Ashwagandha as an Evidence-Based Adaptogen: Bridging Clinical and Preclinical Insights for Stress and Anxiety Management

Abstract

Background: Withania somnifera (L.) Dunal (Ashwagandha) is an Ayurvedic Rasayana traditionally used for stress and anxiety. Clinical trials report symptomatic benefits, while preclinical studies suggest mechanisms including HPA-axis modulation and anti-inflammatory effects. Objective: To systematically compare clinical efficacy, safety, and mechanistic preclinical evidence for Ashwagandha in stress and anxiety. Methods: We searched PubMed, Scopus, Web of Science, Cochrane CENTRAL, Clinical Trial Registry of India and Google Scholar (first 200 results) from database inception to [insert last search date] for randomized controlled trials (RCTs) and preclinical studies assessing Ashwagandha’s anxiolytic or anti-stress effects. Two reviewers independently screened studies and extracted data following PRISMA 2020. Risk of bias was assessed using Cochrane RoB 2.0 (clinical) and SYRCLE (preclinical). Where outcomes were sufficiently homogenous we planned pooled analyses; otherwise we present a qualitative synthesis. Full search strings are provided in Supplementary File 1. Results: Nine RCTs (≈650 participants) and 12 preclinical studies met inclusion criteria. RCTs reported consistent reductions in perceived stress and anxiety scores and decreased serum cortisol; adverse events were mild and infrequent. Preclinical studies demonstrated HPA-axis attenuation (↓ACTH/corticosterone), enhanced GABAergic signalling, reduced proinflammatory cytokines (IL-6, TNF-α), increased BDNF, and antioxidant effects mechanisms coherent with clinical observations. Risk of bias across clinical trials varied; most studies were small and of short duration (≤12 weeks).Conclusion: Clinical evidence supports Ashwagandha’s short-term efficacy and tolerability for stress and mild–moderate anxiety; preclinical data provide plausible mechanistic explanations. Future large RCTs with standardized extracts, longer follow-up, and biomarker endpoints are recommended