Ashwagandha (Withania somnifera)
1. Identity: Botanical Classification, Names, and Forms
Withania somnifera (L.) Dunal belongs to the nightshade family Solanaceae and is commonly known as Ashwagandha. It is pharmacologically a significant medicinal plant of the Indian sub-continent, used in Ayurvedic and indigenous systems of medicine for more than 3,000 years. The plant is also referred to in English as "Indian Winter cherry" or "Indian Ginseng." The structural resemblance of withanolides to ginsenosides, the active constituents of Panax ginseng, has led to W. somnifera being referred to as "Indian Ginseng."
The name "Ashwagandha" derives from Sanskrit, translating to "smell of a horse." This name signifies two key attributes: the herb's distinctive aroma and its reputed ability to impart the vigor and strength of a horse.
This small shrub, a member of the Solanaceae family, is native to the Indian subcontinent and is also found in southern Europe, Africa, and Australia.
Common Forms and Preparations
- Ashwagandha is commonly available as a churna, a fine sieved powder that can be mixed with water, ghee (clarified butter) or honey.
- Supplements typically contain ashwagandha root, leaf, or root/leaf extracts.
- KSM-66: KSM-66 is extracted from the root only and standardized to 5% withanolides. It is the most clinically studied form with 22+ trials, and tends to be more energizing.
- Sensoril: Sensoril uses both root and leaf extract, is standardized to 10% withanolides, and tends to be more calming.
- Shoden: Shoden beads are standardized to deliver 21 mg of withanolide glycosides per day.
- Doses in traditional Ayurvedic medicine range from 3 to 6 grams of root powder daily, far above modern supplement capsule doses.
2. Traditional and Historical Use
Withania somnifera, commonly known as Ashwagandha, is an important medicinal plant that has been used in Ayurvedic and indigenous medicine for over 3,000 years.
Ashwagandha has its footprint in the original course book of Ayurveda — Charaka Samhita and Susruta Samhita — since ancient times. These texts record the first references to Ashwagandha with its significant nomenclature, useful parts, properties, action, and eloquent uses. In later works, enhanced knowledge with traditional uses continued even today.
It is one of the most important herbs of Ayurveda used for millennia as a Rasayana for its wide-ranging health benefits. Rasayana is described as an herbal or metallic preparation that promotes a youthful state of physical and mental health and expands happiness. These types of remedies are given to small children as tonics, and are also taken by the middle-aged and elderly to increase longevity.
In Ayurveda, ashwagandha is often used in formulations prescribed for stress, strain, fatigue, pain, skin diseases, diabetes, gastrointestinal disease, rheumatoid arthritis, and epilepsy. It is also used as a general tonic to improve energy levels, health, and longevity, and topically as an analgesic.
Traditional Preparations
- In Ayurveda, Ashwagandha has traditionally been prepared in a variety of ways, including powders, decoctions, and formulations combined with other ingredients.
- Ashwagandha Churna: A fine powder mixed with honey, milk, or ghee, often consumed daily to rejuvenate the body and mind.
- Decoctions: Boiled with water or milk to extract its therapeutic compounds for internal use.
- Herbal pastes: Combined with other herbs and applied externally to soothe inflammation or promote skin health.
- Classical texts often describe combining herbs with carriers such as ghee or honey as part of traditional preparation methods, based on Ayurvedic principles.
According to Anne Van Arsdall, Withania somnifera was called apollinaris and also glofwyrt in the Old English Herbarium, and had a legend that Apollo found it first and gave it to the healer Aesculapius.
3. Key Constituents and Active Compounds
Ashwagandha is a rich reservoir of pharmaceutically bioactive constituents known as withanolides — a group of 300 naturally occurring C-28 steroidal lactones with an ergostane-based skeleton.
The major chemical constituents of the Withania genus, the withanolides, are a group of naturally occurring C28-steroidal lactone triterpenoids built on an intact or rearranged ergostane framework, in which C-22 and C-26 are appropriately oxidized to form a six-membered lactone ring.
At present, more than 12 alkaloids, 40 withanolides, and several sitoindosides (a withanolide containing a glucose molecule at carbon 27) have been isolated and reported from aerial parts, roots, and berries of Withania species.
Principal Bioactive Classes
- Withanolides: Most of the biological activities of W. somnifera have been attributed to two key withanolides, namely withaferin-A and withanolide-D. The first withanolide isolated from W. somnifera was Withaferin-A.
- Sitoindosides: Sitoindoside IX and sitoindoside X, which are acyl steryl glucosides and glycowithanolides, have been isolated from the root.
- Alkaloids: Among the various alkaloids, withanine is the main constituent. The other alkaloids include somniferine, somnine, somniferinine, withananine, anaferine, and anahydrine.
- Additional phytochemicals: The biologically active chemical constituents include alkaloids (isopelletierine, anaferine), steroidal lactones (withanolides, withaferins), saponins containing an additional acyl group (sitoindoside VII and VIII), and withanolides with a glucose at carbon 27 (sitoindoside IX and X).
- The active principles such as sitoindosides VII–X and withaferin-A possess free radical scavenging properties.
4. Mechanisms of Action
The bioactive compounds of ashwagandha modulate the hypothalamic-pituitary-adrenal (HPA) axis, inhibit NF-κB, induce Nrf2 activation, and affect gamma-aminobutyric acid (GABA)ergic signaling, collectively contributing to its anti-inflammatory, antioxidant, and anxiolytic actions.
HPA Axis and Cortisol Regulation
The precise mechanisms through which ashwagandha's compounds lower cortisol levels remain incompletely understood; they are believed to act both directly — by interacting with glucocorticoid receptors and influencing the HPA axis — and indirectly, through sedative and hypnotic effects via modulation of gamma-aminobutyric acid (GABA). This effect on the HPA axis, a main regulator of the stress response, is evident through lowered morning cortisol levels (a biomarker of stress) following ashwagandha supplementation.
Neuromodulatory Effects
Research conducted at the Department of Pharmacology, University of Texas Health Science Center indicated that extracts of ashwagandha produce GABA-like activity, which may account for the herb's anti-anxiety effects. GABA (gamma-aminobutyric acid) is an inhibitory neurotransmitter in the brain.
Ashwagandha root extract treatment improved behavioral parameters in preclinical models and favorably modulated biochemical markers, including elevated serotonin and brain-derived neurotrophic factor (BDNF) levels and reduced cortisol, adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), and proinflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α).
Molecular Targets
Several research groups worldwide have discovered various molecular targets of W. somnifera, such as inhibiting the activation of nuclear factor kappa-B (NF-κB) and promoting apoptosis of cancer cells. Molecular docking studies have revealed that withanolide-A inhibits acetyl-cholinesterase in the brain, which could be a potential mechanism relevant to Alzheimer's disease. Withanolide-A also reduces the expression of the N-methyl-D-aspartate (NMDA) receptor, which is responsible for memory loss in epileptic rat models.
Endocrine Effects
The main mechanism related to reproductive health appears to be based on the HPA axis, as a decrease in cortisol levels and an increase in hormones such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in men have been found. Other studies demonstrate that active substances from W. somnifera cause an increase in the secretion of triiodothyronine (T3) and thyroxine (T4) by the thyroid gland and a subsequent decrease in the level of thyroid-stimulating hormone (TSH) in accordance with the hypothalamus–pituitary–thyroid (HPT) axis.
5. Scientific Evidence by Area of Use
Note: Studies reviewed below are human or clinical trials unless otherwise specified. Many areas have relatively small sample sizes and short durations, and evidence strength is characterized accordingly.
5.1 Stress and Anxiety
Evidence strength: Moderate-to-good, from multiple RCTs and meta-analyses, with methodological caveats.
Many clinical trials have looked at the use of ashwagandha for a variety of health conditions. However, many of the studies have had small sample sizes and have used a variety of ashwagandha preparations.
A systematic review and meta-analysis evaluated the effects and safety of ashwagandha on psychosomatic functions related to stress and anxiety. A comprehensive search was conducted in MEDLINE, EMBASE, PubMed, PsychINFO, and the Cochrane Library for articles published from January 2000 to January 2022. Randomized controlled trials examining the effects of ashwagandha on stress and anxiety were included.
Nine randomized controlled trials involving 558 patients were eligible for this study. The findings of the meta-analysis showed a significant effect of ashwagandha formulations on the Perceived Stress Scale (PSS) (MD = −4.72, 95% CI = [−8.45 to −0.99]), Hamilton Anxiety Scale (HAS) (MD = −2.19, 95% CI = [−3.83 to −0.55]), and serum cortisol levels (MD = −2.58, 95% CI = [−4.99 to −0.16]) compared to the placebo group.
A more recent 2025 meta-analysis further corroborated these findings. A total of 15 studies were included with a combined sample size of 873 patients. Ashwagandha supplementation significantly reduced anxiety compared with placebo according to the Hamilton Anxiety Rating Scale (HAM-A). It resulted in a statistically significant reduction of cortisol levels, PSS scale, and HAM-A scale.
Doses in included studies ranged from 125 to 600 mg daily for 30–90 days; both root alone and root-and-leaf combined formulations were used.
The strength of findings is hampered by the small sample sizes used and short treatment duration, with no study greater than 8 weeks. Divergent ashwagandha extracts with varying treatment doses were also used across these studies.
In an 8-week, randomized, double-blind, placebo-controlled study, ashwagandha was associated with greater reductions in anxiety, morning cortisol, C-reactive protein, pulse rate, and blood pressure in chronically stressed adults.
5.2 Sleep
Evidence strength: Moderate, from several RCTs and one meta-analysis; effects are small-to-moderate in magnitude.
A total of five randomized controlled trials containing 400 participants were analyzed in one PLOS ONE meta-analysis. Ashwagandha extract exhibited a small but significant effect on overall sleep (Standardized Mean Difference −0.59; 95% Confidence Interval −0.75 to −0.42). The effects on sleep were more prominent in the subgroup of adults diagnosed with insomnia, at treatment dosages ≥600 mg/day, and at treatment duration ≥8 weeks. Ashwagandha extract was also found to improve mental alertness on rising and anxiety levels, but showed no significant effect on quality of life. No serious side effects were reported.
In one study, 150 healthy men and women aged 18 to 65 years with self-reported sleep problems were randomized to take an ashwagandha root and leaf extract (Shoden) or placebo for 6 weeks. The extract was standardized to contain 21 mg of withanolide glycosides per 60-mg capsule, and participants took two capsules each day.
Ashwagandha root extract showed sleep-inducing potential, was well tolerated, and improved sleep quality and sleep onset latency in patients with insomnia at a dose of 300 mg extract twice daily. The authors concluded it could be of potential use to improve sleep parameters in patients with insomnia and anxiety, but that further large-scale studies are needed.
There is a paucity of clinical evidence regarding the long-term safety and efficacy of ashwagandha extract on sleep.
5.3 Physical Performance and Muscle Strength
Evidence strength: Moderate, primarily from studies in men; effects on VO2 max and muscle strength are replicated, but most trials are small and short-term.
Ashwagandha extracts have been shown to increase athletic performance in both the general healthy adult population and professional/elite athletes. VO2 max, a measure of cardiovascular fitness, has been shown to increase by 6–14% over study periods of 4–12 weeks. Ashwagandha extracts have also been found to increase muscle mass and strength, and improve muscle recovery. Dosages used have been in the range of 330–1,000 mg per day.
In an 8-week, randomized, prospective, double-blind, placebo-controlled clinical study, 57 young male subjects (18–50 years old) with little experience in resistance training were randomized into treatment and placebo groups. Subjects in the treatment group consumed 300 mg of ashwagandha root extract twice daily, while the control group consumed starch placebos. Both groups underwent resistance training for 8 weeks.
A recent systematic review demonstrated that supplementation with 250–500 mg of ashwagandha extract daily for 4 to 13 weeks significantly decreased morning cortisol levels in adults experiencing higher stress levels.
5.4 Testosterone and Male Fertility
Evidence strength: Preliminary-to-moderate for testosterone; limited but encouraging for fertility parameters.
There is some limited evidence that suggests that taking ashwagandha for 2 to 4 months may increase testosterone levels and sperm quality.
The main mechanism appears to be based on the HPA axis, as a decrease in cortisol levels and an increase in hormones such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in men have been found, which results in stress level reduction and improvement in fertility.
5.5 Cognitive Function
Evidence strength: Preliminary-to-moderate; positive results from a number of small RCTs, but larger, longer trials are needed.
Clinical trials with standardized ashwagandha extracts have shown reductions in stress-related biomarkers, along with improvements in cognitive performance, sleep quality, and mood parameters.
A pilot study was designed to evaluate the efficacy and safety of ashwagandha in improving memory and cognitive functioning in adults with mild cognitive impairment (MCI). A prospective, randomized, double-blind, placebo-controlled study was conducted in 50 adults. Subjects were treated with either ashwagandha root extract (300 mg twice daily) or placebo for eight weeks. After eight weeks, the ashwagandha treatment group demonstrated significant improvements compared with the placebo group in both immediate and general memory, as well as significantly greater improvement in executive function, sustained attention, and information-processing speed.
A double-blind, randomized, placebo-controlled clinical study evaluated the effect of ashwagandha root extract sustained-release capsule 300 mg (Prolanza™) on cognitive functions, stress levels, sleep quality, overall well-being, and safety in stressed subjects. Subjects (130 healthy cognitively sound adults aged 20–55 years) having a Perceived Stress Scale (PSS) score of 14–24 were randomized to receive either ashwagandha SR or placebo. Subjects took one capsule of ashwagandha SR or placebo daily for 90 consecutive days. The Cambridge Neuropsychological Test Automated Battery (CANTAB) reported significantly improved recall memory, and the total error rate in recalling patterns significantly decreased at visit 4 in the ashwagandha SR group vs. the placebo group.
Results support the contention that ashwagandha supplementation (225 mg) may improve some measures of memory, attention, vigilance, and executive function while decreasing perceptions of tension and fatigue in younger healthy individuals.
Studies on healthy populations are limited. Eight weeks of 600 mg ashwagandha root extract has been shown to improve memory, executive function, sustained attention, and processing speed in Indian adults aged 50 years with early dementia.
5.6 Thyroid Function
Evidence strength: Preliminary; one double-blind RCT in subclinical hypothyroidism; limited data in healthy populations.
In 50 adults with subclinical hypothyroidism, KSM-66 at 600 mg/day for 8 weeks decreased TSH by 1.85 mIU/L and increased T3 and T4 vs. placebo. A 12-month safety study found T3 increased from 123.14 to 132.25 ng/dL (within normal range). These effects suggest ashwagandha may interact with thyroid medications and affect thyroid hormones in people without thyroid disease.
5.7 Women's Health and Menopause
Evidence strength: Preliminary; a small number of RCTs specifically in perimenopausal and postmenopausal women.
In 91 perimenopausal women, KSM-66 at 600 mg/day for 8 weeks slightly reduced symptom severity (−3.37 vs. −1.16 points on a 44-point scale), reduced hot flashes by approximately 1 per day, increased estradiol, and decreased FSH. In a separate cohort of 60 perimenopausal women, KSM-66 at 600 mg/day for 8 weeks improved quality of life by approximately 12 points and reduced stress by ~46%, though hot flash frequency did not significantly decrease.
In 123 postmenopausal women (mean age 51), Sensoril at 125 mg or 250 mg twice daily for 6 months improved quality of life, bone resorption biomarkers, and at the higher dose, lumbar spine bone mineral density vs. placebo.
5.8 Female Sexual Function
Evidence strength: Preliminary; one small double-blind RCT.
In 50 women (ages 21–50) with low sexual desire or arousal, KSM-66 at 300 mg twice daily for 2 months significantly improved overall sexual function, arousal, lubrication, and satisfaction vs. placebo, though sexual desire did not significantly improve.
5.9 Neuroprotection (Preclinical Evidence)
Evidence strength: Preclinical only; no robust human trials yet.
Neuroprotective actions have been demonstrated in preclinical animal and cell models of Alzheimer's and Parkinson's disease. Preclinical studies also showed neuroprotective and anti-inflammatory properties that may protect against cartilage damage in osteoarthritis, and improvements in hyperglycemia, hyperinsulinemia, and insulin sensitivity in a murine model of type 2 diabetes.
6. Body Systems and Health Areas of Association
- Neuroendocrine / Stress Response: HPA axis modulation, cortisol reduction, adaptogenic activity.
- Central Nervous System: Anxiolytic and GABAergic effects; cognition, mood, sleep regulation.
- Endocrine System: Ashwagandha can have a positive effect on the functioning of the endocrine system, including improving the secretory function of the thyroid gland, normalizing adrenal activity, and multidirectional improvement in the functioning of the reproductive system.
- Musculoskeletal and Athletic Performance: Muscle mass and strength, VO2 max, exercise recovery.
- Reproductive / Hormonal: Testosterone, sperm quality, LH, FSH in men; estradiol and FSH in perimenopausal women.
- Immune and Inflammatory: NF-κB inhibition and promotion of apoptosis of cancer cells (preclinical data).
- Cardiovascular: Some evidence for blood pressure reduction in stress-related contexts (clinical studies).
7. Dosage Forms and Dosages Reported in Clinical Studies
Doses in traditional Ayurvedic medicine range from 3 to 6 grams of root powder daily, far above modern supplement capsule doses.
Supplements typically contain ashwagandha root, leaf, or root/leaf extracts. Available dosage forms include capsules, tablets, and powders.
The following dosages have been reported in peer-reviewed clinical studies:
- Stress/Anxiety: Doses ranged from 125 to 600 mg daily for 30–90 days; both root alone and root-and-leaf combined formulations were used.
- Sleep: Ashwagandha root extract at a dose of 300 mg twice daily improved sleep quality and sleep onset latency in a 10-week study in patients with insomnia. A randomized, double-blind, placebo-controlled trial found that 120 mg of standardized ashwagandha extract (Shoden®) taken once daily for six weeks significantly improved sleep quality, sleep efficiency, total sleep time, and reduced sleep latency and wake after sleep onset. Another study in elderly adults used a higher dose of 600 mg/day of ashwagandha root extract for 12 weeks, resulting in significant improvements in sleep quality, mental alertness upon waking, and overall well-being.
- Athletic Performance / Muscle Strength: Subjects in one resistance training trial consumed 300 mg of ashwagandha root extract twice daily. Dosages used across athletic performance trials have been in the range of 330–1,000 mg per day.
- Thyroid Function: KSM-66 at 600 mg/day for 8 weeks in adults with subclinical hypothyroidism.
- Female Sexual Function: KSM-66 at 300 mg twice daily for 2 months.
- Postmenopausal Bone Health: Sensoril at 125 mg or 250 mg twice daily for 6 months.
- Cognitive Function (Stressed Adults): 300 mg standardized ashwagandha SR once daily for 90 consecutive days.
- Sensoril (stress/anxiety): Effective doses of 125 to 250 mg daily have been used in clinical trials.
Most studies last 2–3 months; long-term safety beyond six months is less defined.
8. Safety Considerations and Drug Interactions
General Safety Profile
Despite widespread use, ashwagandha is considered generally safe and without major adverse effects. In clinical trials, there have been no reports of serum enzyme elevations occurring during therapy and no mention of serious adverse events or hepatotoxicity.
Among included studies in the stress/anxiety meta-analysis, four reported mild to moderate adverse events. The findings indicate that ashwagandha formulations have beneficial effects on stress and anxiety overall.
Liver Toxicity (Hepatotoxicity)
Although it is rare, there have been a number of cases that link liver injury to ashwagandha supplements. Ashwagandha has not been implicated in causing serum enzyme elevations during therapy but recently has been implicated in cases of clinically apparent liver injury.
The NIH classifies ashwagandha as a liver toxicity grade B, which basically means it is likely a cause of clinically apparent liver injury. The supplement liver toxicity data is likely highly underreported because there is no obligation to report adverse events. Hepatologists are only seeing a small proportion of the millions of people taking ashwagandha as a supplement.
A USP safety review noted the long history of apparent safe usage in traditional Ayurvedic practices and at that time there were no reported serious adverse events for products containing ashwagandha. However, it should be cautioned that history of use may not be adequately reported, the scope of adverse events may not be observable, use levels may not be reported, and there can be great variability in botanical raw material.
Gastrointestinal side effects, immune hypersensitivity, liver toxicity, and endocrine disruption have been reported, particularly with prolonged or excessive usage. Metabolic transformation via cytochrome P450 enzymes can form reactive intermediates, leading to oxidative stress and hepatotoxicity.
A molecular study suggested an important role for the withanolide withanone in ashwagandha-induced liver injury. It is one of the more representative withanolides of ashwagandha and the main metabolite in significant amounts in the extract. Withanone consists of electrophilic functional groups associated with adverse drug reactions, referred to as toxicophores, responsible for toxicity.
Endocrine Effects and HPA Axis Suppression
The endocrine-modulating activity of ashwagandha has been implicated in thyrotoxicosis and adrenal suppression.
A case report described a 55-year-old postmenopausal woman who presented with Cushingoid features and progressive weight gain over a year. Evaluation revealed low basal cortisol levels and a suboptimal response to the ACTH stimulation test, indicative of adrenal insufficiency. Further investigation uncovered her consistent use of approximately 950 mg of ashwagandha daily for over a year.
Contraindications and Special Populations
- Ashwagandha should be avoided during pregnancy and should not be used while breastfeeding.
- Ashwagandha is not recommended for people who are about to have surgery, or for those who have autoimmune or thyroid disorders.
- Because ashwagandha may increase testosterone levels, people with hormone-sensitive prostate cancer should avoid its use.
Drug Interactions
There is evidence that ashwagandha might interact with some medications, including those for diabetes and high blood pressure, medicines that decrease the immune system response (immunosuppressants), sedatives, anti-seizure medications (anticonvulsants), and thyroid hormone medications.
Subsequent studies should emphasize pharmacogenomic responsiveness given potential variability in cytochrome P450 (CYP)-mediated metabolism and genetic differences in stress-response pathways.
Overall Evidence Limitations
The existing research base has methodological shortcomings, including heterogeneity in the preparation of extracts, small sample sizes, variability in endpoints, and possible funding-related biases. These results signify that more clinical trials should be conducted to prove efficacy and other potential therapeutic effects in human settings.
References
- National Center for Complementary and Integrative Health (NCCIH) — Ashwagandha: Usefulness and Safety
- NIH Office of Dietary Supplements — Ashwagandha: Is it helpful for stress, anxiety, or sleep? Health Professional Fact Sheet
- NIH LiverTox® — Ashwagandha (NCBI Bookshelf)
- Kaur P, et al. Steroidal Lactones from Withania somnifera, an Ancient Plant for Novel Medicine. PMC 2018.
- Bashir A, et al. An updated review on phytochemistry and molecular targets of Withania somnifera (L.) Dunal (Ashwagandha). Frontiers in Pharmacology, 2023.
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- Wiciński M, et al. Can Ashwagandha Benefit the Endocrine System? A Review. Int J Mol Sci, 2023.
- Cureus — Ashwagandha as an Adaptogenic Herb: A Comprehensive Review of Immunological and Neurological Effects, 2025.
- Endocrinology, Diabetes & Metabolism Case Reports — From herbal hope to hormonal havoc: chronic ashwagandha use and HPA axis suppression, 2026.
- Liver Dangers of Herbal Products: A Case Report of Ashwagandha-Induced Liver Injury. PMC, 2023.
- Withania somnifera (Ashwagandha) supplementation: a review of its mechanisms, health benefits, and role in sports performance. Nutrition & Metabolism, 2025.
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- University of Colorado Anschutz Medical Campus — Ashwagandha is Popular for Boosting Health — But Could it Hurt Your Liver?
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