Clinical Trial Finds Saffron Effective in the Treatment of Mild Depression and Anxiety in Youth

Saffron (Crocus sativus, Iridaceae) has been shown to be effective in treating mild to moderate depression and anxiety in adults. This is attributed to its antioxidant, anti-inflammatory, and possibly monoaminergic properties. Despite the body of research on its use in adults, saffron has not been studied in the treatment of depression and anxiety in youth. The authors conducted a parallel, 8-week, randomized, double-blind, placebo-controlled clinical trial to assess the effectiveness of a standardized saffron extract in youth aged 12-16 years with mild to moderate depression and anxiety.

The trial was conducted at Murdoch University; Perth, Western Australia, Australia. Subjects were recruited between March and June 2017 through social media, television, and radio announcements and assigned to either an intervention or placebo group using a randomization calculator. The trial included physically healthy, English-speaking, male and female youth between the ages of 12 and 16. Depression and anxiety symptoms were assessed using the youth and parent versions of the Revised Child Anxiety and Depression Scale (RCADS). Subjects were included if their total score on either scale or any subscale was above the 60th percentile, so long as no score was above the 90th percentile. Exclusion criteria included any other diagnosed psychiatric disorder within the past 12 months, current or planned mental health treatment, suicidal ideation or self-harm, current or past chronic illness or neurological problems, significant learning disability, and use of pharmaceutical drugs, herbal supplements, or illegal drugs. The initial screening was completed by a parent in an online questionnaire and then followed by a phone interview by the primary investigator with a parent. A final call with the youth was arranged if necessary.

The saffron was grown in Alborea, Spain, and stigmas were extracted to produce a standardized extract (affron®; supplied by Pharmactive Biotech Products SL; Madrid, Spain). Saffron tablets (prepared by Lipa Pharmaceuticals Ltd.; Minto, New South Wales, Australia) contained 14 mg of this extract. The visually identical placebo included the same nonactive ingredients as the saffron tablet (microcrystalline cellulose and calcium hydrogen phosphate). Subjects were instructed to take 1 tablet twice a day for an 8-week period. Compliance was self-reported by pill counts by parents and children at weeks 2, 4, 6, and 8.

Changes in youth scores on the RCADS were the primary outcome measures. The RCADS includes the following subscales: separation anxiety, social phobia, generalized anxiety, panic, obsessions/compulsions, and depression. Each is rated on a 0- to 4-point Likert scale. Subscales are combined to produce a Total Anxiety Scale and Total Internalizing Scale (which includes all 6 subscores). Both a youth self-report version and a parent-report version were conducted at baseline and at weeks 2, 4, 6, and 8. The authors used the youth scores as the primary outcome measure because these better correlate with other validated measures, and parent scores were used as secondary outcome measures.

Data were analyzed with independent t-test, Chi-square, and repeated measures analysis of variance using Statistical Package for the Social Sciences (SPSS) v24. The authors also compared the percentage of responders across treatment conditions, where a responder was defined as anyone who had a greater than 50% reduction in the RCADS internalizing score. Cohen’s d was used to calculate the effect size for the total and subscale scores of the RCADS.

Of the 80 subjects enrolled in the study, 68 completed the requirements for treatment, which included taking more than 80% of their tablets and completing all questionnaires. Four subjects withdrew from the saffron group, and 8 from the placebo group. Reasons for dropping out included inconsistent or refused participation, failure to complete questionnaires, worsening mental health, initiation of mental health treatment, and headaches/nausea (1 in the placebo group). There were no significant differences in demographics or questionnaire scores between the 2 groups at baseline (P>0.05 for all).

For the RCADS youth scores, there was a significant multivariate time by group interaction (P=0.049), as well as significant univariate time by group interactions for the separation anxiety (P=0.003), social phobia (P=0.023), and depression (P=0.016) subscales. There were also significant between-group differences at certain time points for generalized anxiety and obsessions/compulsions. The saffron group experienced a 33% reduction in symptoms compared to 17% in the placebo group (P=0.029). Similarly, the saffron group had a significantly higher percentage of responders than the placebo group (37% and 11%, respectively, P=0.014). Cohen’s d analysis indicated a small effect size for obsessions/compulsions and a moderate effect size for total internalizing and separation anxiety. Visually (in Figure 2), it appeared that a greater percentage of the decline in mean scores occurred in the first 2 weeks in the saffron group for all 6 subscales.

For the parent scores, there was a nonsignificant multivariate time by group interaction (P=0.749), but significant univariate between-group differences for generalized anxiety, social phobia, and obsessions/compulsions. Parental scores suggested a 40% improvement in the saffron group compared to a 26% improvement in the placebo group (P=0.026). There was no significant between-group difference in the percentage of responders (i.e., those for whom parental scores declined 50%). There was a small effect size for obsessions/compulsions and a moderate effect size for the panic subscale.

Adverse reactions were minor, and there was no significant difference in reactions between the 2 groups (P value not given). There was a greater frequency of headaches in the placebo group, and 1 subject in that group dropped out due to stomachache and nausea.

Based on the results of this clinical trial, saffron may be effective in treating the symptoms of mild to moderate depression and anxiety in youth, specifically internalizing, separation anxiety, depression, and social phobia. The authors acknowledge that, as this was the first study of its kind, further research is needed to determine the ideal dose (as higher doses have shown greater efficacy in adults) and confirm benefits in studies of longer duration. Similarly, results were based on youth self-reports and parental reports. Future trials could include other reporting mechanisms, such as clinician-rated measures, since there were, unsurprisingly, differences between self-reports and parent reports of effectiveness. (The authors laudably acknowledge that parents’ scores may reflect parental as well as youth psychological issues, and that youth exposure to saffron would not affect the parents.) Finally, the exclusion of subjects with any score above the 90th percentile or tendency to self-harm means that those in this study were not severely depressed, so efficacy for that condition in youth remains unknown.

The study was funded by Pharmactive Biotech Products SL. The company was not involved in the study design, implementation, or analysis. One of the authors (Inarejos-García) is employed by Pharmactive Biotech Products SL.


Lopresti AL, Drummond PD, Inarejos-García AM, Prodanov M. affron®, a standardized extract from saffron (Crocus sativusL.) for the treatment of youth anxiety and depressive symptoms: A randomized, double-blind, placebo-controlled study. J Affect Disord. May 2018;232:349-357. doi: 10.1016/j.jad.2018.02.070.