Table 3.

Studies on pharmacological activities relating to anti-depressant-like effects of saffron. BDI, Beck depression inventory; HAE, hydro-alcoholic extract; PCI, percutaneous coronary intervention; CAD, coronary artery disease; HAM-D, Hamilton Depression Rating Scale; PMS: premenstrual syndrome; GAD, generalized anxiety disorder; MMT, methadone maintenance treatment.

Aim of the Research	Type of Study	No. of Patients	Treatment	Time of Treatment (Weeks)	Results	References
Comparison of saffron and imipramine	Double-blind, randomized trial	30	Stigma of saffron, 30 mg/day	6	The effect of stigma of saffron was similar to imipramine in the treatment of mild to moderate depression.	[86]
Hydro-alcoholic extract of saffron versus fluoxetine	Double-blind, randomized pilot trial	40	Stigma of saffron, 30 mg/day	6	The effect of stigma of saffron was similar to fluoxetine in the treatment of mild to moderate depression.	[85]
Saffron (petal) in the treatment of mild to moderate depression	Double-blind, randomized, and placebo-controlled trial	40	Petal of saffron, 30 mg/day	6	The outcome on the HAM-D showed that the petal of saffron could produce a significantly better effect than the placebo.	[109]
Comparison of petal of saffron and fluoxetine	Double-blind, randomized trial	40	Petal of saffron, 15 mg/day (morning and evening)	8	Petal of saffron was found to be similarly effective to fluoxetine in the treatment of mild to moderate depression.	[87,110]
40 and 80 mg HAE of saffron against fluoxetine	Double-blind, randomized, clinical trial	60	Saffron, 40 and 80 mg/day + fluoxetine (30 mg)	6	Effective in treatment of mild to moderate depressive disorders.	[88,111]
Saffron with fluoxetine in PCI patients	Double-blind, randomized, clinical trial	40	Saffron (30mg/day)	6	Effective as fluoxetine (40 mg/day) in improving depressive symptoms of patients who were suffering from major depressive disorder (MDD).	[112]
Saffron and crocin in improving mental and sexual health in CAD patients	Double-blind, placebo-controlled, randomized, clinical trial	58	Stigma of saffron, 30 mg/day OR	8	The outcome of BDI-II scores significantly decreased after 8 weeks of intervention.	[113]
Saffron in the treatment of PMS	Double-blind, randomized, and placebo-controlled trial	50	30 mg, saffron petal during pre-menstrual syndrome	8	The depression measured significantly decreased.	[114]
Saffron versus citalopram in the major depressive disorder with anxious distress	Double-blind, controlled, clinical trial	66	30 mg, saffron stigma	6	Effective against moderate to major depression.	[107]
Saffron as an add-on therapy to sertraline in mild to moderate generalized anxiety disorder	Double-blind, randomized, controlled trial	40	500-mg capsule containing 450 mg of saffron (type not recorded)	6	Decreased mild to moderate generalized anxiety disorder with saffron as well as with sertraline.	[108]
Crocin on depression in subjects with metabolic syndrome	Randomized, double-blind, controlled, clinical trial	33	30 mg, saffron (crocin)	8	Decreased depressive symptoms in patients with metabolic syndrome.	[115]
Saffron improved depression and reduced homocysteine level in patients with major depression	Randomized, double-blind study	40	30 mg, saffron (stigma) and 20 mg, fluoxetine	4	The BDI score decreased in patients with major depression.	[116]
Comparison of saffron versus fluoxetine in treatment of mild to moderate post-partum depression	Double-blind, randomized, clinical trial	60	30 mg, saffron (stigma)	6	Significantly decreased mild to moderate depression and post-menopausal hot flashes.	[110]
Affron®, a standardized extract from saffron	Randomised, double-blind, placebo-controlled study	80	14 mg, saffron (stigma)	8	Significant reduction in mild to moderate depression.	[117]
Saffron in the treatment of anxiety and depression	Double-blind, randomized, and placebo- controlled trial	60	100 mg, saffron (stigma)	12	Significant decrease in mild to moderate depression.	[118]
Saffron (petal) in the treatment of mild to moderate depression	Double-blind, randomized, and placebo-controlled trial	36	30 mg, saffron (stigma) and 40 mg, fluoxetine	4	No significant decrease.	[119]
Effects of saffron on depression and lipid profile	Double-blind comparative study	40	30 mg, saffron (petal)	6	Decrease in major depression of those who met DSM-IV criteria.	[109]
Saffron stigma in mothers suffering from mild to moderate post-partum depression	Double-blind, randomized, placebo-controlled trial	40	30 mg, saffron (type not recorded) and 20 mg, fluoxetine	4	Significant decrease in major depression.	[120]
Crocin in major depressive disorder	Randomized, double-blind, placebo-controlled, pilot clinical trial	78	30 mg, saffron (stigma)	8	Significant decrease in mild to moderate depression.	[111]
Crocin on psychological parameters in patients under MMT	Randomized clinical trial	46	30 mg, saffron (crocin) and 20 mg, fluoxetine	4	Significant decrease in major depression.	[121]
Crocin on psychological parameters in patients under MMT	Randomized, double-blind, placebo-controlled trial	50	30 mg per day, saffron (crocin)	8	Improved depression symptoms during methadone maintenance treatment (MMT).	[122]
	Double-blind, randomized, and placebo- controlled trial	28	150 mg per day, saffron	6	Increased serotonin and happiness were further heightened in supplemented group. Anandamide, dopamine, and β-endorphin were significantly increased under suplementeation, whereas placebo remained unchanged.	[123]