Therapeutic Potential of Saffron in Depression: A Critical Appraisal of Clinical Evidence

Abstract

Saffron (Crocus sativus L.) has attracted increasing scientific interest because of its potential antidepressant effects. Randomized controlled trials suggest that saffron may be superior to placebo for mild-to-moderate depressive symptoms, while several short-term studies have reported outcomes broadly similar to fluoxetine, sertraline, citalopram, and imipramine. This review does not simply summarize efficacy data; it critically examines why positive efficacy signals have not yet translated into a well-defined clinical recommendation. Recent meta-analyses show an important discrepancy between significant improvements on self-reported measures such as the Beck Depression Inventory and less consistent findings on clinician-rated Hamilton Depression Rating Scale scores. Furthermore, most head-to-head comparisons with antidepressants were not designed as formal equivalence or non-inferiority trials. Heterogeneity in saffron preparations, active constituent concentrations, plant parts, doses, and standardization methods further limits generalizability. Current evidence supports saffron as a promising phytotherapeutic option, particularly for mild-to-moderate depressive symptoms and potentially as an adjunct to conventional treatment. However, its precise place in evidence-based depression care remains uncertain. Well-powered, multicenter, long-term randomized trials using chemically standardized preparations and clinically meaningful outcomes are required before saffron can be considered an established alternative to conventional antidepressants.

Keywords

• Saffron
• Crocus sativus
• depression
• antidepressant
• crocin
• phytotherapy

Safranın Depresyondaki Terapötik Potansiyeli: Klinik Kanıtların Eleştirel Değerlendirilmesi

Abstract

Safran (Crocus sativus L.), depresif belirtiler üzerindeki potansiyel etkileri nedeniyle son yıllarda giderek artan sayıda klinik araştırmaya konu olmuştur. Randomize kontrollü çalışmalar, safranın özellikle hafif ve orta şiddette depresyonda plaseboya üstün olabileceğini; bazı kısa süreli çalışmalarda ise fluoksetin, sertralin, sitalopram ve imipramin gibi antidepresanlarla benzer sonuçlar verebildiğini düşündürmektedir. Bu derlemenin amacı, safranın yalnızca etkinlik verilerini özetlemek değil, olumlu etkinlik sinyallerinin neden henüz güçlü ve standartlaştırılmış bir klinik öneriye dönüşmediğini eleştirel olarak değerlendirmektir. Güncel meta-analizlerde Beck Depresyon Ölçeği gibi öz-bildirim araçlarında anlamlı iyileşme bildirilmesine karşın, klinisyen tarafından değerlendirilen Hamilton Depresyon Ölçeği sonuçlarının aynı tutarlılığı göstermemesi önemli bir kanıt uyumsuzluğuna işaret etmektedir. Ayrıca antidepresanlarla yapılan karşılaştırmaların çoğu formal eşdeğerlik veya non-inferiority tasarımında değildir. Preparatların aktif bileşenleri, kullanılan bitki bölümü, dozları ve standardizasyon yöntemlerindeki farklılıklar da genellenebilirliği sınırlandırmaktadır. Mevcut kanıtlar safranın özellikle hafif-orta depresif belirtilerde ve tamamlayıcı tedavi yaklaşımında umut verici olabileceğini göstermektedir. Bununla birlikte standart antidepresanların kanıtlanmış bir alternatifi olarak kabul edilmeden önce daha güçlü, uzun süreli ve standardize çalışmalara ihtiyaç vardır.

Keywords

• Safran
• Crocus sativus
• depresyon
• antidepresan
• krosin
• fitoterapi

References

1. 1. Lopresti, A. L., & Drummond, P. D. (2014). Saffron (Crocus sativus) for depression: A systematic review of clinical studies and examination of underlying antidepressant mechanisms of action. Human Psychopharmacology: Clinical and Experimental, 29(6), 517-527. https://doi.org/10.1002/hup.2434
2. 2. Akhondzadeh, S., Tahmacebi-Pour, N., Noorbala, A. A., Amini, H., Fallah-Pour, H., et al. (2005). Crocus sativus L. in the treatment of mild to moderate depression: A doubleblind, randomized and placebo-controlled trial. Phytotherapy Research, 19(2), 148-151. https://doi.org/10.1002/ptr.1647
3. 3. Moshiri, E., Akhondzadeh Basti, A., Noorbala, A. A., Jamshidi, A. H., Abbasi, S. H., et al. (2006). Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: A double-blind, randomized and placebo-controlled trial. Phytomedicine, 13(9- 10), 607-611. https://doi.org/10.1016/j.phymed.2006.08.006
4. 4. Noorbala, A. A., Akhondzadeh, S., Tahmacebi-Pour, N., & Jamshidi, A. H. (2005). Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: A double-blind, randomized pilot trial. Journal of Ethnopharmacology, 97(2), 281-284. https://doi.org/10.1016/j. jep.2004.11.004
5. 5. Akhondzadeh, S., Fallah-Pour, H., Afkham, K., Jamshidi, A. H., & Khalighi-Cigaroudi, F. (2004). Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: A pilot double-blind randomized trial. BMC Complementary and Alternative Medicine, 4, 12. https://doi. org/10.1186/1472-6882-4-12
6. 6. Hausenblas, H. A., Saha, D., Dubyak, P. J., & Anton, S. D. (2013). Saffron (Crocus sativus L.) and major depressive disorder: A meta-analysis of randomized clinical trials. Journal of Integrative Medicine, 11(6), 377-383. https://doi.org/10.3736/ jintegrmed2013056
7. 7. Marx, W., Lane, M., Rocks, T., Ruusunen, A., Loughman, A., et al. (2019). Effect of saffron supplementation on symptoms of depression and anxiety: A systematic review and meta-analysis. Nutrition Reviews, 77(8), 557-571. https://doi.org/10.1093/ nutrit/nuz023
8. 8. Dai, L., Chen, L., & Wang, W. (2020). Safety and efficacy of saffron (Crocus sativus L.) for treating mild to moderate depression: A systematic review and meta-analysis. The Journal of Nervous and Mental Disease, 208(4), 269-276. https://doi. org/10.1097/NMD.0000000000001118

9. 9. Mahmoudi, R., Mohammadi-Sartang, M., Servatyari, K., & Rafieipour, N. (2026). Effect of saffron on depression, anxiety and mood disorder: A GRADE assessed systematic review and meta-analysis of 34 randomized controlled trials. Nutritional Neuroscience, 29(7), 816-837. https://doi. org/10.1080/1028415X.2025.2602153
10. 10. Siddiqui, S. A., Redha, A. A., Snoeck, E. R., Singh, S., Simal-Gandara, J., et al. (2022). Anti-depressant properties of crocin molecules in saffron. Molecules, 27(7), 2076. https://doi. org/10.3390/molecules27072076
11. 11. Khazdair, M. R., Boskabady, M. H., Hosseini, M., Rezaee, R., & Tsatsakis, A. M. (2015). The effects of Crocus sativus (saffron) and its constituents on nervous system: A review. Avicenna Journal of Phytomedicine, 5(5), 376-391.
12. 12. Ghajar, A., Neishabouri, S. M., Velayati, N., Jahangard, L., Matinnia, N., et al. (2017). Crocus sativus L. versus citalopram in the treatment of major depressive disorder with anxious distress: A double-blind, controlled clinical trial. Pharmacopsychiatry, 50(4), 152-160. https://doi.org/10.1055/s-0042-116159
13. 13. Ahmadpanah, M., Ramezanshams, F., Ghaleiha, A., Akhondzadeh, S., Sadeghi Bahmani, D., et al. (2019). Crocus sativus L. (saffron) versus sertraline on symptoms of depression among older people with major depressive disorders: A doubleblind, randomized intervention study. Psychiatry Research, 282, 112613. https://doi.org/10.1016/j.psychres.2019.112613
14. 14. Shafiee, A., Jafarabady, K., Seighali, N., Mohammadi, I., Rajai Firouz Abadi, S., et al. (2025). Effect of saffron versus selective serotonin reuptake inhibitors (SSRIs) in treatment of depression and anxiety: A meta-analysis of randomized controlled trials. Nutrition Reviews, 83(3), e751-e761. https:// doi.org/10.1093/nutrit/nuae076
15. 15. Ghaderi, A., Asbaghi, O., Reiner, Ž., Kolahdooz, F., Amirani, E., et al. (2020). The effects of saffron (Crocus sativus L.) on mental health parameters and C-reactive protein: A meta-analysis of randomized clinical trials. Complementary Therapies in Medicine, 48, 102250. https://doi.org/10.1016/j. ctim.2019.102250