ABSTRACT: Is Saffron Effective for Depression?
Poster Presentation by: Gisoo Imani & Jacqueline Clark
Saffron (Crocus sativus) is a perennial flower cultivated in Turkey, Iran, China, India, Algeria, and parts of Europe,1,4 with 85% of the world’s saffron being produced by Iran.2 The part of the plant that has been used since ancient times as a spice, natural coloring agent, and medicine is the dried stigma from the flower. Each flower contains only three bright red-orange stigmas, which must be cultivated and harvested by hand. To produce just one pound of saffron, approximately 225,000 stigmas must be hand-picked from the flowers, which bloom only once per year in the fall.2,9 As one might imagine, this labor-intensive harvesting process justifies why saffron is the world’s most expensive spice. Traditionally, saffron has been used for a plethora of medical conditions, but its use as treatment for depression has the strongest scientific support thus far.14 Crocin, crocetin, and safranal are the primary chemical constituents isolated from saffron stigmas,4,6 with crocetin appearing to be most responsible for the pharmacological activities of saffron. 7,9 Orally, saffron is well-tolerated in reported doses of 30 mg daily to 100 mg daily for up to 12 weeks, but slightly higher doses of saffron extract used for at least 26 weeks have increased incidence of mild side effects such as dry mouth, anxiety, agitation, drowsiness, nausea, vomiting, constipation, change in appetite, flushing, and headache.9 Saffron is thought to interact with antidiabetic medications due to its combined effect on reducing fasting glucose levels and also with antihypertensive medications due to a potential additive effect of lowering blood pressure.9 Therefore, saffron should be used cautiously in patients taking medication for diabetes or hypertension. The mechanism of action for saffron in depression has yet to be fully elucidated. However, it may exert its antidepressant effect by modulating levels of serotonin, dopamine, and norepinephrine in the brain.9-12 The purpose of this review poster is to determine if there is scientific support for the use of saffron in treating patients with depression.
In a meta-analysis by Toth et al.,12 the antidepressant effect of saffron was evaluated. The purpose of this study was to compare the changes in depression severity in patients receiving saffron at pharmacological doses vs. placebo or conventional antidepressants. Nine randomized controlled trials were quantitatively synthesized. The effect size was calculated using Hedges’ g; risk of bias was assessed using the Cochrane Collaboration tool; and heterogeneity was determined using Cochran’s Q test and Higgin’s I^2. The results showed that saffron had significantly greater efficacy on reducing the severity of mild to moderate depression compared to placebo (g=0.891, 95% CI:0.369-1.412, p=0.001) and was non-inferior to fluoxetine and citalopram (g=-0.246; 95% CI: -0.495-0.004, p=0.053). The authors conclude that saffron is superior to placebo and noninferior to SSRIs in the treatment of mild to moderate depression. Further, they conclude that saffron reduces the severity of depression, although the optimal dose and treatment duration remains unknown.
Another meta-analysis by Hausenblas et al.3 examined the effects of saffron supplementation on symptoms of depression in adult patients with major depressive disorder (MDD). The comparators were placebo or conventional antidepressants. Five randomized, double-blinded controlled trials were included, and a random effects model was used to calculate the weighted mean effect sizes. The findings showed that saffron supplementation significantly decreased symptoms of depression compared to placebo (MES=1.62, p<0.001), and its effects were not significantly different from fluoxetine and imipramine (MES=-0.15, p=0.42). The authors conclude that short-term saffron supplementation may be helpful for treating depression symptoms in adults with MDD.
In a systematic review and meta-analysis by Khaksarian et al.,5 the effectiveness of saffron compared to placebo and fluoxetine in the treatment of depression was evaluated. Eight randomized controlled trials were included; effect sizes were calculated as standardized mean differences (SMD); and heterogeneity was determined using the I^2 test. The results showed that saffron is more effective in treating depression than placebo with a SMD of -0.86 (95% CI: -1.73 to 0.00) and was comparable to fluoxetine with a SMD of 0.11 (95% CI: -0.20 to 0.43). The authors concluded that saffron is more effective than placebo and has comparable efficacy to fluoxetine in improving symptoms of depression.
The findings of the clinical trials presented suggest that saffron may be beneficial as monotherapy and may have comparable effects to traditional antidepressants such as fluoxetine in improving symptoms of depression. Although some methodological limitations and non-negligible heterogeneity in the studies exist, the results were clinically significant. Future research should be conducted to study the long-term effects of saffron in treating depressive symptoms (>12 weeks), the mechanism of action for the antidepressant effects, and the optimal dosing for treatment of depression, since these crucial components for supporting the clinical use of saffron as treatment for depression remain unknown.
- American Botanical Council. Saffron. HerbClip Online, 2018. Accessed: 07/16/2021; Available from: herbalgram.org/resources/herbclip/herbclip-news/2018/saffron/.
- Fulton, A. The Secret History of the World’s Priciest Spice. National Geographic, 2017. Accessed: 07/14/2021; Available from: https://www.nationalgeographic.com/culture/article/history-origin-of-saffron-spice-iran.
- Hausenblas, H.A., et al., Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials. J Integr Med, 2013. 11(6): p. 377-83
- Javadi, B., A. Sahebkar, and S.A. Emami, A survey on saffron in major islamic traditional medicine books. Iran J Basic Med Sci, 2013. 16(1): p. 1-11.
- Khaksarian, M., et al., The efficacy of Crocus sativus (Saffron) versus placebo and Fluoxetine in treating depression: a systematic review and meta-analysis. Psychol Res Behav Manag, 2019. 12: p. 297-305.
- Khan, I.A. and E.A. Abourashed, Natural Ingredients: Saffron, in Leung’s Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics. 2010, John Wiley & Sons, Inc. p. 547-548.
- Leone, S., et al., Phytotherapic use of the Crocus sativus L. (Saffron) and its potential applications: A brief overview. Phytother Res, 2018. 32(12): p. 2364-2375.
- Marx, W., et al., Effect of saffron supplementation on symptoms of depression and anxiety: a systematic review and meta-analysis. Nutr Rev, 2019.
- Natural Medicines, Saffron [Professional Monograph]. 2021, Therapeutic Research Center. Accessed: 07/14/2021; Available from: https://naturalmedicines-therapeuticresearch-com.ezproxy.lib.utah.edu/databases/food,-herbs-supplements/professional.aspx?productid=844#background
- Sarris, J., Herbal medicines in the treatment of psychiatric disorders: 10-year updated review. Phytother Res, 2018. 32(7): p. 1147-1162.
- Shafiee, M., et al., Saffron in the treatment of depression, anxiety and other mental disorders: Current evidence and potential mechanisms of action. J Affect Disord, 2018. 227: p. 330-337.
- Toth, B., et al., The Efficacy of Saffron in the Treatment of Mild to Moderate Depression: A Meta-analysis. Planta Med, 2019. 85(1): p. 24-31.
- Wang, Y., et al., Antidepressant properties of bioactive fractions from the extract of Crocus sativus L. J Nat Med, 2010. 64(1): p. 24-30.
- Woolven, L. and T. Snider Saffron: The Salubrious Spice. HerbalGram: The Journal of the American Botanical Council, 2016. 61-71. Available from: https://www.herbalgram.org/resources/herbalgram/issues/110/table-of-contents/hg110-feat-saffron/