Compound Monograph
Harmaline
Harmaline is a beta-carboline alkaloid and reversible MAO-A inhibitor found in Syrian rue and ayahuasca admixtures.
Classification
Harmaline is a beta-carboline alkaloid, part of the alkaloids class. Nitrogen-containing, often bitter and physiologically potent compounds — the group behind many of the strongest plant medicines and poisons.
Where Does It Come From? (4)
Harmaline is a naturally occurring beta-carboline alkaloid, found in Syrian rue, Banisteriopsis caapi, Passionflower and 1 other source. It is flagged as moderately toxic.
Research & Evidence
Harmaline is a beta-carboline (harmala) alkaloid found in Syrian rue and the ayahuasca vine Banisteriopsis caapi, among other plants. Its best-characterised pharmacological action is reversible inhibition of monoamine oxidase A (MAO-A). In traditional ayahuasca brews this MAO inhibition is what allows orally ingested DMT to remain active long enough to produce effects. On its own harmaline can produce sedation, nausea and, at higher doses, mild visionary or dream-like states, and it has been used experimentally as a model compound for studying tremor.
Monoamine oxidase (MAO) inhibition
Harmaline is a potent, reversible, MAO-A-selective inhibitor, with a reported binding constant (Ki) near 48 nM and IC50 values around 0.1 µM in enzyme assays — nanomolar-to-submicromolar potency that places it, alongside harmine, among the strongest plant MAO inhibitors on record, while its effect on MAO-B is minimal 1Reference 1Inhibition of monoamine oxidase A by beta-carboline derivativesView study →. This selective MAO-A inhibition is the basis of its role in ayahuasca. See the natural MAO inhibitors guide for context.
Toxicity & Safety
Because harmaline inhibits MAO-A, it carries the interaction risks common to MAO inhibitors: combining it with serotonergic drugs (SSRIs, certain other antidepressants, some opioids) or with tyramine-rich foods can be dangerous and potentially cause serotonin toxicity or hypertensive reactions. It commonly causes nausea and vomiting and should be approached with particular caution by anyone taking other medications.
References
- Kim, H., Sablin, S. O., & Ramsay, R. R. (1997). Inhibition of monoamine oxidase A by beta-carboline derivatives. Archives of Biochemistry and Biophysics, 337(1), 137-142. https://pubmed.ncbi.nlm.nih.gov/8990278/