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.


Objective: Herbal remedies play an important role in treatment of psychiatric disorders. The aim of this study was to assess the efficacy of crocin, the main active constituent of saffron, as an adjunctive treatment in major depressive disorder (MDD).

Method: This study was a randomized, double-blind, placebo-controlled, pilot clinical trial. It was carried out during 4 weeks in two groups (placebo and treatment) on 40 MDD patients between 24 and 50 years old in Ibn-e-Sina psychiatric hospital, Mashhad, Iran, from March 2013 to December 2013. The crocin group (n=20) was given one selective serotonin reuptake inhibitor (SSRI) drug (fluoxetine 20mg/day or sertraline 50mg/day or citalopram 20mg/day) plus crocin tablets (30mg/day; 15mg BID) and placebo group (n=20) was administered one SSRI (fluoxetine 20mg/day or sertraline 50mg/day or citalopram 20mg/day) plus placebo (two placebo tablets per day) for 4 weeks. Both groups filled beck depression inventory (BDI), beck anxiety inventory (BAI), general health questionnaire (GHQ), the mood disorder questionnaire (MDQ), side effect evaluation questionnaire, and demographic questionnaire before and after one month intervention.

Results: The crocin group showed significantly improved scores on BDI, BAI and GHQ compared to placebo group (Pvalue<0.0001). The averages of decrease in BDI, BAI and GHQ scores in placebo group were 6.15, 2.6 and 10.3 respectively, whereas the values in crocin group were 17.6, 12.7 and 17.2 after 4 weeks trial.

Limitations: Poor patient compliance with medications and short trial period, small sample size and self-report assessments were the major limitations of this study.

Conclusion: These results demonstrated the effect of crocin in depression and could be administered in treatment of MDD patients.

Keywords: Crocin; Herbal medicine; Major depressive disorder; Saffron (Crocus sativus L.).

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carotenoids / therapeutic use*
  • Citalopram / administration & dosage
  • Crocus*
  • Depressive Disorder, Major / drug therapy*
  • Double-Blind Method
  • Female
  • Fluoxetine / administration & dosage
  • Humans
  • Iran
  • Male
  • Middle Aged
  • Phytotherapy / methods*
  • Pilot Projects
  • Psychiatric Status Rating Scales
  • Serotonin Uptake Inhibitors / administration & dosage*
  • Serotonin Uptake Inhibitors / adverse effects
  • Sertraline / administration & dosage
  • Treatment Outcome


  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Citalopram
  • Carotenoids
  • crocin
  • Sertraline