Saffron

Crocus sativus L. belongs to Iridaceae, the iris family, and is one of about 85 species in the genus Crocus (Aissa and colleagues, Journal of Medicine and Life 2023). Drugs.com’s professional monograph describes it as a bulbous perennial 15–20 cm tall with blue-violet, lily-shaped flowers, each holding orange-red stigmas, the pollen-receiving tips of the female part of the flower, which are collected by hand during a short autumn flowering season. The word saffron is thought to come from the Arabic za’faran, meaning yellow. Saffron crocus is a triploid with three sets of eight chromosomes (3n = 24), and it is male-sterile: it sets no seed and is propagated only by its corms, the swollen underground stems that store the plant’s food reserves (Schmidt and colleagues, New Phytologist 2019). Confusingly, the common name autumn crocus is used both for saffron and for the unrelated, highly poisonous meadow saffron, Colchicum autumnale.

Because it cannot reproduce sexually, all the saffron crocus grown today belongs to a single clone. Its origin was debated for nearly a century. Nemati and colleagues (Molecular Phylogenetics and Evolution 2019) compared genome-wide DNA markers and placed 99.3% of saffron’s gene variants in Crocus cartwrightianus, a wild crocus of south-eastern mainland Greece and the Aegean islands. The wild population closest to saffron grew near Athens, and they concluded that saffron arose in Attica when two different genotypes of C. cartwrightianus combined into a triploid. Multicolor chromosome labeling by Schmidt and colleagues independently showed saffron to be an autotriploid hybrid of C. cartwrightianus types. Kazemi-Shahandashti and colleagues (Frontiers in Plant Science 2022) argue that ancient art and modern genetics both point to domestication in early Greece. As Nemati notes, sterility and propagation by corms then fixed saffron’s favorable traits, long red stigmas included, in one clonal lineage cultivated worldwide.

Corms are usually planted between late May and early October and the flowers are harvested in October and November, mostly by hand and mostly by women, before the stigmas are separated and dried (Aissa). Britannica notes that the three stigmas are handpicked from each flower and dried over charcoal fires. World production is roughly 408 tons a year, and Iran grows about 90% of it, mainly in Khorasan; other producers include India (Kashmir), Spain (Castilla-La Mancha), Italy, Morocco, Greece, and Afghanistan (Aissa). The stigmas contain more than 150 identified compounds. The color comes mainly from crocin (PubChem CID 5281233, C44H64O24), a water-soluble ester of the carotenoid crocetin; the bitter taste from the glycoside picrocrocin; and the aroma from safranal (CID 61041, C10H14O), which forms when picrocrocin breaks down (Drugs.com). The international standard ISO 3632 grades saffron partly by measuring these three compounds.

Saffron’s oldest portraits are Bronze Age frescoes. Kazemi-Shahandashti and colleagues describe a fresco from Knossos on Crete, dated to about 1700 BCE, and the famous ‘Saffron Gatherers’ and ‘Adorants’ frescoes from the building known as Xeste 3 at Akrotiri on Thera (Santorini), from around 1600 BCE. They show crocuses with long, intensely red stigmas overtopping dark violet petals, the hallmark of cultivated saffron, growing in clumps that may represent planting. Linear B tablets include a saffron ideogram and record large amounts traded, and another Akrotiri fresco may show saffron used to color the lips and ears. The Minoan eruption destroyed much of Thera, and no corms or plant remains have been found, so the species in the paintings cannot be confirmed; it was either saffron or its wild parent.

The first written account of cultivated saffron comes from Theophrastus, whose Historia Plantarum of around 350–300 BCE describes its propagation by corms (Kazemi-Shahandashti). Saffron-type crocuses were also cultivated early in Persia, where the spice dyed royal carpets and funeral shrouds. Britannica records that saffron was cultivated by the Arabs in Spain around 961 and appears in an English leechbook, or healing manual, of the 10th century, though it may have vanished from western Europe until the Crusaders reintroduced it. It reached China, Britannica says, with the Mongol invasion, and appears in the Chinese materia medica Bencao gangmu (1552–78). In England the crop gave its name to a town: in the mid-14th century the saffron crocus was introduced around Walden in Essex to provide a yellow dye, and the place became Saffron Walden.

Saffron has been a medicine for as long as it has been a spice. Drugs.com summarizes traditional uses as a sedative, appetite stimulant, aphrodisiac, emmenagogue (a remedy to bring on menstruation), and antidepressant, and for cramps, asthma, menstrual disorders, liver disease, and pain; from the 17th to the 19th centuries it was an ingredient of opium preparations such as laudanum and ‘black drop’. Schmidt and colleagues (Wiener Medizinische Wochenschrift 2007) note that uses against cancer and depressive mood recur throughout its history. Germany’s Commission E gave saffron a negative evaluation for cramps and asthma. Persian traditional medicine used saffron for low mood, and that tradition prompted Akhondzadeh and colleagues in Tehran to run what they described as the first clinical trial of saffron for depression, published in 2004.

Nobody knows exactly how saffron might lift mood. Lopresti and Drummond (Human Psychopharmacology 2014), reviewing the clinical and laboratory work, suggest its antidepressant effects may come from a mix of serotonergic, antioxidant, anti-inflammatory, neuro-endocrine (stress hormone), and neuroprotective actions. Most of that evidence comes from animal and cell studies of saffron extracts and of crocin, crocetin, and safranal, and it shows what is plausible rather than what happens in people. The serotonin link matters in practice, because it is a reason to be careful about combining saffron with antidepressants that also act on serotonin, even though no harmful interaction has been documented (see interactions).

Saffron’s carotenoids are also studied for the eye and the brain. Falsini and colleagues (Investigative Ophthalmology and Visual Science 2010) tested saffron in macular degeneration because crocin and crocetin are antioxidant carotenoids, but suggested its effect on the retina might go beyond simple antioxidant activity. Akhondzadeh and colleagues (Journal of Clinical Pharmacy and Therapeutics 2010) cite laboratory evidence that saffron may inhibit the clumping and deposition of amyloid-beta, the protein that builds up in Alzheimer’s disease. These are hypotheses that motivated small trials; they are not established mechanisms of benefit.

Other effects bear on safety. In a one-week study by Modaghegh and colleagues (Phytomedicine 2008) in 30 healthy volunteers, 400 mg a day of saffron lowered standing systolic and mean arterial blood pressure, while 200 mg did not. An aqueous saffron extract inhibited human platelet aggregation in the test tube, although a study of 200 and 400 mg a day for a week in volunteers found no effect on clotting tests (Drugs.com). Older animal studies found that saffron stimulates the uterus, and Bostan and colleagues (Iranian Journal of Basic Medical Sciences 2017) suggest uterine contraction or bleeding may explain the higher miscarriage rate seen among pregnant women heavily exposed to saffron at harvest.

Depression is where saffron has the most research. The early trials came from Akhondzadeh’s group at Tehran University of Medical Sciences and used 30 mg of saffron stigma a day for six weeks in outpatients with mild to moderate major depression. Saffron matched imipramine 100 mg a day in 30 patients, with fewer anticholinergic side effects such as dry mouth (BMC Complementary and Alternative Medicine 2004); beat placebo in 40 patients (Phytotherapy Research 2005); and matched fluoxetine 20 mg a day in 40 patients (Noorbala and colleagues, Journal of Ethnopharmacology 2005). Ghajar and colleagues (Pharmacopsychiatry 2017) found 30 mg of saffron similar to citalopram 40 mg in 66 people with depression and marked anxiety. Hausenblas and colleagues (Journal of Integrative Medicine 2013) pooled five trials and found a large effect against placebo and no difference from antidepressants; Tóth and colleagues (Planta Medica 2019) pooled nine trials, finding saffron clearly better than placebo and not inferior to the drugs tested; Dai and colleagues (Journal of Nervous and Mental Disease 2020) reached the same conclusion from 12 studies.

Those results deserve honest sizing. Marx and colleagues (Nutrition Reviews 2019) analyzed 23 trials and found large effects on depression and anxiety, but also statistical evidence of publication bias, meaning negative trials may be missing, and a lack of regional diversity. Hausenblas called for larger trials by research teams outside Iran, and Dai asked for larger, longer, multicenter trials in different ethnic groups. Most trials enrolled a few dozen people for six to eight weeks, and very large early effect sizes in small trials often shrink later. Guideline bodies are cautious but positive: the WFSBP and CANMAT taskforce (World Journal of Biological Psychiatry 2022) provisionally recommended saffron for depression, one step below its full recommendation for St. John’s wort, and the 2016 CANMAT guidelines listed saffron as a third-line option for mild to moderate depression.

Newer trials, many from an Australian group testing a standardized extract called affron, are larger and show more modest effects. Lopresti and colleagues (Journal of Psychopharmacology 2019) added 28 mg a day to antidepressants in adults with persistent depression: of 160 enrolled, 139 gave usable data, and clinician-rated symptoms fell 41% versus 21% with placebo, but self-rated symptoms fell equally (27% versus 26%). In 80 teenagers aged 12 to 16 with mild to moderate anxiety or depression, teens reported improvement over eight weeks, but parents’ reports were inconsistent (Journal of Affective Disorders 2018). The largest trial so far, in 202 adults with mild, subclinical depressive symptoms, found a modest benefit over 12 weeks, with 72% versus 54% achieving a meaningful improvement, a large placebo response, and no difference on most secondary measures (Journal of Nutrition 2025). Two of its authors are affiliated with Pharmactive, the Spanish company that makes affron.

Premenstrual syndrome (PMS): Agha-Hosseini and colleagues (BJOG 2008) gave 30 mg of saffron a day or placebo to 50 women aged 20 to 45 for two menstrual cycles and found greater improvement in daily premenstrual symptoms and depression scores. In 120 women with premenstrual dysphoric disorder (PMDD), the severe form, Rajabi and colleagues (Advanced Biomedical Research 2020) found saffron better than placebo on a daily symptom record, with fewer side effects than fluoxetine, although neither drug separated from placebo on depression ratings. Mohammadi and Karimi (Korean Journal of Family Medicine 2026) pooled seven studies with 612 participants, six of them in Iran and one without a placebo group, and found a moderate reduction in PMS symptoms; a smaller effect on period pain disappeared after adjusting for possibly missing studies. The evidence is encouraging but rests on small trials.

Other uses have only a handful of small trials, each needing independent confirmation. In men and women whose depression was stable on fluoxetine but who had sexual side effects, four weeks of 30 mg a day of saffron improved erectile function in a trial of 36 men (Modabbernia and colleagues, Psychopharmacology 2012) and arousal, lubrication, and pain in a trial of 38 women (Kashani and colleagues, Human Psychopharmacology 2013), though not desire or orgasm. In mild to moderate Alzheimer’s disease, saffron matched donepezil in 54 patients over 22 weeks (Psychopharmacology 2010) and beat placebo in a 16-week trial of 46 patients. In age-related macular degeneration, 20 mg a day improved a measure of retinal sensitivity in 25 patients (Falsini 2010), and in 100 patients improved vision by 0.69 letters, less than one letter on an eye chart (Broadhead and colleagues, Graefe’s Archive 2019). The extract Satiereal reduced snacking in 60 mildly overweight women (Gout and colleagues, Nutrition Research 2010), but saffron did not reduce food cravings in 73 overweight women with depression (Akhondzadeh 2020).

Almost all mood and PMS trials used 30 mg of dried stigma, or an extract of it, a day, usually as 15 mg twice daily, for six to 12 weeks. The affron trials used 28 mg a day (14 mg twice daily), the macular degeneration trials 20 mg a day, and the Satiereal snacking trial 176.5 mg of extract a day. Drugs.com notes that clinical studies have used 20–400 mg a day of pure saffron and that a dose-response effect has been suggested. Two Iranian depression trials tested extracts of the purple petals, a cheap by-product, with reportedly satisfactory results, so not every product labeled saffron extract is made from stigmas. Extracts are standardized in different ways, and results from one product cannot be assumed for another.

As a spice, saffron threads are crumbled or steeped into rice, fish stews such as bouillabaisse, paella, risotto alla Milanese, biryani, and festive breads and buns such as Swedish St. Lucia buns and Cornish saffron buns (Britannica; Aissa). Saffron is not generally associated with toxicity in culinary amounts (Drugs.com). Thirty milligrams is a tiny weight, but the trials used measured capsules taken every day, which is not the same as occasional cooking with a pinch of threads of unknown quality, and there is no evidence that saffron in food treats low mood.

Practical points: if you want to try a saffron supplement, choose a single-ingredient product that states the amount of saffron or extract and the plant part, and stay with the trial dose of about 30 mg a day; more is not better. Give it six to eight weeks, the length of most trials, and review with your clinician. Do not stop or reduce an antidepressant to start saffron. For cooking, buy whole threads from a reputable seller, since Aissa and colleagues note that powdered saffron is the form most often adulterated with synthetic dyes, and be suspicious of saffron that is very cheap.