Written by Austin Mao · Last updated: October 2026 · 7 cited studies. This page is not medical advice. Ayahuasca is not approved for the treatment of any medical condition.
Emphasis word: research
What is DMT?
N,N-dimethyltryptamine (DMT) is a tryptamine alkaloid that occurs naturally in many plants and in trace amounts in the mammalian body. In ayahuasca, DMT is the active psychotropic compound; it is concentrated in the leaves of Psychotria viridis (chacruna), brewed together with the vine Banisteriopsis caapi.
Oral DMT alone is not psychoactive. The enzyme monoamine oxidase A (MAO-A) in the gut and liver rapidly degrades it before it can reach systemic circulation. Ayahuasca solves this through the beta-carboline alkaloids in the vine: harmine, harmaline, and tetrahydroharmine, which reversibly inhibit MAO-A and allow oral DMT to become bioavailable (Riba 2003).
Once systemic, DMT binds primarily to serotonin 2A receptors (5-HT2A) on cortical pyramidal neurons, with additional affinity at 5-HT1A, 5-HT2C, and sigma-1 sites. This receptor profile overlaps with, but is not identical to, psilocin, the active metabolite of psilocybin. The subjective experience is correspondingly related but distinct in time-course and phenomenology.
Plant input
DMT-containing leaves (Psychotria viridis) brewed with the beta-carboline-rich vine (Banisteriopsis caapi).
MAO inhibition
Beta-carbolines (harmine, harmaline, tetrahydroharmine) reversibly inhibit gut MAO-A, preventing first-pass degradation of DMT.
Oral DMT bioavailability
With MAO suppressed, oral DMT becomes systemically available, a route normally inactive without MAOI co-administration.
5-HT2A binding
DMT binds primarily to serotonin 2A receptors on cortical pyramidal neurons; additional affinity at 5-HT1A, 5-HT2C, and sigma-1.
Altered consciousness
Acute perceptual, affective, and cognitive shifts over four to six hours, followed by post-session reflection and integration.
Ayahuasca in clinical research
Published clinical work on ayahuasca is smaller in scale than the psilocybin literature, but several studies are worth reading directly.
Osório and colleagues (2015) reported a preliminary open-label study in six patients with recurrent depression, finding significant reductions in HAM-D and MADRS scores within hours of a single session, sustained at 21-day follow-up. Sanches and colleagues (2016) extended this in a larger open-label sample (n=17) combining clinical measures with SPECT neuroimaging, reporting reduced depression scores alongside altered regional blood-flow patterns in left nucleus accumbens, right insula, and left subgenual area.
The strongest single piece of evidence comes from Palhano-Fontes and colleagues (2019), a randomized, double-blind, placebo-controlled trial in treatment-resistant depression (n=29). A single ayahuasca dose lowered MADRS depression scores more than placebo at days 1, 2 and 7. The day-7 response rate was 64% vs 27%, and the difference in remission was a trend (p=0.054). It remains a single small randomized trial, and no large trial has been located.
For broader context across psychedelic compounds, dos Santos and colleagues (2016) published a systematic review covering ayahuasca, psilocybin, and LSD trials from the prior twenty-five years. The review catalogs both the signal and the methodological limits, small samples, expectancy effects, short follow-up windows. See /research/methodology for how we read and report on this body of work.
Cited studies
Osório FL, Sanches RF, Macedo LR, et al. (2015).
Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report. Revista Brasileira de Psiquiatria.
Open-label study (n=6) reporting significant reductions in HAM-D and MADRS scores within hours of a single ayahuasca session, sustained at 21-day follow-up.
Sanches RF, de Lima Osório F, dos Santos RG, et al. (2016).
Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a SPECT neuroimaging study. Journal of Clinical Psychopharmacology.
Open-label study (n=17) combining clinical depression measures with SPECT imaging; reported reduced symptoms and altered blood-flow patterns in left nucleus accumbens, right insula, and left subgenual area at day 1 and day 21.
Palhano-Fontes F, Barreto D, Onias H, et al. (2019).
Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychological Medicine.
Randomized, double-blind, placebo-controlled trial in treatment-resistant depression (n=29). Reported significant antidepressant effect of a single ayahuasca dose versus placebo at day 1 and day 7 on MADRS.
Morales-García JA, Calleja-Conde J, Lopez-Moreno JA, et al. (2020).
N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo. Translational Psychiatry.
Preclinical study reporting that DMT promotes neurogenesis in adult mouse hippocampus and improves performance on memory tasks, supporting a neuroplasticity-linked mechanism.
Morales-García JA, de la Fuente Revenga M, Alonso-Gil S, et al. (2017).
The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro. Scientific Reports.
Cell-culture study reporting that harmine, tetrahydroharmine and harmaline from B. caapi stimulated neural stem cell proliferation and differentiation in vitro.
dos Santos RG, Osório FL, Crippa JAS, et al. (2016).
Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years. Therapeutic Advances in Psychopharmacology.
Systematic review across ayahuasca, psilocybin, and LSD clinical trials. Catalogs the strength and limits of the evidence base across depression, anxiety, and substance-use contexts.
Riba J, Valle M, Urbano G, et al. (2003).
Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics. Journal of Pharmacology and Experimental Therapeutics.
Controlled pharmacokinetic study characterizing the time-course of oral DMT bioavailability in the presence of beta-carboline MAO inhibitors, plus cardiovascular and subjective profile.
The ceremonial arc: preparation, ceremony, integration
I find it helpful to think of ayahuasca work as a three-phase arc: preparation, ceremony, integration. That arc is how we organize our own practice. It is not a research finding, and no study has tested whether preparation or integration support changes what ayahuasca does. The ceremony itself lasts four to six hours, and everything around it is ours to design.
Preparation
Dietary restrictions, intention setting, medical screening, and medication review led by your prescriber.
Ceremony
The brew is taken in a held setting. Effects last four to six hours, with facilitators present throughout.
Integration
The weeks after: structured reflection, somatic work, and returning to daily life. This is our practice, not a tested protocol.
Neuroplasticity: a hypothesis, not a finding
One hypothesis for why change might last is experience-dependent plasticity. Morales-García and colleagues (2020) reported in vivo evidence that DMT promotes adult neurogenesis in mouse hippocampus and improves performance on memory-related tasks. Earlier preclinical work on classic psychedelics broadly has shown increases in dendritic spine density in rodents. Morales-Garcia and colleagues also reported in 2017 (Scientific Reports) that alkaloids of Banisteriopsis caapi stimulated neurogenesis in vitro. These are preclinical findings; no human study has measured a plasticity window after ayahuasca, and no trial has tested whether integration support lengthens its effects. See /science/neuroplasticity for what was measured after psilocybin and for how long.
Cultural context and respect
Ayahuasca has been used in healing and spiritual ceremonies by Amazonian peoples for generations, long before the Western research literature. I treat the published research as one lens among several, not the only or the primary one, and I do not present it as a replacement for the cultural wisdom that surrounds this medicine.
Safety considerations
Because the beta-carbolines in ayahuasca are reversible MAO-A inhibitors, ayahuasca interacts with a wide range of medications and dietary compounds. Our nurse practitioner reviews every medical intake. The most important categories to flag:
- SSRIs and SNRIs: concurrent use with an MAO inhibitor carries serotonin syndrome risk. Your prescriber leads any taper, and you never stop or change a medication on your own. Tapering often takes one to two months.
- Tyramine-containing foods: aged cheeses, cured meats, fermented soy, and certain alcoholic beverages can trigger hypertensive responses when MAO is inhibited. A pre-ceremony diet is part of standard preparation.
- Other psychiatric medications and stimulants: every medication and supplement gets reviewed in our medical intake. See medications and safety.
- Personal or family history of psychosis: was a screening exclusion in published trials. Our nurse practitioner decides each case.