Peganum harmala, widely recognized as Syrian Rue, is a perennial herbaceous plant with a woody rootstock. It thrives in arid and semi-arid environments across regions like the eastern Mediterranean, North Africa, and Central Asia. This plant is known for its distinct white flowers and small, round seed capsules containing numerous dark, oily seeds.
Historical Uses
Historically, Peganum harmala has been culturally and traditionally important across various regions. In the Middle East and Central Asia, its dried capsules were often strung and hung in homes or vehicles as a protective charm against the “evil eye”. Ancient Iranian sources, such as the Gathas, describe the burning of the seeds and other parts of the plant to produce dense, intoxicating smoke during Zoroastrian rituals, with an extract also being consumed as a drink.
The plant has also been identified in ancient Mesopotamian cuneiform texts dating back to 2000 BC. In folk medicine, various parts of Peganum harmala, including its seeds, bark, and roots, were used to address conditions like colic, tapeworm infections, and recurring fevers. Some evidence suggests its use in Coptic Egyptian rituals and even as an abortifacient. Furthermore, a red dye known as “Turkey red” was extracted from its seeds and commonly used in Western Asia for dyeing carpets.
Understanding Its Active Compounds
The primary bioactive compounds in Peganum harmala are harmala alkaloids, including harmine, harmaline, and tetrahydroharmine. These alkaloids are most concentrated in the seeds, with harmine and harmaline accumulating in dry seeds at approximately 4.3% and 5.6% by weight, respectively. Roots also contain these compounds, though in lower concentrations.
These harmala alkaloids are reversible monoamine oxidase inhibitors (MAOIs), particularly of monoamine oxidase A (MAO-A). MAO-A is an enzyme in the body that breaks down certain neurotransmitters, such as serotonin and norepinephrine. By inhibiting this enzyme, harmala alkaloids can increase the levels of these neurotransmitters in the brain, leading to psychopharmacological effects. This action also allows other psychoactive compounds, like dimethyltryptamine (DMT), to become orally active when consumed alongside Peganum harmala.
Safety and Potential Risks
Despite its historical uses, Peganum harmala consumption carries safety concerns due to its potent effects and toxicity. The plant can induce adverse reactions, including nausea, vomiting, and dizziness. More severe reactions can include visual and auditory hallucinations, confusion, agitation, tremors, convulsions, and even life-threatening respiratory depression and coma.
The MAOI activity of harmala alkaloids means that Peganum harmala can interact with many medications and substances. Concomitant use with other MAOI agents or tyramine-containing foods is strongly contraindicated, as this can lead to a potentially severe increase in neurotransmitter levels. Additionally, the plant’s constituents can interfere with drug metabolism by affecting cytochrome P450 enzymes. This interaction can alter how other medications are broken down in the body, potentially leading to increased drug levels and heightened toxicity.