Chapter 03 of 06
Harmine and harmaline, why Syrian rue seeds are MAO inhibitors
How much harmine and harmaline Syrian rue seeds contain, what monoamine oxidase does, and why blocking it makes the seeds risky in combination.
Syrian rue seeds are rich in two alkaloids, harmine and harmaline, that block the enzyme monoamine oxidase A (MAO-A). In a Spanish laboratory study, dry seeds contained 4.3 percent harmine and 5.6 percent harmaline by weight (Herraiz et al., 2010). That concentration is the reason the seeds deserve respect even when you only grow or burn them.
The beta-carbolines in the seed
Harmine and harmaline belong to the beta-carbolines, a group of indole alkaloids. The name harmine comes from the plant itself. The same compounds occur in a few other plants, most famously the Amazonian vine Banisteriopsis caapi; this site does not cover that vine or the brew made from it.
Herraiz and colleagues measured the main beta-carbolines in different parts of the plant:
| Plant part | Harmine | Harmaline | Other beta-carbolines |
|---|---|---|---|
| Dry seeds | 4.3 % | 5.6 % | harmalol 0.6 %, tetrahydroharmine 0.1 % |
| Roots | 2.0 % | not reported | harmol 1.4 % |
| Stems and leaves | low | low | |
| Flowers | absent | absent |
Other studies report lower figures for the same seeds; reviews give ranges from well under 1 percent to the 4 to 6 percent above, and total beta-carbolines of at least 5.9 percent in one analysis. Wild seed differs by region, harvest and storage, and nobody tests the seeds sold for gardens. Assume a high content.
The seeds contain a second group of alkaloids as well. Peganine (vasicine) and a peganine glycoside reached 1 and 3.9 percent of dry seed weight in a follow-up study. Those quinazoline alkaloids did not contribute to MAO inhibition (Herraiz et al., 2017).
What monoamine oxidase does
Monoamine oxidases are enzymes that break down monoamines: neurotransmitters such as serotonin and noradrenaline, and amines that come in with food, such as tyramine. There are two forms. MAO-A handles serotonin and noradrenaline and much of the tyramine in food; MAO-B prefers other amines.
When MAO-A is blocked, those amines are cleared more slowly. That is where the danger of combinations comes from. Two problems follow:
- Too much serotonin. Combined with medicines or drugs that raise serotonin, an MAO inhibitor can cause serotonin syndrome: agitation, fast heartbeat, high blood pressure, fever, muscle twitching and confusion (MedlinePlus).
- Too much tyramine. Tyramine releases noradrenaline. With MAO-A blocked, a meal rich in tyramine can raise blood pressure sharply. This is the "cheese reaction" known from the old MAOI antidepressants (MedlinePlus on phenelzine).
How strongly the seeds block the enzyme
Very strongly. Herraiz and colleagues tested extracts on human MAO-A in the laboratory. Seed extract halved the enzyme's activity at a concentration of 27 micrograms per litre; root extract needed 159 micrograms per litre. The effect from seed came from harmaline and harmine together. Both extracts were poor inhibitors of MAO-B.
The study also found the inhibition to be reversible and competitive. The alkaloids occupy the enzyme without destroying it, so its activity returns as the body clears them. The classic MAOI medicines, such as phenelzine, block the enzyme irreversibly; MedlinePlus warns that phenelzine can stay active in the body for several weeks after the last dose.
Reversible does not mean harmless. How long the block from Syrian rue lasts in a person, and how large the tyramine risk is at a given amount of seed, has not been properly measured. The poisonings described on the risks page show that the seeds alone can put people in intensive care.
What this means for growing, smoke and dye
- Growing a plant exposes you to very little. Wash your hands after handling seed and fresh capsules, and keep seed away from children and animals.
- Burning esfand releases alkaloids with the smoke; the Iron Age censers from Qurayyah were identified through exactly those compounds. How much reaches someone in a ventilated room is unknown. If you take a serotonergic medicine, the cautious choice is to stay out of the smoke.
- Dyeing produces an extract. Handle the dyebath as a chemical: gloves, no kitchen pots, no children nearby.
The seeds sold for gardens are the same seeds, so store a bag like any other garden chemical: closed, labelled and out of reach.
There is no safe way to give advice on eating or drinking the seeds, and this site does not. Read the risks and documented poisonings next, or go back to the plant.