MAO-Inhibiting Preparations and Interactions

Urgent help first

Serotonin syndrome can be life-threatening. Signs include agitation, fast heartbeat, fever, heavy sweating, muscle spasms, tremor and confusion. [1] Reviews add extreme and fluctuating vital signs, muscle rigidity and seizure activity as signs that need immediate medical attention. [2] In the US call 911 for these symptoms. For a possible poisoning, US Poison Help is 1-800-222-1222 (other countries: poison help by country). Anyone taking prescribed medicines should not stop them on their own because of this page; talk with the prescriber first.

What "MAO-inhibiting" means

Monoamine oxidase (MAO) is an enzyme that breaks down serotonin, dopamine, norepinephrine and some dietary compounds. An MAO inhibitor (MAOI) slows that enzyme. Some prescription antidepressants are MAOIs, and some plant preparations contain natural compounds that also inhibit MAO. The best-known example is ayahuasca, an Amazonian ceremonial brew whose MAO inhibitors come from Banisteriopsis caapi and whose DMT comes from Psychotria viridis or Diplopterys cabrerana. [3] A 2020 systematic review of 16 papers found that the main research narrative is that the MAO inhibitors in ayahuasca prevent the breakdown of DMT. [4] A 2026 modeling paper describes the harmala alkaloid harmine as a reversible MAO-A inhibitor that enables DMT to work by mouth. [5]

The same property is what raises interaction concern: MAO inhibition affects how the body handles other serotonin-related medicines and some foods and drugs. For the preparation itself see ayahuasca, harmala alkaloids and DMT versus ayahuasca. DMT and ayahuasca are not the same thing.

What the sources report

This page uses the labels evidence of harm, insufficient evidence and preclinical, explained in how we label evidence.

Prescription MAOIs, from a drug label. The US label for the MAOI antidepressant phenelzine says patients on it should not take serotonin-acting agents, and lists fluoxetine, paroxetine, sertraline, citalopram and venlafaxine among examples, because serious and sometimes fatal reactions have been reported. [6] The same label says it should not be used with dextromethorphan or with central nervous system depressants such as alcohol and certain narcotics. [6] This is a prescription medicine label, not ayahuasca data. It shows how seriously the MAO-inhibiting class is treated by the regulator. Label: approved medicine (phenelzine; US FDA, depression).

Ayahuasca and SSRIs. A 1998 paper warned that the MAO-inhibiting harmala alkaloids in ayahuasca combined with SSRI antidepressants may cause a serotonin syndrome with potentially grave outcome. [7] That is a warning from pharmacology, not a trial. A 2026 computer-modeling study predicted that fluoxetine and paroxetine increase exposure to harmine and moderately raise DMT concentrations, and suggested a clinically relevant interaction. The model used data from six volunteers, so the result is a prediction. [5] Label: preclinical for the modeling, insufficient evidence for measured human outcomes.

A reported case. A 2026 case report described a 46-year-old man who developed severe serotonin syndrome with respiratory failure after ingesting ayahuasca over three days, then over-the-counter dextromethorphan (a cough ingredient) and diphenhydramine. He needed a breathing tube and intensive care and recovered within days. The authors called severe serotonin syndrome from ayahuasca rarely documented and said the case underscores the need for clinician awareness. [3] One case cannot give a rate, and the report cannot separate the contributions of each substance.

Serotonin toxicity in general. A 2022 review states that true serotonin toxicity typically arises with a serotonergic overdose or when a drug that raises serotonin is combined with an MAOI. Serotonergic psychotropics without MAOIs were described as low risk combined with psychedelics without MAOIs, while some combinations carry significant risk. [2] The review's point is that risk depends on the specific pair, not on a blanket rule. See serotonergic medicines and substance-specific evidence.

What is not covered here

We do not give waiting periods, stopping schedules or "safe" combinations. None of the sources we read provides a verified schedule suitable for the public, and that decision belongs with a prescriber. Proper evidence not found for validated rules that tell a person which medicines are safe alongside ayahuasca. We checked PubMed for ayahuasca medication interactions and found a review, a modeling study and case reports, but no controlled human interaction trial.

Other MAO-inhibiting products

Proper evidence not found this session for interaction data on other plant or synthetic products that inhibit MAO. We searched PubMed for ayahuasca interaction literature and read only the sources listed below. For general herb guidance see herb safety and interactions.

Special groups

• People taking antidepressants, ADHD medicines, migraine medicines or cough and cold products: these can interact with MAO inhibition; a pharmacist or prescriber can review the exact list.
• People with heart conditions or high blood pressure: the phenelzine label lists hypertensive crisis risk with some foods and drugs. [6]
• Mental health conditions: see psychedelic adverse effects and contraindications.

Safety and legal note

This is not medical or legal advice. For general interaction concepts see how interactions work, and bring the full medicine list to a health professional.