Saffron (Crocus sativus L.) is a flowering plant in the iris family used in various domains for its taste, aroma, pigment, and medicinal properties. Saffron, sometimes called “red gold”, is the most expensive spice in the world and is produced predominantly in Iran.^[4] The most prized part of the saffron plant is the dried red stigmas, which contain over 150 bioactive compounds including carotenoids (crocin, crocetin), terpenes (picrocrocin, safranol), and many other phytochemicals.^[5]

Saffron is a potent antioxidant and has shown consistent benefits for depression.^[6]

When used in people with minor to moderate depression, saffron appears to be superior to placebo and comparable to some commonly used antidepressants (e.g., fluoxetine, citalopram) for reducing symptoms of depression and achieving remission.^[7][8][9] Saffron may also reduce symptoms of anxiety, but this effect is less clearly established.^[7]

While the evidence is promising, nearly all of the clinical trials have been conducted in Iran, sample sizes have been small (<100 people), and durations have been short (≤12 weeks). Larger and longer trials in more diverse populations are needed to further validate these effects and determine whether the benefits persist over time.

The most common side effects of saffron include nausea, changes in appetite, dry mouth, headache, anxiety, and drowsiness.^[10] Changes in blood parameters have been reported in studies using doses of 60–400 mg daily, although it’s not clear if this has any clinical implications.^[11][10] At excessively high doses (1,200–2,000 mg), saffron has been reported to cause vomiting, diarrhea, and bleeding.^[1] Supplementing with isolated crocin (one of the active compounds in saffron) at normal doses may raise serum creatinine levels, which could indicate a risk of kidney damage.^[2]

There are concerns regarding the quality of saffron supplements. Some of the important compounds in saffron are sensitive to light, oxygen, and temperature. Further, the way saffron is grown, harvested, and processed can alter its chemical composition. Due to its high economic value, saffron has also historically been prone to adulteration.^[12] These factors may lead to large variations in the types and amounts of active compounds found in a saffron supplement which could impact its effectiveness. Choosing a supplement that is third-party tested can help ensure its quality.

Lastly, most of the research on saffron has been conducted in Iran, and its effects on other populations require further validation.

Saffron contains many active compounds, but crocin, crocetin, safranol, and picrocrocin are considered to be the most important.^[13] Following consumption, some of these compounds are transformed within the gastrointestinal tract, and the main compound found in the blood seems to be crocetin (although more research is needed in this department).^[5]

Preclinical research suggests that saffron can influence the brain in a variety of ways, which likely explains its effects on mood and cognition. Saffron may prevent the reuptake of certain neurotransmitters — like dopamine, serotonin, and norepinephrine — which allows their effects to persist for longer.^[8] Saffron may also interact with the HPA axis, leading to reduced levels of cortisol, and might influence neuroplasticity by increasing brain-derived neurotrophic factor (BDNF).^[9]

As an antioxidant, saffron may increase the expression of nuclear factor erythroid 2–related factor 2 (Nrf2), leading to increased levels of antioxidant enzymes and an overall improved antioxidant capacity.^[14][6] In animal studies, saffron has reduced oxidative stress in brain tissue.^[15]