Ashwagandha: From Ancient Rasayana to Modern Clinical Trials

Few botanical ingredients bridge the ancient and the modern quite like ashwagandha. Known to botanists as Withania somnifera and referred to in Sanskrit as the herb that imparts “the strength of a horse,” ashwagandha has been a cornerstone of Ayurvedic medicine for over 3,000 years. Today, it is one of the most researched adaptogenic herbs in the world, with a rapidly growing body of clinical evidence that is drawing attention from both the scientific community and the wellness industry.

This article traces ashwagandha’s remarkable journey, from its origins in ancient Indian healing traditions to the randomized controlled trials (RCTs) that are now testing its effects under the rigorous standards of modern evidence-based medicine.

The Rasayana Tradition: 3,000 Years of Recorded Use

In the Ayurvedic system of medicine, ashwagandha holds the status of a “Rasayana” — a class of herbal preparations traditionally believed to promote longevity, vitality, and overall rejuvenation. The concept of Rasayana is central to Ayurveda and roughly translates to “path of essence,” referring to practices and substances thought to nourish the body’s fundamental tissues.

Ancient Ayurvedic texts, including the Charaka Samhita (estimated to have been composed between the 2nd century BCE and 2nd century CE), describe ashwagandha as a balya (strength-promoting), vajikarana (supporting reproductive health), and medhya (cognition-enhancing) herb. It was traditionally prepared as a churna (powder) mixed with warm milk and ghee, or as part of complex multi-herb formulations.

The plant itself is a small, woody shrub belonging to the Solanaceae family — the same botanical family as tomatoes and eggplant. It grows natively across the Indian subcontinent, parts of the Middle East, and areas of Africa. The name “winter cherry” reflects the small red fruit it produces, though it is the root that has been most valued in traditional medicine. The plant thrives in arid, semi-tropical climates and is today cultivated primarily in the Indian states of Madhya Pradesh, Rajasthan, and Gujarat.

The Chemistry: What Makes Ashwagandha Unique

The biological activity of ashwagandha is attributed primarily to a group of naturally occurring compounds called withanolides — steroidal lactones that are structurally similar to certain human hormones. More than 80 bioactive compounds have been identified in ashwagandha, including withanolides, alkaloids, saponins, glycosides, and volatile oils. However, the withanolides are considered the most pharmacologically relevant.

Two withanolides have received particular research attention: withaferin A, which has been studied for its potential effects on cellular signaling pathways, and withanolide D, which has been explored for its interaction with stress-response systems. The concentration of these compounds varies significantly depending on the plant part used (root vs. leaf), the geographical origin, the cultivation conditions, and the extraction method employed. This variability is important because it means that not all ashwagandha supplements are chemically equivalent — a point we will return to later.

A 2024 pharmacokinetic study found that extracts standardized to higher withanolide glycoside content (35%) showed significantly longer serum half-lives compared to extracts with lower concentrations (2.5%), suggesting that the chemical profile of an extract may meaningfully affect how the body absorbs and processes its active compounds.

Understanding Adaptogens: The HPA Axis Connection

Ashwagandha is classified as an “adaptogen” — a term first coined by Soviet pharmacologist Nikolai Lazarev in 1947 to describe substances that help the body resist physical, chemical, and biological stressors. While the concept has roots in both Russian and Indian traditional medicine, the scientific framework for understanding adaptogens centers on the hypothalamic-pituitary-adrenal (HPA) axis.

The HPA axis is the body’s central stress-response system. When you encounter a stressor, the hypothalamus releases corticotropin-releasing hormone (CRH), which signals the pituitary gland to release adrenocorticotropic hormone (ACTH), which in turn stimulates the adrenal glands to produce cortisol — the primary stress hormone. Under normal conditions, cortisol follows a circadian rhythm, peaking in the morning and declining through the day. Chronic stress can dysregulate this system, leading to persistently elevated cortisol levels.

According to systematic reviews of human clinical trials, ashwagandha supplementation (typically 250–600 mg daily for 4–13 weeks) has been associated with reductions in morning cortisol levels ranging from approximately 11% to 33% in stressed adults compared to placebo. The proposed mechanisms include direct interaction with glucocorticoid receptors, GABAergic activity (GABA is the brain’s primary inhibitory neurotransmitter), and downstream anti-inflammatory effects. However, the precise mechanisms are still being mapped, and researchers note that these pathways likely interact in complex ways.

From Tradition to Trials: What the Clinical Research Shows

Stress and Anxiety

The most extensively studied application of ashwagandha is its effect on perceived stress and anxiety. A 2021 systematic review identified seven randomized controlled trials involving 491 adults, all from India, who either had self-reported high stress or a diagnosed anxiety disorder. Participants who took ashwagandha for 6–8 weeks generally showed greater reductions in stress and anxiety scores compared to those taking a placebo.

More recent trials have reinforced these findings across different populations. A 2024 study at the University of Colorado found that students taking ashwagandha root extract reported increased well-being, a sense of calm, and described their stress as more “manageable” compared to the placebo group. A separate 2024 trial of 131 chronically stressed adults found that an ashwagandha extract significantly reduced perceived stress while also lowering levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α).

It is worth noting that a provisional recommendation for ashwagandha in generalized anxiety disorder has been issued by a taskforce created by the World Federation of Societies of Biological Psychiatry, though the authors emphasized that stronger recommendations require more data.

Sleep Quality

Several clinical trials have examined ashwagandha’s effects on sleep. In one notable study, 150 healthy adults with self-reported sleep problems took either ashwagandha root and leaf extract or a placebo for six weeks. The ashwagandha group reported a 72% improvement in sleep quality scores, compared to 29% in the placebo group. Benefits included improved sleep efficiency, reduced time to fall asleep, and greater total sleep time.

These sleep-related benefits appear to be more pronounced in people with existing sleep difficulties than in good sleepers, suggesting that ashwagandha may support sleep through its calming effects on the stress-response system rather than acting as a direct sedative.

Cognitive Function

A smaller but growing body of research has explored ashwagandha’s effects on memory and cognitive performance. A 2024 randomized, double-blind trial found statistically significant improvements in episodic memory, working memory, and attention accuracy in the ashwagandha group compared to placebo over an 8-week period. The effect sizes were moderate, and the researchers emphasized that larger, longer studies are needed to confirm these findings.

Physical Performance

Multiple studies have examined ashwagandha’s effects on exercise performance and recovery. A 2020 meta-analysis of four RCTs found a small but statistically significant improvement in VO₂max (a measure of cardiorespiratory fitness) with ashwagandha supplementation. Other trials have reported improvements in muscle strength and recovery markers, though the quality and size of these studies varies.

Safety: What the Evidence Shows

Short-term clinical trials (typically 30–112 days) have generally found ashwagandha root extract to be well tolerated, with adverse event rates comparable to placebo groups. A landmark 2025 prospective, multicenter, observational study followed 191 healthy adults taking standardized ashwagandha root extract for 12 months — the longest safety study of its kind. No serious adverse events were reported, and safety was assessed across hepatic function, renal health, thyroid activity, and hormonal balance.

However, the safety picture is not without nuance. A small number of case reports have documented liver-related adverse events in individuals using ashwagandha products, leading some European regulators to raise concerns. Researchers have noted that these case reports often involved products containing multiple ingredients or non-standardized extracts, making it difficult to attribute the effects specifically to ashwagandha. Traditional Ayurvedic practice has historically used only the root (not the leaves or aerial parts), and some experts believe this distinction may be relevant to the safety discussion.

As with any botanical product, potential interactions with medications should be considered. Limited in vitro data suggests possible interactions with certain cytochrome P450 enzymes, though the clinical relevance of these findings has not been established. Consultation with a healthcare provider is advisable before beginning any new supplement regimen, particularly for individuals taking prescription medications or managing health conditions.

Not All Extracts Are Equal: The Standardization Question

One challenge in interpreting ashwagandha research is the wide variety of extract types used across different studies. Some trials use root-only extracts; others use a combination of root and leaf. Withanolide concentrations can range from 2.5% to 35% depending on the extraction method and standardization approach. This variability makes direct comparison between studies difficult and partly explains why some trials show strong effects while others are more modest.

The scientific community is increasingly recognizing that the specific chemical profile of an ashwagandha extract — not just the milligram dose on the label — matters for both efficacy and safety. Ongoing work in analytical chemistry is helping to better characterize these extracts, but standardized methods for quality comparison are still evolving.

What We Know and What We’re Still Learning

Well established: Ashwagandha has been used safely in traditional medicine for thousands of years. Withanolides are the primary bioactive compounds responsible for its effects. Multiple RCTs show consistent associations between ashwagandha supplementation and reductions in perceived stress and cortisol levels. Short-term and 12-month safety data in healthy adults are reassuring.

Actively being studied: The precise mechanisms by which ashwagandha modulates the HPA axis. Whether its effects on sleep, cognition, and physical performance are clinically meaningful at a population level. How different extract types, doses, and standardization levels affect outcomes. Long-term safety in diverse populations and in combination with medications.

Still uncertain: Optimal dosing for specific outcomes. Whether benefits observed in stressed populations extend to those without elevated stress. The relevance of isolated case reports of liver injury to the broader safety profile. How individual genetic and microbiome variation affects response.

An Ancient Herb in a Modern Evidence Landscape

Ashwagandha occupies a fascinating position in the world of botanical science — an ingredient with millennia of traditional use that is now being subjected to the rigors of randomized, placebo-controlled clinical trials. The early evidence is encouraging, particularly for stress management and sleep support, but the field is still maturing. Larger, longer, more diverse trials are needed, and the question of extract standardization remains central.

What is clear is that ashwagandha’s journey from Rasayana to RCT represents something broader: the growing convergence of traditional botanical knowledge and modern evidence-based medicine. As research continues, our understanding of this ancient herb will only deepen.

As with any dietary supplement, it is important to consult with a qualified healthcare professional before making changes to your regimen, particularly if you are pregnant, nursing, taking medications, or managing a health condition.

Disclaimer: This article is for educational and informational purposes only. It is not intended to diagnose, treat, cure, or prevent any disease. The information provided does not constitute medical advice. Always consult with a qualified healthcare professional regarding any health concerns or before making changes to your diet, lifestyle, or supplement routine.

Selected References for Further Reading:

Prajapati, B.L. et al. (2025). Safety of 12-months administration of ashwagandha standardized root extract in healthy adults. Phytotherapy Research. DOI: 10.1002/ptr.70096

Lucius, K. (2025). Clinical evidence for the use of ashwagandha, Withania somnifera. Integrative Cancer Therapies.

Lopresti, A.L. et al. (2019). An investigation into the stress-relieving and pharmacological actions of an ashwagandha extract. Medicine, 98(37), e17186.

Pratte, M.A. et al. (2014). An alternative treatment for anxiety: a systematic review of human trial results. Journal of Alternative and Complementary Medicine, 20(12), 901–908.

Cheah, K.L. et al. (2021). Effect of ashwagandha extract on sleep: a systematic review and meta-analysis. PLoS ONE, 16(9), e0257843.

NIH Office of Dietary Supplements (2025). Ashwagandha: Is it helpful for stress, anxiety, or sleep? Health Professional Fact Sheet.