The Anti-Anxiety Properties of Ashwagandha (Withania somnifera): A Review

Ahmadi Koulaei, Sheyda; Eshraghi, Azadeh; Aslani, Hamidreza; salari, zahra; Abdollahi, Elaheh; Shariatpanahi, Marjan

doi:10.47176/rjms.31.27

Volume 31, Issue 1 (3-2024) RJMS 2024, 31(1): 1-15 | Back to browse issues page

‎ 10.47176/rjms.31.27

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Ahmadi Koulaei S, Eshraghi A, Aslani H, salari Z, Abdollahi E, Shariatpanahi M. The Anti-Anxiety Properties of Ashwagandha (Withania somnifera): A Review. RJMS 2024; 31 (1) :1-15
URL: http://rjms.iums.ac.ir/article-1-8429-en.html

The Anti-Anxiety Properties of Ashwagandha (Withania somnifera): A Review

Sheyda Ahmadi Koulaei

, Marjan Shariatpanahi

Department of Pharmacology and Toxicology, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran , Abdollahi.e@iums.a.ir

Abstract: (662 Views)

Background & Aims: Among psychological problems, anxiety disorders are one of the most common complications and affect one eighth of the world's population. The increase in both rate of anxiety disorders and financial burden imposed on the country's health system led to more attention in treatment of these disorders. Unfortunately, despite the good efficacy of common drug treatments, these treatments also have high unwanted side effects. For this reason, researchers are trying to find drugs with better effectiveness and fewer side effects. In the meantime, medicinal plants, as a great source of natural compounds, have a high popularity among the general public. On the other hand, it is important to use medicinal plants as a great source of anti-anxiety bioactive compounds. Ashwagandha medicinal plant (Withania somnifera L. Dunal), which is known as the king of medicinal plants in Ayurvedic medicine, is widely used in reducing anxiety, according to reliable sources. Therefore, this research is dedicated to the efficacy of this plant in preclinical and clinical studies, a review of phytochemical compounds, possible mechanisms and safety of Ashwagandha consumption. This article reviews the findings and data available in articles from 1990 to January 2023 in PubMed, Scopus and Google Scholar databases. So far, several studies have confirmed the effects of Ashwagandha in reducing anxiety-like behaviors in various animal models such as stress, sleep deprivation, social isolation and neuroinflammation. In many animal models, anti-anxiety effects have been reported from a variety of extracts (aqueous, methanolic, ethanolic and hydroalcoholic) derived from the root and leaves of Ashwagandha plant with different extraction methods, and these results suggest the possibility of the presence of multiple bioactive compounds. Ashwagandha plant has also been investigated in human studies and numerous results confirm that this plant can play a role in improving anxiety disorders. In these studies, dried plant root powder, aqueous, alcoholic and hydroalcoholic extracts were used. In most of these clinical trials, the patented and available Ashwagandha extracts (KSM-66®, Sensoril®, Essentra® and Shoden®) were used in daily doses between 125 and 1000 mg in tablet and capsule form, for 6 to 12 weeks. Some human studies also used dried plant root granules up to a daily dose of 12 grams. The anti-stress activity of Ashwagandha is most commonly attributed to its effects on the GABA receptor system, antioxidant and anti-inflammatory activities, although other possible mechanisms have been proposed. GABA is the most important inhibitory neurotransmitter in the central nervous system, and the GABAergic neurotransmitter system plays a key role in the regulation of anxiety. GABA agonist drugs exert their inhibitory effects by activating GABA type A receptors. There is significant pre-clinical evidence that shows that the effective compounds of Ashwagandha also have anti-anxiety effects by stimulating GABA_A receptors. However, attempts to identify which compound in Ashwagandha are responsible for GABA_A receptor activity have been difficult. Therefore, further research is needed to identify the interactions of withanolides with GABA_A receptors, the possible sites of interaction in the GABA_A receptor complex, and whether specific subunits of GABA_A receptors are more sensitive to the compounds of this plant. The brain is particularly sensitive to oxidative stress. Studies conducted over the past few years suggested that anxiety disorders are associated with decreased antioxidant defense capacity and increased oxidative damage. Oxidative stress has been implicated in the pathophysiology of anxiety disorders by causing inflammation. Peripheral inflammation is also thought to directly contribute to neuroinflammation and oxidative stress in the brain. While oxidative stress and inflammation have both been implicated in the pathogenesis of anxiety, a definitive cause-and-effect relationship for both has yet to be found. Although mainly the effects of the glucocorticoids cortisol and corticosterone (the main stress hormones in humans and rodents, respectively) are attributed to determining the level of stress and not anxiety, there are studies in this field that show that cortisol can be important in the pathogenesis of anxiety disorders. In two randomized, double-blind clinical trials that investigated the anti-anxiety effects of Ashwagandha plant, the level of cortisol serum was examined approximately 4 and 8 weeks after consuming the extract of this plant and it was determined that Ashwagandha plant extract can significantly reduce serum cortisol level especially after 8 weeks. In traditional Ayurveda and Unani systems of medicine, the roots of Ashwagandha have a long history of use as an adaptogen. Adaptogens help the body adapt to stress by normalizing physiological processes. In addition, adaptogens can deal with the consequences of stress by preventing and reducing abnormalities and diseases caused by stress on the endocrine glands and the immune system. Assuming that anxiety is a chronically present stress, Ashwagandha has been shown to be effective by affecting the hypothalamic pituitary-adrenal (HPA) axis, as well as by controlling key mediators of the stress response, such as heat shock proteins (Hsp70), cortisol, and nitric oxide. Most studies have identified withanolides as the main compounds with neurological activity in Ashwagandha. However, only a few of the withanolides in Ashwagandha have been evaluated for their neuroprotective effects, and the results are conflicting. Finally, there are limited studies linking withanolides to the neuropsychological effects of Ashwagandha, and other classes of natural compounds may also play a role in these effects. Further studies aimed at investigating the compounds or groups of compounds purified from different types of Ashwagandha plant extracts can help to clarify this issue. However, the possibility of synergistic or additive effects between the components should also be considered. In the review of clinical trials that were done on Ashwagandha, no serious side effects or changes in vital signs, blood and biochemical parameters such as hemoglobin, neutrophil percentage, platelet count, alkaline phosphatase (ALP) enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed. In some cases, confusion, dizziness, and drowsiness have been reported as mild to moderate transient side effects. Analysis of data from a comprehensive study on all age groups and both sexes showed that consuming the permitted amounts of Ashwagandha does not result in any serious side effects.

Keywords: Anti-Anxiety Properties, Ashwagandha, The mechanism of the effect

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Type of Study: review article | Subject: Pharmacy