Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: A double-blind, randomized and placebo-controlled trial
Introduction
Depression, which is thought to result from biochemical changes in the brain, is a common disease of adulthood (Judd, 1995; Donoghue and Tylee, 1996; De Smet and Nolen, 1996; Demyttenaere, 1997). This affective disorder afflicts about 5% of the adult population in the USA at any specific time (Judd, 1995). The optimal goals during the treatment of depression are to maximize efficacy and minimize the adverse events during acute, continuation and maintenance phases (Richelson, 1994). Although there are many products used for the treatment of depression, including MAOIs, TCAs and SSRIs, most of these drugs produce several adverse reactions, such as anticholinergic effects, orthostatic hypotension, arrhythmias and sexual dysfunction (Demyttenaere, 1997; MacDonald, 1997). Thus, there is a need for more effective and less toxic agents (Richelson, 1994). Plants extracts are some of the most attractive sources of new drugs and have been shown to produce promising results for the treatment of depression (De Smet and Nolen, 1996; Ernst, 1995).
Saffron is the world's most expensive spice and apart from its traditional value as a food additive, recent studies indicate its potential as an anticancer agent and memory enhancer (Rios et al., 1996; Abe and Saito, 2000; Abdullaev, 2002). The value of saffron (dried stigmas of Crocus sativus L.) is determined by the existence of three main secondary metabolites: crocin and its derivatives which are responsible for color; picrocrocin, responsible for taste; and safranal responsible for odor. Indeed, saffron contains in excess of 150 volatile and aroma-yielding compounds. It also has many non-volatile active components, many of which are carotenoids, including zeaxanthin, lycopene, β-carotenes and polysaccharides. However, saffron's golden yellow orange color is primarily the result of α-crocin (Rios et al., 1996; Abe and Saito, 2000; Abdullaev, 2002). This plant belongs to the Iridaceae family and as a therapeutic plant, saffron is considered an excellent aid for stomach ailments and an antispasmodic, helps digestion and increases appetite. It has been reported that C. sativus has antiinflammatory, anticancer, antioxidant and antiplatelet effects. Moreover, according to Commission E, C. sativus, is applicable for treatment of nervous disorders, spasms and asthma (Rios et al., 1996; Abe and Saito, 2000; Abdullaev, 2002). It also relieves renal colic, reduces stomach ache and relieves tension (Rios et al., 1996; Hosseinzadeh and Younesi, 2002). Quantities of 10 g or more can cause an abortion and the lethal dose in human is 20 g. Saffron is used for depression in Persian traditional medicine (Hosseinzadeh and Younesi, 2002; Karimi et al., 2001; Akhondzadeh et al., 2004; Noorbala et al., 2005). Indeed, it is a Persian herb with a history as long as the Persian Empire itself. Iran, the world's largest producer of saffron has been investing in research into saffron's potential medicinal uses. Much of the work surrounds its traditional application for alleviating depression (Karimi et al., 2001; Akhondzadeh et al., 2004, Akhondzadeh et al., 2005; Noorbala et al., 2005). The clinical findings suggest that saffron is a safe and effective antidepressant. For example, in a randomized, double-blind study, 30 mg of saffron (stigma of C. sativus) extract (in capsules) given for 6 weeks resulted in significant alleviation of depression compared to those on placebo, and did so without evident side effects (Akhondzadeh et al., 2005). This study was a follow-up to a preliminary trial in which the same saffron preparation performed as well as imipramine for treating depression in a double-blind trial (Akhondzadeh et al., 2004). In further preliminary work, saffron was compared to the drug fluoxetine; it was found that saffron performed as well as the drug in the treatment of depression (Noorbala et al., 2005). In addition, in a recent pre-clinical study, it has been reported that petal of C. sativus, the part of this herb that is very cheap compared to stigma of C. sativus (saffron), has antidepressant effect (Karimi et al., 2001). Our objective was to assess the efficacy of petal of C. sativus in the treatment of mild-to-moderate depression in a 6-week double-blind, placebo-controlled and randomized trial.
Section snippets
Methods
This was a 6-week randomized and double-blind clinical trial. The trial was conducted in the outpatient clinic of Roozbeh Psychiatric between July 2004 and March 2006.
Results
No significant differences were identified between patients randomly assigned to groups 1 or 2 conditions with regard to basic demographic data including age and gender (Table 1). Thirty-six patients completed the trial. In the C. sativus and placebo group, the number of dropouts were 1 and 3, respectively. Although the number of dropouts in the placebo group was higher than the saffron group, no significant difference was observed in the two groups in terms of dropout ().
Discussion
Mental illness imposes a tremendous burden on the Western world. Mental disorders can strike early in life, and they are increasing in incidence in an aging population experiencing neurodegenerative diseases (Judd, 1995). The search for new and more effective therapeutic agents includes the study of plants used in traditional medicine systems to treat mental disorders (Richelson, 1994). After decades of predominant reliance on synthetic antidepressants, the treatment of mildly and moderately
Acknowledgment
This study was supported by a grant from Tehran University of Medical Sciences to Dr. Shahin Akhondzadeh.
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