Background:
Saffron (Crocus sativus L) is the dried stigmas and styles of the blue-purple saffron flower. It is considered the world’s most expensive spice because each flower produces only 3 of the little red strands. Iran grows 94% of the Saffron supply.
Mechanism of action:
Unknown, but thought to come from 4 major compounds: crocins, crocetin, picrocrocin, and safranal.
Some potential mechanisms include:
1. Antioxidant effects. Depression causes stress on the body and antioxidants can help to prevent damage.
2. Anti-inflammatory effects. People with depression have higher markers of inflammation. Decreasing inflammation in the brain can help decrease long-term damage.
3. Hypothalamus-pituitary-adrenal (HPA) effects. Saffron may lower the HPAs response to stress.
4. Neuroprotective effects. Saffron was shown to increase brain-derived neurotrophic factor (BDNF) in rats. BDNF is like a fertilizer for brain cells and helps them to grow stronger.
Dosing:
30mg daily.

Effectiveness:
(1) A study assessed 40 patients with depression. The patients received either Fluoxetine 40mg daily or Saffron 30mg daily for 6 weeks. Saffron and Fluoxetine showed similar remission and response rates to depression. There was no difference in side effects between the two groups. This is fascinating to see a piece of a flower comparing well to a prescription antidepressant medication.
(2) A study compared Saffron 30mg daily with Imipramine 100mg daily for 6 weeks. Imipramine is an older antidepressant medication in the TCA drug class. Saffron was shown to be as effective as Imipramine with less side effects.
Saffron has shown to be comparable to two antidepressant medications from different drug classes!
Safety:
Natural medicines database considers Saffron possibly safe with short term use. Saffron is possibly unsafe in high doses or with long term use. One study showed very small decreases in white blood cell count, red blood cell count, and platelets. Saffron is likely unsafe in pregnancy.
Medication interactions:
Saffron may interact with blood pressure medications. Saffron alone decreases blood pressure, so using it with blood pressure medications can theoretically decrease blood pressure too much.
Side effects:
Saffron lowers blood pressure, lowers certain blood counts, and some people are allergic to Saffron.
Other:
Be wary of imitators. Some sellers sell fake products. One way to tell is to place the saffron in hot water. Fake products leak dye and turn the water red. The real saffron, although deep red, turns the water yellow.
Antidepressants used in Bipolar disorder can sometimes work “too well” and cause someone to flip from depression to mania. Saffron can do this as well.
My experience:
I bought and used the Lidoma Saffron pictured above. It is relatively inexpensive and is available on Amazon. I grab around 12-15 strands and just add it to hot water. The tea is a bright yellow color and has a mild enjoyable taste. This is the supplement that has worked best for me. I noticed the largest increase in my mood after taking Saffron for a week or two. The long term safety has not been established, but I have not had any issues so far. I sometimes just eat the strands raw if I don’t have time to make tea. This is not as enjoyable, but it gets the job done.
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References:
1. Lopresti A, Drummond P. Saffron (Crocus sativus) for depression: a systematic review of clinical studies and examination of underlying antidepressant mechanisms of action. Hum. Psychopharmacol Clin Exp 2014;29:517-527.
2. Shahmansouri N, Farokhnia M, Abbasi SH. A randomized, double-blind, clinical trial comparing the efficacy and safety of Crocus sativus L. with fluoxetine for improving mild to moderate depression in post percutaneous coronary intervention patients. J Affect Disord. 2014 Feb;155:216-22.
3. Akhondzadeh S, Fallah-Pour H, Afkham K, et al. Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial [ISRCTN45683816].BMC Complement Altern Med. 2004 Sep 2;4:12.