Drug: Ayahuasca

What It Is

Ayahuasca is an Amazonian brew made from two plants: a leaf that carries the psychedelic DMT, and a vine that keeps the DMT active when swallowed. Indigenous groups across the western Amazon have used it for generations in healing and spiritual practice. In the twentieth century, two Brazilian churches, the Uniao do Vegetal and Santo Daime, built formal religious traditions around the brew. Those traditions have since spread to North America and Europe. The research attention is narrower and recent: a small set of studies in depression, most of them from a single group.

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. Swallowed on its own, DMT is broken down in the gut and liver by an enzyme called monoamine oxidase before it reaches the brain. By mouth it has almost no effect.

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. Intense nausea and vomiting almost always come with it; the tradition treats this as part of the process and calls it the purge. The MAO inhibition outlasts the visual effects; it is an active drug interaction for as long as the alkaloids are in the body.

What It Does

The strongest single piece of evidence 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. By day seven, 64 percent of the ayahuasca group had responded, against 27 percent on placebo, and the gap between the groups widened across the week. It ran at one site, on one dose, in fewer than 30 people, with no follow-up past three weeks.

Two open-label studies from the same research group, one in six patients and one in 17, reported large drops in depression scores that held up to three weeks. Neither had a control group, and the authors said as much.

A systematic review pooled these small ayahuasca trials alongside the psilocybin and LSD studies. Its measured conclusion was plain: the results are promising, and the evidence base is a handful of small studies. The largest head counts come from surveys of people who already drink ayahuasca in ceremony, some running to thousands of respondents across dozens of countries. Those surveys report a link between ceremonial use and better mood and wellbeing. But the people who take the trouble to answer are not a random group, so a survey cannot show the brew caused the change.

One limitation affects every study here. The experience is unmistakable, so almost no one in a trial stays truly blind to whether they drank ayahuasca or placebo. Expectation is then hard to separate from the drug effect. A second limit is the setting: nearly all of this happens in a prepared ceremony with support, and that support may itself be part of what helps.

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, not 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, not 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

DMT activates the serotonin 5-HT2A receptor, the same receptor central to psilocybin and LSD. Switching that receptor on appears to raise the flexibility of activity across the cortex and to loosen the fixed, self-focused thought patterns of depression.

In the open-label SPECT study, brain blood flow rose after dosing in the nucleus accumbens, the insula, and the subgenual area, three regions tied to mood.

The controlled evidence is one small trial, and the mechanism work is early. So far researchers have only observed the brain change. They have not shown it causes the improvement in mood.

Taken alongside an SSRI or SNRI antidepressant, another MAO inhibitor, or another serotonergic drug, the brew can push serotonin to life-threatening levels.

Where the Law Stands

US law classifies DMT as Schedule I, the most restricted category, and ayahuasca as a preparation falls under the same classification. That is far more restrictive than the research is developed. The exceptions are narrow. In 2006 the Supreme Court ruled that the Uniao do Vegetal could use the brew as a sacrament under the Religious Freedom Restoration Act. Santo Daime congregations have won similar protection in the courts. Outside those recognized exemptions, use is illegal under federal law, and in most other countries the brew stays controlled or investigational. Nothing here is a route to obtaining it; it is a description of where the law currently stands.

Go Deeper

• Psychedelics in mental health: the wider field 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 depression treatments, and where an investigational option like this one sits among the ones with a longer record.
• Yang Sheng: the preventive tradition of nourishing life, and the grounding daily practices it puts first.

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. Clear thought, steady emotion, and settled sleep are read as signs of a rooted Shen. A mind flooded, disoriented, or thrown into fear is a disturbance of the Shen, and the tradition treats it as something to calm and anchor. The tradition's aim is grounding: settling the Shen, harmonizing the Heart and Liver, and rooting a scattered mind back in the body. It does this through stillness, breath, and regular life.

Read through that lens, a brew that brings hours of visions and fear could be seen as forcefully stirring the Shen. The heavy vomiting reads as a strong draining of Stomach and Spleen Qi, taxing for a weak or deficient person. The tradition would approach it with great care, and would especially avoid it in someone already depleted, agitated, or unsettled. The wider preventive tradition of Yang Sheng, nourishing life, would put grounding practices first: stillness, breath, sleep, and a settled daily rhythm.

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, not 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 from drug interactions

The vine blocks the enzyme that clears serotonin. Taken alongside an SSRI or SNRI antidepressant, another MAO inhibitor, or another serotonergic drug, the brew can push serotonin to life-threatening levels. The migraine triptans, tramadol, and dextromethorphan carry the same risk. High serotonin brings 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. These can spike blood pressure. Anyone on psychiatric medication is in exactly this interaction territory, and stopping an antidepressant carries its own risks that a prescribing clinician should manage.

It strains the heart and the stomach

Ayahuasca raises heart rate and blood pressure during the experience. That is a concern for anyone with heart disease or uncontrolled hypertension. Intense nausea and vomiting are near-universal, 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.

Ayahuasca shows a preliminary antidepressant signal in a tiny body of research. It is also a potent brew whose central mechanism is a hazardous drug interaction. Read the evidence at its modest strength. Take the serotonin-syndrome and psychiatric risks seriously.

Common Questions

Can Ayahuasca Be Used as a Treatment?

Not as an approved medicine, and no doctor can prescribe it. The studied benefit came from vetted volunteers in a prepared room with support on hand, a very different setting from an unknown-strength brew taken alone. For depression that standard antidepressants have not lifted, the levers with the longest record come first: regular movement, good sleep, morning daylight, and whole food. All of these carry real antidepressant evidence. Those are the free, self-directed steps in the depression guide. After them, a conversation with a qualified mental-health clinician is the step the evidence supports for what standard care has not reached.