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Crocin from Saffron Found to Be Effective for Obsessive Compulsive Disorder


Reviewed: 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 Clin Exp. February 2021;36(4):e2780. doi:10.1002/hup.2780.

Obsessive-compulsive disorder (OCD) is a condition defined by recurrent, intrusive, and unwanted thoughts and repetitive behaviors. It is a chronic and heterogeneous disorder that affects 1-2% of the general population and 1-3% of adolescents and children. Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmaceutical treatment. However, SSRIs are not effective in all patients and may provide only temporary relief from symptoms.

Saffron (Crocus sativus, Iridaceae) stigmas have been used traditionally for a variety of purposes, including as an antispasmodic, calmative, expectorant, and emmenagogue (menstruation stimulant). Pharmacological research on saffron has shown it to have positive effects for sleep-quality improvement and as an antidepressant, antitumor, anticonvulsant, and anti-inflammatory agent. It has also been reported to improve memory and learning. Crocin, a water-soluble carotenoid pigment found in saffron, is thought to be responsible for many of the plant’s reported health effects, and it has been shown to have anti-inflammatory, antioxidant, cardioprotective, neuroprotective, and antidepressant properties. The authors of the reviewed study conducted an eight-week double-blind, randomized clinical trial to evaluate the effects of crocin on patients with mild-to-moderate OCD compared to fluoxetine, an SSRI.

The study took place between July 2018 and September 2019 at a psychiatric clinic in Mashhad, Iran. Included patients were 18-60 years old with diagnosed OCD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Patients had a score of 12-25 on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS; indicating mild or moderate OCD) and did not receive any psychiatric medication during the six weeks before the trial. Researchers excluded individuals with any other psychiatric disorder, alcohol or other substance addiction, or “sensitivity to medications.” Individuals who were breast feeding, pregnant, or had any significant medical illness that could prevent the patient from finishing the trial were also excluded.

Saffron stigmas were obtained from the Saharkhiz Saffron Company (Mashhad, Iran). Crystallization and extraction were performed at the BuAli Research Institute of Mashhad University of Medical Sciences (MUMS). The resulting saffron extract contained more than 90% crocin. Researchers in the Industrial Pharmacy Lab at MUMS prepared 15 mg capsules of crocin powder with microcrystalline cellulose powder as a filler. A 20 mg fluoxetine capsule similar in shape and size was used as a positive control. Both groups received one capsule daily for the first four weeks of the study, then were instructed to take two capsules daily during the last four weeks. It was not stated if the capsules were taken in the morning or evening. The authors asked patients not to take any other psychiatric medication or behavioral therapy during the trial.

OCD symptoms were assessed using the Y-BOCS and Hamilton Anxiety Rating Scale (HAM-A) at baseline, week 4, and week 8. Patients were telephoned weekly to assess symptoms, adverse effects, and compliance.

Of the 58 patients included, eight discontinued the study. Five individuals discontinued treatment in the crocin group due to adverse effects (n = 2), sensitivity to the medication (n = 1), or withdrawn consent (n = 2). In the fluoxetine group, three participants discontinued treatment due to adverse effects (n = 1) or withdrawn consent (n = 2). The mean age was 32.8 ± 8.6 in the crocin group (with 76% women) and 27.8 ± 7.1 in the fluoxetine group (with 80% women).

Both groups saw significant improvements in Y-BOCS scores at week 4 (P = 0.001 for both) and week 8 (P = 0.0001 for both) compared to baseline. Both groups also saw significant improvements from baseline in HAM-A scores at week 4 (P = 0.163 and P = 0.01, respectively) and week 8 (P = 0.01 and P = 0.008, respectively). There was no significant difference between the crocin and fluoxetine groups at week 8 for Y-BOCS and HAM-A scores. The number of patients with moderate OCD in the crocin group decreased from 52% to 12% at week 8.

There were 16 reported adverse events in the fluoxetine group and seven in the crocin group. The fluoxetine group reported gastrointestinal problems (n = 5), drowsiness (n = 7), change in weight (n = 2), chest pain (n = 1), and dry mouth (n = 1). The crocin group reported sweating (n = 2), menorrhagia (heavy or prolonged menstrual bleeding; n = 3), allergy (n = 1), and hair loss (n = 1).

The daily dose of crocin used in this clinical trial is much higher than that which is usually evaluated. Saffron extracts that provide about 1 mg of crocins daily typically are used in human clinical trials, compared to the daily dose of 15 to 30 mg of crocins used in this study. This may explain the series of adverse effects found in the crocin group, most of which are not normally found in patients using saffron extracts. Previous studies have found beneficial effects for OCD, mood, anxiety, and depression using lower doses of crocins from saffron extracts.

The authors concluded that crocin is effective in treating OCD with fewer observed side effects than fluoxetine. Study limitations include the small population size, OCD heterogeneity, reliance on self-report assessments, treatment compliance issues, short study timeframe, and lack of a placebo group. Further research on the mechanisms of action and a larger trial with a placebo group should be conducted.