The antidepressant potential of saffron (Crocus sativus L.): molecular mechanisms, neurotransmitter modulation, gut-brain axis interactions, and clinical efficacy in major depressive disorder

Abstract

Depression, a prevalent and debilitating mental health disorder, affects approximately 280 million people worldwide, according to the World Health Organization (WHO). It is estimated that 5 of adults, including 4 of men and 6 of women, experience depression, with the prevalence increasing to 5.7 in individuals over 60 years old. Despite the availability of pharmacological treatments, many individuals experience insufficient relief or adverse side effects, highlighting the need for alternative therapies. This review comprehensively examines the current scientific evidence on the mechanisms by which saffron (Crocus sativus L.) and its bioactive compounds-crocin, crocetin, and safranal-exert antidepressant effects. Key mechanisms include the modulation of neurotransmitter systems, anti-inflammatory properties, antioxidant activities, and the regulation of neurotrophic factors. Additionally, saffron’s impact on epigenetic modulation and gut-brain axis interactions are explored. Clinical studies supporting the efficacy of saffron in alleviating depressive symptoms are discussed, along with considerations for dosage, safety, and future research directions. This review aims to provide a thorough understanding of saffron’s potential as a natural antidepressant and its mechanisms of action, contributing to the growing body of literature on alternative treatments for depression. © The Author(s), under exclusive licence to Springer Nature B.V. 2025.