Saffron (Crocus sativus L.) as a Promising Complementary Treatment for Depression: A Review of Basic and Clinical Studies

Depression is a mood disorder that has profound effects on both mental and physical health, leading to decreased quality of life, cognitive issues, and increased susceptibility to various diseases. Current treatments mainly depend on pharmaceutical medications, which can have associated side effects. In this context, the use of natural remedies, including medicinal plants such as saffron, has gained attention for their potential in alleviating depression symptoms. Saffron, known for its calming, anti-anxiety, and anti-inflammatory properties, has emerged as a promising natural treatment option for depression.

A comprehensive literature search was conducted in the PubMed and Google Scholar databases for studies published between 2019 and 2024. The search terms included "saffron and depression," "crocin and depression," "saffronal and depression," and "saffron compounds and mood disorders." Studies were included if they focused on the effects of saffron and its compounds on depression, with full-text access available. Studies that only contained abstracts or were written in languages other than English were excluded.

The reviewed studies indicate that saffron and its active compounds, particularly crocin and safranal, exhibit significant antidepressant effects. These effects are attributed to the modulation of neurotransmitter systems such as serotonin, dopamine, norepinephrine, and GABA, as well as the reduction of inflammation and the increase in antioxidant activity within the brain. Moreover, saffron has been shown to positively influence the brain-derived neurotrophic factor (BDNF) and neurogenesis, further contributing to the reduction of depression symptoms. In preclinical animal models, saffron’s antidepressant effects were demonstrated through behavioral tests such as the forced swimming test (FST) and tail suspension test (TST), where saffron-treated animals showed significant improvements in depressive behaviors. The antidepressant effects of saffron can be attributed to several neurobiological mechanisms. Crocin and safranal, two of saffron’s primary bioactive compounds, act by inhibiting the reuptake of dopamine, norepinephrine, and serotonin, thereby increasing their availability in the brain. Additionally, saffron has antioxidant properties that protect neurons from oxidative damage, and it regulates the hypothalamic-pituitary-adrenal (HPA) axis, which plays a key role in stress and mood regulation. Furthermore, saffron’s impact on neuroinflammation and its ability to modulate neurotransmitter systems like GABA and glutamate contribute to its antidepressant effects. These mechanisms collectively help improve neuronal plasticity and restore mood balance, making saffron a promising adjunctive treatment for depression.

Saffron appears to be a promising natural remedy for alleviating depression, particularly in cases where conventional treatments have been insufficient. Its active compounds, crocin and safranal, exert antidepressant, anti-inflammatory, antioxidant, and neuroprotective effects, making saffron a viable alternative or complementary treatment to traditional pharmacological interventions. However, further clinical studies with larger sample sizes and long-term follow-up are needed to confirm the efficacy and safety of saffron in treating depression in clinical settings.