Withania somnifera (WS), widely known as Ashwagandha, is an adaptogen that has gained global attention, prompting extensive scientific exploration into its potential applications for neuropsychiatric and neurodegenerative disorders. Rigorous studies on WS roots and leaves reveal compelling anti-stress and anti-anxiety properties in both animal and human subjects, with promising results extending to the alleviation of symptoms related to depression and insomnia. Mechanistically, WS demonstrates modulation of the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal medullary (SAM) axes—crucial components of the body's stress response system—while impacting GABAergic and serotonergic pathways. Beyond traditional uses, WS has demonstrated neuropharmacological potential, garnering attention for addressing neurodegenerative disorders. Amidst its versatile applications, WS's standout feature lies in its stress-relieving properties, crucial in the context of neuropsychiatric disorders like anxiety, depression, and insomnia, where dysregulated stress pathways play a pivotal role.
In six studies, WS consistently exhibited significant anti-stress effects when administered in various capsule forms, such as KSM-66 Ashwagandha®, Sensoril®, and Shoden®. This adaptogen consistently reduced stress markers, including PSS, DASS, and GHQ-28 scores, and resulted in lower serum cortisol levels compared to placebos. Its anti-stress efficacy is attributed to glucocorticoid reduction and immune modulation, positioning WS as a promising candidate for mitigating stress-related physiological changes.
For anxiety, WS showed consistent improvement in anxiety, as measured by tools like the Hamilton Anxiety Rating Scale (HAM-A). Notably, studies like Lopresti et al. (2019) reported significant decreases in HAM-A scores with specific WS preparations. Research into WS's anti-anxiety effects focuses on the GABA receptor system and its antioxidant and anti-inflammatory activities. While the GABAergic system plays a crucial role in anxiety regulation, WS's ability to modulate GABAA receptors and exhibit antioxidant and anti-inflammatory activity contributes to its potential anti-anxiety effects. However, identifying specific responsible compounds remains a challenge.
Regarding depression, WS's anti-depressant effects are linked to antioxidant and serotonergic activities. The oxidative stress hypothesis of depressive disorders (theorizes a link between oxidative stress and depressive disorders) aligns with WS's demonstrated antioxidant and anti-inflammatory activities in animal models. WS's potential as an anti-depressant candidate stems from its ability to counteract oxidative stress in the brain. Evidence from animal studies indicates WS's serotonergic activity, crucial in anti-depressant effects. However, limited human studies have yet to measure neurotransmitter levels in response to WS, necessitating further investigation.
In studies on insomnia/sleep, WS consistently demonstrated positive results. Supplementation with WS consistently improved insomnia measures, encompassing sleep quality, sleep latency, sleep efficiency, total sleep time, wake after sleep onset, and daytime alertness. WS's positive impact on sleep may be attributed to its activation of GABAergic neurotransmission, and it demonstrated chronomodulatory effects on the brain, influencing key factors in regulating antioxidant enzymes and maintaining daily rhythms. However, additional studies are needed to establish a minimum effective dose for improving sleep, particularly in populations with sleep disturbances.
Withania somnifera (WS) exhibits promising anti-anxiety, anti-depressant, and sleep-promoting properties, as evidenced by animal and limited human trials. However, the variability in products, standardization levels, and doses used introduces significant heterogeneity, and unknown herb-herb and herb-drug interactions, especially in specific products from human trials, pose challenges. While WS shows potential for stress-related neuropsychiatric conditions, conclusive clinical recommendations are hindered by these uncertainties. Rigorous studies, utilizing standardized products and doses, are essential to determine the safety and efficacy of WS in clinical management. Despite these gaps, WS demonstrates a favorable safety profile and offers a potential multi-condition therapeutic approach, emphasizing its role in enhancing resilience against stress and related neuropsychiatric ailments.
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762185/