Harmala alkaloids (harmine, harmaline, tetrahydroharmine) — interactions

The β-carbolines in Syrian rue and the ayahuasca vine. Reversible, competitive, MAO-A selective — pharmacologically a RIMA, and the reason an orally-inactive tryptamine becomes orally active.

Also known as: Syrian rue, Peganum harmala, Banisteriopsis caapi, caapi, ayahuasca vine. Category: plant.

What it does, mechanism by mechanism

MAO-A inhibition — inhibits, strong

Blocks monoamine oxidase A, the enzyme that breaks down serotonin, noradrenaline and dietary tyramine. Two separate hazards come off one enzyme: serotonin accumulates (toxicity) and dietary tyramine is no longer destroyed in the gut wall (pressor response).

Harmine and harmaline are potent competitive MAO-A inhibitors in human tissue; tetrahydroharmine additionally inhibits serotonin reuptake.

Sources: Herraiz T 2010, Callaway JC 1999, Riba J 2003 · more on MAO-A inhibition

Serotonin reuptake inhibition — inhibits, weak

Blocks the serotonin transporter (SERT), raising synaptic serotonin. Additive with anything else that raises serotonin; combined with MAO inhibition it is the classic lethal pairing.

Tetrahydroharmine component.

Sources: Callaway JC 1999 · more on Serotonin reuptake inhibition

Specific combinations

What a clean result means here

A clean result means NO DOCUMENTED INTERACTION IN THIS DATASET. It does not mean safe, and it is not a clearance. Most substances are not in this dataset at all, and for many pairs that are, nobody has ever studied the combination.

In this dataset

  • Monoamine oxidase inhibition (prescription MAOIs, RIMAs, linezolid, methylene blue, harmala alkaloids)
  • Serotonergic drugs and the serotonin-toxicity mechanism
  • Dietary tyramine and L-dopa loads
  • The major cytochrome P450 pathways: CYP3A4, CYP2D6, CYP1A2, CYP2C9, CYP2C19 — inhibition and induction
  • P-glycoprotein inhibition and induction
  • 11β-HSD2 inhibition (the licorice mechanism) and the potassium consequences that follow it
  • QT prolongation as an additive pharmacodynamic axis
  • Culinary seasonings and common foods with documented pharmacological activity
  • A selected set of narrow-therapeutic-index drugs where those shifts matter most

Not in this dataset

  • Any substance not named in this dataset — which is most substances. There are tens of thousands of marketed drugs and this table holds fewer than a hundred entries.
  • Phase-2 conjugation (UGT, SULT, NAT2, COMT) except where a specific entry names it. The oilahuasca corpus turns heavily on phase 2 and this engine models it only in passing.
  • Pharmacogenomics. CYP2D6 and CYP2C19 are strongly polymorphic; a poor metaboliser and an ultra-rapid metaboliser can have opposite outcomes from the same pair, and this engine does not know your genotype.
  • Dose, timing, duration, formulation and route — all of which change whether a documented interaction is clinically real for you.
  • Renal and hepatic impairment, age, pregnancy, and body composition.
  • Additive sedation, respiratory depression, bleeding risk, hypoglycaemia and most other pharmacodynamic axes beyond the ones listed above.
  • Herb–herb interactions outside the named entries, and essentially the whole botanical world: most plants have no interaction literature at all.
  • Allergy, intolerance, and contamination or adulteration of unregulated products.
  • Anything published after the last-reviewed date below.

72 substances, 20 mechanisms, 64 citations. Last reviewed . Primary literature (every DOI resolved against the Crossref API) and FDA drug labelling. There is no free, openly-licensed, comprehensive drug-interaction dataset to draw on; NLM retired its Drug Interaction API on 2024-01-02 and DrugBank's interaction set is a commercial licence.

References

  1. Herraiz T, González D, Ancín-Azpilicueta C, Arán VJ, Guillén H (2010). β-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO). Food and Chemical Toxicology. doi:10.1016/j.fct.2009.12.019
  2. Callaway JC, McKenna DJ, Grob CS, et al. (1999). Pharmacokinetics of Hoasca alkaloids in healthy humans. Journal of Ethnopharmacology. doi:10.1016/S0378-8741(98)00168-8
  3. Riba J, Valle M, Urbano G, Yritia M, Morte A, Barbanoj MJ (2003). Human Pharmacology of Ayahuasca: Subjective and Cardiovascular Effects, Monoamine Metabolite Excretion, and Pharmacokinetics. The Journal of Pharmacology and Experimental Therapeutics. doi:10.1124/jpet.103.049882

Every DOI above was resolved against the Crossref API on 2026-09-09 and the returned title checked against the one printed here. Three DOIs in the first draft resolved to real but different papers and were corrected before publication.

Last reviewed . All interaction pages.