Ashwagandha and the Mind Ashwagandha (Withania somnifera) is a staple therapeutic in the Indian Ayurvedic system of medicine- a Rasayana or an “adaptogen" used for the treatment of memory and cognitive deficit following injury, illness, or simply old age. Preclinical studies have indicated a potential role of ashwagandha as a nootropic, promoting cognitive function and enhancing memory, presumably due to its cholinomimetic activity. Studies suggest that Withania somnifera may treat a broad spectrum of symptoms in serious mental illness: it "provides significant benefits, with minimal side effects, for negative, general, and total symptoms and stress in patients with recent exacerbation" [1] and recently, that was replicated for depression and anxiety symptoms [2]. It also improves cognitive capacity in bipolar disorder and appears to have a benign side-effect profile [3]. Results have been promising for neurological disorders such traumatic brain injury, brain tumor, and neurodegenerative pathologies. Efficacy of ashwagandha extracts and isolated constituents has been reported in experimental models of neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), which are associated with the disruption of neural networks and premature death of neurons. Clinical studies with ashwagandha have shown promise in bipolar disorder, enhancing cognitive and psychomotor performance, and ameliorating cognitive dysfunction. ...daily treatment with ashwagandha for a period of eight weeks produced significant enhancement versus placebo in a battery of cognitive tests designed to assess memory, executive function, and attention and information-processing speed. 1 Ashwagandha root has been found to possess antioxidant, neuroprotective, antiinflammatory, antidepressant, anxiolytic, and immunomodulating activities. Plant- derived compounds from ashwagandha have shown significant potential as an acetylcholinesterase inhibitor, which would support its utility for the treatment of MCI and AD. See: Efficacy and Safety of Ashwagandha (Withania somnifera (L.) Dunal) Root Extract in Improving Memory and Cognitive Functions https://doi.org/10.1080/19390211.2017.1284970 Working memory can be modulated by drugs having dopaminergic activity and a number of studies have found that ashwagandha root can stimulate the dopaminergic system of the brain. A number of animal studies and clinical trials support the nootropic activity of ashwagandha. Evidence indicating neuroprotective effects of ashwagandha supports its therapeutic efficacy in MCI and AD patients Ashwagandha also possesses anti-stress, anxiolytic, and sedative properties. These may be indirectly involved in improving memory and cognition in human subjects, as stress, anxiety, and sleep disorders can affect normal cognitive function Withania somnifera can bring significant changes in neurological baseline functions, with the "postulation that it can be applied clinically in prevention, and possibly repair, of central nervous system disorders" [4]. It is proposed to be beneficial in stress - it "effectively improves an individual's resistance towards stress and thereby improves self-assessed quality of life." [5] anxiety and depression [6], OCD [7], bipolar [8] and schizophrenia [9]. The potential of W. somnifera for neural regeneration has been explored. Use of the leaves While the roots are traditionally used, the leaves possess higher content of active withanolides, Withaferin-A and Withanone, as compared to the roots [10]. Nootropic and CNS therapeutic properties of the leaf have been claimed [11]. Withaferin-A is a potent leptin sensitiser with additional antidiabetic actions and resulted in a 20-25% reduction of body weight in overweight mice [12]. It improves insulin sensitivity [13]. Anti-neuroinflammatory properties have been ascribed to the leaf [14] along with neuroprotective properties [15] Withaferin-A shows anti-neuroinflammatory [16] anti-Aβ properties [17] and dopamine- restoring [18] properties. Improvement of cognitive dysfunction has been ascribed to Withanone [19] including inhibition of AChE, anti-Aβ, protection against oxidative stress and anti-inflammatory effects. Many toxicological studies have demonstrated that Ashwagandha, in its reasonable dose, is a non-toxic, safe and edible herb - despite that, there is sometimes movement away from 2 the cytotoxic constituents towards root extracts which may be less effective [1] https://www.ncbi.nlm.nih.gov/pubmed/29995356' [2] https://www.ncbi.nlm.nih.gov/pubmed/31046033 [3] https://www.ncbi.nlm.nih.gov/pubmed/24330893 [4] https://www.naturalmedicinejournal.com/journal/effect-ashwagandha-tests-cognitive- and-psychomotor-performance [5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573577/ [6] https://examine.com/supplements/ashwagandha/ [7] https://www.ncbi.nlm.nih.gov/pubmed/27515872 [8] https://www.ncbi.nlm.nih.gov/pubmed/29995356 [9] https://www.ncbi.nlm.nih.gov/pubmed/29995356 [10] https://www.ncbi.nlm.nih.gov/pubmed/27936030 [11] https://www.ncbi.nlm.nih.gov/pubmed/26361721 [12] https://www.ncbi.nlm.nih.gov/pubmed/27479085 [13] https://www.ncbi.nlm.nih.gov/pubmed/30417321 [14] https://www.ncbi.nlm.nih.gov/pubmed/27550017 [15] https://www.ncbi.nlm.nih.gov/pubmed/25789768 [16] https://www.ncbi.nlm.nih.gov/pubmed/26266054 [17] https://www.ncbi.nlm.nih.gov/pubmed/30356847 [18] https://www.ncbi.nlm.nih.gov/pubmed/30544122 [19] https://www.ncbi.nlm.nih.gov/pubmed/29108796 3