From Mood to Memory: Unlocking Saffron's Potential in Brain Health.

Depression, anxiety, mild cognitive impairment (MCI), and Alzheimer's disease (AD) pose ongoing therapeutic challenges, particularly in aging populations. Conventional pharmacologic treatments often have delayed onset, limited efficacy, and unfavorable side effects, prompting interest in natural alternatives. Saffron ( L.), a spice long used in traditional medicine, has emerged as a promising candidate due to its multimodal neuroprotective properties. This review evaluated the clinical efficacy, safety, and mechanistic profile of saffron in the treatment of mood and cognitive disorders. A targeted literature search identified multiple double-blind randomized controlled trials (RCTs) and meta-analyses comparing saffron to standard pharmacologic agents or placebo. In depression, RCTs using 30 mg/day of saffron for six weeks showed comparable improvements in Hamilton Depression Rating Scale (HAM-D) scores to fluoxetine (20 mg/day), with significant reductions from baseline and no difference in adverse events. An adjunctive study using crocin (an active ingredient of saffron; 15 mg twice daily) also demonstrated additive effects alongside selective serotonin reuptake inhibitors (SSRIs). In cognitive disorders, saffron (30 mg/day) showed non-inferiority to donepezil (10 mg/day) and memantine (20 mg/day) in patients with mild-to-moderate and moderate-to-severe AD. Trials lasting 16 to 52 weeks demonstrated significant improvements on validated cognitive scales such as Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) and Clinical Dementia Rating - Sum of Boxes (CDR-SB), with fewer gastrointestinal side effects compared to standard treatments. Meta-analyses confirm the superiority of saffron over placebo and its equivalence to conventional drugs, with no serious adverse events. Saffron represents a safe, well-tolerated, and culturally integrated intervention with growing evidence for use in psychiatric and neurologic disorders. Larger, multicenter trials with biomarker validation and standardized extract formulations are needed to confirm its role in clinical practice.