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Ashwagandha
Ashwagandha ( Withania somnifera; WS ) is an Ayurvedic herb that has been used as a broad-spectrum remedy in India for centuries, with the roots being classified as a “rasayana,” a medicine used to enhance both physical and mental performance (1). WS has recognised anti-inflammatory (2,3) and antioxidant properties (4) and is often referred to as “Indian Ginseng” due to its use in India to “balance life forces” during stress and ageing. It is often included in formulations for the treatment of musculoskeletal conditions and as a broad tonic to increase energy and improve general health. However, it has only recently been investigated in laboratory settings specifically for the treatment of stress and anxiety.
It has been reported that WS comprises over 35 chemical constituents, of which the biologically active compounds are alkaloids, steroidal lactones, saponins containing an additional acyl group, and withanolides with a glucose at carbon 27 (4). Withaferin A and Withanolide D are thought to be important active constituents with regard to the adaptogenic effects of this plant (5,6). WS has been shown to possess GABA-mimetic properties (7,8) and it is thought that these properties may underlie the anxiolytic effects of WS. Antioxidant activity of glycowithanolides may also explain the anti-stress effects of WS (1).
Anxiety and Stress
Anxiolytic effects and increased stress tolerance have been demonstrated with WS treatment in preclinical studies (9-12). In a comparative study of WS and Panax ginseng , both plant extracts significantly reduced stress compared with saline control (13). Additionally, the anxiolytic effects of WS have been found to be comparable to benzodiazepines, as anxiolytic effects equal to lorazepam (14). This indicates that WS may have similar efficacy to prescription drugs, but with a more favourable side-effect profile.
A recent systematic review of 62 WS human trials included five randomised placebo- controlled trials (RCTs) in human subjects and also included a treatment arm with WS as a remedy for stress or anxiety (15). In an RCT in clinically anxious patients, a significantly greater proportion of patients receiving WS met the criteria for response than those in the placebo group following 6-week treatment (16). A more recent study by Auddy (17) demonstrated a dose-dependent improvement for HAM score, suggesting that higher doses may be more effective for the treatment of anxiety.
Cooley (18) divided participants with moderate to severe anxiety of longer than 6 weeks’ duration into two groups who received either weekly counselling sessions from a naturopathic doctor as well as WS, or cognitive-behavioural therapy (CBT) sessions and placebo. Anxiety was significantly reduced in the naturopathic care group compared with the psychotherapy group.
Chandrasekhar reported ashwagandha delivered significant improvements in scores on the Perceived Stress Scale (PSS-10) and the General Health Questionnaire (GHQ-28), as well as reductions in levels of serum cortisol using a non-clinical adult sample (19).
Executive Function and Memory
A prospective RCT of WS in 50 adults over 8 weeks, demonstrated a significantly greater improvement in executive function, sustained attention, and information processing speed as indicated by validated tests compared to placebo. WS to be found to be effective in enhancing both immediate and general memory in people with mild cognitive impairment (20).
In a double-blind, RCT, WS was assessed in subjects under chronic stress. Primary efficacy measures were Perceived Stress Scale and Food Cravings Questionnaire. Secondary efficacy measures were Oxford Happiness Questionnaire, Three-Factor Eating Questionnaire, serum cortisol, body weight, and body mass index. WS resulted in significant improvements in primary and secondary measures (21).
References
1. Kulkarni SK, Dhir A. Withaniasomnifera : an Indian ginseng. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(5):1093–105.
2. Provino R. The role of adaptogens in stress management. Australian J Med Herbalism. 2010;22(2):41–9.
3. Alramadhan E et al. Dietary and botanical anxiolytics. Med Sci Monit. 2012;18(4):RA40–8
4. Mishra LC, Singh BB, Dagenais S. Scientifi c basis for the therapeutic use of Withaniasomnifera (ashwagandha): a review. Altern Med Rev. 2000;5(4):334–46.
5. Schliebs R et al. Systemic administration of defined extracts from Withaniasomnifera (Indian Ginseng) and Shilajit differentially affects cholinergic but not glutamatergic and gabaergic markers in rat brain. Neurochem Int. 1997;30(2):181–90.
6. Matsuda H et al. Structures of withanosides I, II, III, IV, V, VI, and VII, new withanolide glycosides, from the roots of Indian Withaniasomnifera DUNAL. and inhibitory activity for tachyphylaxis to clonidine in isolated guinea-pig ileum. Bioorg Med Chem. 2001;9(6):1499–507.
7. Kulkarni S et al. GABA receptor mediated anticonvulsant action of Withaniasomnifera root extract. Indian Drugs. 1993;30(7):305–12.
8. Mehta A et al. Pharmacological effects of Withaniasomnifera root extract on GABAA receptor complex. Indian J Med Res. 1991;94:312–5.
9. Bhattacharya SK, Muruganandam AV. Adaptogenic activity of Withaniasomnifera : an experimental study using a rat model of chronic stress. Pharmacol Biochem Behav. 2003;75(3):547–55.
10. Bhattacharya SK et al. Anti-stress activity of sitoindosides VII and VIII, new acylsterylglucosides from Withaniasomnifera . Phytother Res. 1987;1(1):32–7.
11. Archana R, Namasivayam A. Antistressor effect of Withaniasomnifera . J Ethnopharmacol. 1998;64(1):91–3.
12. Dadkar VN, Ranadive N, Dhar H. Evaluation of antistress (adaptogen) activity of Withaniasomnifera (ashwagandha).Ind J Clin Bio Chem. 1987;2:101–8.
13. Grandhi A, Mujumdar AM, Patwardhan B. A comparative pharmacological investigation of Ashwagandha and Ginseng. J Ethnopharmacol. 1994;44(3):131–5.
14. Bhattacharya SK et al. Anxiolytic-antidepressant activity of Withaniasomnifera glycowithanolides: an experimental study. Phytomedicine. 2000;7(6):463–9.
15. Pratte MA et al. An alternative treatment for anxiety: a systematic review of human trial results reported for the Ayurvedic Herb Ashwagandha ( Withaniasomnifera ). J Altern Complement Med. 2014;20(12):901–8.
16. Andrade C et al. A double-blind, placebo-controlled evaluation of the anxiolytic effi cacy ff an ethanolic extract of Withaniasomnifera . Indian JPsychiatry. 2000;42(3):295.
17. Auddy B, Hazra PJ, Mitra PA. A standardized Withaniasomnifera extract signifi cantly reduces stress-related parameters in chronically stressed humans: a double-blind, randomized, placebo-controlled study. J Am Nutraceutical Assoc. 2008;11:50–6.
18. Cooley K et al. Naturopathic care for anxiety: a randomized controlled trial ISRCTN78958974. PLoS One. 2009;4(8):e6628.
19. K. Chandrasekhar, J Kapoor, S Anishetty- 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 J Psychol Med. 2012 Jul-Sep; 34(3): 255–262.
20. Choudhary D, Bhattacharyya S, Bose S. Efficacy and Safety of Ashwagandha (Withania somnifera (L.) Dunal) Root Extract in Improving Memory and Cognitive Functions. Journal of Dietary Supplements. 2017 Nov 2;14(6):599-612.
21. Choudhary D, Bhattacharyya S, Joshi K. Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract: A Double-Blind, Randomized, Placebo-Controlled Trial. Journal of evidence-based complementary & alternative medicine. 2017 Jan;22(1):96-106.
