Syrian Rue

The seed is esfand in Persian and harmal in Arabic, and its best-known traditional use is as smoke rather than medicine. The seeds are thrown onto hot coals and the smoke passed through a room, over a person or around a doorway as protection against the evil eye, at weddings, births and house-movings across Iran, Turkey and Central Asia.

It is used against misfortune and illness in general rather than against a named complaint, and the smoke also serves as a disinfectant and insect repellent for the room.

The plant is a longstanding and contested candidate for the ancient Indo-Iranian sacrament soma/haoma.

In traditional Iranian medicine the seed is the main medicinal part. It is described as carminative, galactagogue, diuretic, emmenagogue, antithrombotic and analgesic ^{36Reference 36Mina et al. · 2015ReviewMedicinal properties of Peganum harmala L. in traditional Iranian medicine and modern phytotherapy: a reviewView study →}. It has also been taken for heavy menstrual bleeding ^{40Reference 40Moshiri et al. · 2013Case reportPeganum harmala intoxication, a case reportView study →}.

Across the Middle East and North Africa, including Morocco, the seed is used as an emmenagogue and abortifacient ^{38Reference 38Achour et al. · 2012Case reportPeganum harmala L. poisoning and pregnancy: two cases in Morocco — case reportView study →}. In Moroccan traditional medicine it is also used as a sedative ^{39Reference 39Berdai et al. · 2014Case reportPeganum harmala L. intoxication in a pregnant woman — case reportView study →}.

In Pakistan the plant is known as harmal or ispand. The seed powder is used for asthma, colic and jaundice, as a remedy for tapeworm, and to lower the fever of chronic malaria ^{43Reference 43GhafoorPeganum harmala LinnView study →}.

A decoction of the seeds is given for laryngitis. The seeds are also regarded as a lactagogue, a stimulant and an abortifacient ^{43Reference 43GhafoorPeganum harmala LinnView study →}.

The smoke is considered antiseptic, and wounds are fumigated with burning seeds and leaves ^{43Reference 43GhafoorPeganum harmala LinnView study →}.

In recent psychedelic practice the seed is taken by mouth for its MAO-inhibiting alkaloids. Because the β-carbolines reversibly inhibit monoamine oxidase A, they prevent the breakdown of DMT in the gut, and the seed is combined with DMT-containing plants such as chacruna to make orally active ayahuasca analogues (“anahuasca”).

The doses used overlap the seed’s toxic range. The same MAO inhibition also makes the combination interact dangerously with serotonergic drugs and tyramine-rich foods.

Seed extracts inhibit human MAO-A with an IC₅₀ of about 27 µg/L, an effect attributed quantitatively to harmaline and harmine ^{1Reference 1Herraiz et al. · 2010In vitroHerraiz, T., González, D., Ancín-Azpilicueta, C., Arán, V. J., & Guillén, H. (2010). β-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO) — in vitro. Food and Chemical Toxicology. https://pubmed.ncbi.nlm.nih.gov/20036304/View study →}. Inhibiting MAO-A raises synaptic serotonin, dopamine and noradrenaline, as a pharmaceutical MAOI does.

In rats exposed to chronic unpredictable mild stress, P. harmala seed extract at 150 mg/kg reduced depressive-like behaviour, lowered brain MAO-A and corticosterone, and restored monoamines and BDNF/TrkB signalling ^{4Reference 4Tekşen et al. · 2024AnimalPeganum harmala L. seed extract attenuates anxiety and depression in rats by reducing neuroinflammation and restoring BDNF/TrkB signalling and monoamines after chronic unpredictable mild stress — rat in vivoView study →}.

Isolated harmine reproduces antidepressant-like and antioxidant effects in rat prefrontal cortex and hippocampus ^{5Reference 5Réus et al. · 2010AnimalHarmine and imipramine promote antioxidant activities in prefrontal cortex and hippocampus — rat in vivoView study →}, though a controlled/socially-defeated rat study found its behavioural benefit was delayed and modest ^{6Reference 6Giacobbo et al. · 2020AnimalChronic harmine treatment has a delayed effect on mobility in control and socially defeated rats — rat in vivoView study →}.

The one human study, a Phase 1 trial of oral harmine, found that it can be given with minimal side effects below 2.7 mg/kg. It did not test whether harmine treats depression ^{3Reference 3Ables et al. · 2024RCTA Phase 1 single ascending dose study of pure oral harmine in healthy volunteers — randomised Phase 1 clinical trialView study →}.

Gap: every efficacy signal is preclinical or extrapolated from MAO pharmacology; no trial has tested Syrian rue or harmine as a treatment for depression, and the seed’s MAOI toxicity makes self-medication dangerous.

The main anti-inflammatory mechanism is suppression of NF-κB signalling by harmine: screening the seven main P. harmala alkaloids, harmine (with harmol) blocked TNF-α– and LPS-induced NF-κB activation in macrophages and cut IL-1β, IL-6 and TNF-α in an LPS-challenged mouse ^{7Reference 7Liu et al. · 2017In vitroHarmine is an inflammatory inhibitor through the suppression of NF-κB signalling — mouse in vivo / in vitroView study →}.

The signal is replicated across disease models — a methanolic leaf extract (200–600 mg/kg) reduced paw oedema, arthritis scores and inflammatory markers in adjuvant-induced arthritic rats ^{8Reference 8Akhtar et al. · 2022AnimalAppraisal of anti-arthritic and anti-inflammatory potential of the folkloric medicinal plant Peganum harmala — rat in vivoView study →}, harmine alleviated LPS-induced acute lung injury in mice via the CSF3/MAPK/NF-κB axis ^{9Reference 9Zhai et al. · 2025AnimalHarmine alleviates LPS-induced acute lung injury by inhibiting CSF3-mediated MAPK/NF-κB signalling — mouse in vivoView study →}, and it attenuated cardiac hypertrophy in hypertensive rats through the same NF-κB inhibition, independent of blood pressure ^{10Reference 10Huang et al. · 2022AnimalHarmine is an effective therapeutic small molecule for the treatment of cardiac hypertrophy — rat in vivoView study →}.

All of this work is in rodents, and apart from the leaf-extract study, all of it uses harmine.

This is the largest body of preclinical work, almost all on harmine as a single molecule rather than the seed. Across independent studies harmine dose-dependently suppresses proliferation, migration, invasion and epithelial–mesenchymal transition in breast (via PI3K) ^{11Reference 11Yao et al. · 2023In vitroHarmine suppresses the malignant phenotypes and PI3K activity in breast cancer — in vitroView study →}, ovarian (via HDAC7/RECK restoration) ^{12Reference 12Bao et al. · 2025In vitroHarmine inhibits ovarian cancer migration, invasion and EMT by inhibiting HDAC7 to restore RECK expression — in vitro / in vivoView study →} and pancreatic cancer (via DYRK1A-mediated RAS/MAPK inhibition) ^{14Reference 14Liu et al. · 2025In vitroHarmine suppresses pancreatic cancer through DYRK1A-mediated hyper-activated RAS/MAPK inhibition — in vitro / in vivoView study →}, and it induces homologous-recombination deficiency by targeting CDK9, synergising with PARP inhibitors in ovarian-cancer cells ^{13Reference 13Zhang et al. · 2025In vitroTargeting CDK9 with harmine induces homologous recombination deficiency and synergizes with PARP inhibitors in ovarian cancer — in vitro / in silicoView study →}. The β-carboline scaffold’s anticancer chemistry — kinase, topoisomerase and tubulin interactions — is reviewed in depth ^{15Reference 15Aaghaz et al. · 2021ReviewAaghaz, S., et al. (2021). β-Carbolines as potential anticancer agents — review. European Journal of Medicinal Chemistry. https://pubmed.ncbi.nlm.nih.gov/33684825/View study →}.

Gap: entirely in vitro and xenograft, at purified-harmine doses unrelated to crude-seed exposure; no clinical oncology data exist, and harmine’s MAO-inhibiting toxicity would complicate any therapeutic use.

Rodent evidence is consistent: hydroalcoholic seed extract (30–120 mg/kg) lowered glucose, HbA1c and lipids in streptozotocin-diabetic rats ^{16Reference 16Komeili et al. · 2016AnimalEvaluation of antidiabetic and antihyperlipidemic effects of Peganum harmala seeds in diabetic rats — rat in vivoView study →}, separate STZ-rat work showed antidiabetic and β-cell-regenerative effects ^{17Reference 17Khazaei et al. · 2025AnimalAntidiabetic effects of Peganum harmala seed extract on streptozotocin-induced diabetes in rats — rat in vivoView study →}, and an ethanolic extract cut blood glucose comparably to metformin in normal and diabetic rats ^{18Reference 18Singh et al. · 2008AnimalPreliminary studies on the hypoglycemic effect of Peganum harmala L. seeds ethanol extract on normal and streptozotocin-induced diabetic rats — rat in vivoView study →}. Harmine also inhibits DYRK1A: combined with a GLP-1 receptor agonist it expanded human β-cell mass in a mouse xenograft, one of the few agents shown to increase human β-cell numbers in vivo ^{19Reference 19Rosselot et al. · 2024AnimalHarmine and exendin-4 combination therapy safely expands human β-cell mass in vivo in a mouse xenograft system — mouse in vivoView study →}.

Gap: whole-seed data are rodent-only; the β-cell result is for isolated harmine in a xenograft model, not the herb, and no human antidiabetic trial exists.

Antiparasitic activity is documented both in vitro and in animals. Crude seed extract reduced Leishmania major promastigotes with an IC₅₀ near 59 µg/mL and, applied topically, shrank cutaneous lesions and parasite counts in infected mice ^{20Reference 20Rahimi-Moghaddam et al. · 2011In vitroIn vitro and in vivo activities of Peganum harmala extract against Leishmania major — animal in vivoView study →}.

Other work confirms in vitro/ex vivo activity against L. major ^{21Reference 21Rokni et al. · 2021In vitroPeganum harmala and Nigella sativa: anti-leishmanial activity against Leishmania major promastigotes and amastigotes — in vitro / ex vivoView study →}.

Purified constituents carry it further in vivo: the quinazoline vasicine (peganine) was orally active against visceral leishmaniasis in hamsters (~80% at 100 mg/kg) ^{22Reference 22Khaliq et al. · 2009AnimalPeganine hydrochloride dihydrate, an orally active antileishmanial agent — animal in vivoView study →}, and harmine reduced hamster spleen parasite load, with efficacy improving in liposomal and nanoparticle carriers ^{23Reference 23Lala et al. · 2004AnimalHarmine: evaluation of its antileishmanial properties in various vesicular delivery systems — animal in vivoView study →}.

The effective doses were either high or given in delivery formulations, not as the seed.

Harmine shows a reproducible anti-resorptive effect. It inhibits RANKL-induced osteoclast differentiation and bone resorption in vitro and prevented bone loss in ovariectomised osteoporosis-model mice at 10 mg/kg/day, acting through c-Fos/NFATc1 suppression ^{25Reference 25Yonezawa et al. · 2011In vitroHarmine, a β-carboline alkaloid, inhibits osteoclast differentiation and bone resorption in vitro and in vivo — animal in vivoView study →}.

A separate group found harmine additionally promotes bone-sparing “type H” vessel formation via preosteoclast PDGF-BB in ovariectomised mice ^{24Reference 24Huang et al. · 2018AnimalHarmine enhances type H vessel formation and prevents bone loss in ovariectomized mice — mouse in vivoView study →}.

None of this has been tested with the whole seed.

Antinociception is dose-dependent and reproducible in mice. A total alkaloid seed extract produced up to 100% pain reduction in the formalin test (ED₅₀ ≈ 25–28 mg/kg), tracking with harmaline content ^{26Reference 26Monsef et al. · 2004AnimalAntinociceptive effects of Peganum harmala L. alkaloid extract on mouse formalin test — mouse in vivoView study →}, and a separate alkaloid extract (12.5–25 mg/kg) was active across writhing, formalin and hot-plate models, partly reversed by naloxone — indicating a central, partly opioid-mediated component alongside a peripheral one ^{27Reference 27Farouk et al. · 2008AnimalEvaluation of the analgesic effect of alkaloid extract of Peganum harmala L.: possible mechanisms involved — mouse in vivoView study →}.

Gap: rodent behavioural models only; no human analgesic data, and the active doses overlap the herb’s toxic/psychoactive range.

An n-butanol seed extract was bactericidal against multidrug-resistant Pseudomonas aeruginosa (MIC 500 µg/mL, ~100% kill at 24 h) and disrupted biofilm, with the active compound identified as harmaline ^{28Reference 28Khadraoui et al. · 2022In vitroAntibacterial and antibiofilm activity of Peganum harmala seed extract against multidrug-resistant Pseudomonas aeruginosa — in vitroView study →}.

Alkaloids from fruit and flower likewise showed selective antibacterial effects in vitro ^{29Reference 29Iranshahy et al. · 2019In vitroChemical composition and antibacterial properties of Peganum harmala — in vitroView study →}.

The MICs are high relative to any likely blood level, and no infection model has been run.

Beyond mood, the alkaloids show cognitive/anti-amnesic effects in rodents. An aerial-part extract and its alkaloid fraction reversed scopolamine-induced memory deficits in mice, correlating with acetylcholinesterase inhibition and raised acetylcholine ^{30Reference 30Liu et al. · 2017AnimalAnti-amnesic effect of extract and alkaloid fraction from aerial parts of Peganum harmala on scopolamine-induced memory deficits in mice — mouse in vivoView study →}, and isolated harmine extracts were cerebroprotective against sodium-nitrite hypoxia and ethanol neurodegeneration in young mice, improving memory and MAO-A inhibition without neurotoxicity at the doses used ^{31Reference 31Biradar et al. · 2013AnimalCerebroprotective effect of isolated harmine alkaloids extracts of seeds of Peganum harmala L. on sodium-nitrite-induced hypoxia and ethanol-induced neurodegeneration in young mice — mouse in vivoView study →}.

The same MAO-A and acetylcholinesterase inhibition is also the source of the herb’s interaction and toxicity risk.

Seed extracts and the β-carbolines scavenge DPPH and other radicals in vitro ^{32Reference 32Berrougui et al. · 2006In vitroVasorelaxant effects of harmine and harmaline extracted from Peganum harmala L. seeds in isolated rat aorta — in vitro (isolated tissue)View study →}, and in vivo harmine raised superoxide dismutase and catalase and lowered lipid/protein oxidation in rat brain ^{5Reference 5Réus et al. · 2010AnimalHarmine and imipramine promote antioxidant activities in prefrontal cortex and hippocampus — rat in vivoView study →}.

In the arthritis model the extract’s DPPH activity paralleled its anti-inflammatory effect ^{8Reference 8Akhtar et al. · 2022AnimalAppraisal of anti-arthritic and anti-inflammatory potential of the folkloric medicinal plant Peganum harmala — rat in vivoView study →}.

The quinazoline alkaloids are weak scavengers, so the activity belongs to the β-carbolines and the polyphenols.

Harmine and harmaline relaxed noradrenaline- or KCl-precontracted rat aorta in a dose-dependent manner; harmaline’s effect was partly endothelium/NO-dependent while harmine’s was not, both involving L-type calcium-channel and phosphodiesterase mechanisms ^{32Reference 32Berrougui et al. · 2006In vitroVasorelaxant effects of harmine and harmaline extracted from Peganum harmala L. seeds in isolated rat aorta — in vitro (isolated tissue)View study →}. The quinazoline vasicinone showed a separate vasorelaxant action against phenylephrine-induced contraction ^{33Reference 33Astulla et al. · 2008In vitroAlkaloids from the seeds of Peganum harmala showing antiplasmodial and vasorelaxant activities — in vitroView study →}.

Gap: isolated-tissue organ-bath data only — no whole-animal blood-pressure study and no human data.

MAO inhibition. Harmine and harmaline are potent, reversible, competitive MAO-A inhibitors, shown directly on the human enzyme ^{1Reference 1Herraiz et al. · 2010In vitroHerraiz, T., González, D., Ancín-Azpilicueta, C., Arán, V. J., & Guillén, H. (2010). β-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO) — in vitro. Food and Chemical Toxicology. https://pubmed.ncbi.nlm.nih.gov/20036304/View study →}. While MAO-A is inhibited, tyramine-rich foods (aged cheese, cured meats, fermented products) and many medicines and supplements — SSRIs and other antidepressants, certain stimulants, over-the-counter cold remedies — can trigger a hypertensive crisis or serotonin syndrome ^{36Reference 36Mina et al. · 2015ReviewMedicinal properties of Peganum harmala L. in traditional Iranian medicine and modern phytotherapy: a reviewView study →}. Because the inhibition is reversible, the window is shorter than with irreversible pharmaceutical MAOIs, but the interaction is still dangerous.

Overdose. A woman who took about 50 g of seed for heavy menstrual bleeding developed nausea, vomiting, dizziness, tremor, ataxia, confusion and low blood pressure, and recovered within a day ^{40Reference 40Moshiri et al. · 2013Case reportPeganum harmala intoxication, a case reportView study →}. More severe cases have involved kidney failure needing dialysis, liver injury, and bleeding and ischaemia in the brain ^{37,39Reference 37El Amri et al. · 2021Case reportFatal poisoning of pregnant women by Peganum harmala L.: a case reportView study →Reference 39Berdai et al. · 2014Case reportPeganum harmala L. intoxication in a pregnant woman — case reportView study →}. The authors of these reports note that very high doses can be fatal ^{37,39Reference 37El Amri et al. · 2021Case reportFatal poisoning of pregnant women by Peganum harmala L.: a case reportView study →Reference 39Berdai et al. · 2014Case reportPeganum harmala L. intoxication in a pregnant woman — case reportView study →}. Reviews also list slow heart rate and hallucinations ^{36Reference 36Mina et al. · 2015ReviewMedicinal properties of Peganum harmala L. in traditional Iranian medicine and modern phytotherapy: a reviewView study →}. A 28-day rat study found dose-dependent toxicity from repeated doses of the total alkaloid extract ^{35Reference 35Wang et al. · 2019AnimalSubchronic toxicity and concomitant toxicokinetics of long-term oral administration of total alkaloid extracts from seeds of Peganum harmala Linn: a 28-day study in rats — rat in vivoView study →}.

Pregnancy. In rats, a methanol extract of the aerial parts reduced litter size in a dose-dependent way ^{41Reference 41Shapira et al. · 1989AnimalAbortifacient potential for the epigeal parts of Peganum harmala — rat in vivoView study →}. Several of the human poisonings were in pregnant women. One woman, 22 weeks pregnant, developed uterine contractions and lost the pregnancy, and was left with cerebellar ataxia and nerve damage ^{39Reference 39Berdai et al. · 2014Case reportPeganum harmala L. intoxication in a pregnant woman — case reportView study →}. Two other pregnant women in Morocco recovered, with good outcomes for mother and child ^{38Reference 38Achour et al. · 2012Case reportPeganum harmala L. poisoning and pregnancy: two cases in Morocco — case reportView study →}.

Drug metabolism. In human liver microsomes, harmaline and harmine inhibited CYP2D6 and harmine inhibited CYP3A4 ^{46Reference 46Zhao et al. · 2011In vitroInhibition of human cytochrome P450 enzymes 3A4 and 2D6 by β-carboline alkaloids, harmine derivatives — in vitroView study →}. The two alkaloids are themselves broken down mainly by CYP2D6 and CYP1A2, and mice carrying the human CYP2D6 gene cleared both faster ^{46,47Reference 46Zhao et al. · 2011In vitroInhibition of human cytochrome P450 enzymes 3A4 and 2D6 by β-carboline alkaloids, harmine derivatives — in vitroView study →Reference 47Yu et al. · 2003In vitroContribution of individual cytochrome P450 isozymes to the O-demethylation of the psychotropic beta-carboline alkaloids harmaline and harmine — in vitro / mouse in vivoView study →}.

In liver cancer cells, a seed extract raised gene expression of CYP1A2, CYP2C19 and CYP3A4 and lowered that of CYP2B6, CYP2D6 and CYP2E1; enzyme activity was not measured ^{48Reference 48El Gendy et al. · 2009In vitroPeganum harmala L. differentially modulates cytochrome P450 gene expression in human hepatoma HepG2 cells — in vitroView study →}. Reviews cite this as a reason the plant may alter levels of drugs these enzymes clear ^{36Reference 36Mina et al. · 2015ReviewMedicinal properties of Peganum harmala L. in traditional Iranian medicine and modern phytotherapy: a reviewView study →}. MAO-A inhibition remains the interaction that matters most.