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Ayahuasca is a traditional Amazonian plant preparation, classically brewed from the vine Banisteriopsis caapi together with N,N-dimethyltryptamine (DMT) containing plants such as Psychotria viridis. Its defining pharmacological feature is a synergy between two plant classes: DMT supplies the psychedelic activity, while beta-carboline alkaloids from the caapi vine, chiefly harmine and harmaline, reversibly inhibit monoamine oxidase A (MAO-A). DMT is normally destroyed in the gut and liver and is therefore nearly inactive by mouth, but MAO-A inhibition protects it long enough to reach the brain, rendering an otherwise orally inactive tryptamine profoundly psychoactive. Once systemic, DMT acts as an agonist at serotonin 5-HT2A, 5-HT1A, and 5-HT2C receptors to produce the visionary state, and controlled clinical trials have begun to examine ayahuasca as a rapid-acting antidepressant.
- Deep introspective and visionary psychedelic experience
- Rapid antidepressant signal in early controlled trials
- MAO-A inhibition that makes oral DMT active, a unique two-plant pharmacological synergy
- Intense nausea, vomiting, and diarrhea
- Raised blood pressure and heart rate
- Anxiety and disorientation
- Serotonin syndrome risk with serotonergic drugs
Mechanism
The central mechanism of ayahuasca is pharmacokinetic synergy. Oral DMT alone is rapidly deaminated by MAO-A in the intestinal wall and liver, giving negligible . The beta-carbolines harmine and harmaline in Banisteriopsis caapi are reversible, competitive MAO-A inhibitors, and by blocking this metabolism they allow DMT to enter the circulation and cross into the brain. Physiologically based pharmacokinetic models of the brew confirm that harmine inhibition of MAO-A in liver and lung is what raises and prolongs DMT exposure.
Once DMT reaches the central nervous system it behaves as a classical serotonergic psychedelic, activating receptors as its principal action, with additional agonism at and 5-HT2C receptors and interactions at sigma-1 and trace amine sites contributing to the overall experience. Human studies show a dose-dependent psychedelic and stimulant profile with characteristic electroencephalographic changes, and clinical work links a single session to increases in serum brain-derived neurotrophic factor and modulation of the awakening response, changes proposed to underlie the observed antidepressant effects.
receptor fingerprint
Monoamine oxidase A (MAO-A)Reversible inhibitor (via harmine and harmaline)
receptorAgonist (via DMT)
receptorAgonist (via DMT)
5-HT2C receptorAgonist (via DMT)
Sigma-1 receptorAgonist (via DMT)
Safetyrisks and cautions, not medical advice
Because ayahuasca combines an MAO-A inhibitor with a serotonergic psychedelic, it carries the interaction risks of any monoamine oxidase inhibitor. Combining it with selective serotonin reuptake inhibitors, other serotonergic drugs, or with tyramine-rich foods can precipitate serotonin syndrome or hypertensive reactions, and modeling work specifically flags clinically relevant interactions between ayahuasca alkaloids and SSRIs. Acute sessions commonly produce vomiting, diarrhea, transient blood-pressure and heart-rate increases, anxiety, and disorientation, and the state can be psychologically destabilizing for vulnerable individuals or those with personal or family histories of psychosis. It should never be treated as casually compatible with existing antidepressant or psychiatric medication. Not medical advice.
Subjective profileweighing the evidence above
The antidepressant signal from early controlled trials is genuine, but the MAO-A inhibition is not a footnote; combining it with SSRIs, other serotonergic drugs or tyramine-rich food risks serotonin toxicity or a hypertensive reaction. The vomiting and blood-pressure spikes are standard, not a bad brew.
Resources
No suppliers are provided for compounds like this. This entry is here for reference.
Research
- 2001first citedSubjective effects and tolerability of the South American psychoactive beverage Ayahuasca in he…
- 2026most recentPredicting drug-drug interactions between ayahuasca alkaloids and SSRIs using physiologically b…
- 1.Neurobiological research on N,N-dimethyltryptamine (DMT) and its potentiation by monoamine oxidase (MAO) inhibition: from ayahuasca to synthetic combinations of DMT and MAO inhibitors.
- 2.Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial.
- 3.Cortisol Modulation by Ayahuasca in Patients With Treatment Resistant Depression and Healthy Controls.
- 4.Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial.
- 5.Subjective effects and tolerability of the South American psychoactive beverage Ayahuasca in healthy volunteers.
- 6.Topographic pharmaco-EEG mapping of the effects of the South American psychoactive beverage ayahuasca in healthy volunteers.
- 7.Development of a physiologically based pharmacokinetic model of N,N-dimethyltryptamine, harmine, and their interactions from ayahuasca in rats and humans.
- 8.Predicting drug-drug interactions between ayahuasca alkaloids and SSRIs using physiologically based pharmacokinetic modeling.
- 9.Modification of the effects of 5-methoxy-N,N-dimethyltryptamine on exploratory behavior in rats by monoamine oxidase inhibitors.
- 10.β-carboline-independent antidepressant-like effect of the standardized extract of the barks of Mimosa tenuiflora (Willd) Poir. occurs via 5-HT(2A/2C) receptors in mice.
10 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Why does ayahuasca need two plants?
One plant supplies DMT, the psychedelic; the other supplies beta-carbolines that inhibit MAO-A. Without that enzyme block, the gut and liver would destroy DMT before it could act.
Is ayahuasca dangerous with antidepressants?
Yes, this is a serious concern. As an MAO-A inhibitor it can interact with SSRIs and other serotonergic drugs to cause serotonin syndrome, so it is not compatible with routine casual use alongside psychiatric medication.
Why do people vomit during ayahuasca?
Nausea and vomiting, often called the purge, are extremely common and reflect the combined gastrointestinal actions of the tryptamine and beta-carboline alkaloids.
Adverse effects
- Intense nausea, vomiting, and diarrhea
- Raised blood pressure and heart rate
- Anxiety and disorientation
- Serotonin syndrome risk with serotonergic drugs
Notes and cautions
- Psychological destabilization in vulnerable users