Ashwagandha and Stress: What the Evidence Actually Shows

By Jack Zheng, MS Pharmacy — Founder of MIHIYO Labs

Summary

Ashwagandha (Withania somnifera) shows a more consistent cortisol-lowering signal than an effect on how stressed people feel. Across randomized trials, standardized root extracts at 240 to 600 mg daily lowered serum cortisol by about 23 to 28 percent from baseline, with smaller or no reductions on placebo, over 8 to 12 weeks. A 2024 meta-analysis of nine trials reported significant cortisol and anxiety reductions, yet a separate 2025 review found no significant change in perceived stress. The effect also depends on a swallowed dose far too large for an oral dissolving strip (ODS). MIHIYO Labs formulates mood support from ingredients that fit a low-dose film instead.

Does ashwagandha actually reduce stress?

The honest answer is: it depends on what you measure. Ashwagandha shows a fairly consistent cortisol-lowering signal in controlled trials — cortisol being the body's main stress hormone. Whether that translates into people feeling less stressed is where the evidence gets messier.

That split matters more than most marketing admits, and it is the reason I am writing about an ingredient that is not in any MIHIYO strip. Ashwagandha is one of the most visible and frequently studied adaptogens on the shelf right now, and customers ask me about it constantly. As a pharmacist, I would rather walk through what the data supports — and where the dosage form quietly decides whether the ingredient can work at all — than sell around the question.

What is ashwagandha, and how is it supposed to work?

Ashwagandha is the root of Withania somnifera, a shrub used in Ayurvedic medicine and now sold as a standardized extract. It is classed as an adaptogen — a compound proposed to raise the body's resistance to stress rather than acting like a sedative on a single receptor.

The active compounds are withanolides, naturally occurring steroidal lactones, with much of the pharmacology attributed to withaferin A and related molecules — though non-withanolide constituents such as alkaloids and sitoindosides may also contribute. A 2025 review in Cureus describes the proposed mechanism in two parts (Jamnekar et al., 2025⁷). First, preclinical and mechanistic research suggests withanolides may act on the hypothalamic-pituitary-adrenal (HPA) axis — the hormonal loop that releases cortisol under stress — by suppressing corticotropin-releasing hormone and improving the feedback sensitivity that normally tells the body to stop producing cortisol. Second, some withanolides appear to interact with GABA-A receptors, the same inhibitory channels benzodiazepines act on, which the review links to a possible anxiety-reducing effect without the heavy sedation of a drug.

These are plausible, largely animal- and lab-based mechanisms. The HPA-axis story in particular is consistent with the human cortisol data below. But a mechanism is a hypothesis about why something works — it is not proof that it works in people, and it is worth keeping the two separate.

What do the randomized trials and meta-analyses show?

The clinical case for ashwagandha rests on a stack of small randomized controlled trials, now pulled together by several meta-analyses. The cortisol signal is the strongest and most repeatable part of that record.

The most-cited single trial is Chandrasekhar and colleagues (2012), published in the Indian Journal of Psychological Medicine (Chandrasekhar et al., 2012¹). In 64 chronically stressed adults, 300 mg of a full-spectrum root extract taken twice daily for 60 days reduced serum cortisol by 27.9 percent from baseline, versus a 7.9 percent drop on placebo (p = 0.002), alongside a 44 percent fall on the Perceived Stress Scale. Lopresti and colleagues (2019), in Medicine (Baltimore), used a different concentrated extract at 240 mg once daily for 60 days in 60 adults and found a 23 percent reduction in morning cortisol against a slight rise on placebo (p < 0.001), with anxiety scores (HAM-A) down 41 percent versus 24 percent (Lopresti et al., 2019²).

Pooling these and others, peer-reviewed meta-analyses generally support a cortisol-lowering signal, while conclusions on perceived stress are less consistent. A 2024 meta-analysis in Explore of nine randomized trials and 558 participants found a perceived-stress mean difference of −4.72, a Hamilton anxiety mean difference of −2.19, and a serum-cortisol mean difference of −2.58 versus placebo (Arumugam et al., 2024⁵). A 2025 RCPsych congress abstract published in a BJPsych Open supplement — reviewed by the conference's academic faculty rather than through the journal's standard peer-review process — pooled 15 trials and 873 adults and likewise reported significant cortisol, anxiety, and perceived-stress reductions (Bachour et al., 2025⁴); I treat it as supporting rather than primary evidence for that reason.

Why the cortisol drop does not always match how people feel

Here is the tension a careful reader should sit with: lowering cortisol and lowering felt stress are not the same outcome, and the studies do not always move together.

A 2025 meta-analysis in Nutrition and Health set out to test exactly this. Across seven studies measuring cortisol and six measuring perceived stress (488 participants), ashwagandha produced a clear, significant cortisol reduction of −1.16 µg/dL (p < 0.001) — but no significant effect on perceived stress (standardized mean difference −0.355, p = 0.40) (Albalawi et al., 2025⁶). A larger, longer 2023 trial of a newer extract pointed the same way: in 120 stressed, fatigued adults over 12 weeks, perceived-stress scores fell about equally in both groups, with no significant separation from placebo (p = 0.867), even though fatigue and heart-rate variability did improve (Smith et al., 2023³).

So the picture is not that ashwagandha "does nothing." It is that the biochemical effect (cortisol down) is more reliable than the subjective effect (feeling calmer), and the gap may reflect a strong placebo response on questionnaire-based stress, short trial lengths, or genuinely modest real-world benefit. That distinction is exactly the kind of thing I think a supplement buyer deserves to hear plainly rather than have flattened into "clinically shown to reduce stress."

What this means for MIHIYO and the oral dissolving strip format

Ashwagandha is a good test of the question this whole brand is built around: does the dosage form fit the ingredient? For ashwagandha, an oral dissolving strip — a thin polymer film that dissolves against the oral tissues in 30 to 60 seconds — is the wrong tool, and I want to be direct about why.

The effective doses in every trial above are 240 to 600 mg of standardized extract per day. A thin oral film can practically carry only a small fraction of that before it becomes too thick to dissolve comfortably or hold against the mucosa. Formulation reviews of orodispersible films describe drug loading as a core limitation of the format: because films are small, light, and thin, they are generally best suited to potent, low-dose actives, and increasing the drug load can compromise film thickness, disintegration, mechanical properties, and patient acceptability (Ferlak et al., 2023⁹). You cannot put a 300 mg botanical dose into a strip and keep the mouthfeel and dissolution behavior that make the format work in the first place. From a formulation-design perspective — not a clinical claim — ashwagandha is a swallow-it ingredient: a capsule or tablet is the honest delivery vehicle for that payload.

There is a second, quieter reason. The strip format earns its keep when the route is the limiting variable — when crossing the oral mucosa meaningfully changes how much of the dose reaches the blood, as it does for low-dose melatonin or for the onset of caffeine (see why the dosage form matters as much as the ingredient). Ashwagandha's benefit is not framed in the literature as a first-pass or bioavailability problem that a mucosal route solves; it is a daily-dosing, weeks-to-effect ingredient. The strip would add no advantage even if the dose fit.

It is worth being precise about the format itself, too. An oral dissolving strip disintegrates in the mouth, and part of every dose is inevitably swallowed — so how much actually crosses the oral mucosa depends on the specific formulation and its contact time, not on the strip format by itself. The mucosal route is a design goal a film can be built toward for the right low-dose molecule; it is not an automatic property of being a film.

That is why our Mood-Boost ODS, formulated to support a sense of calm, is built around 5-HTP and L-theanine rather than ashwagandha: those actives are dosed low enough to fit a film, and at least one of them has a plausible route rationale. I would rather leave a popular ingredient off the label than pretend a format suits it when the milligrams say otherwise.

Where the ashwagandha evidence falls short

Even setting the dosage form aside, the ashwagandha literature has real limits worth stating.

The trials are small and short. Most enroll 60 to 130 people and run 8 to 12 weeks, so long-term safety and durability of effect are not well established. The extracts also differ — KSM-66, Shoden, Witholytin and others vary in withanolide standardization and dose — which means results from one branded extract do not automatically transfer to the unstandardized powder in a cheap capsule. Meta-analyses repeatedly flag this heterogeneity.

Safety is not trivial either. The NIH LiverTox database classifies ashwagandha as a likely cause of clinically apparent liver injury, usually mild-to-moderate and resolving within one to four months of stopping the product — though rare severe cases, including acute liver failure, have been described, and it advises against use in people with cirrhosis or advanced liver disease (LiverTox, 2024¹⁰). A 2024 case report in Cureus illustrates the pattern: a healthy 22-year-old developed jaundice and an ALT of 315 IU/L after roughly 1,800 mg over two days at label-recommended dosing, recovering over about nine weeks (Almuzghi et al., 2024⁸). Ashwagandha can also raise thyroid hormone levels, which is a problem for anyone with hyperthyroidism or on thyroid medication. The NIH's National Center for Complementary and Integrative Health notes ashwagandha may be safe short-term (up to about three months) but that its long-term safety is not established, and advises avoiding it during pregnancy and breastfeeding and using caution in people with thyroid or autoimmune disorders, those facing surgery, or anyone taking diabetes, blood-pressure, immunosuppressant, sedative, anticonvulsant, or thyroid medications (NCCIH, 2023¹¹). Commercial herbal products can also be mislabeled or adulterated. None of this makes ashwagandha unusually dangerous, but "natural" is not the same as "without contraindications," and it is worth a conversation with a clinician if you take other medications.

The bottom line

The ashwagandha stress evidence is a genuine signal with honest edges: standardized extracts at 240 to 600 mg daily lower cortisol by roughly 23 to 28 percent from baseline in controlled trials, anxiety scores tend to improve, but the effect on how stressed people actually feel is inconsistent across the best meta-analyses. It is a reasonable, reasonably-supported ingredient — taken as a swallowed capsule, at a standardized dose, by someone without thyroid, liver, or pregnancy concerns. It is not a fit for an oral dissolving strip, because the effective dose is far too large for a film and the benefit does not hinge on a mucosal route. At MIHIYO Labs, I would rather tell you that than sell you a strip the milligrams can't justify.

References

1. Chandrasekhar K, Kapoor J, Anishetty S. 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. Indian Journal of Psychological Medicine. 2012. PMID: 23439798. DOI: 10.4103/0253-7176.106022. https://pmc.ncbi.nlm.nih.gov/articles/PMC3573577/
2. Lopresti AL, Smith SJ, Malvi H, Kodgule R. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. Medicine (Baltimore). 2019. PMID: 31517876. DOI: 10.1097/MD.0000000000017186. https://pmc.ncbi.nlm.nih.gov/articles/PMC6750292/
3. Smith SJ, Lopresti AL, Fairchild TJ. Exploring the efficacy and safety of a novel standardized ashwagandha (Withania somnifera) root extract (Witholytin®) in adults experiencing high stress and fatigue in a randomized, double-blind, placebo-controlled trial. Journal of Psychopharmacology. 2023. PMID: 37740662. DOI: 10.1177/02698811231200023. https://pmc.ncbi.nlm.nih.gov/articles/PMC10647917/
4. Bachour S, et al. Effects of Ashwagandha Supplements on Cortisol, Stress, and Anxiety Levels in Adults: A Systematic Review and Meta-Analysis. BJPsych Open. 2025. DOI: 10.1192/bjo.2025.10136. https://pmc.ncbi.nlm.nih.gov/articles/PMC12242034/
5. Arumugam V, et al. Effects of Ashwagandha (Withania Somnifera) on stress and anxiety: A systematic review and meta-analysis. Explore (NY). 2024. PMID: 39348746. DOI: 10.1016/j.explore.2024.103062. https://pubmed.ncbi.nlm.nih.gov/39348746/
6. Albalawi AA. Dual impact of Ashwagandha: Significant cortisol reduction but no effects on perceived stress – A systematic review and meta-analysis. Nutrition and Health. 2025. DOI: 10.1177/02601060251363647. https://journals.sagepub.com/doi/abs/10.1177/02601060251363647
7. Jamnekar PP, Dehankar TJ, Bedre RV, Dharan BG, Agravat B, Agravat H. Ashwagandha as an Adaptogenic Herb: A Comprehensive Review of Immunological and Neurological Effects. Cureus. 2025. PMID: 41356880. DOI: 10.7759/cureus.96183. https://pmc.ncbi.nlm.nih.gov/articles/PMC12680924/
8. Almuzghi F, Abdelmalik A, Abuhlaiga M. Ashwagandha-Induced Hepatic Injury: A Case Report. Cureus. 2024. PMID: 39553154. DOI: 10.7759/cureus.71576. https://pmc.ncbi.nlm.nih.gov/articles/PMC11564894/
9. Ferlak J, Guzenda W, Osmałek T. Orodispersible Films—Current State of the Art, Limitations, Advances and Future Perspectives. Pharmaceutics. 2023. DOI: 10.3390/pharmaceutics15020361. PMC: 9965071. https://pmc.ncbi.nlm.nih.gov/articles/PMC9965071/
10. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Ashwagandha. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Updated 2024. Bookshelf ID: NBK548536. https://www.ncbi.nlm.nih.gov/books/NBK548536/
11. National Center for Complementary and Integrative Health. Ashwagandha: Usefulness and Safety. NIH NCCIH. Updated March 2023. https://www.nccih.nih.gov/health/ashwagandha

Note on reference 4: Bachour et al. (2025) is a congress abstract in a BJPsych Open supplement, reviewed by the conference's academic faculty rather than the journal's standard peer-review process. It is cited here as supporting, not primary, evidence.

By Jack Zheng, MS Pharmacy — Founder of MIHIYO Labs. Focused on the R&D of high-bioavailability, fast-absorption oral dissolving strips.