Withanolides are a group of naturally occurring steroidal lactones found primarily in the Withania somnifera plant, also known as Ashwagandha. The use of Withanolide-containing extracts for mood and stress support originates from traditional Ayurvedic medicine, where Ashwagandha is considered an adaptogen. In recent years, scientific interest has focused on the potential of Withanolides to influence neurotransmitter systems, including serotonin.

Preclinical studies suggest that Ashwagandha extracts and isolated Withanolides may modulate serotonin receptors and increase serotonin levels in the brain, potentially contributing to anxiolytic and antidepressant-like effects in animal models (Bhattacharya et al., 2000; Choudhary et al., 2013). Human clinical trials are limited but indicate possible benefits for anxiety and stress reduction, which may be mediated through effects on the serotonin system (Lopresti et al., 2019). However, direct evidence linking Withanolides to serotonin modulation in humans is sparse, and most studies use whole-plant extracts rather than isolated Withanolides.

In summary, while there is some scientific rationale and preliminary evidence supporting the use of Withanolides for serotonin-related functions, the overall quality of evidence remains modest (rating 2/5), and more robust human studies are needed to confirm these effects.