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).



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