Ashwagandha — Withania somnifera

Common & Latin Names

Common names: Ashwagandha, Indian ginseng, Winter cherry Latin name: Withania somnifera (L.) Dunal Sanskrit: Ashwagandha (meaning “smell of the horse” — referring both to the root’s scent and its reputation for conferring the strength and vitality of a stallion) TCM name: Shui Qie (睡茄) — not a classical TCM herb but increasingly integrated into modern Chinese integrative practice Hindi: Asgandh

Plant Family & Parts Used

Family: Solanaceae (nightshade family — related to tomato, potato, and belladonna) Parts used: Primarily the root (most studied, richest in withanolides). Leaves are also used in traditional preparations and contain withanone and withaferin A. Berries used topically in traditional practice. Habitat: Native to the dry regions of India, the Middle East, and northern Africa. Grows in arid, subtropical climates. Cultivated extensively in Madhya Pradesh, Rajasthan, and Gujarat, India.

Traditional Uses

Ayurvedic Medicine (3,000+ years)

Ashwagandha is one of the most important herbs in Ayurveda, classified as a Rasayana — a rejuvenative tonic that promotes longevity, vitality, and resistance to disease. In the Charaka Samhita (one of the foundational Ayurvedic texts, circa 600 BCE), ashwagandha is described as a Balya (strength-promoting), Vajikara (aphrodisiac), and Medhya Rasayana (intellect-promoting) herb.

Traditional Ayurvedic uses include:

• Shoshira (emaciation, debility, failure to thrive in children)
• Kshaya (wasting diseases, tuberculosis)
• Infertility and sexual debility in men and women
• Vata disorders: anxiety, insomnia, tremors, nervous exhaustion
• Joint pain and inflammation (Amavata — rheumatic conditions)
• Preparation of Ashwagandha Churna (powder mixed with ghee, warm milk, and honey) and Ashwagandharishta (fermented liquid preparation)

Western Herbalism

Classified as a premier adaptogen in modern Western herbal practice. Used for chronic stress, adrenal fatigue/HPA axis dysregulation, insomnia, anxiety, cognitive decline, hypothyroidism support, and immune modulation. It entered Western awareness primarily through the adaptogen research of Israel Brekhman and the subsequent work of David Winston and Steven Maimes.

Indigenous & Folk Traditions

In traditional African medicine (particularly South Africa, where Withania somnifera grows wild), the root has been used for inflammation, fevers, and as a general tonic. In the Middle East, it has folk use as a sedative and treatment for skin diseases.

Active Compounds & Pharmacology

Primary Phytochemicals

Withanolides (steroidal lactones): The signature compounds of ashwagandha, comprising over 40 identified structures. The most studied include:

• Withaferin A: Potent anti-inflammatory and anti-cancer compound. Inhibits NF-kB signaling, angiogenesis (via vimentin binding), and proteasome activity. Primarily concentrated in leaves.
• Withanolide D: Immunomodulatory. Enhances Th1 immunity.
• Withanoside IV and V: Neuroprotective. Converted to sominone in the body, which promotes neurite outgrowth and dendrite extension.
• Withanone: Anti-aging and neuroprotective effects.

Sitoindosides (withanolide glycosides): Sitoindosides VII-X are potent anti-stress and immunomodulatory compounds isolated from the root.

Alkaloids: Including isopelletierine, anaferine, cuseohygrine, anahygrine, tropine. Contribute to sedative and anxiolytic effects.

Other compounds: Saponins, iron, flavonoids, condensed tannins, steroidal saponins.

Mechanisms of Action

1. HPA Axis Modulation: Ashwagandha reduces cortisol by attenuating CRH (corticotropin-releasing hormone) output from the hypothalamus. It acts as a bidirectional adaptogen — normalizing cortisol whether elevated (Stage 1 HPA dysfunction) or depleted (Stage 3). The withanolides appear to modulate glucocorticoid receptor sensitivity, enhancing negative feedback so the axis self-corrects.

2. GABAergic Activity: Withanolides are positive allosteric modulators of GABA-A receptors, explaining the anxiolytic and sleep-promoting effects without cognitive impairment. This is a different binding site than benzodiazepines — no dependency or tolerance develops.

3. Thyroid Support: Ashwagandha stimulates thyroid hormone production. A study by Sharma et al. (2018, Journal of Alternative and Complementary Medicine) demonstrated significant increases in serum T4 and T3 in subclinical hypothyroid patients. Mechanism likely involves enhanced TSH signaling and direct thyrocyte stimulation.

4. Neuroprotection and Neuroregeneration: Withanosides promote neurite outgrowth, axonal regeneration, and dendrite extension via the sominone metabolite. Withaferin A inhibits beta-amyloid aggregation. Ashwagandha enhances BDNF (brain-derived neurotrophic factor) expression and supports acetylcholine synthesis.

5. Anti-inflammatory: Withaferin A is a potent NF-kB inhibitor. Ashwagandha also inhibits COX-2 and reduces pro-inflammatory cytokines (TNF-alpha, IL-6, IL-1beta). WFA inhibits NLRP3 inflammasome activation.

6. Immunomodulation: Enhances natural killer cell activity, macrophage function, and Th1 immune responses. Increases IgG and IgM antibody production. Simultaneously calms excessive Th2/allergic responses.

7. Testosterone and Reproductive Support: In men, ashwagandha significantly increases testosterone, luteinizing hormone, and sperm quality. Mechanisms include reduced oxidative stress in testicular tissue, enhanced StAR protein expression (cholesterol transport into mitochondria for steroidogenesis), and cortisol reduction (cortisol directly suppresses GnRH and testosterone production).

Clinical Evidence

Key Clinical Trials

Chandrasekhar, K., Kapoor, J., & Anishetty, S. (2012). “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, 34(3), 255-262.

• 64 adults with chronic stress, randomized to KSM-66 300mg twice daily or placebo for 60 days
• Results: 27.9% reduction in serum cortisol (p<0.0006). Significant reductions on all stress-assessment scales (PSS, GHQ-28, DASS). Improved sleep quality.
• This remains the most frequently cited ashwagandha RCT for cortisol reduction.

Lopresti, A.L., Smith, S.J., Malvi, H., & Kodgule, R. (2019). “An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study.” Medicine, 98(37), e17186.

• 60 adults, KSM-66 240mg daily or placebo for 60 days
• Results: Significant reduction in morning cortisol (p=0.031), DHEA-S increase (p=0.004), testosterone increase (p=0.038). Hamilton Anxiety Rating Scale improved significantly.
• Notable for demonstrating hormonal benefits beyond cortisol alone.

Langade, D., Kanchi, S., Salve, J., Debnath, K., & Ambegaokar, D. (2019). “Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Insomnia and Anxiety: A Double-blind, Randomized, Placebo-controlled Study.” Cureus, 11(9), e5797.

• 58 participants, ashwagandha root extract 300mg twice daily for 10 weeks
• Results: Significant improvement in sleep quality (SOL, SE, PSQI), reduction in anxiety (HAM-A)

Wankhede, S., Langade, D., Joshi, K., Sinha, S.R., & Bhattacharyya, S. (2015). “Examining the effect of Withania somnifera supplementation on muscle strength and recovery.” Journal of the International Society of Sports Nutrition, 12, 43.

• 57 young male subjects, 300mg KSM-66 twice daily for 8 weeks during resistance training
• Results: Significantly greater increases in muscle strength (bench press, leg extension), muscle size, testosterone levels, and significantly greater reduction in exercise-induced muscle damage and body fat percentage.

Sharma, A.K., Basu, I., & Singh, S. (2018). “Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients: A Double-Blind, Randomized Placebo-Controlled Trial.” Journal of Alternative and Complementary Medicine, 24(3), 243-248.

• 50 subjects with elevated TSH (4.5-10 mIU/L), 600mg ashwagandha root extract daily for 8 weeks
• Results: Significant normalization of TSH, T3, and T4 levels versus placebo.

Systematic Reviews

Bonilla, D.A., et al. (2021). “Effects of Ashwagandha (Withania somnifera) on Physical Performance: Systematic Review and Bayesian Meta-Analysis.” Journal of Functional Morphology and Kinesiology, 6(1), 20. — Confirmed significant improvements in VO2max, strength, and recovery.

Pratte, M.A., et al. (2014). “An Alternative Treatment for Anxiety: A Systematic Review of Human Trial Results Reported for the Ayurvedic Herb Ashwagandha.” Journal of Alternative and Complementary Medicine, 20(12), 901-908. — Five RCTs analyzed, all showed significant anxiolytic effects.

Therapeutic Applications

Conditions

• HPA axis dysregulation (all stages — calms excess cortisol in Stage 1, supports depleted cortisol in Stage 3)
• Generalized anxiety disorder
• Insomnia and sleep quality impairment
• Subclinical and clinical hypothyroidism (as adjunct)
• Male infertility and low testosterone
• Cognitive decline and memory impairment
• Exercise performance and recovery
• Chronic fatigue
• Immune modulation (autoimmunity and immunodeficiency)

Dosage Ranges

• KSM-66 extract (standardized to 5% withanolides): 300-600mg daily. Most studied form.
• Sensoril extract (standardized to 10% withanolides from leaves+roots): 125-250mg daily. Higher withanolide concentration — lower milligram dose needed.
• Root powder (churna): 3-6g daily, traditionally mixed with warm milk, ghee, or honey.
• Tincture (1:3 or 1:5 in 45% alcohol): 2-4mL, 2-3 times daily.
• Ashwagandharishta (traditional fermented preparation): 15-30mL twice daily.

Forms

Best absorbed with fat (lipophilic withanolides). Taking with meals or milk improves bioavailability. Morning dosing for energy and thyroid support. Evening dosing for sleep and cortisol reduction. Can be split AM/PM for comprehensive effects.

Safety & Contraindications

Generally Well Tolerated

Ashwagandha has an excellent safety profile across clinical trials, with adverse effects similar to placebo in most studies. The LD50 in animal studies is extremely high (1500mg/kg in rats — equivalent to roughly 100g for a human).

Contraindications

• Pregnancy: Traditionally classified as an abortifacient in high doses in Ayurvedic texts. Withaferin A has shown embryotoxicity in animal models. Avoid during pregnancy.
• Nightshade sensitivity: As a member of Solanaceae, ashwagandha may trigger reactions in individuals with nightshade intolerance (rare but possible).
• Hyperthyroidism or Graves’ disease: Ashwagandha stimulates thyroid hormone production. Adding it to an already overactive thyroid can worsen symptoms. Contraindicated unless thyroid is controlled and monitored.
• Autoimmune conditions (nuanced): Because ashwagandha enhances immune function, theoretical concern exists for autoimmune flares. In practice, ashwagandha is immunomodulatory rather than purely immunostimulatory — it tends to balance rather than amplify. However, caution is warranted in active autoimmune flares, particularly Hashimoto’s (paradox: it helps thyroid but may stimulate antibodies in some patients).
• Pre-surgical: Discontinue 2 weeks before surgery due to potential CNS depressant and blood pressure effects under anesthesia.

Drug Interactions

• Thyroid medications (levothyroxine): Ashwagandha may potentiate effects, requiring dose adjustment. Monitor TSH closely.
• Sedatives and anxiolytics (benzodiazepines, barbiturates): Additive CNS depression possible.
• Immunosuppressants: Theoretical concern of counteracting immunosuppressive drugs.
• Antihypertensives: Ashwagandha may lower blood pressure — additive effect.
• Diabetes medications: Ashwagandha lowers blood sugar — monitor for hypoglycemia.

Side Effects (Uncommon)

GI discomfort (usually with high doses on an empty stomach), drowsiness (at higher doses), rare thyroid over-stimulation. Very rare: liver injury reports exist but are confounded by product contamination and multi-ingredient formulas.

Energetics

Ayurvedic Classification

• Rasa (taste): Tikta (bitter), Kashaya (astringent), Madhura (sweet — the sweet after-taste emerges as the herb is metabolized)
• Virya (energy/potency): Ushna (warming)
• Vipaka (post-digestive effect): Madhura (sweet)
• Dosha effects: Primarily pacifies Vata and Kapha. Its warming virya may slightly increase Pitta in excess, though its adaptogenic nature moderates this.
• Dhatu (tissue) affinity: Mamsa (muscle), Asthi (bone), Majja (nerve/marrow), Shukra (reproductive)
• Srotas (channel) affinity: Mamsavaha (muscular), Majjavaha (nervous), Shukravaha (reproductive), Annavaha (digestive)
• Prabhava (special potency): Medhya Rasayana — specific rejuvenative for the mind and nervous system

TCM Classification (Modern Integration)

Though not a classical TCM herb, modern integrative practitioners classify ashwagandha as:

• Temperature: Warm
• Flavor: Bitter, slightly sweet
• Meridian entry: Kidney, Liver, Heart
• Actions: Tonifies Kidney Yang and Kidney Jing, calms Shen, nourishes Heart Blood, strengthens Wei Qi
• TCM pattern correspondence: Kidney Yang Deficiency with Shen disturbance — the patient who is exhausted, cold, has low libido, poor memory, and anxiety. This is ashwagandha’s sweet spot.

Functional Medicine Integration

Ashwagandha is arguably the single most versatile herb in functional medicine practice. It addresses multiple nodes simultaneously:

HPA Axis Protocol

The first-line adaptogen in Stage 1 (cortisol-lowering: Chandrasekhar 2012 showed 27.9% reduction) and valuable in Stage 3 (adrenal recovery support through axis normalization rather than stimulation). It does not simply lower or raise cortisol — it restores the axis’s ability to self-regulate.

Thyroid Protocol

Adjunct in subclinical hypothyroidism (Sharma 2018). Supports T4 to T3 conversion. Addresses the adrenal-thyroid connection — many patients with “thyroid resistance” actually have HPA dysfunction preventing thyroid hormone utilization. Ashwagandha treats both axes simultaneously.

Gut-Brain Axis

Reduces stress-induced gut permeability (cortisol opens tight junctions). Anti-inflammatory effects benefit the intestinal mucosa. Modulates the gut-brain vagal pathway through GABAergic and serotonergic activity.

Immune Modulation

Enhances NK cell activity and Th1 immunity while modulating excessive Th2/inflammatory responses. Useful in chronic infection protocols and as immune support during illness recovery.

Metabolic Health

Improves insulin sensitivity (cortisol reduction plus direct effects on glucose metabolism), supports lean body mass (testosterone enhancement), reduces visceral fat.

Men’s Health Protocol

Supports testosterone production, sperm quality, exercise recovery, and stress resilience — the four pillars of male vitality in functional medicine.

Four Directions Connection

Primary Direction: Serpent (South — Physical Body)

Ashwagandha’s deepest affinity is with the Serpent direction — the physical body, the instinctual self, the root. It strengthens the body from the ground up: muscles, bones, reproductive capacity, immune resilience. In Ayurveda, it is the herb that gives the “strength of a horse” — raw physical vitality. The Serpent teaches us to shed what no longer serves and to heal through direct, embodied action. Ashwagandha does exactly this at the physiological level — it helps the body shed the accumulated damage of chronic stress and rebuild from the foundation.

Secondary Direction: Jaguar (West — Emotional Healing)

The anxiolytic and sleep-promoting effects of ashwagandha serve the Jaguar’s domain — the emotional body, the shadow, the place where we face fear and transform it. Chronic anxiety lives in the Jaguar’s territory. Ashwagandha’s GABAergic activity calms the fear response without numbing it, allowing the emotional processing that the Jaguar demands. It helps us step into the cave of our own shadow without being overwhelmed.

Tertiary: Eagle (East — Spiritual Vision)

Through its classification as a Medhya Rasayana — a rejuvenative of the mind — ashwagandha supports the clarity and stillness required for spiritual practice. In the yogic tradition, a calm nervous system is the prerequisite for meditation. The Eagle sees from the highest vantage — and ashwagandha clears the fog that prevents us from rising to that perspective.

References

1. Chandrasekhar, K., Kapoor, J., & Anishetty, S. (2012). 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, 34(3), 255-262.

2. Lopresti, A.L., Smith, S.J., Malvi, H., & Kodgule, R. (2019). An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract. Medicine, 98(37), e17186.

3. Langade, D., Kanchi, S., Salve, J., Debnath, K., & Ambegaokar, D. (2019). Efficacy and Safety of Ashwagandha Root Extract in Insomnia and Anxiety. Cureus, 11(9), e5797.

4. Wankhede, S., Langade, D., Joshi, K., Sinha, S.R., & Bhattacharyya, S. (2015). Examining the effect of Withania somnifera supplementation on muscle strength and recovery. Journal of the International Society of Sports Nutrition, 12, 43.

5. Sharma, A.K., Basu, I., & Singh, S. (2018). Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients. Journal of Alternative and Complementary Medicine, 24(3), 243-248.

6. Pratte, M.A., et al. (2014). An Alternative Treatment for Anxiety: A Systematic Review of Human Trial Results Reported for the Ayurvedic Herb Ashwagandha. Journal of Alternative and Complementary Medicine, 20(12), 901-908.

7. Bonilla, D.A., et al. (2021). Effects of Ashwagandha on Physical Performance: Systematic Review and Bayesian Meta-Analysis. Journal of Functional Morphology and Kinesiology, 6(1), 20.

8. Singh, N., Bhalla, M., de Jager, P., & Gilca, M. (2011). An Overview on Ashwagandha: A Rasayana (Rejuvenator) of Ayurveda. African Journal of Traditional, Complementary and Alternative Medicines, 8(5S), 208-213.

9. Mirjalili, M.H., Moyano, E., Bonfill, M., Cusido, R.M., & Palazon, J. (2009). Steroidal lactones from Withania somnifera, an ancient plant for novel medicine. Molecules, 14(7), 2373-2393.

10. Dar, N.J., Hamid, A., & Ahmad, M. (2015). Pharmacologic overview of Withania somnifera, the Indian Ginseng. Cellular and Molecular Life Sciences, 72(23), 4445-4460.