Ashwaganda (WS): Anxiety and Stress

Brief description of patient problem/setting: A 23-year-old College Female with pmhx of anxiety presents to Urgent care complaining of stress. The patient states that googled told her Ashwagandha (WS) helps with anxiety and stress, and she wants to know if it is true.

Search Question: In adults older than 18, is Ashwagandha (WS) more effective than no intervention in preventing and alleviating anxiety and stress? 

Question Type: What kind of question is this? (Boxes now checkable in Word)

– Prevention and Treatment

If the highest level of evidence to answer your question will be meta-analysis or systematic review, what other types of study might you include if these are not available (or if there is a much more current study of another type)? Please explain your choices.

If Meta-analysis or systematic review is not available, another type of study I would use to answer my question is a Cohort study. Cohort studies are longitudinal studies that focus on a common characteristic which in this study would be stress and the effect of Ashwagandha in relieving stress. Cohort studies are also useful in examining prognosis.

PICO search terms: 

P	I	C	O
Stress	Ashwagandha	No intervention	Relieve Stress and Anxiety
Nervous Tension	Withania Somnifera		Improving Symptoms
Anxiety	Ayurveda Herb		Prevent stress and anxiety
Stress and Anxiety			Decrease Cortisol Levels

Search tools and strategy used:

PubMed:

Ashwagandha (MESH Major Topic) AND Stress OR Anxiety → 36 articles

– Year: 2013 – 2023→ 29 articles

– Year: 2013- 2023, Full text → 12 articles

– Year: 2013- 2023, Full text, RCT, Systematic Review and Meta-Analysis → 4 articles

TRIP database:

Stress (P), Ashwagandha (I), Improving symptoms(O) → 6 articles

– Year: 2014- 2023 →5 articles

– Year: 2014, RCT, Meta-Analysis, systematic review → 1 article

Anxiety (P), Ashwagandha (I), Improving symptoms(O) → 7 articles

– Year: 2014- 2023 →4 articles

– Year: 2014, RCT, Meta-Analysis, systematic review → 1 article

Google Scholar:

Ashwagandha AND Stress OR Anxiety→ 5,300 articles

– Year 2013- 2023 → 3,590 articles

– Year: 2013 – 2023, Review Articles –> 887 articles 

Search for these articles were narrowed down using what year they were published and whether they were based in the United States or another country. I ensured that the articles considered stressed adults. I also ensured that each article had a way to calculate the study groups stress levels. I also ensure to read through the abstract for decent sample sizes and that they focus on the improvement or alleviation of stress due to the use of Ashwagandha

Results Found:  

1. Lopresti AL, Smith SJ, Malvi H, Kodgule R. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. Medicine (Baltimore). 2019 Sep;98(37):e17186. doi: 10.1097/MD.0000000000017186. PMID: 31517876; PMCID: PMC6750292.

Abstract:

Background: Ashwagandha (Withania somnifera (L.) Dunal) is a herb traditionally used to reduce stress and enhance wellbeing. The aim of this study was to investigate its anxiolytic effects on adults with self-reported high stress and to examine potential mechanisms associated with its therapeutic effects.

Methods: In this 60-day, randomized, double-blind, placebo-controlled study the stress-relieving and pharmacological activity of an ashwagandha extract was investigated in stressed, healthy adults. Sixty adults were randomly allocated to take either a placebo or 240 mg of a standardized ashwagandha extract (Shoden) once daily. Outcomes were measured using the Hamilton Anxiety Rating Scale (HAM-A), Depression, Anxiety, and Stress Scale -21 (DASS-21), and hormonal changes in cortisol, dehydroepiandrosterone-sulphate (DHEA-S), and testosterone.

Results: All participants completed the trial with no adverse events reported. In comparison with the placebo, ashwagandha supplementation was associated with a statistically significant reduction in the HAM-A (P = .040) and a near-significant reduction in the DASS-21 (P = .096). Ashwagandha intake was also associated with greater reductions in morning cortisol (P < .001), and DHEA-S (P = .004) compared with the placebo. Testosterone levels increased in males (P = .038) but not females (P = .989) over time, although this change was not statistically significant compared with the placebo (P = .158).

Conclusions: These findings suggest that ashwagandha’s stress-relieving effects may occur via its moderating effect on the hypothalamus-pituitary-adrenal axis. However, further investigation utilizing larger sample sizes, diverse clinical and cultural populations, and varying treatment dosages are needed to substantiate these findings.

I choose this article because it had a standard dose for ashwagandha and tested the levels of stress based upon cortisol levels

2. Pratte MA, Nanavati KB, Young V, Morley CP. An alternative treatment for anxiety: a systematic review of human trial results reported for the Ayurvedic herb ashwagandha (Withania somnifera). J Altern Complement Med. 2014 Dec;20(12):901-8. doi: 10.1089/acm.2014.0177. PMID: 25405876; PMCID: PMC4270108.

Abstract: 

Objective: To assess existing reported human trials of Withania somnifera (WS; common name, ashwagandha) for the treatment of anxiety.

Method/Design: Systematic review of the literature, with searches conducted in PubMed, SCOPUS, CINAHL, and Google Scholar by a medical librarian. Additionally, the reference lists of studies identified in these databases were searched by a research assistant, and queries were conducted in the AYUSH Research Portal. Search terms included “ashwagandha,” “Withania somnifera,” and terms related to anxiety and stress. Inclusion criteria were human randomized controlled trials with a treatment arm that included WS as a remedy for anxiety or stress. The study team members applied inclusion criteria while screening the records by abstract review.

Intervention: Treatment with any regimen of WS.

Outcome measures: Number and results of studies identified in the review.

Results: Sixty-two abstracts were screened; five human trials met inclusion criteria. Three studies compared several dosage levels of WS extract with placebos using versions of the Hamilton Anxiety Scale, with two demonstrating significant benefit of WS versus placebo, and the third demonstrating beneficial effects that approached but did not achieve significance (p=0.05). A fourth study compared naturopathic care with WS versus psychotherapy by using Beck Anxiety Inventory (BAI) scores as an outcome; BAI scores decreased by 56.5% in the WS group and decreased 30.5% for psychotherapy (p<0.0001). A fifth study measured changes in Perceived Stress Scale (PSS) scores in WS group versus placebo; there was a 44.0% reduction in PSS scores in the WS group and a 5.5% reduction in the placebo group (p<0.0001). All studies exhibited unclear or high risk of bias, and heterogenous design and reporting prevented the possibility of meta-analysis. 

Conclusions: All five studies concluded that WS intervention resulted in greater score improvements (significantly in most cases) than placebo in outcomes on anxiety or stress scales. Current evidence should be received with caution because of an assortment of study methods and cases of potential bias.

I choose this article because it is a systematic review that focused on the use of Ashwagandha on anxiety and stress. This fits the aforementioned patient’s condition perfectly as she has a past medical history of anxiety and is currently experiencing stress.

3. Akhgarjand C, Asoudeh F, Bagheri A, Kalantar Z, Vahabi Z, Shab-Bidar S, Rezvani H, Djafarian K. Does Ashwagandha supplementation have a beneficial effect on the management of anxiety and stress? A systematic review and meta-analysis of randomized controlled trials. Phytother Res. 2022 Nov;36(11):4115-4124. doi: 10.1002/ptr.7598. Epub 2022 Aug 25. PMID: 36017529.

Abstract: 

Introduction: Clinical trial studies revealed conflicting results on the effect of Ashwagandha extract on anxiety and stress. Therefore, we aimed to evaluate the effect of Ashwagandha supplementation on anxiety as well as stress.

Methods: A systematic search was performed in PubMed/Medline, Scopus, and Google Scholar from inception until December 2021. We included randomized clinical trials (RCTs) that investigate the effect of Ashwagandha extract on anxiety and stress. The overall effect size was pooled by random-effects model and the standardized mean difference (SMD) and 95% confidence interval (CIs) for outcomes were applied. Overall, 12 eligible papers with a total sample size of 1,002 participants and age range between 25 and 48 years were included in the current systematic review and meta-analysis.

Results: We found that Ashwagandha supplementation significantly reduced anxiety (SMD: -1.55, 95% CI: -2.37, -0.74; p = .005; I2 = 93.8%) and stress level (SMD: -1.75; 95% CI: -2.29, -1.22; p = .005; I2 = 83.1%) compared to the placebo. Additionally, the non-linear dose-response analysis indicated a favorable effect of Ashwagandha supplementation on anxiety until 12,000 mg/d and stress at dose of 300-600 mg/d.

Conclusion: Finally, we identified that the certainty of the evidence was low for both outcomes. The current systematic review and dose-response meta-analysis of RCTs revealed a beneficial effect in both stress and anxiety following Ashwagandha supplementation. However, further high-quality studies are needed to firmly establish the clinical efficacy of the plant.

I choose this article because it is a systematic review, had a large sample size of 1,002 individuals and age range of 25 to 48. 

4. Speers AB, Cabey KA, Soumyanath A, Wright KM. Effects of Withania somnifera (Ashwagandha) on Stress and the Stress- Related Neuropsychiatric Disorders Anxiety, Depression, and Insomnia. Curr Neuropharmacol. 2021;19(9):1468-1495. doi: 10.2174/1570159X19666210712151556. PMID: 34254920; PMCID: PMC8762185.

Abstract: 

Background: Withania somnifera (WS), also known as Ashwagandha, is commonly used in Ayurveda and other traditional medicine systems. WS has seen an increase in worldwide usage due to its reputation as an adaptogen. This popularity has elicited increased scientific study of its biological effects, including a potential application for neuropsychiatric and neurodegenerative disorders.

Objective: This review aims to provide a comprehensive summary of preclinical and clinical studies examining the neuropsychiatric effects of WS, specifically its application in stress, anxiety, depression, and insomnia.

Methods: Reports of human trials and animal studies of WS were collected primarily from the PubMed, Scopus, and Google Scholar databases.

Results: WS root and leaf extracts exhibited noteworthy anti-stress and anti-anxiety activity in animal and human studies. WS also improved symptoms of depression and insomnia, though fewer studies investigated these applications. WS may alleviate these conditions predominantly through modulation of the hypothalamic-pituitary-adrenal and sympathetic-adrenal medullary axes, as well as through GABAergic and serotonergic pathways. While some studies link specific withanolide components to its neuropsychiatric benefits, there is evidence for the presence of additional yet unidentified active compounds in WS.

Conclusion: While benefits were seen in the reviewed studies, significant variability in the WS extracts examined prevents a consensus on the optimum WS preparation or dosage for treating neuropsychiatric conditions. WS generally appears safe for human use; however, it will be important to investigate potential herb-drug interactions involving WS if used alongside pharmaceutical interventions. Further elucidation of active compounds of WS is also needed.

I choose this article because it reviewed the use of Ashwagandha and its neurophysiologic affects. The study evaluated many different mental disorders and reviewed the pros and cons of using Ashwagandha in humans.

5. Lopresti, A. L., & Smith, S. J. (2021). Ashwagandha (Withania somnifera) for the treatment and enhancement of mental and physical conditions: A systematic review of human trials. Journal of Herbal Medicine, 28, 100434.

Abstract: 

Introduction: Ashwagandha is a medicinal plant that has been used in Ayurvedic and indigenous medicine for over 3000 years. Because interest and the popularity of ashwagandha has increased in several Western countries, there are an increasing number of human trials evaluating its efficacy across a range of conditions.

Methods: Based on the PRISMA guidelines, human trials assessing the effects of ashwagandha on mental and/or physical conditions, and/or human performance, used as a stand-alone or adjunct intervention, and delivered as a single ingredient, were eligible for inclusion in this systematic review. Forty-one studies were identified examining the effects of ashwagandha on stress and anxiety, sexual function and fertility, athletic performance, cognitive performance, pain, fatigue, thyroid function, schizophrenia, diabetes, obsessive-compulsive disorder, insomnia, hypercholesterolemia, and tuberculosis.

Results: Results from most of these studies indicated positive effects from ashwagandha intake, although treatment dose, duration, and extract types varied significantly. Moreover, trials often comprised of small sample sizes and were primarily conducted in India (32 studies). Overall, the strongest evidence for therapeutic efficacy of ashwagandha is the alleviation of stress and anxiety symptoms.

Conclusions: The results from this systematic review suggest ashwagandha has a potentially large array of therapeutic applications. However, while promising, the significant heterogeneity across studies and the limited number of investigations means further research utilizing robust and adequately powered study designs are required.

I chose this article because it is a systematic review and assessed human trial studies that looked at the effects of ashwagandha on mental and/or physical conditions and/or human performance.

6. Salve J, Pate S, Debnath K, et al. (December 25, 2019) Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults: A Double-blind, Randomized, Placebo-controlled Clinical Study. Cureus 11(12): e6466. DOI 10.7759/cureus.6466

Abstract: 

Background: Stress, anxiety, and impeded sleep are a frequent feature of life in modern societies. Across socio-economic strata, stress, anxiety, and ineffective sleep detract from healthful living and serve as precursors of various ailments. The use of herbs to offset these antecedents and outcomes have greatly increased in recent years. Ashwagandha, an adaptogenic Ayurvedic herb, has been often used to combat and reduce stress and thereby enhance general wellbeing. While there have been other studies documenting the use of Ashwagandha for stress resistance, this is the first study to use a high-concentration root extract while also varying the dosage substantially. Therefore, this is the first study to offer insight into dose-response of a high concentration root extract.

Material and methods: In this eight-week, prospective, randomized, double-blind, placebo-controlled study, the stress-relieving effect of Ashwagandha root extract was investigated in stressed healthy adults. Sixty male and female participants with a baseline perceived stress scale (PSS) score >20 was randomized to receive capsules of Ashwagandha extract 125 mg, Ashwagandha extract 300 mg or identical placebo twice daily for eight weeks in a 1:1:1 ratio. Stress was assessed using PSS at baseline, four weeks, and eight weeks. Anxiety was assessed using the Hamilton-Anxiety (HAMA) scale and serum cortisol was measured at baseline and at eight weeks. Sleep quality was assessed using a seven-point sleep scale. A repeat measures ANOVA (general linear model) was used for assessment of treatment effect at different time periods. Post-hoc Dunnett’s test was used for comparison of two treatments with placebo.

Results: Two participants (one each in 250 mg/day Ashwagandha and placebo) were lost to follow-up and 58 participants completed the study. A significant reduction in PSS scores was observed with Ashwagandha 250 mg/day (P < 0.05) and 600 mg/day (P < 0.001). Serum cortisol levels reduced with both Ashwagandha 250 mg/day (P < 0.05) and Ashwagandha 600 mg/day (P <0.0001). Compared to the placebo group participants, the participants receiving Ashwagandha had significant improvement in sleep quality.

Conclusion: Ashwagandha root aqueous extract was beneficial in reducing stress and anxiety.

I chose this article because it was a randomized double blinded study that focused both on anxiety and stress.

Author (Date)	Level of Evidence	Sample / Setting	Outcomes Studied	Key Findings	Limitations and Biases
Lopresti, 2019	Double-Blinded RCT	– 60 participants-Aged between 18 and 65 with a HAM score between 6 and 17-Capsules of 240 mg of WS was given or placebo- 60-day study with participants evaluated every 15 days	-Hamilton Anxiety Score (HAM)- DASS- 21: Depression, Anxiety, Stress Scale-21- DHEA, Testosterone and Cortisol Blood levels	– A reduction in HAM, DASS, DHEA, Testosterone and Cortisol levels was seen across the WS group compared to the placebo group.-Women had a higher decrease in DHEA and cortisol level when given WS compared to men in the WS group.-Men in the WS group had a higher increase in testosterone compared to women in the WS group	-Participants were healthy and had mild stress only.- Did not examine the impact of feeding habits, economic conditions, and daily occupation on the anti-stress effects of ashwagandha.- No follow-up after intake cessation
Pratte, 2014	Systematic Review	-5 studies were included	– Hamilton Anxiety Score (HAM), Beck Anxiety Inventory scores (BAI), Perceived Stress Scale (PSS) were used to quantify how much the drug decreased Stress and Anxiety levels	Study 1: -88.2% response in WS group vs. 50% in placebo group (p = 0.026)-A reduction in HAM Scores 12 or below. Study 3: -Final BAI scores decreased by 56.5% in NC group and 30.5% in PT group ( p < .0001) Greater improvement in BAI for NC versus PT ( p = 0.003Study 4: -Greater decrease in PSS (44.0% versus 5.5%; p < 0.0001), GHQ-28 and DASS ( p < 0.0001), and cortisol (27.9% versus 7.9%; p = 0.002) for WS versus placeboStudy 5: -Greater improvement in WS versus placebo in anxious mood (p < 0.001)Significant differences between WS and control groups.- WS is a safe herbal supplement for general use because of the lack of severity and frequency of adverse effects.	– Shortage of studies used in this review- Study 1 had a small sample size, a short duration study of 6 weeks and a dropout rate of nearly 50%- All studies had different dosages for WS- All studies had a diversity of methods and outcomes used- Article focuses on Study 1 more than other articles.- No clear inclusion criteria given
Akhgarjand, 2022	Meta- Analysis	-12 studies with 1,002 participants- 555 participants in the intervention group and 447 participants in the control group- 8 -12 weeks in duration- Participants were either healthy or had stress, history of chronic stress, insomnia, Generalized Anxiety Disorder (GAD), Schizophrenia or schizoaffective disorder or bipolar disorder	-HAM- Depression, Anxiety, Stress Scale (DASS)- PSS (Perceived Stress Scale)	– In Stress studies, there was a significant improvement in anxiety scores in the WS group compared to the placebo group- In anxiety studies, WS groups that were given 600 mg or more had significantly lower anxiety levels when compared with lower than 600 mg groups and placebo- WS Dosages less than 12,000 mg/dl are effective in reducing stress and anxiety	-Individuals with various health conditions were added into the study which could affect the findings.-Ashwagandha supplementation was administered in different dosages and different age groups.
Speers, 2021	Systematic Review	-6 human studies  – aged 18-75 years old- populations included participants who were healthy, stressed, overweight, or obese, experiencing chronic work stress, diagnosed with anxiety, and diagnosed with schizophrenia or schizoaffective disorder-Participants from each study ranged from 52 to 130.- Each study used starch as a placebo and a dosage of 150- 200 mg for WS	– HAM, DASS, PSS scores-Testosterone, DHEA and cortisol serum levels-Hematologic safety markers	– Decrease in HAM, DASS, and PSS scores in intervention group (WS) compared to placebo- Decreased testosterone, DHEA and cortisol serum levels in intervention group compared to placebo.- WS was effective in decreasing stress in GAD, bipolar disorder, schizophrenia and improve sleep quality.	– Each study used a different formula of WS (capsule vs. dry fruit)-Limited timeline-3 out of 5 studies stopped following up after cessation of WS- Tested in healthy individuals who were not medically diagnosed with stress
Lopresti, 2021	Systematic Review	– 41 Studies- 7 Randomized double-blind placebo-controlled studies with 491 participants in total that focus on anxiety and stress- 6- 8 week in duration- Aged between 18 – 65 years old who are experiencing mid to high stress	-PSS- HAM- serum cortisol, DHEA, and testosterone levels- Sleep quality questionnaire	– WS is significantly greater in decreasing PSS, HAM and serum cortisol levels compared to placebo- Higher WS dosages lead to greater efficacy	– Different formulas and dosages of WS given in each study- Varied duration of study with the longest one being 3 months-Relied on subjective information for sleep quality
Salve et. Al, 2019	Double-Blinded RCT	-8 weeks long- 60 participants between 18 and 55 who are experiencing high stress (PSS > or equal to 20)- 3 study groups: 1 group taking 250 mg of WS, another taking 600 mg of WS and a placebo group	-PSS – HAM  – Serum Cortisol- Sleep quality rating	– Compared to placebo, ASH associated with significantly greater reductions in PSS (both doses), HAM-A (600 mg), sleep quality rating (both doses), and serum cortisol (both doses).- Results suggests greater efficacy with the higher ASH dose.	-Short duration of study-Small sample size- No follow up after cessation of using WS to evaluate for the long-term effects of WS- Small sample size

Conclusions:

Article 1(Lopresti et al, 2019): 

Summary – Lopresti et al., conducted a randomized double blinded placebo-controlled study that looked at the effects of ashwagandha (WS) on stress and anxiety. By using three major scores/scales and blood work the researchers were able to quantify the effects of WS on anxiety and stress. They found that ashwagandha’s stress-relieving effects may occur via its moderating effect on the hypothalamus-pituitary-adrenal axis.  

Magnitude of Evidence: In the study it was found that the use of Ashwagandha lead to a decrease in HAM scores, DASS-21 and in cortisol levels. There was a 41% reduction in HAM-A was observed over time in the ashwagandha group (F4,116= 15.09, P<.001) and 24% reduction in placebo group. A 30% reduction in HAM-A was observed over time in the ashwagandha group (F4,116=7.03, P<.001) and a 10% reduction in the placebo group (F4,116= 3.37, P=.012). A 23% reduction in cortisol with an 8% decrease in DHEA was observed over time (F2,58=10.25, P= <.001) with no significant difference seen in placebo group for both cortisol and DHEA. There was an 11% increase in testosterone observed in the WS group compared to the placebo group that had no change in testosterone levels.  

Article 2 (Pratte et al): 

Summary: Pratte et al., concluded that Ashwagandha is a safe herbal supplement for general use because of the lack of severity and frequency of adverse effects. Multiple different anxiety and stress scores/scales were used to quantify the effectiveness of WS. There was a significant difference across all studies between WS and control groups that found WS to be more effective in decreasing stress and anxiety level. Pratte et al. also voiced their concern over the dosage for Ashwagandha as different dosages were used across all 5 studies.

Magnitude of Evidence: There was a decrease in BAI scores by 56.5% in Ashwagandha (WS) group and 30.5% in physiotherapy group (p < .0001) leading to a greater improvement in BAI for W versus PT (p = 0.003). In terms of Stress, the researchers found that there was a greater decrease in PSS (44.0% versus 5.5%; p < 0.0001), GHQ-28 and DASS (p < 0.0001), and cortisol (27.9% versus 7.9%; p = 0.002) for WS versus placebo.

Article 3 (Akhgarjand et al.)

Summary: Akhgarjand et al., performed a meta-analysis using 12 studies that had 1002 participants in total. The researchers found that WS is effective in reducing and improving stress and anxiety. They found that WS was particularly beneficial in healthy participants and individuals 40 years old or older when a dosage of 600 mg or more was given for anxiety. Thus, the researchers concluded that the reduction in anxiety was considerable at higher dosages of WS than lower ones.

Magnitude of Evidence: Ashwagandha supplementation significantly reduced anxiety com-pared to the placebo (SMD: – 1.55, 95% CI: – 2.37, – 0.74; p=.005), with a significant degree of heterogeneity between studies (I2=93.8%, p<.001). healthy subjects (SMD: – 0.82; 95% CI: -1.15, – 0.48; p<.001), people with 40 years or older (SMD: – 2.05; 95% CI: – 3.14, – 0.96; p<.001) and supplementation doses≥600 mg/d (SMD: – 2.30; 95% CI: – 3.52 to -1.08; p<.001) had the greatest benefit from Ashwagandha supplementation. WS had a significant reduction in the stress following Ashwagandha supplementation (SMD: -1.75; 95% CI -2.29, – 1.22; p=.005). There is a correlation between the dosage of WS given and its effects on anxiety. Based upon the researchers there was a linear reduction in anxiety until 12,000 mg/d of Ashwagandha dose.

Article 4 (Speers et al): 

Summary: All in all, Speers et al., found that in human trials, WS decreased stress and anxiety levels and improved sleep quality. The researchers hypothesized that WS anti-stress effect attributed to its reduction in glucocorticoids and immune modulation. In one of the studies reviewed by Speers et al., found that WS decreased stress in schizophrenic participants, and another found that it decreased anxiety in GAD participants when used in combination with SSRIs.

Magnitude of Evidence:  There is a significantly decrease in stress and anxiety levels with the use of WS. One study found that a daily administration of 240 mg Shoden® (biosimilar of WS) for 60 days significantly decreased HAM-A (but not DASS) scores compared to placebo. Another study found that in those with GAD (Generalized Anxiety Disorder) 12 g of a dried WS root preparation decreased all measured anxiety scores from baseline values more than placebo.

Article 5 (Lopresti et al., 2021): 

Summary: Lopresti et al., performed a systemic review on the effects of Ashwagandha on anxiety, stress, sexual function, general wellbeing etc. In their review, they found 7 randomized double-blind placebo-controlled studies that focused on anxiety and stress. In those studies, it was found that Ashwagandha decreases and alleviates anxiety and stress. They also found that Ashwagandha was only beneficial for improving anxiety when given at higher dosages.

Magnitude of Evidence: Compared to the placebo, there were also greater reductions in several (but not all) symptom scores such as fatigue, feelings of impending doom, sleeplessness, forgetfulness, irritability, and an inability to concentrate in the ashwagandha-treated groups. Ashwagandha was also associated with greater decreases in serum cortisol (all doses), c-reactive protein (CRP) (all doses), blood pressure (all doses), fasting blood glucose (250 and 500 mg groups only. Based on a HAM-A score < 12, there was an 88 % response rate in the ashwagandha group and a 50 % response rate in the placebo group.

Article 6 (Salve et al): 

Summary: Although, Salve et al., had a small sample size, they found that Ashwagandha is effective in decreasing stress and anxiety levels. They used sleep quality questionnaires, anxiety and stress scales/scores and serum cortisol levels to quantify stress and anxiety levels. They also found that the dosage of WS given had a positive correlation with the amount decrease in PSS and HAM scores. For example, the researchers found that 600 mg WS is more effective in reducing anxiety than placebo and 250 mg WS.

Magnitude of Effects: The mean PSS was significantly lower (p < 0.05) in the Ashwagandha 250 group (95%CI 13.93-16.07) and (p < 0.05) in the Ashwagandha 600 group (95% CI 12.92-15.38). The reduction in mean PSS relative to the baseline was significantly higher than in the placebo group (95% CI 15.12-18.14) for both the Ashwagandha 250 group (p < 0.05) and in the Ashwagandha 600 group (p < 0.001).  HAM levels were significantly lower in the 600 mb WS group compared to placebo. However, HAM scores were not significantly lower in the 250 WS group compared to placebo.

Clinical Bottom Line: 

Ashwagandha (Withania somnifera (WS)) is an evergreen shrub that grows in Asia and Africa. It is often used holistically to relieve stress due to its adaptogen effects. In its ayurvedic formulation, it is thought to possess anti-stress abilities, improve fatigue, anxiety, diabetes, gastrointestinal disease, and many more other properties.

Clinically, Ashwagandha is beneficial in improving and relieving stress and anxiety. As per Akhgarjand et al., WS is more beneficial in healthy adults and those who are 40 years old or older. Researchers also found that the higher the dosage of WS the more effective it is in relieving stress and anxiety (Salve et al). Although, these 6 studies provided evidence of the effectiveness of Ashwagandha, they all had severe limitations and biases. Some of common limitations were small sample size, different dosages, and preparations of Ashwagandha and the cessation of follow up after finishing WS (Lopresti et al.). Therefore, the long-lasting effects of WS could not be studied.

Additional research using standardized dosing and in populations diagnosed with stress and anxiety needs to be done to validate the effectiveness of WS. Also, the long-lasting effects of WS, herb- herb and herb-drug interactions remain elusive making it imperative to research the herb more before determining its clinical use. Therefore, I would inform the patient that due to the significant variability in the dose and products found in recent studies, a definitive clinical recommendation for the use of WS cannot be given.

PDF of Articles:

Phytotherapy Research – 2022 – Akhgarjand.pdf
Salve et al.pdf
Pratte et al.pdf 
Lopresti et al, 2019.pdf
Lopresti,2021.pdf
Speers et al.pdf