Exploring the Potential of Saffron as a Therapeutic Agent in Depression Treatment: A Comparative Review

Abstract

Depression is a significant mental health challenge globally. While traditional antidepressants are effective, they often have unwanted side effects. Saffron, a natural spice derived from Crocus sativus L., has emerged as a potential alternative therapy for depression. Researchers have found that its components such as crocin, crocetin, and safranal have been found to mitigate depressive symptoms through neurotransmitter regulation, anti-inflammatory effects, and neuroprotection. Clinical trials suggest that the effectiveness of saffron in treating mild to moderate depression is comparable to that of standard medications, and animal studies support these results, showing behavioral improvements with saffron treatment. Saffron is particularly appealing due to its safety and lower incidence of side effects, making it suitable for those sensitive to conventional drugs. Additionally, its antioxidant properties may offer further health benefits. However, challenges such as determining the appropriate dosage, prohibitive cost, and the limited availability of quality saffron need to be addressed. Most research on saffron's efficacy is short-term; thus, long-term studies are essential to understand its full therapeutic potential and ongoing antidepressant effects. While saffron is safe in terms of its culinary value, higher therapeutic doses require careful monitoring for drug interactions and side effects. In summary, saffron represents a promising direction in depression treatment, with benefits potentially matching those of standard treatments and a better safety profile. However, further research is necessary to establish clear guidelines for its use, optimize dosing, and assess long-term outcomes. Saffron offers a natural treatment path for depression, but its use must be controlled and supported by scientific evidence.

Keywords: Depression; antidepressant; crocin; phytoconstituents; saffron.

Figure 1

The main pathomechanisms of depression. The main structures associated with the pathogenesis of depression are the prefrontal cortex and limbic system (including the hippocampus and the amygdala) according to the comprehensive, immuno-endocrinological theory of the development of depression, this disease results from the action of multiple exogenous and endogenous factors. Details are given in the text. HPA, hypothalamic-pituitary-adrenal axis; 5HT, 5-hydroxytryptamine; NA, noradrenaline; DA, dopamine.

Figure 2

Potential therapeutic applications of saffron.

Figure 3

Structure of different parts of the saffron plant.

Figure 4

Chemical structures of major components in saffron.

Figure 5

Adenylate cyclase-activating polypeptide (PACA), extracellular regulated protein kinase (ERK), response element binding protein (CREB), cyclic adenosine monophosphate (cAMP), adenosine triphosphate (ATP), and adenylyl cyclase (AC) are the mechanisms by which saffron crocin exhibits neuroprotection activation (B) and reduces the effects of stress (A).

Figure 6

Illustration of the mechanism of inhibiting norepinephrine (NE) reuptake and serotonin-reuptake by (A) crocin and (B) safranal, respectively.