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    Saffron Effectiveness to Alleviate Depression Symptoms and Cortisol Level of Medical Students with Mild–Moderate Depression: A Randomized Controlled Trial

    Fhirastika Annisha Helvian1,2, Saidah Syamsuddin1★, Erlyn Limoa1, Irfan Idris3, Indrawaty Suhuyanli1, Ilhamuddin Ilhamuddin1, Sonny Teddy Lisal1★ Corresponding author

    1. 1Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia.
    2. 2School of Medicine, Universitas Islam Negeri Alauddin, Makassar, South Sulawesi, Indonesia.
    3. 3Department of Physiology, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia.

    CORRESPONDENCE

    Saidah Syamsuddin

    Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia.

    idasyam70@gmail.com

    Received: 20-08-2025; Revised: 25-09-2025; Accepted: 05-11-2025.

    Volume 17, Issue 3 · pp. 355–364 · PUBLISHED 2026 · DOI: 10.1177/0976500X251399510

    View on J Pharmacol. Pharmacother. original site ↗

    ABSTRACT

    Background: Medical students experience a heightened risk of depression and necessitate effective, low-side-effect interventions. Objectives: This study evaluates the efficacy of saffron in decreasing salivary cortisol levels and alleviating mild depressive symptoms in medical students. Materials and Methods: A randomized controlled trial (RCT) was conducted with eligible undergraduate medical students. Participants were assigned to either the intervention group, which received saffron tablets, or the placebo group for an 8-week duration. Depressive symptoms were assessed using the Hamilton Depression Rating Scale (HDRS), while salivary cortisol levels were measured via enzyme-linked immunosorbent assay (ELISA). Measurements were taken at baseline, week 4, and week 8. Results: Among 56 participants (28 in each group), the saffron group exhibited significantly lower HDRS scores compared to the placebo group at week 8 (10.5 vs. 18; p < .001), alongside a notable downward trend (p < .001). No significant differences in HDRS were observed at week 4 (p = .302). Salivary cortisol levels did not show significant differences between groups (p > .05), although the saffron group exhibited a decreasing trend while the placebo group showed an increasing trend. Conclusion: Saffron demonstrates efficacy in reducing mild to moderate depressive symptoms among medical students, although it does not lead to significant changes in salivary cortisol levels.

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      Helvian, F. A., Syamsuddin, S., Limoa, E., Idris, I., Suhuyanli, I., Ilhamuddin, I., & Lisal, S. T. (2026). Saffron Effectiveness to Alleviate Depression Symptoms and Cortisol Level of Medical Students with Mild–Moderate Depression: A Randomized Controlled Trial. Journal of Pharmacology and Pharmacotherapeutics, 17(3), 355–364. https://doi.org/10.1177/0976500X251399510