preparations and serotonin reuptake inhibitors: a potential combination for severe adverse interactions

In ceremonial and trial use, vomiting and nausea are the most common adverse effects

The survey drew on experienced religious users who answered an online questionnaire, and it found most adverse effects were transient and gastrointestinal, with a minority reporting persistent negative effects. Repeated vomiting is dehydrating and taxing for a frail or unwell person, and the vomiting reported across trials confirms it is a near-universal feature rather than a rare event.Durante et al., risk assessment of ayahuasca use in a religious context: self-reported risk factors and adverse effectsSanches et al., antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a SPECT study

Serotonin syndrome is the danger that has hurt people

The vine inhibits monoamine oxidase, the enzyme that clears serotonin. Taking the brew alongside an SSRI or SNRI antidepressant, another MAO inhibitor, the migraine triptans, tramadol, dextromethorphan, or other serotonergic drugs can drive serotonin to dangerous levels, causing agitation, high fever, rapid heart rate, rigidity, and in severe cases death. Older MAO-inhibitor pharmacology also flags tyramine-rich foods such as aged cheese and cured meats, which can spike blood pressure. Anyone on psychiatric medication is in exactly this interaction territory, and stopping an antidepressant carries its own risks that only a prescribing clinician should manage.

It strains the heart and the stomach

Ayahuasca raises heart rate and blood pressure during the experience, which is a concern for anyone with heart disease or uncontrolled hypertension. Intense nausea and vomiting are near-universal and treated as part of the ceremony, and repeated vomiting is dehydrating and hard on a frail or unwell body.

Psychiatric history changes the risk sharply

A personal or family history of bipolar disorder or of psychosis is the most important caution, because serotonergic psychedelics can trigger mania or, in vulnerable people, prolonged psychosis. A survey of religious users found that those with a psychiatric diagnosis reported adverse effects more often. This is not a setting to work through a fragile or unstable state.

This is education, not a guide to using it

This page describes the research, the setting, and the risks. It carries no dosing, no sourcing, and no instructions. DMT is a Schedule I substance in the United States, legal only inside recognized religious exemptions, and use elsewhere is investigational. The studied results come from screened patients in prepared, supported settings, which is a very different situation from drinking an unknown-strength brew outside any medical or protective structure.

Ayahuasca shows an early, real, and very preliminary antidepressant signal in a tiny body of research, and it is a potent brew whose central mechanism is a hazardous drug interaction. The stance here is to inform: read the evidence at its true and modest strength, take the serotonin-syndrome and psychiatric risks seriously, and, for anything touching your own care or medication, talk it through with a qualified clinician.

Common Questions

Does ayahuasca actually help depression?

The early signal is real and the evidence is thin. One randomized placebo-controlled trial in about 29 people with treatment-resistant depression found that a single dose eased symptoms within a day and that 64 percent had responded at seven days against 27 percent on placebo. A few open-label studies without a control group point the same way. That is one small controlled trial and a handful of uncontrolled ones, so the size of the benefit is not established, and most people drink it in a ceremony where expectation is hard to separate from the drug.

Why does it need two plants?

Because the psychedelic on its own does not work by mouth. The active compound, DMT, is broken down in the gut by an enzyme called monoamine oxidase before it can reach the brain. The second plant, the vine, contains harmala alkaloids that block that enzyme, which lets the DMT stay active when swallowed. That same enzyme blockade is what makes the brew dangerous to combine with many antidepressants and other drugs.

What is the most serious risk?

Serotonin syndrome. The vine inhibits monoamine oxidase, so combining the brew with an SSRI or SNRI antidepressant, another MAO inhibitor, or other serotonergic drugs can push serotonin to life-threatening levels. Beyond that, it raises heart rate and blood pressure, brings on heavy vomiting, and can trigger mania or psychosis in someone with a bipolar or psychotic history. Anyone on psychiatric medication is in direct interaction territory.

Is it legal?

Mostly not. DMT is a Schedule I controlled substance in the United States, and ayahuasca falls under the same classification. The exception is recognized religious use: the Uniao do Vegetal and Santo Daime churches have won legal protection to use it as a sacrament. Outside those exemptions its use is illegal under federal law, and in most other countries it is controlled or investigational. This page describes the law and is not a way to obtain anything.

Go Deeper

• Psychedelics in mental health: the wider picture of psilocybin, MDMA, and the approved drug esketamine, where the trial evidence is larger and the same blinding and setting limits apply.
• Depression: what actually helps: the full range of treatments for depression, where an investigational option like ayahuasca sits against the better-established ones.
• Yang Sheng: the preventive tradition of nourishing life, and the grounding practices the Chinese medicine view points to first.