Psilocybin and harmala alkaloids
CautionNatural MAO-A inhibitor · also: syrian rue, peganum harmala, banisteriopsis caapi, ayahuasca vine, harmine
Psilocybin and harmala alkaloids (Syrian rue, ayahuasca vine): caution, the harmala dose is unmeasured, so how much it changes the trip cannot be predicted.
Substantially amplified and extended effects, plus additive nausea. The dose of the harmala is usually unmeasured, so the multiplier is unknowable.
Claims re-checked against the cited sources:
Why it happens
Harmine and harmaline are potent, reversible, competitive inhibitors of MAO-A, the same mechanism as moclobemide. Peganum harmala seeds contain several percent of these alkaloids by weight, so plant material can carry a large and variable dose. How much this changes psilocin levels in people has not been measured.
What is known
Widely reported in practice. The MAO-A mechanism is well characterised; the interaction magnitude with psilocybin specifically is not.
- 2010
- Dry Peganum harmala seeds contained harmine and harmaline at about 4.3% and 5.6%; seed extracts were potent reversible, competitive MAO-A inhibitors (IC50 27 micrograms per litre) and poor MAO-B inhibitors. Herraiz et al., 'beta-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO)', Food Chem Toxicol
- 2024
- Banisteriopsis caapi, used in ayahuasca, contains harmine and harmaline, which make oral DMT active by blocking its breakdown by MAO. Halman et al., 'Drug-drug interactions involving classic psychedelics: a systematic review', J Psychopharmacol
- 2024
- MAO-A converted psilocin into only minimal amounts of 4-HIAA in vitro, so the size of any harmala effect on psilocin is uncertain. Thomann et al., 'In vitro and in vivo metabolism of psilocybin's active metabolite psilocin', Front Pharmacol
Safety guidance
- Start with a small fraction of a psilocybin dose you already know, because the multiplier is unknown.
- Expect more nausea and vomiting; plan for it.
- Do not combine harmala with antidepressants, stimulants or other serotonergic drugs.
- If you take any prescribed medication, check with a prescriber or pharmacist before using harmala at all.
When to seek help
Get urgent help for a severe headache, chest pain, pounding heart, high fever, rigid or twitching muscles, or confusion that does not ease. Emergency red flags.
Common questions
Is this like ayahuasca?
It uses the same harmala alkaloids that make oral DMT active in ayahuasca. With psilocybin, which is active orally without them, the size of the boost is unknown.
How much stronger will it be?
Nobody knows. Harmala content varies by plant part and batch, and the effect on psilocin has not been measured.
Do I need to avoid cheese and other tyramine foods?
Harmala alkaloids are reversible MAO-A inhibitors like moclobemide, whose label does not require diet restrictions, but harmala doses are unmeasured, so caution with large amounts of aged or fermented food is sensible.
Sources
How we research this: sources, evidence grading, review and updates.