WARNING: MAOIs, including the harmala alkaloids (harmine, harmaline, THH) found in ayahuasca and Peganum harmala, have serious, well documented interactions with many common medications and recreational drugs. These aren't limited to SSRIs and stimulants:
SSRIs in particular typically need to be stopped for a substantial washout period beforehand, often several weeks, though this varies by drug and should be discussed with a doctor rather than decided from a forum post.
A note on food and MAOIs: unlike older irreversible pharmaceutical MAOIs, the harmala alkaloids are reversible, competitive MAO-A inhibitors (RIMAs). This means the classic "no cheese ever" warnings associated with older antidepressant MAOIs don't transfer directly, since a large tyramine load can partly outcompete the alkaloid at the enzyme, and MAO-B remains available as a backup pathway for tyramine clearance. That said, this isn't zero risk. Large amounts of aged, cured, or fermented foods (aged cheese, cured meats, tap beer) close to a strong dose can still provoke a reaction in some people, so real caution with large tyramine loads is warranted even if the old absolute food bans are overstated.
For more information:
- SSRIs/SNRIs (e.g., Prozac, Zoloft, Effexor): risk of serotonin syndrome
- Stimulants (MDMA, amphetamines, cocaine): risk of severe hypertensive crisis from increased norepinephrine/serotonin activity on top of MAO inhibition. Documented fatalities from combining amphetamines with pharmaceutical MAOIs are reviewed here: https://www.psychotropical.com/wp-content/uploads/14.20-MAOI_stimulants_2.pdf (see case report citations 28 to 34). The same risk logic applies to cocaine and MDMA
- Meperidine (Demerol): contraindicated. The FDA label states meperidine has occasionally caused unpredictable, severe, and sometimes fatal reactions in patients who took an MAOI within the prior 14 days: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/005010s058lbl.pdf
- Tramadol, fentanyl, and methadone: weaker serotonergic activity than meperidine but still carry real risk and are generally best avoided with MAOIs
- Dextromethorphan (DXM): found in many OTC cough/cold medicines (anything with "DM" in the name); can cause serotonin syndrome, elevated blood pressure, or brief psychosis
- Other MAOIs (including pharmaceutical ones, or methylene blue, which is itself a potent MAO-A inhibitor sometimes used outside clinical settings)
- Serotonin-boosting supplements: St. John's Wort, 5-HTP, L-tryptophan, and SAMe. These raise serotonergic activity through different mechanisms (precursor loading, reuptake inhibition) but all carry documented serotonin syndrome risk when combined with an MAOI
SSRIs in particular typically need to be stopped for a substantial washout period beforehand, often several weeks, though this varies by drug and should be discussed with a doctor rather than decided from a forum post.
A note on food and MAOIs: unlike older irreversible pharmaceutical MAOIs, the harmala alkaloids are reversible, competitive MAO-A inhibitors (RIMAs). This means the classic "no cheese ever" warnings associated with older antidepressant MAOIs don't transfer directly, since a large tyramine load can partly outcompete the alkaloid at the enzyme, and MAO-B remains available as a backup pathway for tyramine clearance. That said, this isn't zero risk. Large amounts of aged, cured, or fermented foods (aged cheese, cured meats, tap beer) close to a strong dose can still provoke a reaction in some people, so real caution with large tyramine loads is warranted even if the old absolute food bans are overstated.
For more information:
- Wikipedia's MAOI interactions list: Monoamine oxidase inhibitor - Wikipedia
- Detailed MAOI food/drug interaction reference compiled by Dr. Ken Gillman: https://psychotropical.com/wp-content/uploads/2017/12/MAOI_diet_drug_interactions_2016.pdf
- Peer reviewed background on serotonin syndrome mechanisms and presentation: Serotonin Syndrome With Concomitant Antidepressant and Tramadol: A Case Report - PMC
- Pharmacological review of ayahuasca compound interactions, Ruffell et al., Brazilian Journal of Psychiatry 2020: https://www.scielo.br/j/rbp/a/s6rDBPvF99z7JccZf3gHNdz/
- NEI/Stahl "Practical Guide to Using MAOIs" (2012), a prescriber-focused myth versus pharmacology breakdown covering tyramine, cold medications, stimulants, anesthesia, tricyclics, painkillers, and psychotropic combinations in detail. Written for pharmaceutical MAOIs rather than harmala alkaloids specifically, but the underlying pharmacology is a useful supplementary reference: https://cdn.neiglobal.com/content/e...c-12-hlfday-02/slides_at-enc-12-hlfday-02.pdf
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