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Molecule guide

DMT and ayahuasca: what the research shows

DMT is a short-acting psychedelic; ayahuasca is an Amazonian brew containing it. Early depression trials, drug-interaction risks and evidence strength.

ReviewedLast updated September 25, 2026

Also known as N,N-dimethyltryptamine, SPL026 (DMT fumarate), Ayahuasca / hoasca

At a glance

Type
DMT is a classic psychedelic (a tryptamine). Ayahuasca is a traditional brew of two Amazonian plants that contains DMT.
How it acts
DMT activates serotonin 2A (and 1A) receptors. The vine in ayahuasca blocks the enzyme that would otherwise break DMT down in the gut.
Approved uses
None.
Legal status
Schedule III in Canada, with religious exemptions for some ayahuasca churches. Schedule I in the US, with a religious exemption upheld by the Supreme Court in 2006.
How it's given in research
Pure DMT by IV infusion, with effects lasting minutes. Ayahuasca as a drink, with effects lasting hours.
Strongest evidence
Two small randomised depression trials, rated Low.
Biggest risk
Ayahuasca can interact dangerously with many medicines, including common antidepressants.

Evidence by condition

How strong the research is for each use, on our four-level evidence scale.

Major depression (IV DMT) Low

A 34-person phase IIa randomised trial found one IV dose of DMT with support reduced depression scores more than placebo at two weeks. Benefits lasted up to three months in open-label follow-up.

Treatment-resistant depression (ayahuasca) Low

A 29-person randomised trial found one dose of ayahuasca reduced depression more than placebo over seven days, with 64% responding compared with 27%.

What it is

DMT (N,N-dimethyltryptamine) is a classic psychedelic found in many plants, and in trace amounts in the human body.4 Given by IV infusion, its effects begin almost immediately, peak within about two minutes, and are largely gone within 30 minutes.4

Ayahuasca is a brew traditionally used by Indigenous groups in the northwestern Amazon, in Brazil, Peru, Colombia and Ecuador. It’s made from two plants: leaves that contain DMT (Psychotria viridis), and the Banisteriopsis caapi vine, which contains compounds called β-carbolines, such as harmine.7 DMT swallowed on its own is broken down in the gut. The vine’s compounds block that breakdown, so ayahuasca is active when drunk, and its effects last hours.6

How it works in the brain

DMT activates serotonin receptors, especially the 5-HT2A receptor targeted by psilocybin and LSD, as well as 5-HT1A.7 The β-carbolines in ayahuasca are MAO inhibitors: they block monoamine oxidase, the enzyme that breaks down DMT and other brain chemicals such as serotonin.6

Key studies

IV DMT for depression, 2026. In a phase IIa trial, 34 adults with moderate to severe depression received a single IV dose of DMT or placebo, with psychological support. At two weeks, depression scores had dropped by 7.35 points more with DMT. Everyone could then have a DMT dose in an open-label phase, and benefits lasted up to three months.1 A phase 1 study in healthy volunteers had first tested doses and safety.3

Ayahuasca for treatment-resistant depression, 2019. In a double-blind trial, 29 people received one dose of ayahuasca or a placebo drink. Ayahuasca reduced depression more at days 1, 2 and 7. At day 7, 64% had responded, compared with 27% on placebo.2

Safety and risks reported in research

In the DMT depression trial, side effects were mostly mild to moderate, commonly pain at the infusion site, nausea and brief anxiety. No serious adverse events occurred.1

Ayahuasca is different. In a global survey of 10,836 people, 69.9% reported acute physical effects, mainly vomiting, and 2.3% needed medical attention afterwards. 55.9% reported difficult mental health effects in the following weeks or months, although most saw these as part of a positive process.5

  • Canada: DMT is Schedule III under the Controlled Drugs and Substances Act.8 Since 2017, Health Canada has granted section 56 exemptions to a small number of named religious groups, including Santo Daime churches and the UDV, to import and use ayahuasca as a sacrament. The exemptions don’t extend to anyone else.9
  • United States: DMT is Schedule I. In 2006, the Supreme Court unanimously ruled that the government hadn’t justified banning the UDV church’s sacramental use of ayahuasca (hoasca) under religious freedom law.10

History in brief

  • Traditional use: Ayahuasca used for healing and ritual by Indigenous groups in the northwestern Amazon.7
  • 1994: Dose-response study of IV DMT in humans published.4
  • 2006: US Supreme Court upholds a church’s sacramental ayahuasca use.10
  • 2017: First Canadian religious exemptions for ayahuasca.9
  • 2019: First randomised trial of ayahuasca for treatment-resistant depression.2
  • 2026: Phase IIa trial of IV DMT for depression published.1

Myths vs evidence

The claim“Your brain releases a flood of DMT when you die.”

What the evidence says Unproven

DMT occurs naturally in the body in tiny amounts, but there's no direct evidence in humans that it floods the brain at death. This is a popular hypothesis, not an established finding.4

The claim“Ayahuasca is natural, so it's safe with any medication.”

What the evidence says False

The vine in ayahuasca contains MAO-inhibiting compounds, which can interact seriously with other drugs, including many antidepressants.6 In a survey of more than 10,000 people, 2.3% needed medical attention after use.5

See all myths vs evidence →

Frequently asked questions

What is the difference between DMT and ayahuasca?

DMT is a single compound. Swallowed on its own, it's broken down in the gut before it can act. Ayahuasca combines a DMT-containing leaf with a vine whose compounds block that breakdown, so the brew is active when drunk. The effects then last hours instead of minutes.

Why are researchers interested in DMT?

Mainly because it's so short. IV DMT effects peak within about two minutes and are mostly gone within 30 minutes. That could make a psychedelic treatment session far shorter than with psilocybin.

Is ayahuasca legal in Canada?

DMT is a Schedule III controlled substance. Since 2017, Health Canada has granted exemptions to a small number of named religious groups to import and use ayahuasca in their ceremonies. Outside those exemptions, it isn't legal. Talk to a qualified health professional about your own situation.

How is DMT different from 5-MeO-DMT?

They're related but different molecules. 5-MeO-DMT acts more strongly on 5-HT1A receptors and tends to produce fewer visual effects. See our 5-MeO-DMT guide.

Clinical trials

Showing 8 of 14 active trials in our tracker.

See all trials in the tracker →

References

  1. Erritzoe D, et al. A short-acting psychedelic intervention for major depressive disorder: a phase IIa randomized placebo-controlled trial. Nature Medicine. 2026;32(2):591–598. Source
  2. Palhano-Fontes F, 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. Source
  3. James E, et al. Safety, tolerability, pharmacodynamic and wellbeing effects of SPL026 (dimethyltryptamine fumarate) in healthy participants: a randomized, placebo-controlled phase 1 trial. Frontiers in Psychiatry. 2024;14:1305796. Source
  4. Strassman RJ, et al. Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale. Archives of General Psychiatry. 1994;51(2):98–108. Source
  5. Bouso JC, et al. Adverse effects of ayahuasca: results from the Global Ayahuasca Survey. PLOS Global Public Health. 2022;2(11):e0000438. Source
  6. Malcolm BJ, Lee KC. Ayahuasca: an ancient sacrament for treatment of contemporary psychiatric illness? Mental Health Clinician. 2017;7(1):39–45. Source
  7. Dos Santos RG, et al. Ayahuasca: pharmacology, safety, and therapeutic effects. CNS Spectrums. 2024;30(1):e2. Source
  8. Government of Canada. Controlled Drugs and Substances Act (S.C. 1996, c. 19), Schedule III. Source
  9. ICEERS. Ayahuasca legal status: Canada (section 56 exemptions for religious groups since 2017). Source
  10. Gonzales v. O Centro Espírita Beneficente União do Vegetal, 546 U.S. 418 (2006). Source