Ashwagandha contains a group of naturally occurring compounds called withanolides, which are responsible for most of its biological effects. Over 300 individual withanolides have been identified in the plant, along with alkaloids, flavonoids, saponins, and other plant chemicals. The two most studied are withaferin A and withanolide D, which drive the stress-reducing and anti-inflammatory properties the plant is known for.
The Key Active Compounds
Withanolides are steroidal compounds built on an ergostane skeleton, a structure similar to hormones your body already produces. This structural similarity is part of why they can interact with hormone receptors and stress-response pathways. Withaferin A, the first withanolide ever isolated from ashwagandha (identified in 1965), is the most extensively researched. It can bind to glucocorticoid receptors in the brain, which are the same receptors your body’s stress hormone, cortisol, uses.
Beyond withanolides, ashwagandha contains alkaloids like somniferine, withamine, and anaferine; plant sterols like beta-sitosterol; amino acids like cysteine; and phenolic compounds including chlorogenic acid and scopoletin. It also contains withanosides, which are sugar-bound versions of withanolides that may behave differently in the body. Researchers have isolated at least seven distinct withanosides from root extracts alone.
How These Compounds Affect Your Body
The most well-documented effect is cortisol reduction. Clinical trials consistently show ashwagandha lowers cortisol levels in stressed adults, with reductions ranging from about 11% to 33% depending on the study and the population. One trial found a 27.9% drop in blood cortisol from baseline; another reported up to 30.5% in a dose-dependent pattern, meaning higher doses produced larger reductions.
This happens through your body’s stress command center, the hypothalamic-pituitary-adrenal (HPA) axis. When you’re stressed, this system triggers cortisol release from your adrenal glands. Withanolides appear to dial down this response at multiple points. Withaferin A binds directly to glucocorticoid receptors and promotes their movement into the cell nucleus, where they can suppress inflammatory signaling pathways. Essentially, the compounds mimic part of what cortisol does at the receptor level, which may signal the body to produce less of it.
Ashwagandha also interacts with GABA receptors, the same calming brain receptors targeted by sleep medications and anti-anxiety drugs. Research shows it increases GABA content in the brain and boosts the expression of both GABA-A and GABA-B receptors, along with serotonin receptors. Interestingly, it’s not the withanolides doing this. Studies have confirmed that withaferin A and withanolide A alone don’t activate GABA receptors, meaning other compounds in the whole plant extract are responsible for the calming and sleep-promoting effects.
Root vs. Leaf: Different Parts, Different Chemistry
Not all ashwagandha products contain the same thing. The root is what traditional Ayurvedic medicine has used for centuries and what most clinical research is based on. It contains a balanced, predictable range of withanolides. Leaf extracts are cheaper to produce but vary more in their chemical composition, which makes their effects less consistent and their long-term safety less well understood.
Some supplements blend root and leaf material without making this clear on the label. If consistency matters to you, look for products that specify “root extract” rather than just “ashwagandha extract.”
What Standardized Extracts Contain
Because the raw plant’s chemistry varies with growing conditions, soil quality, and harvesting time, most clinical research uses standardized extracts with a guaranteed percentage of withanolides. The two most common branded extracts are KSM-66 and Sensoril, and they differ in meaningful ways.
KSM-66 is made exclusively from the root and standardized to 5% withanolides. Sensoril uses both root and leaf material and is standardized to 10% withanolides. The higher withanolide percentage in Sensoril doesn’t necessarily mean it’s “stronger” because the specific withanolide profile differs between root-only and root-leaf blends, and because other non-withanolide compounds also contribute to the plant’s effects.
Clinical studies on stress and anxiety have used daily doses ranging from 120 to 600 mg of standardized extract, typically taken for 4 to 12 weeks. The most common protocol is 150 to 600 mg per day, split into one or two doses taken with water.
What to Watch For in Supplements
Ashwagandha supplements are not tightly regulated for contaminants. The UK’s Food Standards Agency has noted there are no established safe limits for its use in food supplements and has specifically flagged the need for more data on heavy metal levels in finished products. Since ashwagandha is a root crop, it can absorb lead, arsenic, and other metals from soil. Third-party testing certifications (like NSF or USP seals) offer some assurance that a product has been screened.
Certain people should avoid ashwagandha entirely. The National Center for Complementary and Integrative Health advises against its use during pregnancy, while breastfeeding, or before surgery. It’s also not recommended for people with autoimmune conditions, thyroid disorders, or hormone-sensitive prostate cancer (since it may raise testosterone). Ashwagandha can interact with medications for diabetes, high blood pressure, thyroid conditions, and seizures, as well as with sedatives and immunosuppressants.