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Saffron for depression

iran_saffron_threads

According to ancient Greek mythology, Hermes and his friend Krokos were horse-playing and Hermes accidentally killed Krokos through a head injury, with three blood drops from his head falling on the top of a flower, creating three stigmata and naming this plant thereafter Krokos (Crocus)[1]. Thus the ancient and godly identification of this plant and saffron.

Saffron is the dried stigma (the top part in the center of a flower which receives the pollen and on which germination takes place) of the blue-purple flower Crocus sativus L., and it has a long history of use as a spice, coloring agent, and medicine. Due to how saffron is grown and harvested, saffron is considered one of the world’s most expensive spices (upwards of $11,000 per kg, requiring 450,000 hand-picked stigmas)[2]. Apart from its traditional value as a spice and coloring agent (originally for the Persian carpet industry), saffron has a long history of medicinal use spanning over 2,500 years[3].

This use of saffron in traditional medicine included for cramps, asthma, menstruation disorders, liver disease, and painful dysmenorrhoea[4], among many other uses.  Evidence from recent in vitro and in vivo research indicates that saffron has potential anti-carcinogenic, anti-mutagenic, antioxidant, and memory-enhancing properties[5] [6].

Neurodegenerative disorders

Administration of saffron 30 mg/day (15 mg twice daily) was found to be as effective as a leading medication for mild to moderate Alzheimer’s disease (donepezil) in a placebo-controlled double bind for treatment in subjects of 55 years and older[7] but with a better side effect profile.  Although there are a growing number of non-human animal studies and theories why saffron could be neuroprotective for Alzheimer’s Disease and other neurodegenerative conditions, clinical studies are too few to make any tentative conclusions to date.

Mood disorders

In two randomized, double-blind, placebo-controlled trials, saffron was effective for the treatment of mild to-moderate depression[8] [9].

A systematic review of randomized control trials examining the effectiveness of saffron in mood disorders revealed a statistically significant effect on improved mood on subjects clinically diagnosed with depression[10]; the dosing was typically 30 mg/ day.

In clinical studies, the use of saffron extract at doses of 20–30 mg/day twice daily for the treatment of mild to moderate depression has been compared with currently marketed antidepressants such as fluoxetine[11] (20 mg/day twice daily) and imipramine[12] (100 mg/day three times daily). So these comparative evaluations revealed that saffron was equally effective as chemically synthesized marketed pharmaceutics, in mild or moderate depression without causing the typical side effects of the artificial preparations.

Saffron may act in a manner similar to antidepressants to improve mood by inhibiting serotonin reuptake[13] or there could be multiple pathways involving, for example, its antioxidant, anti-inflammatory properties.

Saffron contains in excess of 150 volatile and aroma-yielding compounds and many non-volatile active components, many of which are carotenoids[14] . Safranal is the compound primarily responsible for saffron’s aroma.  Safranal has shown to have anti-convulsant and anxiolytic effects[15] as well as antidepressant properties[16]

Premenstrual Syndrome (PMS)

One randomized controlled trial examined the effects of saffron supplementation on premenstrual syndrome[17]. It was found that found that women with regular menstrual cycles experiencing premenstrual syndrome who took 30 mg/d of saffron supplementation for eight weeks reported relief in premenstrual symptoms and depression levels compared to placebo.  Remarkably, just the aroma alone – without otherwise any oral intake of saffron was itself found effective in relief of PMS symptoms in another placebo controlled double blind study[18], indicating effectiveness at very small does and the likely active component being Safranal.

References

[1] Koulakiotis, N., Pittenauer, E., Halabalaki, M., Skaltsounis, L., Allmaier, G., & Tsarbopoulos, A. (2011). Isolation and Tandem Mass Spectometric Characterization of Selected Crocus sativus L. (Saffron) Bioactive Compounds.Planta Med Planta Medica, 77(12). doi:10.1055/s-0031-1282560

[2] Gohari, A., Saeidnia, S., & Mahmoodabadi, M. (2013). An overview on saffron, phytochemicals, and medicinal properties. Pharmacognosy Reviews Phcog Rev,7(1), 61. doi:10.4103/0973-7847.112850

[3] Srivastava, R., Ahmed, H., Dixit, R., D., & Saraf, S. (2010). Crocus sativus L.: A comprehensive review. Pharmacognosy Reviews, 4(8), 200. doi:10.4103/0973-7847.70919

[4] Kianbakht, S., & Ghazavi, A. (2011). Immunomodulatory Effects of Saffron: A Randomized Double-Blind Placebo-Controlled Clinical Trial. Phytother. Res. Phytotherapy Research, 25(12), 1801-1805. doi:10.1002/ptr.3484

[5] Abdullaev, F., & Espinosa-Aguirre, J. (2004). Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detection and Prevention, 28(6), 426-432. doi:10.1016/j.cdp.2004.09.002

[6] Bathaie, S. Z., & Mousavi, S. Z. (2010). New Applications and Mechanisms of Action of Saffron and its Important Ingredients. Critical Reviews in Food Science and Nutrition, 50(8), 761-786. doi:10.1080/10408390902773003

[7] Akhondzadeh, S., Sabet, M. S., Harirchian, M. H., Togha, M., Cheraghmakani, H., Razeghi, S., . . . Moradi, A. (2010). ORIGINAL ARTICLE: Saffron in the treatment of patients with mild to moderate Alzheimer’s disease: A 16-week, randomized and placebo-controlled trial. Journal of Clinical Pharmacy and Therapeutics, 35(5), 581-588. doi:10.1111/j.1365-2710.2009.01133.x

[8] Akhondzadeh, S., Tahmacebi-Pour, N., Noorbala, A., Amini, H., Fallah-Pour, H., Jamshidi, A., & Khani, M. (2005). Crocus sativus L. in the treatment of mild to moderate depression: A double-blind, randomized and placebo-controlled trial.Phytother. Res. Phytotherapy Research, 19(2), 148-151. doi:10.1002/ptr.1647

[9] Moshiri, E., Basti, A. A., Noorbala, A., Jamshidi, A., Abbasi, S. H., & Akhondzadeh, S. (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. doi:10.1016/j.phymed.2006.08.006

[10] Hausenblas, H. A., Heekin, K., Mutchie, H. L., & Anton, S. (2015). A systematic review of randomized controlled trials examining the effectiveness of saffron (Crocus sativus L.) on psychological and behavioral outcomes. Journal of Integrative Medicine, 13(4), 231-240. doi:10.1016/s2095-4964(15)60176-5

[11] Noorbala, A., Akhondzadeh, S., Tahmacebi-Pour, N., & Jamshidi, A. (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. doi:10.1016/j.jep.2004.11.004

[12] Akhondzadeh, S., Fallah-Pour, H., Afkham, K., Jamshidi, A., & 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 [ISRCTN45683816]. BMC Complementary and Alternative Medicine BMC Complement Altern Med, 4(1). doi:10.1186/1472-6882-4-12

[13] 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. doi:10.3736/jintegrmed2013056

[14] Sampathu, S. R., Shivashankar, S., Lewis, Y. S., & Wood, A. B. (1984). Saffron ( Crocus Sativus Linn.) — Cultivation, processing, chemistry and standardization.C R C Critical Reviews in Food Science and Nutrition, 20(2), 123-157. doi:10.1080/10408398409527386

[15] Hosseinzadeh, H., & Talebzadeh, F. (2005). Anticonvulsant evaluation of safranal and crocin from Crocus sativus in mice. Fitoterapia, 76(7-8), 722-724. doi:10.1016/j.fitote.2005.07.008

[16] Hosseinzadeh, H., Karimi, G., & Niapoor, M. (2004). Antidepressant Effect Of Crocus Sativus L. Stigma Extracts And Their Constituents, Crocin And Safranal, In Mice. Acta Hortic. Acta Horticulturae, (650), 435-445. doi:10.17660/actahortic.2004.650.54

[17] Agha-Hosseini, M., Kashani, L., Aleyaseen, A., Ghoreishi, A., Rahmanpour, H., Zarrinara, A., & Akhondzadeh, S. (2008). Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: A double-blind, randomised and placebo-controlled trial. BJOG: Int J O & G BJOG: An International Journal of Obstetrics and Gynaecology, 115(4), 515-519. doi:10.1111/j.1471-0528.2007.01652.x

[18] Fukui, H., Toyoshima, K., & Komaki, R. (2011). Psychological and neuroendocrinological effects of odor of saffron (Crocus sativus).Phytomedicine, 18(8-9), 726-730. doi:10.1016/j.phymed.2010.11.013