Ashwagandha For Anxiety And Stress Regulation: A Systematic Review Of Efficacy And Mechanisms

Abstract

We conducted a systematic review to evaluate the efficacy, safety, and mechanistic underpinnings of Withania somnifera (Ashwagandha) supplementation for anxiety and stress regulation in adult populations. The central hypothesis posits that Ashwagandha modulates the hypothalamic-pituitary-adrenal (HPA) axis and GABAergic signaling pathways, thereby reducing perceived stress, anxiety symptoms, and serum cortisol levels. Our methodology employed a systematic search and screening process that identified four double-blind, placebo-controlled randomized controlled trials (RCTs) with a total of 256 participants, ranging from 30 to 60 days in duration. The most consistent finding was a reduction in cortisol levels following supplementation, with one trial reporting a 27.9% decrease in serum cortisol relative to placebo and another observing significantly lower plasma cortisol and ACTH at doses of 250 mg and 500 mg per day. However, a trial using a withanolide glycoside-dominant extract found no significant between-group difference in salivary cortisol, though it noted increases in DHEA-S and testosterone. Evidence for GABAergic mechanisms in humans was extremely limited; none of the four RCTs reported EEG power bands or GABA receptor imaging, and only one trial measured neurosteroids. All four RCTs demonstrated improvements in stress or anxiety measures, with adverse events generally mild and comparable to placebo. A critical finding was the complete absence of gut microbiome data in any included RCT, precluding planned mediation analyses of the gut-brain axis. This review highlights significant heterogeneity in formulations, dosing, and outcome measurement, alongside critical gaps in mechanistic data, long-term safety, and microbiome outcomes. Therefore, future research must employ standardized extracts, harmonized endpoints, longer follow-up durations, and rigorous investigation of GABAergic and gut-brain axis mechanisms to substantiate clinical recommendations.