In 1847, a German chemist isolated a compound from the seeds of a desert shrub that grows across Iran, Turkey, and Central Asia. He named it harmine, after the plant’s Arabic name, harmal. A century later, when South American ethnobotanists analyzed the Amazonian ayahuasca vine, they found the same compound. They had already given it a different name: telepathine. Chemical analysis proved harmine and telepathine were the same molecule.
Two continents. Two unrelated plant traditions. One alkaloid.
The plant is Peganum harmala, known in English as Syrian rue, though it is not a rue and has no special connection to Syria. Its seeds contain harmine and harmaline, both potent inhibitors of the enzyme monoamine oxidase A (MAO-A). This is the same mechanism that makes ayahuasca work: block MAO-A in the gut, and compounds that the body would normally destroy on contact, like dimethyltryptamine (DMT), survive long enough to reach the brain.
That biochemical fact is interesting on its own. What makes it extraordinary is the history. Some scholars believe this plant is the lost Soma of the Rig Veda, the sacred substance that 114 hymns of the oldest Indo-Iranian scripture praise as the drink of immortality. Across the Islamic world, from Tehran to Marrakech, people burn its seeds to ward off the evil eye. In 2025, archaeologists found the earliest dated evidence of its use in Iron Age Arabia, approximately 2,700 years ago. At Mount Sinai Hospital in New York, researchers are developing harmine as a treatment for diabetes, because it is the only compound out of 100,000 screened that makes human insulin-producing cells multiply.
The Plant
Peganum harmala is a perennial shrub, 30 to 80 centimeters tall, native to a range stretching from the eastern Mediterranean through Iran and Central Asia to western China. It prefers saline, disturbed soil in arid climates. The white flowers are unremarkable. The seed capsules split open when ripe and scatter small, dark brown seeds. The plant is tough, drought-resistant, and invasive enough that the USDA has been confiscating seeds at American customs since March 2022.
Unlike henbane and belladonna, which belong to the nightshade family and work through anticholinergic mechanisms, Syrian rue operates on an entirely different pharmacological axis: monoamine oxidase inhibition. Dioscorides called it peganon agrion, “wild rue,” distinguishing it from true rue (Ruta graveolens). It is not related to rue at all. Galen used multiple names: moly (possibly the same word Homer used for the herb that protected Odysseus from Circe), armolan (from the Arabic harmal), and besasan (a Syrian name). The taxonomy has been reshuffled more than once. The plant now sits in the family Nitrariaceae, having been moved out of Zygophyllaceae.
The seeds are the pharmacological payload. According to Herraiz and colleagues (2010, Food and Chemical Toxicology), dry seeds contain approximately 5.6% harmaline and 4.3% harmine by weight, along with smaller amounts of harmalol, tetrahydroharmine, and harmol. The roots carry lower concentrations. Both harmine and harmaline are beta-carboline alkaloids that selectively and reversibly inhibit MAO-A, with an IC50 of 27 micrograms per liter for seed extracts. “Reversible” is the key word. Unlike the pharmaceutical MAO inhibitors prescribed for depression (phenelzine, tranylcypromine), harmala alkaloids release the enzyme after their effect wears off, which reduces the risk of dangerous interactions with tyramine-rich foods.
The alkaloid harmine was first isolated from Peganum harmala seeds in 1847. When the same compound was later found in the Amazonian ayahuasca vine, it had already been given a different name: telepathine. Chemical analysis proved them identical.
The Soma Question
The Rig Veda, composed between approximately 1500 and 1200 BCE, dedicates its entire ninth book, 114 hymns, to a substance called Soma. The Avesta, the Zoroastrian scripture, describes the same substance under the name Haoma in Yasna 9-11. Both words derive from a common Proto-Indo-Iranian root, sauma-. The texts describe a sacred plant that is pressed between stones, filtered through sheep’s wool, mixed with milk and water, and consumed during rituals. Its effects include immortality, illumination, and communion with the gods.
The botanical identity of Soma has been lost for centuries. Three candidates dominate the debate.
The Mushroom
R. Gordon Wasson, a banker turned ethnomycologist, published Soma: Divine Mushroom of Immortality in 1968. He identified Soma with Amanita muscaria, the fly agaric mushroom, drawing parallels with Siberian shamanic practices where the mushroom’s psychoactive compounds pass through urine and can be consumed secondhand. The book was bold and influential.
It did not survive scrutiny. John Brough of Cambridge pointed out in 1971 that the Rig Veda describes pressing stalks through a wool filter. Mushrooms have no stalks to press and no juice to filter. Wasson never resolved this. Terence McKenna observed that Amanita’s effects are “arguably more deliriant than hallucinogenic,” inconsistent with the Vedic descriptions of clarity and cosmic vision. Indian scholars Dash and Padhy noted that both mushroom consumption and urine drinking were prohibited practices in the Manusmriti. Wasson’s hypothesis opened the conversation but convinced fewer scholars over time.
The Desert Weed
David Stophlet Flattery and Martin Schwartz published Haoma and Harmaline through the University of California Press in 1989. Their argument was pharmacological and linguistic. Peganum harmala, they claimed, was the only plant native to the Iranian plateau with hallucinogenic properties. The Persian name esfand (also espand) derives from Avestan spenta, meaning “sacred” or “holy,” the same word that forms Spenta Mainyu, the Holy Spirit of Zoroastrianism. A plant whose name is the word for “sacred” in the language of the scripture that describes the sacred drink.
The argument is elegant. The objections are serious. Harry Falk, writing in 1989, noted that neither the Vedic nor the Avestan texts describe hallucinations. They describe alertness and stamina, wakefulness and physical strength. Harmaline causes nausea, sedation, and visual disturbance. The Haoma ceremony involves nocturnal rituals where participants stay awake, dancing and singing. A sedative is the wrong drug for the job.
The preparation is another problem. The texts describe pressing stalks for juice. The psychoactive parts of Peganum harmala are the seeds, not the stalks. Seeds are not pressed through wool filters. And harmal grows everywhere across India and Iran. If it was the original Soma, there was no reason for its identity to be lost. The “lost plant” narrative requires the plant to have become unavailable, and harmal never did.
The Stimulant
The third candidate is Ephedra, and it has the quietest but most durable support. Harry Falk (1989), Harri Nyberg (1997), and Jan Houben (1999) all converged on it. The plant has stalks that can be pressed. It grows in mountains. Its active compound, ephedrine, produces alertness and sustained wakefulness, the effects the texts describe. Houben concluded: “Despite strong attempts to do away with Ephedra, its status as a serious candidate still stands.”
The strongest argument is continuity. Modern Zoroastrians still use Ephedra. Parsi communities in India import twigs from Afghanistan’s Hari River valley because the plant does not grow on the Indian subcontinent. Zoroastrians in the Yazd province of Iran use local Ephedra, called hom or homa. They have been doing this for as long as anyone can trace.
The objection is the ecstasy. Rig Veda 10.119, “The Soma-Drinker Praises Himself,” describes an experience that goes far beyond stimulation: “One of my wings is in the sky; the other I dragged below. I am the greatest of the great, raised to the firmament.” That is not what ephedrine does. Either the hymn is poetic exaggeration of a stimulant’s effects, or Soma was something stronger than Ephedra. The debate hinges on how literally you read the poetry.
No scholarly consensus exists. Ephedra has the strongest institutional support, Peganum harmala the strongest pharmacological case for the visionary passages, and the mushroom theory the widest popular recognition with the weakest evidence. This is Position Three territory: three candidates, each with real evidence and real problems, and a question that 150 years of scholarship has not closed.
The Archaeological Record
For most of the debate’s history, it was fought on textual grounds. Scholars argued over Sanskrit and Avestan adjectives. That changed in 2025.
In May 2025, a team led by Barbara Huber of the Max Planck Institute of Geoanthropology and Marta Luciani of the University of Vienna published results from the oasis settlement of Qurayyah in northwestern Saudi Arabia. Using HPLC-MS/MS analysis on organic residues from Iron Age fumigation devices, they detected harmine, harmaline, and tetrahydroharmine. The site dates to approximately 700 BCE. This is the earliest radiometrically dated material evidence of Peganum harmala being used for fumigation anywhere in the world.
The Qurayyah find does not resolve the Soma question. It shows the plant being burned, not pressed for juice. But it confirms that people in the ancient Near East used harmal’s psychoactive compounds deliberately, in a ritual context, roughly 2,700 years ago.
Six years earlier, Ren and colleagues published a 2019 study in Science Advances on braziers from the Jirzankal Cemetery in the Pamir Mountains of western China. Gas chromatography detected cannabis residue with elevated THC levels in 2,500-year-old wooden braziers used in funerary rituals. This was cannabis, not harmal, but it demonstrated the same practice: ritual fumigation with psychoactive plants at the crossroads of Central Asia, in the broader region where the Soma/Haoma traditions originated.
The most ambitious archaeological claims came from Viktor Sarianidi, who excavated Gonur Tepe and Togolok 21 in Turkmenistan during the 1990s and 2000s. These sites, dated to the second millennium BCE, belong to the Bactria-Margiana Archaeological Complex (BMAC). Sarianidi claimed to have found rooms where “haoma/soma was brewed,” with traces of Ephedra, cannabis, and poppy on ritual implements. The claims generated excitement. Then Harri Nyberg examined Sarianidi’s specimens in 1995 and could not confirm the Ephedra identification. The Gonur Tepe evidence remains contested.
The Living Tradition
An Iranian grandmother places seeds on hot charcoal. They pop and crackle. She waves the smoke over her grandchild’s head and through the rooms of the house, murmuring cheshm-e bad dur: may the evil eye be far. She does not know about MAO-A inhibitors or beta-carboline alkaloids. She knows that this is what her mother did, and her grandmother before that.
The burning of esfand (also espand) against the evil eye is one of the most widespread folk practices in the Islamic world. Iran, Turkey, Morocco, Pakistan, Afghanistan: the seeds, the charcoal, the popping, the smoke waved around the head. The occasions are specific and repeated. When guests visit and praise your home or children. When a baby is born. At weddings and engagements. When moving into a new house. During Nowruz, the Persian New Year, when seeds are formed into small incense balls called sepetan and burned throughout every room.
The practice predates Islam by at least a millennium. The name esfand descends from Avestan spenta, “sacred.” A Shi’ite tradition holds that “there is an angel in each of the plant’s leaves and seeds, its root drives away sorrow and magic, and the devil stays a distance of seventy houses away from homes in which it is kept.” The tradition absorbed the plant without knowing its pharmacology. Or perhaps it knew the pharmacology in a different vocabulary.
In Turkey, the plant is called üzerlik. Dried capsules are strung and hung in homes and cars as protection. The seeds also produce a red dye, “Turkish red,” used for centuries in carpet-making regions. In Morocco, the seeds are called harmel and burned with alum and frankincense during wedding nights “to fan the flames of desire.” In Baluchistan, seeds are burned to “neutralize the enchantments of a jin and banish all evil spirits.” In northern Pakistan, Hunza shamans inhale harmal vapors, which they call supandur, to induce trance and “call the spirits.” This last use is the most explicitly psychoactive folk practice documented in the region and the closest to what the Soma/Haoma texts might be describing.
A 2021 study in Environmental Monitoring and Assessment tested whether the folk practice has a basis in fact. Researchers burned 10 grams of Peganum harmala seeds for 10 minutes in a 60-cubic-meter room. The bacterial removal rate was 92.8%. The active compound in the smoke was harmine, which showed antimicrobial activity against all test strains. The mechanism involved accumulation of reactive oxygen species in microorganisms, cell membrane damage, and interference with DNA synthesis. An Iranian grandmother’s incense is a genuine disinfectant.
A 2021 study found that burning 10 grams of Peganum harmala seeds for 10 minutes in a room achieved a 92.8% bacterial removal rate. The active compound was harmine. The folk practice of burning esfand as household purification turns out to be a genuine disinfectant.
The Molecule in the Lab
In 2015, researchers at Mount Sinai Hospital in New York screened over 100,000 potential drug compounds looking for one that could make human insulin-producing beta cells multiply. Adult beta cells are normally quiescent. In Type 1 diabetes, the immune system destroys them. In Type 2 diabetes, they become dysfunctional and decline. If you could make them grow back, you could treat both diseases at their root.
Out of 100,000 compounds, one worked: harmine.
The mechanism: harmine inhibits an enzyme called DYRK1A (dual-specificity tyrosine-regulated kinase 1A), which normally keeps adult beta cells from dividing. Harmine takes off the brakes. In 2022, a Phase 1 clinical trial gave pharmaceutical-grade harmine to 25 healthy adults. No hallucinations, no psychoactive effects, no safety issues. The doses that drive beta cell proliferation are far below the doses that alter consciousness.
In 2024, the research took another step. Harmine combined with a GLP-1 receptor agonist (exenatide, a drug already used for Type 2 diabetes) produced a 700% increase in beta cell mass in mice carrying transplanted human beta cells. Blood sugar normalized within one week and stayed normal for three months. The work, published in collaboration with City of Hope, is moving toward clinical application.
The molecule that Vedic priests may have consumed to feel immortal, that Iranian grandmothers burn to protect children from the evil eye, is being developed as a cure for diabetes. Harmine does not care about the context. It inhibits the same enzyme in a Zoroastrian fire temple and in a New York laboratory.
The antidepressant research runs parallel. Harmine increases hippocampal BDNF levels and restores astrocytic functions in animal models. A single dose of ayahuasca, which contains harmine, has been reported to produce rapid and sustained antidepressant effects in human patients. Neuroprotective studies are investigating potential applications for Parkinson’s and Alzheimer’s disease.
Mount Sinai researchers screened over 100,000 compounds looking for one that could make human insulin-producing beta cells multiply. Only one worked: harmine, the primary alkaloid in Syrian rue. A Phase 1 trial in 2022 showed no psychoactive effects at therapeutic doses.
Two Continents, One Mechanism
The convergence remains the central mystery.
In the Amazon, indigenous peoples discovered that combining the ayahuasca vine (Banisteriopsis caapi, containing harmine and harmaline) with leaves from Psychotria viridis or Diplopterys cabrerana (containing DMT) produces a visionary brew. The vine’s MAO inhibitors prevent the gut from destroying the leaf’s DMT. Neither plant does anything remarkable on its own. Combined, they produce one of the most powerful psychoactive experiences documented by ethnobotanists.
In the Old World, Peganum harmala provides the same MAO inhibitor. The question is whether anyone in the ancient Near East or Central Asia combined it with a DMT-containing plant to produce the same effect. The honest answer: we do not know. No documented historical tradition of combining harmal with DMT-containing plants has been identified. The Hunza shamans of Pakistan inhale harmal smoke alone. The esfand tradition is fumigation, not ingestion with a second plant. Claims that Middle Eastern Acacia species contain DMT are not supported by published phytochemical analysis. Only Australian Acacia species have confirmed DMT content.
In August 2025, a study in Frontiers in Psychiatry gave nine healthy volunteers an oral formulation of Australian Acacia extract (confirmed DMT source) combined with Peganum harmala. The participants rated the experience “similar to ayahuasca.” The combination works. The question is whether anyone in the ancient world figured that out, and if so, whether any record of the practice survives. For now, the parallel is biochemical, not historical. Two plant traditions on two continents arrived at the same enzyme. Whether they took the same next step remains an open question.
The Name
The etymologies carry their own history.
The Persian esfand descends from Middle Persian spand, from Proto-Iranian spanta-, “holy” or “sacred.” This is Flattery and Schwartz’s strongest argument: the word for this plant is the word for “sacred” in the language of the Avesta. The Arabic harmal traces back through Classical Syriac armalā to Akkadian anamiru, meaning “medical and ritual herb.” The oldest Semitic name already classifies the plant as both medicine and sacrament.
The English name is a double misnomer. “Syrian” probably reflects early European encounters with the plant through Levantine trade routes. “Rue” comes from Dioscorides calling it “wild rue,” peganon agrion, but the plant belongs to a different family entirely. It is not from Syria and not a rue. The name stuck anyway.
What We Know and What We Do Not
The plant, the alkaloids, the 2,700-year-old archaeological evidence from Qurayyah, the folk practice across the Islamic world, the antimicrobial smoke, the beta cell research: all confirmed, all documented.
The Soma identification is not settled and may never be. Three candidates remain on the table, each with evidence and problems. The “Old World ayahuasca” parallel is biochemically demonstrated but historically undocumented. The gap between what the molecule can do and what ancient peoples did with it is filled with speculation on one side and silence on the other.
What we can say: Peganum harmala has been used deliberately by human beings for at least 2,700 years, in contexts that range from household fumigation to shamanic trance to royal ritual. The molecule harmine, isolated from its seeds in 1847, turned out to be the same compound in the most famous psychoactive brew in the world. That molecule inhibits an enzyme that keeps insulin-producing cells from dividing, and a clinical trial at Mount Sinai showed it can do this safely in humans.
An Iranian grandmother burns it against the evil eye. A Mount Sinai pharmacologist tests it against diabetes. A Flattery scholar reads it as the lost Soma. A Hunza shaman inhales it to call the spirits. The plant grows in the desert, in dry saline soil, unremarkable to anyone who does not know what the seeds contain. It has been there for thousands of years. It will be there long after the debate is settled or forgotten.
