A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults

Key finding

60-day double-blind RCT (n=64) using 300mg KSM-66 ashwagandha twice daily significantly reduced perceived stress (PSS) and serum cortisol vs placebo.

CONTEXT: Stress is a state of mental or emotional strain or tension, which can lead to underperformance and adverse clinical conditions. Adaptogens are herbs that help in combating stress. Ayurvedic classical texts, animal studies and clinical studies describe Ashwagandha as a safe and effective adaptogen. AIMS: The aim of the study was to evaluate the safety and efficacy of a high-concentration full-spectrum extract of Ashwagandha roots in reducing stress and anxiety and in improving the general well-being of adults who were under stress. SETTINGS AND DESIGN: Single center, prospective, double-blind, randomized, placebo-controlled trial. MATERIALS AND METHODS: A total of 64 subjects with a history of chronic stress were enrolled into the study after performing relevant clinical examinations and laboratory tests. These included a measurement of serum cortisol, and assessing their scores on standard stress-assessment questionnaires. They were randomized to either the placebo control group or the study drug treatment group, and were asked to take one capsule twice a day for a period of 60 days. In the study drug treatment group, each capsule contained 300 mg of high-concentration full-spectrum extract from the root of the Ashwagandha plant. During the treatment period (on Day 15, Day 30 and Day 45), a follow-up telephone call was made to all subjects to check for treatment compliance and to note any adverse reactions. Final safety and efficacy assessments were done on Day 60. STATISTICAL ANALYSIS: t-test, Mann-Whitney test. RESULTS: The treatment group that was given the high-concentration full-spectrum Ashwagandha root extract exhibited a significant reduction (P<0.0001) in scores on all the stress-assessment scales on Day 60, relative to the placebo group. The serum cortisol levels were substantially reduced (P=0.0006) in the Ashwagandha group, relative to the placebo group. The adverse effects were mild in nature and were comparable in both the groups. No serious adverse events were reported. CONCLUSION: The findings of this study suggest that a high-concentration full-spectrum Ashwagandha root extract safely and effectively improves an individual's resistance towards stress and thereby improves self-assessed quality of life.

Abstract sourced from PubMed, a database of the U.S. National Library of Medicine. Displayed in the authors’ own words for context; our critique is in the sections below.

Critique

Often cited as proof ashwagandha reduces stress, but the methodology limits how much weight this single trial can carry. n=64 is modest for detecting the reported effect size. 60 days is a short window for chronic stress claims. Outcomes were a subjective scale (PSS-14) plus a single morning serum cortisol draw — morning cortisol is highly variable day-to-day and is not a robust biomarker of chronic stress compared to diurnal curves or hair cortisol. The KSM-66 extract is manufactured by Ixoreal Biomed, whose involvement appears across many subsequent ashwagandha trials, complicating independent replication. The direction of results has been echoed in later trials, but any one small trial of this design is weak evidence on its own.

What would be more convincing

A 12-week pre-registered RCT with n≥200, independently funded, using diurnal or hair cortisol alongside PSS-14, with a pre-specified MCID on the PSS, would be materially more convincing.

Reviewed 2026-04-21 · Opinion based on verifiable facts in the published paper.