An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study
Open accessAbstract
BACKGROUND: Ashwagandha (Withania somnifera (L.) Dunal) is a herb traditionally used to reduce stress and enhance wellbeing. The aim of this study was to investigate its anxiolytic effects on adults with self-reported high stress and to examine potential mechanisms associated with its therapeutic effects. METHODS: In this 60-day, randomized, double-blind, placebo-controlled study the stress-relieving and pharmacological activity of an ashwagandha extract was investigated in stressed, healthy adults. Sixty adults were randomly allocated to take either a placebo or 240 mg of a standardized ashwagandha extract (Shoden) once daily. Outcomes were measured using the Hamilton Anxiety Rating Scale (HAM-A), Depression, Anxiety, and Stress Scale -21 (DASS-21), and hormonal changes in cortisol, dehydroepiandrosterone-sulphate (DHEA-S), and testosterone. RESULTS: All participants completed the trial with no adverse events reported. In comparison with the placebo, ashwagandha supplementation was associated with a statistically significant reduction in the HAM-A (P = .040) and a near-significant reduction in the DASS-21 (P = .096). Ashwagandha intake was also associated with greater reductions in morning cortisol (P < .001), and DHEA-S (P = .004) compared with the placebo. Testosterone levels increased in males (P = .038) but not females (P = .989) over time, although this change was not statistically significant compared with the placebo (P = .158). CONCLUSIONS: These findings suggest that ashwagandha's stress-relieving effects may occur via its moderating effect on the hypothalamus-pituitary-adrenal axis. However, further investigation utilizing larger sample sizes, diverse clinical and cultural populations, and varying treatment dosages are needed to substantiate these findings. TRIAL REGISTRATION: Clinical Trials Registry-India (CTRI registration number: CTRI/2017/08/009449; date of registration 22/08/2017).
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Withaferin A causes mitochondrial dysfunction.
“Mitochondrial”
From Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects (2021) · cites this paper as [187]
Withaferin A induces ROS.
“dysfunction, induction of”
From Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects (2021) · cites this paper as [187]
Withaferin A inactivates the PI3K/AKT pathway.
“ROS, inactivation of PI3K/”
From Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects (2021) · cites this paper as [187]
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- Authors
- Lopresti, A. L., Smith, S. J., Malvi, H., & Kodgule, R.
- Affiliations
- Murdoch University (AU)
- Heamatology Centre Bhopal, Bhopal, Madhya Pradesh
- Saibaba Healthcare, Wagholi, Pune, Maharashtra, India.
- Corresponding author
- Lopresti, Adrian L.
- Venue
- Medicine
- Published
- 2019-09
- Volume
- 98
- Issue
- 37
- Pages
- e17186
- ISSN
- 0025-7974 (ISSN-L)
- 1536-5964
- PMC
- PMC6750292
- OpenAlex
- W2972365744
- Cited by
- 241
- References
- 42
- Citations by year
- 2026: 59 · 2025: 39 · 2024: 41 · 2023: 41 · 2022: 25 · 2021: 22 · 2020: 14
- FWCI
- 19.66
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Murdoch University Research Portal (submittedVersion)
- Funders
- Arjuna Natural Extracts Ltd (1)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Phytochemicals and Medicinal Plants
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Medicinal Plants and Bioactive Compounds
- Keywords
- Withania somnifera, stress reduction, anxiolytic effects, anxiety, cortisol, dehydroepiandrosterone sulfate, testosterone, hypothalamic-pituitary-adrenal axis, herbal supplementation, adaptogens
- MeSH terms
- Adult, Anxiety, Double-Blind Method, Female, Humans, Hydrocortisone, Male, Phytotherapy, Plant Extracts, Stress, Psychological, Testosterone, Anti-Anxiety Agents, Treatment Outcome, Dehydroepiandrosterone Sulfate
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