"Natural Psychiatrist" Saffron for Insomnia, Anxiety + Depression

Dr. Nicole Sundene

Holistic Psychiatry & Women's Health

Menopausal women recently reported in a June 2023 study feeling happier on saffron! Did you know that saffron has repeatedly been proven as safe and effective for anxiety, insomnia, and depression?

The world’s most expensive spice is not only delicious but important medicine. Saffron costs about twenty dollars per gram because the harvesting process is extremely tedious and each flower only produces three threads of saffron.  Saffron is most commonly used in expensive and exotic dishes, Morrocan and East Indian cooking. The herbal medicinal components of saffron contain powerful antioxidants, vitamins, minerals, beta carotene and mental health benefits! 

The stigma is actually the female reproductive part of the plant which is why its pigments are full of nutrition and antioxidants to attract bees, butterflies, and pollinators. After the crocus blooms the red stigmas come out shortly after. 

Saffron is a warming spice used in risotto, boulibasse, and paella that is plucked from the crocus flower. The saffron stigmas are then dried for use in cooking or as medicine. 

Since so many of my mental health patients have been asking me about saffron, I wanted to share the latest saffron research. We have two new research studies on saffron released in June of 2023! These studies again confirm that saffron made menopausal women happier, and was also safe and effective for anxiety and depression.

Ever since 2014 I have been using saffron on my patients, when I read the research study showing saffron as effective as Prozac for depression. Another study found saffron was safe and effective when combined with the common antidepressants Prozac, Zoloft, and Celexa, and provided a mood boosting synergistic effect.  This is important because there is often grave concern in the holistic psychiatry community that too many medications or herbal supplements may cause "Serotonin Syndrome" which can cause dangerous High Blood Pressure. This did not happen with these medications plus saffron!

Researchers also found saffron was as effective as Ritalin for children with ADHD, with less side effects and potential for stunting of growth. When I worked in conventional medicine, we were always measuring kids on ADHD medications for fear the medication would stunt their growth, and it often did. So this is a good first option to try along with my "ADHD Diet" as oftentimes kids don't need us to kill a fly with a cannonball when they cannot concenterate or hold still, and something gentle and safe like saffron plus an omega-3 rich diet, and food trigger removal is all a lot of the kids I treat for ADHD need. Then I work with their psychiatrist to taper them down from their Adderall, Ritalin, or ADHD medication.

My own experimenting with saffron on many patiens has resulted in it being a totally beneficial and benign substance that lifts mood with little side effects. 

It is so safe that researchers used it in breastfeeding women with postpartum depression and found it to be a safe and effective natural antidepressant for depressed new moms. This is important in my women’s health practice as many new moms are depressed yet also terrified of taking a prescription drug while breastfeeding. In mild to moderate cases of postpartum depression saffron is safe and effective. As well as beneficial when combined with Zoloft in severe postpartum depression. Although most of my mom's need saffron, along with correcting hormone imbalance and nutritional deficiencies that occur postpartum as I discuss on that blog.

The worst thing that happens with saffron that I see happening in my practice is that patients decide they feel fine on saffron, are no longer depressed, and then mistakenly think they don't need to take it anymore. 

Especially when  the saffron pharmacy doesn't text you a million times to refill your saffron, pick up your saffron, and then continuously threaten to put your saffron back on the shelf if you don’t pick it up today like our pharmacies do with prescription antidepressants. So within 1-2 weeks after forgetting to take saffron my patients do report going right back to their depressed blah slumpy state. 

So if you do choose to start saffron put it on autoship please! Saffron in capsules is not super expensive, so figure out how many capsules you need each month of it and put it on autoship when you order your Vitamins.

Other things to consider with saffron is that it shown to be effective for many conditions. Having a synergistic benefit is generally a good thing, except when the patient or their doctor is not aware of how saffron may be impacting certain medications and medical conditions.

Many research studies have been conducted on saffron safety and efficacy. Researchers also found saffron helpful for ADHD, Insomnia, Diabetes Type 2, Alzheimer’s, Stroke Recovery, Allergies, Asthma, Macular Degeneration, Diabetic Eye Disease, Poor Libido, Erectile Dysfunction, and improves Cholesterol, Blood Pressure, and Chronic Pain. The mechanism of action appears to be that saffron is a potent anti-inflammatory herbal medicine that likely works by improving optimal gene expression. 

So keep in mind that you should be supervised by a Naturopathic Doctor if you have medical conditions, or are taking any medications while using saffron as generally I DO need to adjust patient’s medications down. Especially for Anxiety, Depression, Diabetes, High Blood Pressure, High Cholesterol, and Pain. While these are basically good problems to have, a Naturopathic Doctor should be monitoring blood work and blood pressure to ensure your numbers do not become too low as either extreme of too high or too low of blood pressure and blood sugar are not good. 

Now keep in mind another key point about using saffron, is that if you use it alone it is likely not powerful enough for the severe depression cases I treat. This is when I use it as an “Adjunctive Therapy” as it was found safe and effective to combine synergistically with Prozac, Zoloft, and Celexa. It is afterall just a food. But still be careful, especially with things like depression. I would never want to give someone false hope with severe depression that this will be the only medicine they will need. 

Saffron is best for mild and moderate depression and safe as an adjunctive therapy to most prescription antidepressants. Which is important since I commonly hear that antidepressants help my patients somewhat, but do not get their mood to 100%. Until we add saffron! 

Saffron also helped reverse the poor libido side effects many patients on antidepressants experience which makes sense considering that it traditionally has been prescribed and studied for male erectile dysfunction. So things that help men's erectile dysfunction generally help women on antidepressants and/or in menopause that have zero libido.

With the epidemic of mental health issues plaguing the public I continue to regularly blog about mental health, thank you to everyone that follows me and shares my posts on their social media. It brings me great joy as a Women's Health Doctor to see my male friends even sharing this important news for women!

I have a lot of mental health patients in my practice that can look very well put together and can put on an amazing show. Only their doctor knows they are anxious, depressed, spinning out in constant panic attacks, battling PTSD or even suicidal. 

Together we can fight this mental health epidemic. I am asking for everyone’s help as I cant do it without you. Please help me by sharing my posts, text them to your depressed friends. This is free information. While I prefer everyone to work with me so I can properly help them, I also know many people are not aware of other options to prescription drugs, and do not feel "normal" on antidepressants, yet need to take something.

I do also understand that many people cannot afford medical care right now or are unemployed. I also want to bring awareness of this powerful yet gentle and safe natural remedy for depression. So to save our loved ones we all have to do this together.

The other dangers are using cheap fake forms of saffron. Please stick with doctor recommended reputable sources for your supplements, I prefer the Life Extension brand available to my patients in Fullscript, be careful with the Happy Saffron brand as it contains soy, a high dose of zinc, and carnuba wax. So the Life Extension "Optimized Saffron" choice is what I prescribe to my patients as it has 88.25mg of PURE saffron in it. Most depression studies used only 30mg of saffron. So this product is a healthy pure source of saffron, I see it effectively working for my patients, it is double the researched dose, and I trust Life Extension uses reputable sources that are not full of lead as many herbs from India and China are.

Most research studies I have listed below used 15 mg for children and 30mg for most adults. Some studies did use up to 100mg of saffron! So now I am buying myself several bottles and wondering how amazing I could feel mentally and sleep better at night by trying a full 100mg! Crocus petals were also studied to be effective for mental health, if you do grow this plant. 

Thank you for sharing my important holistic nutrition recommendations for depression, anxiety, and PTSD,  Everything is free to read and relatively inexpensive on my blog “Depression Tips” and my "ADHD Diet" is critical for all mental health patients to follow as it contains a high amount of Omega-3's while eliminating trigger foods.

Read more about “Anxiety Herbs”, like Schisandra and Ashwaghanda for more of my favorite mental health natural remedies.

Visit my SCHEDULE page to treat yourself to a Naturopathic visit, so we can get to the “Root Cause” of mental health and chronic disease. I would be happy to help!

Dr. Nicole Sundene, NMD

(480) 837-0900

Dr. Sundene is a Naturopathic Doctor in Scottsdale, Arizona, and is considered a Female Hormone Specialist  in Women's Health and Bioidentical Hormones. She specializes in Holistic Women's Health for Menopause, Thyroid, Hashimotos, PMS, Perimenopause, Autoimmune, Postpartum, Chronic Fatigue, Depression, Anxiety, Food Allergies, Digestion, Dermatology , Acne, Psoriasis, Eczema and Adrenal Hormonal Conditions. In 1999 she began working for a Hormone Doctor prior to starting Naturopathic Medical School. With over 22 years of experience in both Prescription and Natural women's health and hormones she presents to women the best integrated health solutions for their Chronic Disease. She has been an Herbalist for over 27 years and enjoys teaching women how to use herbs to balance their hormones, nutrition and optimize their health. Dr. Sundene relies on blood testing for her hormone metrics. The hormone testing is covered per the patient's insurance plan and conducted at certain points in the woman's menstrual cycle. To learn more about Hormone Testing for Women Visit: Bioidentical Hormones. Follow Dr. Sundene on Instagram, Twitter and Facebook for more tips on Women's Health, Female Hormones and Naturopathy!

References:

1. Ahmad S, Khan A, Rafique H, Tikmani P, Mesiya H, Amin F. Co-administration of saffron and chamomile: to determine the efficacy as an adjuvant therapy for mild to moderate depression in human subjects. A pilot randomized clinical trial. J Pak Med Assoc. 2023 Jun;73(6):1245-1250. doi: 10.47391/JPMA.3915. PMID: 37427624.
2. Delam H, Keshtkaran Z, Shokrpour N, Eidi A, Bazrafshan MR. The effect of Crocus sativus L. (saffron) herbal tea on happiness in postmenopausal women: a randomized controlled trial. BMC Complement Med Ther. 2023 Jun 1;23(1):176. doi: 10.1186/s12906-023-04014-8. PMID: 37264347; PMCID: PMC10233190.
3. Delam H, Keshtkaran Z, Shokrpour N, Eidi A, Bazrafshan MR. The effect of Crocus sativus L. (saffron) herbal tea on happiness in postmenopausal women: a randomized controlled trial. BMC Complement Med Ther. 2023 Jun 1;23(1):176. doi: 10.1186/s12906-023-04014-8. PMID: 37264347; PMCID: PMC10233190.
4. Kazemi T, Mollaei H, Takhviji V, Bijari B, Zarban A, Rostami Z, Hoshyar R. The anti-dyslipidemia property of saffron petal hydroalcoholicextract in cardiovascular patients: A double-blinded randomized clinical trial. Clin Nutr ESPEN. 2023 Jun;55:314-319. doi: 10.1016/j.clnesp.2023.04.002. Epub 2023 Apr 15. PMID: 37202063.
5. Aslani MR, Abdollahi N, Matin S, Zakeri A, Ghobadi H. Effect of crocin of Crocus sativus L. on serum inflammatory markers (IL-6 and TNF-α) in chronic obstructive pulmonary disease patients: a randomised, double-blind, placebo-controlled trial. Br J Nutr. 2023 Aug 14;130(3):446-453. doi: 10.1017/S0007114522003397. Epub 2023 Jan 11. PMID: 36628554.
6. Tajaddini A, Roshanravan N, Mobasseri M, Haleem Al-Qaim Z, Hadi A, Aeinehchi A, Sefid-Mooye Azar P, Ostadrahimi A. The effect of saffron (Crocus sativus L.) on glycemia, lipid profile, and antioxidant status in patients with type-2 diabetes mellitus: A randomized placebo-controlled trial. Phytother Res. 2023 Feb;37(2):388-398. doi: 10.1002/ptr.7600. Epub 2022 Dec 29. PMID: 36580575.
7. Blasco-Fontecilla H, Moyano-Ramírez E, Méndez-González O, Rodrigo-Yanguas M, Martin-Moratinos M, Bella-Fernández M. Effectivity of Saffron Extract (Saffr'Activ) on Treatment for Children and Adolescents with Attention Deficit/Hyperactivity Disorder (ADHD): A Clinical Effectivity Study. Nutrients. 2022 Sep 28;14(19):4046. doi: 10.3390/nu14194046. PMID: 36235697; PMCID: PMC9573091.
8. Jaafarinia A, Kafami B, Sahebnasagh A, Saghafi F. Evaluation of therapeutic effects of crocin in attenuating the progression of diabetic nephropathy: a preliminary randomized triple-blind placebo-controlled trial. BMC Complement Med Ther. 2022 Oct 8;22(1):262. doi: 10.1186/s12906-022-03744-5. PMID: 36209091; PMCID: PMC9548209.
9. Sepahi S, Golfakhrabadi M, Bonakdaran S, Lotfi H, Mohajeri SA. Effect of crocin on diabetic patients: A placebo-controlled, triple-blinded clinical trial. Clin Nutr ESPEN. 2022 Aug;50:255-263. doi: 10.1016/j.clnesp.2022.05.006. Epub 2022 May 18. PMID: 35871933.
10. Lopresti AL, Smith SJ. An examination into the mental and physical effects of a saffron extract (affron®) in recreationally-active adults: A randomized, double-blind, placebo-controlled study. J Int Soc Sports Nutr. 2022 Jun 7;19(1):219-238. doi: 10.1080/15502783.2022.2083455. PMID: 35813851; PMCID: PMC9261746.
11. Mojtahedi S, Hooshmand-Moghadam B, Rosenkranz S, Shourideh Z, Amirshaghaghi F, Shabkhiz F. Improvement of inflammatory status following saffron (Crocus sativus L.) and resistance training in elderly hypertensive men: A randomized controlled trial. Exp Gerontol. 2022 Jun 1;162:111756. doi: 10.1016/j.exger.2022.111756. Epub 2022 Feb 27. PMID: 35235859.
12. Hooshmand Moghadam B, Rashidlamir A, Attarzadeh Hosseini SR, Gaeini AA, Kaviani M. The effects of saffron (Crocus sativus L.) in conjunction with concurrent training on body composition, glycaemic status, and inflammatory markers in obese men with type 2 diabetes mellitus: A randomized double-blind clinical trial. Br J Clin Pharmacol. 2022 Jul;88(7):3256-3271. doi: 10.1111/bcp.15222. Epub 2022 Feb 18. PMID: 35001410.
13.  Tajaddini A, Roshanravan N, Mobasseri M, Aeinehchi A, Sefid-Mooye Azar P, Hadi A, Ostadrahimi A. Saffron improves life and sleep quality, glycaemic status, lipid profile and liver function in diabetic patients: A double-blind, placebo-controlled, randomised clinical trial. Int J Clin Pract. 2021 Aug;75(8):e14334. doi: 10.1111/ijcp.14334. Epub 2021 May 26. PMID: 33960081.
14. Pachikian BD, Copine S, Suchareau M, Deldicque L. Effects of Saffron Extract on Sleep Quality: A Randomized Double-Blind Controlled Clinical Trial. Nutrients. 2021 Apr 27;13(5):1473. doi: 10.3390/nu13051473. PMID: 33925432; PMCID: PMC8145009.
15. Behrouz V, Sohrab G, Hedayati M, Sedaghat M. Inflammatory markers response to crocin supplementation in patients with type 2 diabetes mellitus: A randomized controlled trial. Phytother Res. 2021 Jul;35(7):4022-4031. doi: 10.1002/ptr.7124. Epub 2021 Apr 15. PMID: 33856733. 
16. Kazemi F, Vosough I, Sepahi S, Mohajeri SA. Effect of crocin versus fluoxetine in treatment of mild to moderate obsessive-compulsive disorder: A double blind randomized clinical trial. Hum Psychopharmacol. 2021 Jul;36(4):e2780. doi: 10.1002/hup.2780. Epub 2021 Feb 18. PMID: 33599345.
17. Moghadam BH, Bagheri R, Roozbeh B, Ashtary-Larky D, Gaeini AA, Dutheil F, Wong A. Impact of saffron (Crocus Sativus Linn) supplementation and resistance training on markers implicated in depression and happiness levels in untrained young males. Physiol Behav. 2021 May 1;233:113352. doi: 10.1016/j.physbeh.2021.113352. Epub 2021 Feb 6. PMID: 33556410.
18. Hooshmand-Moghadam B, Eskandari M, Shabkhiz F, Mojtahedi S, Mahmoudi N. Saffron (Crocus sativus L.) in combination with resistance training reduced blood pressure in the elderly hypertensive men: A randomized controlled trial. Br J Clin Pharmacol. 2021 Aug;87(8):3255-3267. doi: 10.1111/bcp.14746. Epub 2021 Feb 21. PMID: 33496985.
19. Gudarzi S, Jafari M, Pirzad Jahromi G, Eshrati R, Asadollahi M, Nikdokht P. Evaluation of modulatory effects of saffron (Crocus sativus L.) aqueous extract on oxidative stress in ischemic stroke patients: a randomized clinical trial. Nutr Neurosci. 2022 Jun;25(6):1137-1146. doi: 10.1080/1028415X.2020.1840118. Epub 2020 Nov 5. PMID: 33151132.
20. Abbaszadeh-Mashkani S, Hoque SS, Banafshe HR, Ghaderi A. The effect of crocin (the main active saffron constituent) on the cognitive functions, craving, and withdrawal syndrome in opioid patients under methadone maintenance treatment. Phytother Res. 2021 Mar;35(3):1486-1494. doi: 10.1002/ptr.6913. Epub 2020 Oct 19. PMID: 33078480.
21. Abbaszadeh-Mashkani S, Hoque SS, Banafshe HR, Ghaderi A. The effect of crocin (the main active saffron constituent) on the cognitive functions, craving, and withdrawal syndrome in opioid patients under methadone maintenance treatment. Phytother Res. 2021 Mar;35(3):1486-1494. doi: 10.1002/ptr.6913. Epub 2020 Oct 19. PMID: 33078480.
22. Ghasemi Sakha F, Azimi Saeen A, Moazzeni SM, Etesam F, Vaezi G. A Randomized, Triple-blind Placebo-controlled Trial to Determine the Effect of Saffron on the Serum Levels of MMP-9 and TIMP-1 in Patients with Multiple Sclerosis. Iran J Allergy Asthma Immunol. 2020 Jun 23;19(3):297-304. doi: 10.18502/ijaai.v19i3.3457. PMID: 32615663.
23. Mobasseri M, Ostadrahimi A, Tajaddini A, Asghari S, Barati M, Akbarzadeh M, Nikpayam O, Houshyar J, Roshanravan N, Alamdari NM. Effects of saffron supplementation on glycemia and inflammation in patients with type 2 diabetes mellitus: A randomized double-blind, placebo-controlled clinical trial study. Diabetes Metab Syndr. 2020 Jul-Aug;14(4):527-534. doi: 10.1016/j.dsx.2020.04.031. Epub 2020 Apr 29. PMID: 32408117.
24. Lopresti AL, Smith SJ, Metse AP, Drummond PD. Effects of saffron on sleep quality in healthy adults with self-reported poor sleep: a randomized, double-blind, placebo-controlled trial. J Clin Sleep Med. 2020 Jun 15;16(6):937-947. doi: 10.5664/jcsm.8376. PMID: 32056539; PMCID: PMC7849671.
25. Hamidi Z, Aryaeian N, Abolghasemi J, Shirani F, Hadidi M, Fallah S, Moradi N. The effect of saffron supplement on clinical outcomes and metabolic profiles in patients with active rheumatoid arthritis: A randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2020 Jul;34(7):1650-1658. doi: 10.1002/ptr.6633. Epub 2020 Feb 11. PMID: 32048365.
26. Abedimanesh N, Motlagh B, Abedimanesh S, Bathaie SZ, Separham A, Ostadrahimi A. Effects of crocin and saffron aqueous extract on gene expression of SIRT1, AMPK, LOX1, NF-κB, and MCP-1 in patients with coronary artery disease: A randomized placebo-controlled clinical trial. Phytother Res. 2020 May;34(5):1114-1122. doi: 10.1002/ptr.6580. Epub 2019 Dec 3. PMID: 31797473.
27. Karimi-Nazari E, Nadjarzadeh A, Masoumi R, Marzban A, Mohajeri SA, Ramezani-Jolfaie N, Salehi-Abargouei A. Effect of saffron (Crocus sativus L.) on lipid profile, glycemic indices and antioxidant status among overweight/obese prediabetic individuals: A double-blinded, randomized controlled trial. Clin Nutr ESPEN. 2019 Dec;34:130-136. doi: 10.1016/j.clnesp.2019.07.012. Epub 2019 Aug 16. PMID: 31677703.
28. Ahmadpanah M, Ramezanshams F, Ghaleiha A, Akhondzadeh S, Sadeghi Bahmani D, Brand S. Crocus Sativus L. (saffron) versus sertraline on symptoms of depression among older people with major depressive disorders-a double-blind, randomized intervention study. Psychiatry Res. 2019 Dec;282:112613. doi: 10.1016/j.psychres.2019.112613. Epub 2019 Oct 12. PMID: 31669837.
29. Ghiasian M, Khamisabadi F, Kheiripour N, Karami M, Haddadi R, Ghaleiha A, Taghvaei B, Oliaie SS, Salehi M, Samadi P, Ranjbar A. Effects of crocin in reducing DNA damage, inflammation, and oxidative stress in multiple sclerosis patients: A double-blind, randomized, and placebo-controlled trial. J Biochem Mol Toxicol. 2019 Dec;33(12):e22410. doi: 10.1002/jbt.22410. Epub 2019 Oct 16. PMID: 31617649.
30. Moravej Aleali A, Amani R, Shahbazian H, Namjooyan F, Latifi SM, Cheraghian B. The effect of hydroalcoholic Saffron (Crocus sativus L.) extract on fasting plasma glucose, HbA1c, lipid profile, liver, and renal function tests in patients with type 2 diabetes mellitus: A randomized double-blind clinical trial. Phytother Res. 2019 Jun;33(6):1648-1657. doi: 10.1002/ptr.6351. Epub 2019 Apr 3. PMID: 30942510.
31. Asadollahi M, Nikdokht P, Hatef B, Sadr SS, Sahraei H, Assarzadegan F, Pirzad Jahromi G. Protective properties of the aqueous extract of saffron (Crocus sativus L.) in ischemic stroke, randomized clinical trial. J Ethnopharmacol. 2019 Jun 28;238:111833. doi: 10.1016/j.jep.2019.111833. Epub 2019 Mar 23. PMID: 30914350.
32. Zilaee M, Hosseini SA, Jafarirad S, Abolnezhadian F, Cheraghian B, Namjoyan F, Ghadiri A. An evaluation of the effects of saffron supplementation on the asthma clinical symptoms and asthma severity in patients with mild and moderate persistent allergic asthma: a double-blind, randomized placebo-controlled trial. Respir Res. 2019 Feb 22;20(1):39. doi: 10.1186/s12931-019-0998-x. PMID: 30795753; PMCID: PMC6387530.
33. Baziar S, Aqamolaei A, Khadem E, Mortazavi SH, Naderi S, Sahebolzamani E, Mortezaei A, Jalilevand S, Mohammadi MR, Shahmirzadi M, Akhondzadeh S. Crocus sativus L. Versus Methylphenidate in Treatment of Children with Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind Pilot Study. J Child Adolesc Psychopharmacol. 2019 Apr;29(3):205-212. doi: 10.1089/cap.2018.0146. Epub 2019 Feb 11. PMID: 30741567.
34. Hosseini SA, Zilaee M, Shoushtari MH, Ghasemi Dehcheshmeh M. An evaluation of the effect of saffron supplementation on the antibody titer to heat-shock protein (HSP) 70, hsCRP and spirometry test in patients with mild and moderate persistent allergic asthma: A triple-blind, randomized placebo-controlled trial. Respir Med. 2018 Dec;145:28-34. doi: 10.1016/j.rmed.2018.10.016. Epub 2018 Oct 19. PMID: 30509713.
35. Umigai N, Takeda R, Mori A. Effect of crocetin on quality of sleep: A randomized, double-blind, placebo-controlled, crossover study. Complement Ther Med. 2018 Dec;41:47-51. doi: 10.1016/j.ctim.2018.09.003. Epub 2018 Sep 8. PMID: 30477864.
36. Broadhead GK, Grigg JR, McCluskey P, Hong T, Schlub TE, Chang AA. Saffron therapy for the treatment of mild/moderate age-related macular degeneration: a randomised clinical trial. Graefes Arch Clin Exp Ophthalmol. 2019 Jan;257(1):31-40. doi: 10.1007/s00417-018-4163-x. Epub 2018 Oct 20. PMID: 30343354.
37. Jalali F, Hashemi SF. The Effect of Saffron on Depression among Recovered Consumers of Methamphetamine Living with HIV/AIDS. Subst Use Misuse. 2018 Oct 15;53(12):1951-1957. doi: 10.1080/10826084.2018.1447583. Epub 2018 Mar 15. PMID: 29543538.
38. Lopresti AL, Drummond PD, Inarejos-García AM, Prodanov M. affron®, a standardised extract from saffron (Crocus sativus L.) for the treatment of youth anxiety and depressive symptoms: A randomised, double-blind, placebo-controlled study. J Affect Disord. 2018 May;232:349-357. doi: 10.1016/j.jad.2018.02.070. Epub 2018 Feb 26. PMID: 29510352.
39. Kashani L, Esalatmanesh S, Eftekhari F, Salimi S, Foroughifar T, Etesam F, Safiaghdam H, Moazen-Zadeh E, Akhondzadeh S. Efficacy of Crocus sativus (saffron) in treatment of major depressive disorder associated with post-menopausal hot flashes: a double-blind, randomized, placebo-controlled trial. Arch Gynecol Obstet. 2018 Mar;297(3):717-724. doi: 10.1007/s00404-018-4655-2. Epub 2018 Jan 13. PMID: 29332222.
40. Cicero AF, Bove M, Colletti A, Rizzo M, Fogacci F, Giovannini M, Borghi C. Short-Term Impact of a Combined Nutraceutical on Cognitive Function, Perceived Stress and Depression in Young Elderly with Cognitive Impairment: A Pilot, Double-Blind, Randomized Clinical Trial. J Prev Alzheimers Dis. 2017;4(1):12-15. doi: 10.14283/jpad.2016.10. PMID: 29188854.
41. Tabeshpour J, Sobhani F, Sadjadi SA, Hosseinzadeh H, Mohajeri SA, Rajabi O, Taherzadeh Z, Eslami S. A double-blind, randomized, placebo-controlled trial of saffron stigma (Crocus sativus L.) in mothers suffering from mild-to-moderate postpartum depression. Phytomedicine. 2017 Dec 1;36:145-152. doi: 10.1016/j.phymed.2017.10.005. Epub 2017 Oct 7. PMID: 29157808.
42. Jam IN, Sahebkar AH, Eslami S, Mokhber N, Nosrati M, Khademi M, Foroutan-Tanha M, Ghayour-Mobarhan M, Hadizadeh F, Ferns G, Abbasi M. The effects of crocin on the symptoms of depression in subjects with metabolic syndrome. Adv Clin Exp Med. 2017 Sep;26(6):925-930. doi: 10.17219/acem/62891. PMID: 29068592.
43. Kell G, Rao A, Beccaria G, Clayton P, Inarejos-García AM, Prodanov M. affron® a novel saffron extract (Crocus sativus L.) improves mood in healthy adults over 4 weeks in a double-blind, parallel, randomized, placebo-controlled clinical trial. Complement Ther Med. 2017 Aug;33:58-64. doi: 10.1016/j.ctim.2017.06.001. Epub 2017 Jun 13. PMID: 28735826.
44. Kermani T, Zebarjadi M, Mehrad-Majd H, Mirhafez SR, Shemshian M, Ghasemi F, Mohammadzadeh E, Mousavi SH, Norouzy A, Moghiman T, Sadeghi A, Ferns G, Avan A, Mahdipour E, Ghayour-Mobarhan M. Anti-Inflammatory Effect of Crocus sativus on Serum Cytokine Levels in Subjects with Metabolic Syndrome: A Randomized, Double-Blind, Placebo- Controlled Trial. Curr Clin Pharmacol. 2017;12(2):122-126. doi: 10.2174/1574884712666170622082737. PMID: 28637418.
45. Lopresti AL, Drummond PD. Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study. J Affect Disord. 2017 Jan 1;207:188-196. doi: 10.1016/j.jad.2016.09.047. Epub 2016 Oct 1. PMID: 27723543.
46. Ghajar A, Neishabouri SM, Velayati N, Jahangard L, Matinnia N, Haghighi M, Ghaleiha A, Afarideh M, Salimi S, Meysamie A, Akhondzadeh S. Crocus sativus L. versus Citalopram in the Treatment of Major Depressive Disorder with Anxious Distress: A Double-Blind, Controlled Clinical Trial. Pharmacopsychiatry. 2017 Jul;50(4):152-160. doi: 10.1055/s-0042-116159. Epub 2016 Oct 4. PMID: 27701683.
47. Kashani L, Eslatmanesh S, Saedi N, Niroomand N, Ebrahimi M, Hosseinian M, Foroughifar T, Salimi S, Akhondzadeh S. Comparison of Saffron versus Fluoxetine in Treatment of Mild to Moderate Postpartum Depression: A Double-Blind, Randomized Clinical Trial. Pharmacopsychiatry. 2017 Mar;50(2):64-68. doi: 10.1055/s-0042-115306. Epub 2016 Sep 5. PMID: 27595298.
48. Tsolaki M, Karathanasi E, Lazarou I, Dovas K, Verykouki E, Karacostas A, Georgiadis K, Tsolaki A, Adam K, Kompatsiaris I, Sinakos Z. Efficacy and Safety of Crocus sativus L. in Patients with Mild Cognitive Impairment: One Year Single-Blind Randomized, with Parallel Groups, Clinical Trial. J Alzheimers Dis. 2016 Jul 27;54(1):129-33. doi: 10.3233/JAD-160304. PMID: 27472878.
49. Mazidi M, Shemshian M, Mousavi SH, Norouzy A, Kermani T, Moghiman T, Sadeghi A, Mokhber N, Ghayour-Mobarhan M, Ferns GA. A double-blind, randomized and placebo-controlled trial of Saffron (Crocus sativus L.) in the treatment of anxiety and depression. J Complement Integr Med. 2016 Jun 1;13(2):195-9. doi: 10.1515/jcim-2015-0043. PMID: 27101556.
50. Meamarbashi A, Rajabi A. Potential Ergogenic Effects of Saffron. J Diet Suppl. 2016;13(5):522-9. doi: 10.3109/19390211.2015.1120259. Epub 2016 Jan 25. PMID: 26811090.
51. Steiner GZ, Yeung A, Liu JX, Camfield DA, Blasio FM, Pipingas A, Scholey AB, Stough C, Chang DH. The effect of Sailuotong (SLT) on neurocognitive and cardiovascular function in healthy adults: a randomised, double-blind, placebo controlled crossover pilot trial. BMC Complement Altern Med. 2016 Jan 13;16:15. doi: 10.1186/s12906-016-0989-0. PMID: 26762282; PMCID: PMC4712609.
52. Azimi P, Ghiasvand R, Feizi A, Hosseinzadeh J, Bahreynian M, Hariri M, Khosravi-Boroujeni H. Effect of cinnamon, cardamom, saffron and ginger consumption on blood pressure and a marker of endothelial function in patients with type 2 diabetes mellitus: A randomized controlled clinical trial. Blood Press. 2016 Jun;25(3):133-40. doi: 10.3109/08037051.2015.1111020. Epub 2016 Jan 12. PMID: 26758574.
53. Sahraian A, Jelodar S, Javid Z, Mowla A, Ahmadzadeh L. Study the effects of saffron on depression and lipid profiles: A double blind comparative study. Asian J Psychiatr. 2016 Aug;22:174-6. doi: 10.1016/j.ajp.2015.10.012. Epub 2015 Nov 10. PMID: 26611571.
54. Mohammadzadeh-Moghadam H, Nazari SM, Shamsa A, Kamalinejad M, Esmaeeli H, Asadpour AA, Khajavi A. Effects of a Topical Saffron (Crocus sativus L) Gel on Erectile Dysfunction in Diabetics: A Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Trial. J Evid Based Complementary Altern Med. 2015 Oct;20(4):283-6. doi: 10.1177/2156587215583756. Epub 2015 May 6. PMID: 25948674.
55.  Pasalar M, Choopani R, Mosaddegh M, Kamalinejad M, Mohagheghzadeh A, Fattahi MR, Ghanizadeh A, Bagheri Lankarani K. Efficacy and safety of jollab to treat functional dyspepsia: a randomized placebo-controlled clinical trial. Explore (NY). 2015 May-Jun;11(3):199-207. doi: 10.1016/j.explore.2015.02.007. Epub 2015 Feb 17. PMID: 25777290.
56. Talaei A, Hassanpour Moghadam M, Sajadi Tabassi SA, Mohajeri SA. Crocin, the main active saffron constituent, as an adjunctive treatment in major depressive disorder: a randomized, double-blind, placebo-controlled, pilot clinical trial. J Affect Disord. 2015 Mar 15;174:51-6. doi: 10.1016/j.jad.2014.11.035. Epub 2014 Nov 26. PMID: 25484177.
57. Farokhnia M, Shafiee Sabet M, Iranpour N, Gougol A, Yekehtaz H, Alimardani R, Farsad F, Kamalipour M, Akhondzadeh S. Comparing the efficacy and safety of Crocus sativus L. with memantine in patients with moderate to severe Alzheimer's disease: a double-blind randomized clinical trial. Hum Psychopharmacol. 2014 Jul;29(4):351-9. doi: 10.1002/hup.2412. PMID: 25163440.
58. Ayatollahi H, Javan AO, Khajedaluee M, Shahroodian M, Hosseinzadeh H. Effect of Crocus sativus L. (saffron) on coagulation and anticoagulation systems in healthy volunteers. Phytother Res. 2014 Apr;28(4):539-43. doi: 10.1002/ptr.5021. Epub 2013 Jun 3. PMID: 23733488.
59. Kashani L, Raisi F, Saroukhani S, Sohrabi H, Modabbernia A, Nasehi AA, Jamshidi A, Ashrafi M, Mansouri P, Ghaeli P, Akhondzadeh S. Saffron for treatment of fluoxetine-induced sexual dysfunction in women: randomized double-blind placebo-controlled study. Hum Psychopharmacol. 2013 Jan;28(1):54-60. doi: 10.1002/hup.2282. Epub 2012 Dec 20. PMID: 23280545.
60. Modabbernia A, Sohrabi H, Nasehi AA, Raisi F, Saroukhani S, Jamshidi A, Tabrizi M, Ashrafi M, Akhondzadeh S. Effect of saffron on fluoxetine-induced sexual impairment in men: randomized double-blind placebo-controlled trial. Psychopharmacology (Berl). 2012 Oct;223(4):381-8. doi: 10.1007/s00213-012-2729-6. Epub 2012 May 3. PMID: 22552758.
61. Fukui H, Toyoshima K, Komaki R. Psychological and neuroendocrinological effects of odor of saffron (Crocus sativus). Phytomedicine. 2011 Jun 15;18(8-9):726-30. doi: 10.1016/j.phymed.2010.11.013. Epub 2011 Jan 15. PMID: 21242071.
62. Akhondzadeh S, Sabet MS, Harirchian MH, Togha M, Cheraghmakani H, Razeghi S, Hejazi SSh, Yousefi MH, Alimardani R, Jamshidi A, Zare F, Moradi A. Saffron in the treatment of patients with mild to moderate Alzheimer's disease: a 16-week, randomized and placebo-controlled trial. J Clin Pharm Ther. 2010 Oct;35(5):581-8. doi: 10.1111/j.1365-2710.2009.01133.x. PMID: 20831681.
63. Akhondzadeh S, Shafiee Sabet M, Harirchian MH, Togha M, Cheraghmakani H, Razeghi S, Hejazi SS, Yousefi MH, Alimardani R, Jamshidi A, Rezazadeh SA, Yousefi A, Zare F, Moradi A, Vossoughi A. A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer's disease. Psychopharmacology (Berl). 2010 Jan;207(4):637-43. doi: 10.1007/s00213-009-1706-1. Epub 2009 Oct 20. PMID: 19838862.
64. Nahid K, Fariborz M, Ataolah G, Solokian S. The effect of an Iranian herbal drug on primary dysmenorrhea: a clinical controlled trial. J Midwifery Womens Health. 2009 Sep-Oct;54(5):401-404. doi: 10.1016/j.jmwh.2008.12.006. PMID: 19720342.
65. Agha-Hosseini M, Kashani L, Aleyaseen A, Ghoreishi A, Rahmanpour H, Zarrinara AR, Akhondzadeh S. Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trial. BJOG. 2008 Mar;115(4):515-9. doi: 10.1111/j.1471-0528.2007.01652.x. PMID: 18271889.
66. Akhondzadeh Basti A, Moshiri E, Noorbala AA, Jamshidi AH, Abbasi SH, Akhondzadeh S. Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Mar 30;31(2):439-42. doi: 10.1016/j.pnpbp.2006.11.010. Epub 2006 Dec 15. PMID: 17174460.
67. Moshiri E, Basti AA, Noorbala AA, Jamshidi AH, Hesameddin Abbasi S, Akhondzadeh S. Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: a double-blind, randomized and placebo-controlled trial. Phytomedicine. 2006 Nov;13(9-10):607-11. doi: 10.1016/j.phymed.2006.08.006. Epub 2006 Sep 18. PMID: 16979327.
68. Akhondzadeh S, Tahmacebi-Pour N, Noorbala AA, Amini H, Fallah-Pour H, Jamshidi AH, Khani M. Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebo-controlled trial. Phytother Res. 2005 Feb;19(2):148-51. doi: 10.1002/ptr.1647. PMID: 15852492.
69. Noorbala AA, Akhondzadeh S, Tahmacebi-Pour N, Jamshidi AH. Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot trial. J Ethnopharmacol. 2005 Feb 28;97(2):281-4. doi: 10.1016/j.jep.2004.11.004. Epub 2005 Jan 6. PMID: 15707766.