Saffron the “Red Gold” and Its CNS Activity: A Challenge for Future Applications in Nutraceuticals

Table 3

Studies involving the use of saffron or saffron extracts in depression.

First author	Group	Daily dose	Sample size	Duration	Outcomes
Mazidi et al. 2016 [76]	Saffron vs placebo	50 mg b.i.d saffron	60 adults	12 weeks	Reduction in BDI and BAI scores with saffron
Lopresti et al. 2018 [77]	Affron® vs placebo	14 mg b.i.d saffron	68 teenagers	8 weeks	Improvements in overall internalizing symptoms, social phobia, depression, and separation anxiety analyzed with RCADS with saffron
Kell et al. 2017 [64]	Affron® vs placebo	28 mg or 22 mg saffron	128 adults	4 weeks	Reduction in negative mood, stress, and anxiety only with 28 mg/day measured with POMPS and PANAS questionnaire, DASS-21 scale, and PSQI
Moghadam et al. 2021 [78]	Saffron + RT vs RT + placebo	150 mg saffron	28 untrained young male	6 weeks	Increase in AEA, 2-AG, dopamine, and beta-endorphin in saffron + RT; increase in serotonin, happiness, and muscular endurance in both groups with a greater increase in the saffron + RT group
Kashani et al. 2018 [79]	Saffron vs placebo	15 mg b.i.d saffron	60 postmenopausal women	6 weeks	Improvements in hot flashes and depressive symptoms measured with HFRDIS and HDRS
Tabeshpour et al. 2017 [80]	Saffron vs placebo	15 mg b.i.d saffron	60 new mothers with BDI-II < 29	8 weeks	Higher reduction in BDI-II scores of saffron; remission in 93% of the saffron group and 43% of the placebo group
Sahraian et al. 2016 [70]	Saffron + fluoxetine vs fluoxetine + placebo	30 mg saffron	40 adults	4 weeks	Improvements in depression severity in both the groups without significant differences
		20 mg fluoxetine
Talaei et al. 2014 [75]	Crocin + SSRI vs SSRI + placebo	15 mg b.i.d crocin	40 MDD adults	4 weeks	Higher reduction in BDI, BAI, and GHQ scores in the saffron group + SSRI
		20 mg fluoxetine or 50 mg sertraline or 20 mg citalopram
Akhondzadeh et al. 2020 [63]	Saffron vs placebo	15 mg b.i.d saffron	73 MMD women with BMI ≥25	12 weeks	Reduction in BDI-II in the saffron group. No effect on food craving
Lopresti et al. 2019 [67]	Affron® vs placebo adjunct to standard antidepressant therapy	14 mg b.i.d saffron	160 adults with persistent depression	8 weeks	Higher reduction in MADRS in the saffron group. No difference in MADRS-S
Kashani et al. 2017 [68]	Saffron vs fluoxetine	15 mg b.i.d saffron	94 adult women with postpartum depression	6 weeks	Significant improvements in HDRS scores in both groups
		20 mg b.i.d fluoxetine			No significant difference between saffron and fluoxetine
Ghajar et al. 2017 [73]	Saffron vs citalopram	30 mg saffron	66 MDD adults with anxious distress	6 weeks	Significant improvements in HAM-D and HAM-A scores in both groups
		40 mg citalopram			No significant difference between saffron and citalopram
Ahmadpanah et al. 2019 [74]	Saffron vs sertraline	60 mg saffron	50 older out-patientswith MDD	6 weeks	Significant improvements in HDRS in both groups
		100 mg sertraline			No significant difference between saffron and sertraline

BDI, Beck Depression Inventory; BAI, Beck Anxiety Inventory; MDD, major depressive disorder; HAM-D, Hamilton Depression Rating Scale; HAM-A, Hamilton Anxiety Rating Scale; HDRS, Hamilton Depression Rating Scale; MADRS, Montgomery-Asberg Depression Rating Scale; GHQ, General Health Questionnaire; SSRI, selective serotonin reuptake inhibitor; AEA, arachidonoylethanolamine; 2-AG, arachidonoylglycerol; RCADS, Revised Children’s Anxiety and Depression Scale; POMPS, primary outcome measure; DASS-21, Depression Anxiety Stress Scale; PSQI, Pittsburgh Sleep Quality Index; HFRDIS, Hot Flashes-Related Daily Interference Scale.