How Can Saffron and Crocin Help Depression?

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Saffron is a well-known traditional remedy for many health conditions including depression. Due to safety concerns, adverse effects, limited efficacy and low tolerability associated with many antidepressant and anti-anxiety medications, saffron and its main active constituent crocin could potentially provide a natural alternative with better safety profile and fewer side effects. Below is a brief of published studies on the treatment of depression with saffron and crocin in the most recent years.
More than 20 clinical studies have been carried out in recent years to prove the effectiveness of saffron in the treatment of depression. In a recent meta-analysis of these studies for efficacy in the treatment of mild to moderate depression, the authors analyzed from the qualified studies and available data of randomized, controlled clinical trials and concluded that saffron is significantly more effective than placebo (g = 0.891; 95% CI: 0.369 – 1.412, p = 0.001), and non-inferior to tested antidepressant drugs including fluoxetine, citalopram, and imipramine (g = − 0.246; 95% CI: − 0.495 – 0.004, p = 0.053)1.
Since crocin is identified as the main active constituent of saffron and primarily responsible for the health effects of saffron, several preclinical studies have confirmed the antidepressant effects of crocin2-4. Crocin was also demonstrated in animal studies to improve anxiety and obsessive-compulsive disorder5,6 and reduce stress-induced anorexia and side effects of stress7. In a recent animal study, the combination of crocin treatment with physical activity is found to provide synergistic effects against anxiety or depression in adult animals and improve morphological deficits induced by adolescent stress8.
Human studies in recent years further indicated that the antidepressant-like properties of saffron are primarily due to crocin.
1. In a 4-week study, crocin (30mg/day) effects on depression were compared with a serotonin reuptake inhibitor drug (fluoxetine, sertraline, and citalopram) in a randomized, double-blind, placebo-controlled, pilot clinical trial9. Results of this human study showed crocin significantly improved scores on BDI, BAI, and GHQ compared to the placebo group. The authors concluded crocin could be administered as an adjunctive treatment in major depressive disorder patients.
2. In another 8-week randomized double-blind controlled clinical study, crocin (30mg/day) significantly reduced the degree of depression at the end of the trial to these patients with metabolic syndrome10.
3. Yet in another 8-week randomized double-blind controlled clinical study, saffron aqueous extract (30mg/day) and crocin (30mg/day) was compared against placebo on health-related quality of life, depression, and sexual desire in coronary artery disease patients11. Both saffron and crocin significantly improved depression and quality of life in these patients with CAD, whereas they have no significant effects on sexual desire.
4. Most recently, an 8-week randomized clinical trial to evaluate the effects of crocin on psychological parameters in patients under methadone maintenance treatment was reported12. Methadone maintenance treatment (MMT) was associated with the symptoms of depression and anxiety, sleep disturbances and sexual dysfunctions. The 8-week crocin (30mg/day) intervention significantly decreased Beck Depression Inventory (b − 6.66; 95% CI, − 9.88, −3.45; P < 0.0001), Beck Anxiety Inventory (b − 4.35; 95% CI, − 5.94, − 2.75; P < 0.0001), general health questionnaire (b − 4.45; 95% CI, − 7.68, − 1.22; P = 0.008) and Pittsburgh Sleep Quality Index (b − 2.73; 95% CI, − 3.74, − 1.73; P <0.0001) in patients under MMT, compared with the placebo. Crocin also significantly improved International Index of Erectile Functions (b 4.98; 95% CI, 2.08, 7.88; P = 0.001) rather than placebo.
Findings from these 4 clinical studies indicate crocin improves depression, anxiety, sleep quality and quality of life.
On the last words, other antioxidants also have potential antidepressant activity. For instance, curcumin was reported to have the potential to ameliorate depressive symptoms13. Therefore, a combination of multiple natural antioxidants could potentially provide synergistic effects and an effective alternative to improve depression and quality of life.

Reference
1. The Efficacy of Saffron in the Treatment of Mild to Moderate Depression: A Meta-analysis. Planta Med 2019; 85(01): 24-31.
2. Saffron in the treatment of depression, anxiety and other mental disorders: Current evidence and potential mechanisms of action. J Affect Disord. 2018; 227: 330–337.
3. Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice. Avicenna J Phytomed, 2015; 5 (5): 458-468.
4. Study of the role of CREB, BDNF, and VGF neuropeptide in long term antidepressant activity of crocin in the rat cerebellum. Iranian J of Pharm Res. 2017, 16 (4): 1452-1462.
5. Effects of the active constituents of Crocus sativus L., crocins, in an animal model of anxiety. Phytomedicine 2008, 15: 1135–1139.
6. Effects of the active constituents of Crocus Sativus L., crocins, in an animal model of obsessive–compulsive disorder. Neuroscience Letters. 2012, 528: 27–30.
7. Saffron (Crocus sativus) Aqueous Extract and its Constituent Crocin Reduces Stress‐induced Anorexia in Mice. Phytother. Res. 2011, 25: 1833–1838.
8. Beneficial effects of physical activity and crocin against adolescent stress induced anxiety or depressive-like symptoms and dendritic morphology remodeling in prefrontal cortex in adult male rats. Neurochemical Research. 2019, published online: https://doi.org/10.1007/s11064-019-02727-2
9. Crocin, the main active saffron constituent, as an adjunctive treatment in major depressive disorder: A randomized, double-blind, placebo-controlled, pilot clinical trial. Journal of Affective Disorders. 2015, 174: 51–56.
10. The effects of crocin on the symptoms of depression in subjects with metabolic syndrome. Adv Clini Exp Med 2017; 26: 925–930
11. Effects of Saffron Aqueous Extract and Its Main Constituent, Crocin, on Health-Related Quality of Life, Depression, and Sexual Desire in Coronary Artery Disease Patients: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial. Iranian Red Crescent Medical Journal. 2017, 19 (9); e13676.
12. The effects of crocin on psychological parameters in patients under methadone maintenance treatment: a randomized clinical trial. Subst Abuse Treat Prev Policy. 2019; 14: 9. doi: 10.1186/s13011-019-0198-1.
13. Clinical use of curcumin in depression: a meta-analysis. J Am Med Dir Assoc. 2017, 18: 503–508.

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