Abstract

This review examines the efficacy of saffron (Crocus sativus L.) supplementation in managing anxiety and depression symptoms. Several peer-reviewed studies, published from 2016 to present, were analyzed exploring for study designs, methodologies, key findings, limitations, and conclusions. The review reveals promising evidence for saffron’s potential as a complementary treatment for mild to moderate anxiety and depression. Further research with larger, long-term trials is warranted to solidify the evidence base.

Introduction

Anxiety and depression are prevalent mental health conditions affecting millions globally. The World Health Organization (WHO) estimates that over 280 million people suffer from depression,[1] while anxiety disorders affect 264 million. Treatments for these conditions typically involve psychotherapy and/or medication. While effective, these approaches can have limitations, including potential side effects, accessibility issues, and treatment resistance. In recent years, there has been growing interest in exploring alternative and complementary therapies for anxiety and depression. One such potential therapy is saffron (Crocus sativus L.), a prized spice known for its culinary applications. Previous studies have suggested saffron’s potential mood-regulating properties.[2]

This review aims to investigate the current evidence for saffron’s effectiveness in managing anxiety and depression in adults. Data has been analyzed from recent randomized, double-blind, placebo-controlled trials (RCTs) to assess saffron’s efficacy compared to placebo and standard antidepressant medications. Limitations in the current research and areas for future exploration are further identified. By synthesizing these findings, this review aims to contribute to a growing body of knowledge regarding saffron’s potential as a complementary therapy for anxiety and depression.

Saffron v. Citalopram for Depression with Anxiety

Several recent studies have explored the potential of saffron supplementation for managing anxiety and depression. One randomized, double-blind, placebo-controlled trial compared saffron (30 mg/d) to the common antidepressant citalopram (40 mg/d) in adults with mild to moderate major depression with anxious features in adults (n = 66). Sixty (60) participants completed the study. After 6 weeks, both groups showed significant improvements in depression and anxiety scores (p < 0.001 in both groups), with no significant difference in efficacy between saffron and citalopram.[3]

Saffron v. Fluoxetine for Postpartum Depression

Similar results emerged from another double-blind, randomized, placebo-controlled trial conducted on postpartum depression, where saffron (15 mg twice daily) showed comparable safety and efficacy to another commonly prescribed SSRI medication, fluoxetine (20 mg twice daily), in treating mild to moderate postpartum depression in women (aged 18–45 with a baseline Hamilton Depression Rating Scale [HDRS] score ≤ 18). The study found no significant difference in the change in HDRS scores between the saffron and fluoxetine groups over the 6‑week period. While 41% of patients in the saffron group and 50% in the fluoxetine group achieved a complete response (≥ 50% reduction in HDRS score), this difference was not statistically significant. The frequency of adverse events was also similar between the two treatment groups.[4]

Saffron as Add-on to Sertraline for Generalized Anxiety Disorder

Building on the prior research, another double-blind, randomized controlled trial investigated the effect of saffron as an add-on therapy to sertraline in 40 patients with mild to moderate generalized anxiety disorder (GAD) diagnosed using DSM‑5 criteria. Participants were randomly assigned to receive either saffron (450 mg/d, n = 20) or a placebo (n = 20) for 6 weeks, in addition to their ongoing sertraline treatment (50 mg). The 14‑item Hamilton Anxiety Rating Scale (HAM‑A) was used to assess treatment effects, while also collecting anthropometric, demographic, and dietary intake data. After adjusting for age, baseline energy intake, baseline HAM‑A score, and weight changes, patients in the saffron group showed a significantly lower mean HAM‑A score at the end of the 6 weeks compared to the placebo group (2.95 v. 5.05; p = 0.005). Within-group analysis indicated a significant decrease in total HAM‑A scores in both groups (p ≤ 0.000). Furthermore, after adjusting for the same covariates, the change in HAM‑A score from baseline was significantly greater in the saffron group compared to the placebo group (−17.25 ± 2.67 v. −15.35 ± 2.30; p = 0.029). The side effects reported were mild and did not lead to any participants stopping the supplementation. The study concluded that saffron as an add-on to sertraline may reduce GAD symptoms.[5]

Meta-Analysis: Saffron’s Broad Effects on Neuropsychiatric Conditions

Further supporting the potential of saffron acting as an antidepressant and an anxiolytic, another systematic review and meta-analysis aimed to evaluate the overall effects of saffron on various neurological and psychiatric conditions, including cognition, depression, anxiety, sleep disorders, ADHD, and OCD. The researchers methodologically searched PubMed/Medline, Web of Science, and Clinical Trials databases up to June 2023 to identify relevant randomized controlled trials (RCTs). The inclusion criteria specified studies where participants, either healthy or with neurological or psychiatric disorders, received saffron or its extracts. The risk of bias was assessed using Cochrane guidelines, and the review adhered to the PRISMA statement. The meta-analysis, conducted using RevMan and STATA software with random-effects or fixed-effects models, included 46 RCTs. The duration of these trials ranged from 4 to 48 weeks.

The results indicated that saffron was significantly more effective than placebo in improving cognition, depression (overall effect size = −4.26, 95% CI −5.76 to −2.77), anxiety (overall effect size = −3.75, 95% CI −5.83 to −1.67), and sleep disorders (overall effect size = −1.91, 95% CI −2.88 to −0.93). Furthermore, saffron was found to be noninferior to conventional drugs in treating cognitive disorders, depression, anxiety, ADHD, and OCD, and it was generally well-tolerated, with few side effects. The authors concluded that saffron may have protective effects in neurological and psychiatric disorders and presents a relatively safe and favorable treatment option.[6]

Meta-Analysis: Saffron for Depression and Anxiety—as a Standalone Treatment and as an Add-on Therapy

Another systematic review and meta-analysis examined the impact of saffron supplementation, both as a standalone treatment and as an add-on therapy, on depression and anxiety symptoms compared to medication or placebo. Following PRISMA guidelines, the researchers systematically reviewed randomized controlled trials. Data extraction involved collecting data to calculate treatment effects, and the quality of the studies was assessed using the Jadad scale. The meta-analysis of 23 studies showed that saffron had a large positive effect size compared to placebo for depressive symptoms (g = 0.99, p < 0.001) and anxiety symptoms (g = 0.95, p < 0.006). Saffron also demonstrated a large positive effect size when used alongside antidepressants for depressive symptoms (g = 1.23, p = 0.028). The authors concluded that saffron may be an effective intervention for depression and anxiety symptoms, but more research is warranted due to limited geographical diversity in the included studies.[7]

Saffron and Anhedonia in Depression

Additionally, another study explored saffron as a potential to treat depression and anhedonia (reduced pleasure and motivation), particularly in milder forms where standard antidepressants may not be ideal. The study explored saffron’s effects in both preclinical models and depressed patients. In rats exhibiting stress-induced motivational anhedonia, repeated saffron treatment improved motivation and response to reward cues. This effect appeared to involve modulation of dopamine signaling and BDNF–TrkB pathways in brain regions associated with reward. In a pilot study with depressed patients, adding saffron to their existing treatment for 8 weeks led to an overall improvement in depressive symptoms and a significant reduction in anhedonia. The researchers concluded that saffron shows promise in improving motivation and could be a helpful add-on treatment for depressed patients experiencing anhedonia.[8]

Earlier Investigations into Saffron’s Potential: Saffron v. Imipramine

Two previous studies investigated saffron’s potential for depression in specific populations. A 6‑week pilot, double-blind, randomized trial (n = 30) compared saffron (30 mg/day TDS) to imipramine (100 mg/day TDS) in adults with depression. Participants met the DSM‑4 for major depression (based on the structured clinical interview for DSM‑4) and also had a baseline Hamilton Rating Scale for Depression score of at least 18. After 6 weeks, both groups showed similar effectiveness in treating mild to moderate depression (p = 0.09), with anticholinergic effects and sedation observed more often in the imipramine group. The study concluded that saffron may offer therapeutic benefits for mild to moderate depression, warranting a larger, placebo-controlled trial.[9]

Saffron for Premenstrual Syndrome

A separate study focused on women with premenstrual syndrome (PMS). This randomized, double-blind, placebo-controlled trial compared a lower dose of saffron (15 mg BID) to a placebo. Women aged 20–45 years with regular menstrual cycles who had been experiencing PMS symptoms for at least 6 months were eligible for the study and met the inclusion criteria. The saffron group demonstrated significant reductions in both total premenstrual daily symptoms and Hamilton Depression Rating Scale scores after two menstrual cycles, with a significant difference observed compared to the placebo group.[10]

Discussion and Conclusion

Based on the analysis of recent randomized controlled trials (RCTs) and meta-analyses focusing on the period from 2016 to the present, this review supports the promising potential of saffron (Crocus sativus L.) supplementation as a complementary therapy for managing mild to moderate anxiety and depression in adults. Notably, several studies demonstrated comparable efficacy between saffron and established antidepressant medications like citalopram [11] and fluoxetine,[12] suggesting its potential as a viable alternative or adjunct treatment. This is further supported by meta-analytic evidence indicating significant positive effects of saffron on both depressive and anxiety symptoms compared to placebo, and even as an add-on to conventional antidepressants.[13]

The findings extend beyond general anxiety and depression, indicating potential benefits for specific populations. For instance, saffron has shown promise in alleviating symptoms of postpartum depression [14] and generalized anxiety disorder when used as an add-on to sertraline.[15] Furthermore, recent research highlights saffron’s potential to address specific depressive symptoms like anhedonia, a challenging aspect of mood disorders. The preclinical findings suggest its mood-regulating effects may involve modulation of dopamine signaling and BDNF–TrkB pathways,[16] warranting further investigation in human trials. The broader impact of saffron on various neuropsychiatric conditions, including cognition and sleep, as highlighted in a comprehensive meta-analysis,[17] further underscores its therapeutic potential. A significant advantage consistently reported across these studies is saffron’s generally well-tolerated nature and favourable safety profile, particularly when compared to conventional antidepressant and antianxiety medications.[18] However, it is crucial to acknowledge the limitations inherent in the current body of research.

Many of the reviewed studies, while providing encouraging results, are characterized by relatively small sample sizes and short durations (typically 6–48 weeks), which may limit the generalizability of the findings and the ability to detect long-term effects. To solidify saffron’s role in evidence-based mental-health care, future research must prioritize larger, long-term trials across diverse populations, as also recommended by previous meta-analyses.[19] Further investigation into the precise mechanisms of action underlying saffron’s effects, optimal dosage regimens, and rigorous standardization of saffron preparations are also essential to ensure consistent and reliable outcomes.

In conclusion, the evidence synthesized in this review suggests that while not definitively a “golden match” yet, saffron holds considerable promise as a complementary therapy for mild to moderate anxiety and depression. Addressing the identified limitations through continued rigorous research will be essential to fully elucidate its clinical utility and integrate it effectively into evidence-based mental-health care.

Future Research Directions

The promising findings from recent studies on saffron for anxiety and depression highlight the need for further exploration in several key areas.

Larger, Long-Term Trials: Most studies reviewed employed relatively short durations (6–48 weeks). To solidify the evidence base and determine the long-term efficacy and safety of saffron, rigorous studies with larger sample sizes and extended durations are necessary.

Mechanism of Action Research: Understanding the biological mechanisms by which saffron exerts its mood-regulating effects is crucial. Investigating these mechanisms can inform the development of more targeted interventions for anxiety and depression.

Dosage Optimization: The optimal dosage of saffron for managing anxiety and depression remains unclear, with the reviewed studies employing a range of dosages (20–450 mg/d). Future research should explore dose-response relationships to identify the most effective and well-tolerated dosage that balances efficacy with tolerability.

Saffron Quality Control: Standardization of the saffron used in research is essential. Variations in origin, processing methods, and potential adulteration can impact the results. Ensuring consistent quality across studies is critical for reliable comparisons and establishing a clear understanding of saffron’s effects.