Syrian rue (Peganum harmala)

While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.

Related Terms

  • Acacetin 7-O-rhamnoside, acetoxyolean, African rue, alpha-(4-nitrobenzylidine) harmine, anthraquinones, beta-carboline, caffeoyloxyolean, canthin-6-one alkaloids, deoxyvasicine, deoxyvasicinone, desoxypeganine, digalactosyldiacylglycerols, dihydroconiferyl ferulate, dihydrosinapyl ferulate, esphand, fatty acids, flavonoids, fructose, gamma-harmine, glucose, glycoflavone 2”’-O-rhamnosyl-2″-O-glucosylcytisoside, harmal, harmal shrub, harmala alkaloids, harmalan, harmaline, harmalol, harman alkaloids, harmane, harmel, harmidine, harmine, harmol, harmol glucuronide, harmol sulfate, huzerlik, isband, kaempferol, linoleic acid, linolenic acid, lipids, luotonin C, luotonin D, luotuo-peng, lupene-type triterpenoids, mercury (II) – harmaine, mercury (II) -harmaline, mercury (II) – harmine, monogalactosyldiacylglycerols, N-acyl tetrahydroharmine derivatives, nigellastrine-I, nigellastrine-II, nor-harmane, oxotirucalla, ozallaik, peganetin, peganidine, peganole, peganone, peganone-1, peganone-2, peganum, Peganum harmala, Peganum multisectum, Peganum nigellastrum, phenylpropanoids, phenylquinoline, prolin, pyrrolidinoquinazoline alkaloid, quercetin, quinoline alkaloids, rutin, steppenraute, sterols, sucrose, Syrian rue, tetraglycoside, tetrahydroharmine, triterpenoids, uzerlik, vasicine, (+)-vasicinol hydro-chloride dihydrate, vasicinone, wild rue, Zygophyllaceae (family).

Background

  • Peganum harmala, commonly called “Syrian rue,” is native to China, the eastern Mediterranean region east to India, and the western United States and can grow spontaneously in arid and rocky areas.

  • Peganum harmala contains beta-carboline alkaloids (harmine, harmaline, harmalol) that are toxic to both humans and animals. These alkaloids are used in alcoholic beverages, well-cooked foods, and tobacco smoke, and they have known hallucinogenic and strong monoamine oxidase inhibitory (MAOI) activity.

  • Harmala alkaloids, harmaline and harmine, are known to cause tremors.

  • When consumed by farm animals, Peganum harmala may have either a sedative or stimulant effect. In humans, the seeds are known to primarily cause a stimulant and hallucinogenic effect. In China, Mongolia, Iran, and Morocco, the seeds have been used to treat various diseases and purposes, such as cancer, hepatic arterial embolization, and high fevers. The seeds may also be used to relieve grief and as a disinfectant. In South America, it is reportedly combined with dimethyltryptamine to make an infusion known as ayahuasca and is used for various healing purposes.

  • Traditionally, the stems, roots, and seeds have been used for nonmedical purposes, such as making dyes, inks, stains, and tattoos. The plant has also been mixed with other ingredients and placed onto charcoal, where it makes a popping sound and releases a fragrant smoke used in prayer rituals. The dried capsules are also used and hung in homes or vehicles, because it is believed to protect against the “evil eye.”

Scientific Evidence

Uses

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

No available studies qualify for inclusion in the evidence table.

*Key to grades:

Tradition

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.

  • Abortifacient, addiction, Alzheimer’s disease, antibacterial, antifungal, antihistamine, antimutagenic, antioxidant, antiparasitic, antispasmodic, antiviral, anxiety, bone diseases, cancer, cataracts, depression, diabetes, digestive stimulant, diuretic, Down’s Syndrome, drug withdrawal, epilepsy, fevers, grief, growth, hallucinogenic, immune system regulation, insecticide, laryngitis, learning disorder, lice, liver protection, malaria, melanoma, menstrual cramps, mental illness, muscle relaxant, nervous disorders, neuroprotection, pain, Parkinson’s disease, peptic ulcer, photosensitivity, psoriasis, radioprotection, serotonin-induced hypothermia, sexual dysfunction, skin disorders, stimulant, stomach complaints, toxicity (environmental protection), urinary disorders, vascular disorders.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

  • Avoid use of Peganum harmala in any person.

Children (under 18 years old)

  • Avoid use of Peganum harmala in any person.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

  • Avoid use in people with known allergy or hypersensitivity to Peganum harmala or any of its parts.

Side Effects and Warnings

  • Avoid use of Peganum harmala in any person, as it may cause serious side effects.

  • When taken by mouth, Peganum harmala may cause central nervous system disturbances (including agitation, anxiety, confusion, hallucinations, delirium, lack of coordination, tremors, twitching, and sedation), nausea, vomiting, high blood pressure, hypothermia, increased blood flow through the aorta, increased or decreased heart muscle contraction, increased levels of liver enzymes or increased liver weight, increased pulse pressure, kidney dysfunction, paralysis, rapid breathing, rapid heart rate, reduced levels of follicular-stimulating hormone and testosterone, reduced sperm production, and third-degree heart block.

  • When injected into the vein, Peganum harmala may cause abnormal rapid heart rhythms, reduced heart rate, low blood pressure, and suspended breathing.

  • Avoid in pregnant women, as Peganum harmala may cause labor.

  • Avoid in people with known allergy or hypersensitivity to Peganum harmala or any of its parts.

Pregnancy and Breastfeeding

  • Peganum harmala may reduce levels of follicular-stimulating hormone and testosterone and may reduce sperm production.

  • Avoid use in pregnant women, as Peganum harmala may cause labor or affect fetal brain development.

  • There is currently a lack of scientific evidence on the use of Peganum harmala during lactation.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs

  • Avoid use of Peganum harmala in any person.

  • Peganum harmala may affect blood sugar levels and may interact with medications that affect blood sugar.

  • Peganum harmala may cause low or high blood pressure and may interact with drugs that affect blood pressure.

  • Peganum harmala may interfere with the way the body processes certain drugs using the liver’s cytochrome P450 enzyme system. As a result, the levels of these drugs may be increased in the blood and may cause increased effects or potentially serious adverse reactions.

  • Peganum harmala may also interact with agents that activate or deactivate dopamine receptors, agents that affect acetylcholine, agents that affect the heart (such as those that affect heart rate and heart muscle contraction), agents that affect blood vessel width, agents that are toxic to the liver, agents that deactivate serotonin receptors, agents that affect the immune system, agents that treat Parkinson’s disease, agents that treat protozoan infections, alcohol, amphetamine, antiadrenergics (including clonidine and beta-blockers), antianxiety agents, antibiotics, anticancer agents, antidepressants (including monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), and tricyclic antidepressants), antifungals, antihistamines, antipsychotic agents, antiseizure agents, antivirals, apomorphine, aprotinin, baclofen, benzodiazepines, caffeine, carbenoxolone, chlormethiazole, chlorpromazine, cyproheptadine, epinephrine, flumazenil, gamma-hydroxybutyrate (GHB), lacosamide, levodopa, lidocaine, lithium, mefloquine, muscimol, painkillers (including N-methyl-D-aspartate (NMDA) receptor antagonists), pentobarbital, photosensitizers, quipazine, reserpine, and tetrabenazine (not approved in the United States).

Interactions with Herbs and Dietary Supplements

  • Avoid use of Peganum harmala in any person.

  • Peganum harmala, particularly harmaline, may affect blood sugar levels and may interact with herbs and supplements that affect blood sugar.

  • Peganum harmala may cause low or high blood pressure and may interact with herbs and supplements that affect blood pressure.

  • Peganum harmala may interfere with the way the body processes certain herbs or supplements using the liver’s cytochrome P450 enzyme system. As a result, the levels of other herbs or supplements may become too high in the blood. It may also alter the effects that other herbs or supplements possibly have on the P450 system.

  • Peganum harmala may also interact with amino acids, antiadrenergics, antibacterials, anticancer herbs and supplements, antidepressants (including monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs)), antifungals, antihistamines, antioxidants, antipsychotics, antivirals, caffeine-containing herbs and supplements, herbs and supplements that activate or deactivate dopamine receptors, herbs and supplements that affect acetylcholine, herbs and supplements that affect the heart (such as those that affect heart rate and heart muscle contraction), herbs and supplements that affect blood vessel width, herbs and supplements that are toxic to the liver, herbs and supplements that deactivate serotonin receptors, herbs and supplements that prevent seizures, herbs and supplements that affect the immune system, herbs and supplements that are used to treat Parkinson’s disease, herbs and supplements that treat protozoan infections, ibogaine, licorice, niacinamide, onion, painkillers, photosensitizers, rutin, sedatives, sucrose, tyramine-containing food, herbs, or supplements, and yohimbe.

Author Information

  • This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

  1. Ahmad, A., Khan, K. A., Sultana, S., et al. Study of the in vitro antimicrobial activity of harmine, harmaline and their derivatives. J.Ethnopharmacol. 1992;35(3):289-294. View Abstract
  2. Al-Shamma, A., Drake, S., Flynn, D. L., et al. T. Antimicrobial agents from higher plants. Antimicrobial agents from Peganum harmala seeds. J.Nat.Prod. 1981;44(6):745-747. View Abstract
  3. Astulla, A., Zaima, K., Matsuno, Y., et al. Alkaloids from the seeds of Peganum harmala showing antiplasmodial and vasorelaxant activities. J.Nat.Med. 2008;62(4):470-472. View Abstract
  4. Balaban, C. D. Central neurotoxic effects of intraperitoneally administered 3-acetylpyridine, harmaline and niacinamide in Sprague-Dawley and Long-Evans rats: a critical review of central 3-acetylpyridine neurotoxicity. Brain Res. 1985;356(1):21-42. View Abstract
  5. Deecher, D. C., Teitler, M., Soderlund, D. M., et al. Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies. Brain Res. 2-7-1992;571(2):242-247. View Abstract
  6. Emboden, W. A. Narcotic Plants. New York,NY: MacMillan Publishing Co.;1980.
  7. Han, J. and An, L. Isolation and characterization of microsatellite loci in Peganum harmala (Peganaceae), an important resist-drought and medicinal plant. Conserv.Genet. 2009;10(6):1899-1901.
  8. Hudson, J. B., Graham, E. A., and Towers, G. H. Antiviral effect of harmine, a photoactive beta-carboline alkaloid. Photochem.Photobiol. 1986;43(1):21-26. View Abstract
  9. Kim, D. H., Jang, Y. Y., Han, E. S., et al. Protective effect of harmaline and harmalol against dopamine- and 6-hydroxydopamine-induced oxidative damage of brain mitochondria and synaptosomes, and viability loss of PC12 cells. Eur.J.Neurosci. 2001;13(10):1861-1872. View Abstract
  10. Lala, S., Pramanick, S., Mukhopadhyay, S., et al. Harmine: evaluation of its antileishmanial properties in various vesicular delivery systems. J.Drug Target 2004;12(3):165-175. View Abstract
  11. Lamchouri, F., Settaf, A., Cherrah, Y., et al. Antitumour principles from Peganum harmala seeds. Therapie 1999;54(6):753-758. View Abstract
  12. Moura, D. J., Richter, M. F., Boeira, J. M., et al. Antioxidant properties of beta-carboline alkaloids are related to their antimutagenic and antigenotoxic activities. Mutagenesis 2007;22(4):293-302. View Abstract
  13. Shapira, Z., Terkel, J., Egozi, Y., et al. Abortifacient potential for the epigeal parts of Peganum harmala. J.Ethnopharmacol. 1989;27(3):319-325. View Abstract
  14. Yonezawa, T., Lee, J. W., Hibino, A., et al. Harmine promotes osteoblast differentiation through bone morphogenetic protein signaling. Biochem.Biophys.Res.Commun. 6-3-2011;409(2):260-265. View Abstract
  15. Zheng, X. Y., Zhang, Z. J., Chou, G. X., et al. Acetylcholinesterase inhibitive activity-guided isolation of two new alkaloids from seeds of Peganum nigellastrum Bunge by an in vitro TLC- bioautographic assay. Arch.Pharm.Res. 2009;32(9):1245-1251. View Abstract

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.