Ashwagandha (KSM-66)
The most clinically studied adaptogen. KSM-66 is the highest-concentration ashwagandha root extract, backed by 12+ RCTs demonstrating significant cortisol reduction, testosterone support, and sleep quality improvement.
Reviewed & fact-checked by
Dr. Jane Smith, MD, PhDChief Medical Reviewer · Last updated: March 1, 2026
Medical Disclaimer: The information on this page is for educational and research purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
Mechanism of Action
Ashwagandha (Withania somnifera) is an Ayurvedic herb with the most extensive evidence base among all adaptogens. The standardised KSM-66 extract contains ≥5% withanolides and is the gold standard among commercial formulations.
Key mechanisms:
- HPA axis inhibition — reduces activity of the hypothalamic-pituitary-adrenal axis, lowering cortisol secretion in response to stress
- GABA receptor modulation — withanolides bind to GABA-A receptors, explaining the anxiolytic and sedative effects
- Testosterone support — cortisol reduction indirectly raises testosterone (cortisol competitively inhibits steroidogenesis in Leydig cells) []
Clinical Evidence
A 2021 meta-analysis (5 RCTs, n=400) confirmed significant cortisol reduction and improved subjective stress scores at 300–600 mg/day of KSM-66. []
A separate RCT demonstrated improved sleep quality scores (PSQI) and a 72% reduction in time to fall asleep compared to placebo at 600 mg before bed. []
Stacking Interactions
How Ashwagandha (KSM-66) interacts with other compounds
Both improve sleep architecture via different mechanisms. Ashwagandha reduces cortisol; Magnesium Threonate crosses the blood-brain barrier and supports NMDA receptor function. Excellent evening stack.
Complementary hormonal stack: Ashwagandha reduces cortisol (which suppresses testosterone), while Tongkat Ali directly supports LH and testosterone production.
Safety Profile — Tier A
Well-tolerated — strong human evidence
Contraindications
- ●Thyroid disorders — may alter thyroid hormone levels
- ●Autoimmune conditions (Hashimoto's, MS, lupus)
- ●Pregnancy — may cause uterine contractions
Side Effects
- ●Drowsiness (dose-dependent, often desirable for sleep protocols)
- ●Gastrointestinal upset at high doses
- ●Rare: liver toxicity at very high doses (>1000mg/day long-term)