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Adv Biomed Res 2023,  12:100

Evaluation of saffron (crocus sativus L) effects on anxiety in hospitalized patients with acute coronary syndrome

1 Department of Nursing, School of Nursing and Midwifery, Kurdistan University of Medical Sciences, Kurdistan, Iran
2 Department of Cardiology, School of Medicine, Kurdistan University of Medical Sciences, Kurdistan, Iran
3 Research Center for Environmental Factors Affecting Health, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
4 School of Nursing and Midwifery, Kurdistan University of Medical Sciences, Kurdistan, Iran

Date of Submission11-Jan-2021
Date of Acceptance11-Sep-2022
Date of Web Publication27-Apr-2023

Correspondence Address:
Dr. Sholeh Shami
Department of Nursing, School of Nursing and Midwifery, Kurdistan University of Medical Sciences, Kurdistan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/abr.abr_6_21

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Background: Anxiety is a common psychiatric condition in cardio-vascular diseases. Saffron appears to have a wide range of therapeutic effects on psychiatric conditions and cardio-vascular disorders. The aim of this study was to determine the effect of saffron on anxiety in hospitalized patients with acute coronary syndrome (ACS).
Materials and Methods: In this clinical investigation, we selected 80 patients with ACS from Tohid Medical Center, Sanandaj. Patients were divided randomly into two groups, intervention group (n = 41), and control group (n = 39), based on how they received saffron and placebo every 12 hours for 4 days, respectively. The Spielberger Anxiety Inventory was completed before and after the intervention in both groups.
Results: There was no significant difference between the intervention and control groups regarding the mean scores of the trait and state anxiety before and after the intervention (P > 0.05).
Conclusion: The present study did not corroborate the therapeutic effects of saffron on reducing anxiety in patients with ACS.

Keywords: Acute coronary syndrome, anxiety, crocus sativus L., saffron

How to cite this article:
Askari F, Seidi J, Naqshbandi MK, Kashefi H, Shami S. Evaluation of saffron (crocus sativus L) effects on anxiety in hospitalized patients with acute coronary syndrome. Adv Biomed Res 2023;12:100

How to cite this URL:
Askari F, Seidi J, Naqshbandi MK, Kashefi H, Shami S. Evaluation of saffron (crocus sativus L) effects on anxiety in hospitalized patients with acute coronary syndrome. Adv Biomed Res [serial online] 2023 [cited 2023 Jun 7];12:100. Available from:

  Introduction Top

Coronary heart disease (CHD) is the leading cause of death in the world. According to the World Health Organization in 2015, CHD took the lives of 8.8 million people worldwide. Acute coronary syndrome (ACS) is a sort of CHD which address to a group of situations that include ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina.[1]

In ACS, more than one-third of the patients experience high levels of anxiety.[2] Watkins' study showed that anxiety is associated with an increased risk of death in patients with CHD, particularly if it is associated with depression.[3] Fear and anxiety increase the respiration rate, blood pressure, cardiac output, cardiac irritability, and the possibility of irregular heart rhythm.[3] Anxiety is associated with development of atherosclerosis too.[4]

Saffron is a Middle-Eastern plant belonging to the lily species, and its dried stigma is known to be the most expensive spice in the world.[5] The favorable profile of saffron in the improvement of mental disorders and cardio-vascular diseases has recently received scientific attention.[6] The benzodiazepine-like effects of saffron on the gamma-aminobutyric acid-receptor complex of benzodiazepines and opioid receptors have been recently demonstrated.[7]

There is no research regarding the effect of saffron on patients who have medically acute conditions. Therefore, this study is designed to determine the effect of saffron on anxiety in patients with ACS during hospitalization.

  Materials and Methods Top

This randomized clinical investigation is undergone on 80 patients with ACS in Tohid Hospital, Sanandaj, Iran, from October 2010 to May 2016.

Patients with ST-segment elevation confirmed by a cardiologist and over 18 years of age were included in this study. Exclusion criteria were allergies to saffron, use of anti-anxiety drugs, history of coagulopathy disorder, INR >2, pregnancy, kidney diseases, and history of psychiatric disorders.

After obtaining informed consent from participants in accordance with the revised Helsinki Declaration of 2013, patients were divided into intervention (n = 41) and control (n = 39) groups using a random number table. The study and placebo capsules were placed in vague, uniform, and uniformly sealed envelopes. Afterward, one of the random codes was assigned to each envelope. The drug was given to the patient every 12 hours for 4 days. The patients, the members of the research team who evaluated the patients, and the statistical consultant were blind to the assigned intervention and control groups.

After preparing the plant from the pharmaceutical market, 120 grams of dried saffron stigma was ground by soaking in three stages with 1800 ml of ethanol, and the extract was diluted. The ethanol extract then evaporated at 35–45°C and filled into the capsules with excipients (powders). 300 mg of bread powder was placed in the placebo and prepared in capsules of the same size and color as the drug capsules. The demographic information form and Spielberger State-Trait Anxiety Inventory (STAI) questionnaire were used to collect data prior to the intervention. The Spielberger Anxiety Questionnaire comprises two parts, namely, overt anxiety and covert anxiety, each of which contains 20 options. These options were rated on a scale of 1–4 in the range of 20–80; they further divided into three groups: mild anxiety (20–40), moderate anxiety (41–60), and severe anxiety (61–80).

The Spielberger questionnaire was completed on the second and fourth days of hospitalization. Laboratory tests including complete blood cell count, serum electrolytes, and cardiac enzymes, including lactate dehydrogenase, creatinephosphokinase, and troponin, and blood urea nitrogen, creatinine, and coagulation tests were performed every 12 hours. Baseline and daily electro-cardiograms were taken too.

During the intervention, the cardiologist was responsible for deciding whether to continue or discontinue the intervention in the event of drug side effects.


In this study, considering a 10% drop, 40 people were assigned to each group according to the study of Lopresti et al.,[8] 0.05 type error, and 70% test.

Mean and standard deviation are calculated for quantitative and frequency variables and percentage for qualitative variables. Chi-square and analysis of covariance (ANCOVA) tests used to analyze the findings.

  Results Top

Of 90 patients who were randomized to study, 80 completed the investigation and ten cases were excluded [Figure 1].
Figure 1: CONSORT flow diagram

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According to the results of Chi-square test, the two groups matched in terms of demographic variable [Table 1].
Table 1: Cognitive characteristics of study group patients

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There was no significant difference between the mean of trait anxiety before the intervention on the second day and after 4 days of the study in the two groups (p > 0.05) [Table 2].
Table 2: Comparison of changes in mean anxiety score between saffron and placebo groups

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There was a significant difference between the mean of state anxiety before the intervention and on the second day (p > 0.05). However, there was no significant difference between the mean of state anxiety on the first and fourth days. In addition, there was no significant difference between the mean of trait anxiety before the intervention with trait anxiety on the second day and the mean of trait anxiety on the second day with the fourth day of the study within the groups [Table 3].
Table 3: Comparison of anxiety at days 2 and 4 in two groups

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  Discussion Top

Based on the results of this study, saffron had no effect on mean scores of overt and covert anxiety compared with placebo on patients with ACS during hospitalization. This means that our study did not support the hypothesis of saffron anti-anxiety effects in reducing anxiety in patients with the ACS.

Moazen-Zade et al.[9] examined the effect of saffron on cognition, anxiety, and depression in 22 patients who underwent on-pump coronary artery bypass graft. They prescribed 15 mg/twice daily saffron for 12 weeks and concluded that they cannot confirm the anti-anxiety effects of saffron.[8] The result of this study is consistent with the results of our study. However, the duration of treatment is not the same.

Mazidi et al.[10] studied saffron effects on 60 patients with anxiety and depression and concluded that it has a significant impact on the treatment of anxiety and depression disorder. The differences between our results with the above-mentioned study has two aspects. First, Mazidi et al. studied about a chronic disorder instead of a state induced by intervention like our study; second, the duration of intervention was 12 weeks instead of 4 days of our study.[9]

Godarzi et al. and Basiri-Moghadam et al. compared the effects of saffron with those of diazepam on reduction anxiety before and after urological surgery[11],[12]; in their study, saffron did not reduce state anxiety, which is consistent with the results of the present study, whereas its effect on trait anxiety was significant. Differences in findings may be related to the study population. Those studies enrolled only the male population, whereas the present study considered both genders.

Shahdadi et al.[13] reported the effect of saffron on reducing anxiety and improving sleep quality in diabetic patients in an out-patient clinic, which is not consistent with the results of the present study. Differences in findings may be because of the differences in sampling method. Hospitalization in coronary care units, invasive procedures such as angiography, and the need for treatments such as percutaneous coronary intervention and coronary artery bypass grafting lead to a high level of anxiety in each patient.[14] This is because human heart is a critical organ, and the dose of saffron used in their study was higher than that of the present study. Because the effect of sedative hypnotics on the central nervous system is dose-dependent,[15] the lethal dose of saffron considered 20.7 grams per day[6]; therefore, the safety margin of saffron is high, making it possible to use higher doses.

The action mechanism of saffron in anxiety and depression in addition to its effect on the GABA receptor complex has been attributed to the modulatory effects of the hypothalamic-pituitary-adrenal axis and the inhibition of the re-absorption of monoamines and serotonin.[4] The therapeutic effects of saffron on neuro-transmitter changes in the brain may be similar to the response to drug therapy in anxiety or slow depression over 2 weeks or more.[6] Accordingly, the short duration of our study compared to most studies, which lasted for at least 6–8 weeks, led to a different outcome.[9],[10] In the present study, no significant side effects were observed, except headache, dizziness, and heaviness of the head. There were no severe side effects in the patients.

The long interval between the admission and the assignment of patients by a cardiologist, the relationship between reduced anxiety and decreased symptoms of the disease at the time of admission, and the sampling during the outbreak of coronavirus disease 2019 could be among the causes of increased anxiety and stress in patients.

  Conclusion Top

Based on our study results, acute and short-time (4 days) administration of saffron has no effects on anxiety in hospitalized patients with ACS.


This article is the result of a master's thesis related to intensive care nursing in Kurdistan University of Medical Sciences (code number IR.MUK.REC.1398.101) that also provided financial support. The researchers would like to express their gratitude and appreciation to the officials of this university, the medical staff of Tohid Hospital in Sanandaj, and the patients who kindly participated in this study.

Financial support and sponsorship

Sanandaj University of Medical Sciences, Deputy of Research and Technology of Kurdistan University of Medical Sciences, Pasdaran Boulevard, Sanandaj, Iran. Postal code: 6617713446, Tel: +98 87 3366 4653, Fax: +98 87 3366 4643. [email protected].

Conflicts of interest

There are no conflicts of interest.

  References Top

Watkins LL, Koch GG, Sherwood A, Blumenthal JA, Davidson JR, O'Connor C, et al. Association of anxiety and depression with all-cause mortality in individuals with coronary heart disease. J Am Heart Assoc 2013;2:e000068.  Back to cited text no. 1
Pitsavos C, Panagiotakos DB, Papageorgiou C, Tsetsekou E, Soldatos C, Stefanadis C. Anxiety in relation to inflammation and coagulation markers, among healthy adults: The ATTICA study. Atherosclerosis 2006;185:320-6.  Back to cited text no. 2
Halimeh A, Farhad RB, Naseh S, Karim N. Comparative efficacy of honey 12.5% and chlorhexidine 0.2% mouthwashes on the oropharyngeal bacterial colonization in mechanically-ventilated patients: A randomized controlled trial. J Tradit Chin Med 2020;40:440-6.  Back to cited text no. 3
Pitsikas N. Constituents of saffron (Crocus sativus L.) as potential candidates for the treatment of anxiety disorders and schizophrenia. Molecules 2016;21:303.  Back to cited text no. 4
Melnyk JP, Wang S, Marcone MF. Chemical and biological properties of the world's most expensive spice: Saffron. Food Res Int 2010;43:1981-9.  Back to cited text no. 5
Hosseinzadeh H, Sadeghnia H. Protective effect of safranal on pentylenetetrazol-induced seizures in the rat: Involvement of GABAergic and opioids systems. Phytomedicine 2007;14:256-62.  Back to cited text no. 6
Bostan HB, Mehri S, Hosseinzadeh H. Toxicology effects of saffron and its constituents: A review. Iran J Basic Med Sci 2017;20:110-21.  Back to cited text no. 7
Lopresti AL, Drummond PD. Saffron (Crocus sativus) for depression: A systematic review of clinical studies and examination of underlying antidepressant mechanisms of action. Hum Psych pharma 2014;29:517-27.  Back to cited text no. 8
Moazen-Zadeh E, Abbasi SH, Safi-Aghdam H, Shahmansouri N, Arjmandi-Beglar A, Hajhosseinn Talasaz A, et al. Effects of saffron on cognition, anxiety, and depression in patients undergoing coronary artery bypass grafting: A randomized double-blind placebo-controlled trial. J Altern Complement Med 2018;24:361-8.  Back to cited text no. 9
Mazidi M, Shemshian M, Mousavi SH, Norouzy A, Kermani T, Moghiman T, et al. 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;13:195-9.  Back to cited text no. 10
Godarzi N, Hamzei A, Basiri Moghadam M, Ghenaati J, Torkamani Noghabi M, Zarif Najafi P, et al. Comparing effect of safranal and diazepam in reducing preoperative anxiety and improving vital symptoms. Horizon Med Sci 2018;24:23-8.  Back to cited text no. 11
Basiri-Moghadam M, Hamzei A, Moslem A-R, Pasban-Noghabi S, Ghorbani N, Ghenaati J. Comparison of the anxiolytic effects of saffron (Crocus sativus. L) and diazepam before herniorrhaphy surgery: A double blind randomized clinical trial. Zahedan J Res Med Sci 2016;18:e6248.  Back to cited text no. 12
Shahdadi H, Balouchi A, Dehghanmehr S. Effect of saffron oral capsule on anxiety and quality of sleep of diabetic patients in a tertiary healthcare facility in southeastern Iran: A quasi-experimental study. Trop J Pharm Res 2017;16:2749-53.  Back to cited text no. 13
Nasseri K, Shahsawari S, Ziaee Z. Comparing the effects of propofol ketamine to propofol-saline on myalgia post electroconvulsive therapy. J Mazandaran Univ Med Sci 2013;23:35-40.  Back to cited text no. 14
Saki K, Bahmani M, Rafieian-Kopaei M. The effect of most important medicinal plants on two important psychiatric disorders (anxiety and depression)-A review. Asian Pac J Trop Med 2014;7:34-42.  Back to cited text no. 15


  [Figure 1]

  [Table 1], [Table 2], [Table 3]


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