Standardized Ashwagandha Extract Significantly Reduces Markers of Stress in Participants with Generalized Anxiety Disorder

by | Jan 27, 2025 | 2024, Ashwagandha, Botanicals, Brain Health, Recent Articles, Stress

Written by Chrystal Moulton, Science Writer. Results from this trial suggests that ashwagandha extract standardized to 35% withanolide glycosides at 60mg and 120mg significantly improved markers of stress in non-depressed high stress patients diagnosed with generalized anxiety disorder with no significant difference between both treatment doses.

man with hands to head, depressed, stressedGeneralized anxiety disorder [GAD] is characterized by difficulty concentrating, sleep disturbance, irritability, muscle tension, fatigued, and restlessness. Individuals who present 3 or more of the aforementioned symptoms are diagnosed with this disorder1. GABA or gamma-aminobutyric acid and serotonin play a key role in generalized anxiety disorder [GAD]2,3. Both neurotransmitters affect the hypothalamic-pituitary-adrenal axis which modulates the body’s stress response2,4. Ashwagandha is an adaptogenic herd used for promoting sleep and reducing stress5,6. Clinical trials have shown that withanolide glycosides, active compounds present in ashwagandha, modulate the hypothalamic-pituitary-adrenal axis by reducing cortisol levels and increasing serotonin and acetylcholine7,8.  Standardized extracts consisting of 35% withanolide glycosides proved effective in reducing stress in participants5,8,9. In the current trial, researchers investigated the effect of a 35% standardized extract of ashwagandha at 60mg and 120mg versus placebo in reducing stress in non-depressed individuals with high stress and anxiety10.

This study was designed as a double blind, randomized, placebo-controlled trial enlisting patients from an outpatient facility. Participants were 18-60 years old, with serum cortisol >25mg/dl, a clinical global impression score ≥4, and Hamilton Anxiety Rating Scale [HAM-A] score ≥20 [with item 1 & 2 on questionnaire ≥2]. Night shift workers were excluded as well as individuals with depression. Upon inclusion, volunteers were allocated on a 1:1:1 basis. Ashwagandha extract using a water and alcohol ratio of 30:70 for extraction was standardized to 35% withanolide glycosides at 60mg and 120mg. Microcrystalline cellulose was used for the placebo. Participants were required to take one capsule of their assigned protocol daily for 60 days. Every 15 days from baseline, researchers assessed HAM-A scores, serum cortisol, and testosterone. Every 30 days from baseline, researchers assessed clinical global impression score [CGI], perceived stress scale scores [PSS], and patient global impression of change [PGIC], which assessed subject change in stress levels. The primary outcome was changes HAM-A scores from baseline to 60 days. Secondary outcomes included changes in serum cortisol and testosterone.

A total of 60 volunteers was allocated to either 60mg ashwagandha extract, 120mg ashwagandha extract, or placebo. Participant compliance to the assigned treatment protocol was 100%. Researchers observed a significant 59% decrease in HAM-A scores in both ashwagandha treatment groups (intervention and time interaction p< 0.0001). Serum cortisol decreased by 66% in the 60mg ashwagandha treatment group and 67% in the 120mg ashwagandha treatment group (intervention and time interaction p< 0.0001). Serum testosterone showed no significant change in female participants. However, in male participants, testosterone levels went up by 33% in the 120mg ashwagandha treatment group and 22% in the 60mg ashwagandha treatment group (intervention and time interaction p< 0.0001). Perceived Stress scale decreased by 53% in the 60mg ashwagandha treatment group and 62% in the 120mg ashwagandha treatment group (intervention and time interaction p< 0.0001). Clinical global impression scores and patient global impression scores also increased significantly by the end of the trial.

Results from this trial suggests that ashwagandha extract standardized to 35% withanolide glycosides at 60mg and 120mg significantly improved markers of stress in non-depressed high stress patients diagnosed with generalized anxiety disorder with no significant difference between both treatment doses. Findings in this study agree with other trials on the effectiveness of ashwagandha on reducing stress. Additional studies will be needed to address clinical application of ashwagandha for generalized anxiety disorder.

Source: Mishra, Deo Nidhi, and Manoj Kumar. “Shoden promotes Relief from stress and anxiety: A randomized, double-blind, placebo-controlled study on healthy subjects with high stress levels.” Heliyon 10, no. 17 (2024).

© 2024 The Authors. 

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Posted January 27, 2025.

Chrystal Moulton BA, PMP, is a 2008 graduate of the University of Illinois at Chicago. She graduated with a bachelor’s in psychology with a focus on premedical studies and is a licensed project manager. She currently resides in Indianapolis, IN.

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