54 replies to this topic

[babcock]

First, a little background derived from wikipedia. Withania somnifera, also known as Ashwagandha, Indian ginseng, Winter cherry, Ajagandha, Kanaje Hindi, Amukkuram in Malayalam and Samm Al Ferakh, is a plant in Solanaceae or nightshade family. It grows as a stout shrub that reaches a height of 170 cm (5.6 ft). In Ayurveda ashwagandha is considered a rasayana herb. This herb is also considered an adaptogen which is an herb that works to normalize physiological function, working on the HPA axis and the neuroendocrine system.

Although I'm starting this thread to discuss relevant neuroprotective effects of Withania somnifera, it is important to note that Withania somnifera is also cited as having:

• Valuable Anti-oxidant effects
• Valuable Anti-Inflammatory effects
• Tumor fighting properties

Neuroprotection:
Withania somnifera falls into what I would consider two different areas of neruoprotective functioning. It has been cited to inhibit anxiety in various different diseases. It has also been cited to neuronal regrowth.

To start with here are a few pieces of research done on anxiety inhibition.

From: Pub Med

Naturopathic care for anxiety: a randomized controlled trial ISRCTN78958974.

Cooley K, Szczurko O, Perri D, Mills EJ, Bernhardt B, Zhou Q, Seely D.

Department of Research and Clinical Epidemiology, The Canadian College of Naturopathic Medicine, Toronto, Canada. kcooley@ccnm.edu
Abstract

BACKGROUND: Anxiety is a serious personal health condition and represents a substantial burden to overall quality of life. Additionally anxiety disorders represent a significant cost to the health care system as well as employers through benefits coverage and days missed due to incapacity. This study sought to explore the effectiveness of naturopathic care on anxiety symptoms using a randomized trial. METHODS: Employees with moderate to severe anxiety of longer than 6 weeks duration were randomized based on age and gender to receive naturopathic care (NC) (n = 41) or standardized psychotherapy intervention (PT) (n = 40) over a period of 12 weeks. Blinding of investigators and participants during randomization and allocation was maintained. Participants in the NC group received dietary counseling, deep breathing relaxation techniques, a standard multi-vitamin, and the herbal medicine, ashwagandha (Withania somnifera) (300 mg b.i.d. standardized to 1.5% with anolides, prepared from root). The PT intervention received psychotherapy, and matched deep breathing relaxation techniques, and placebo. The primary outcome measure was the Beck Anxiety Inventory (BAI) and secondary outcome measures included the Short Form 36 (SF-36), Fatigue Symptom Inventory (FSI), and Measure Yourself Medical Outcomes Profile (MY-MOP) to measure anxiety, mental health, and quality of life respectively. Participants were blinded to the placebo-controlled intervention. RESULTS: Seventy-five participants (93%) were followed for 8 or more weeks on the trial. Final BAI scores decreased by 56.5% (p<0.0001) in the NC group and 30.5% (p<0.0001) in the PT group. BAI group scores were significantly decreased in the NC group compared to PT group (p = 0.003). Significant differences between groups were also observed in mental health, concentration, fatigue, social functioning, vitality, and overall quality of life with the NC group exhibiting greater clinical benefit. No serious adverse reactions were observed in either group. RELEVANCE: Many patients seek alternatives and/or complementary care to conventional anxiety treatments. To date, no study has evaluated the potential of a naturopathic treatment protocol to effectively treat anxiety. Knowledge of the efficacy, safety or risk of natural health products, and naturopathic treatments is important for physicians and the public in order to make informed decisions. INTERPRETATION: Both NC and PT led to significant improvements in patients' anxiety. Group comparison demonstrated a significant decrease in anxiety levels in the NC group over the PT group. Significant improvements in secondary quality of life measures were also observed in the NC group as compared to PT. The whole system of naturopathic care for anxiety needs to be investigated further including a closer examination of the individual components within the context of their additive effect.

In summary, this study took a group of people who suffered from anxiety, randomly divided the group, administered dietary counseling, deep breathing relaxation techniques, a multi vitamin, and withania somnifera (300mg) (WS) to half the group and gave the other half the same minus the WS. After 8 weeks the test groups Beck Anxiety Inventory scores had decreased by 56.5% and the control groups had decrease by 30.5%. With these results two things become obvious, proper diet and stress therapy are capable of reducing anxiety by a significant amount on their own; and WS is capable of controlling anxiety in individuals by a significant amount.

From Pub Med:

Neuroprotective effects of Withania somnifera dunal.: A possible mechanism.

Bhatnagar M, Sharma D, Salvi M.

M.L. Sukhadia University, Udaipur, India. m.maheep@gmail.com
Abstract

Present study was carried out to understand the possible mechanism of neuroprotective action of the root extract of Withania somnifera Dunal (WS). The study is focused on WS mediated inhibition of nitric oxide production, which is known to mediate neurodegeneration during stress. Adult mice (28 +/- 5 g) were exposed to restraint stress for 30 days. Activity of NADPH diaphorase (NADPH-d) and factors (Acetylcholine, serotonin and corticosterone), which regulates NADPH-d activity were studied. Treatment with WS extract for 30 days during stress, significantly reversed the stress induced NADPH-d activation. Observations suggest that inhibition of NADPH-d by WS is not a direct effect of extract on NADPH-d, instead it inhibits via suppressing corticosterone release and activating cholineacetyltransferase, which in turn increase serotonin level in hippocampus to inhibit NADPH-d. Together, the main mechanism underlying the neuroprotective effects of WS can be attributed to its role in the down regulation of nNOS and neurochemical alterations of specific neurotransmitter systems. These observations thus suggest that WS root extract could be developed as a potential preventive or therapeutic drug for stress induced neurological disorders.

In summary, this research studied mice who were exposed to stress induced by restraint. It was observed that administration of WS inhibit nitric oxide production during times of stress via suppression of corticosterone release and activation of choline acetyltransferase (wiki).

Treatment of Neurogenerative Diseases:

From Pub Med:

J Ethnopharmacol. 2009 Sep 25;125(3):369-73. Epub 2009 Aug 8.
Withania somnifera root extract improves catecholamines and physiological abnormalities seen in a Parkinson's disease model mouse.

RajaSankar S, Manivasagam T, Sankar V, Prakash S, Muthusamy R, Krishnamurti A, Surendran S.

Department of Anatomy, Annamalai University, Tamilnadu, India.
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera root extract (Ws)/Ashwagandha/Indian ginseng is a traditional herbal medicine, used over 4000 years in India, shown to have effect on neural growth and locomotor function. Although catecholamines and oxidative stress resulting in neurodegeneration and locomotor disorder are the main events in Parkinson's disease (PD), efficacy of the drug on these molecules and physiological abnormality are not clear. AIM OF THE STUDY: The objective of the study was to examine effect of Ws on catecholamines and physiological abnormalities seen in PD using PD model mouse. MATERIALS AND METHODS: Mouse were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 4 days to show biochemical and physiological abnormalities similar to patients with PD. PD mice were treated with Ws 100mg/kg body weight for 7 or 28 days. Catecholamines: dopamine (DA), 3,4-dihydroxy-phenylacetic acid (DOPAC) and homovanillic acid (HVA); antioxidants: glutathione (GSH) and glutathione peroxidase (GPx); and lipid peroxidation marker (TBARS) were analyzed in the Ws treated and untreated PD mouse striatum. RESULTS: Mouse treated with MPTP showed reduced levels of DA, DOPAC, HVA, GSH and GPx and induced thiobarbituric acid reactive substance (TBARS) level compared to the control. Physiological abnormalities were seen in the mouse as determined by hang test and rotarod test. Oral treatment of PD mouse Ws root extract (100mg/kg body weight) for 7 days or 28 days increased DA, DOPAC and HVA levels and normalized TBARS levels in the corpus striatum of the PD mouse. The 7 days Ws treated mice showed improved motor function as determined by hang test and rotarod test. Treatment with Ws for 28 days increased GSH and GPx levels in the striatum compared to the Ws untreated PD mouse striatum. CONCLUSION: These data suggest that Ws is a potential drug in treating catecholamines, oxidative damage and physiological abnormalities seen in the PD mouse.

In summary, this research induced Parkinson's Disease on a group of mice and administered WS. After administration of the MPTP (PD emulator) mice showed reduced levels of dopamine (DA), 3,4-dihydroxy-phenylacetic acid (DOPAC) and homovanillic acid (HVA), glutathione (GSH) and glutathione peroxidase (GPx) and the group also showed signs of decreased motor function and physiological abnormalities. After administration of WS for 7 days the mice showed increased levels of DA, DOPAC, HVA and normalized TBARS levels. After 28 days of treatment GSH and GPx levels increased as well. This shows significant promised for treatment of Parkinson's as WS appears to positively affect all negative aspects of Parkinson's effects.

This next study is similar to the previous study but I'm incorporating it because the abstract is written in plain english.

From Pub Med:

Neurosci Lett. 2009 Apr 17;454(1):11-5. Epub 2009 Feb 26.
Ashwagandha leaf extract: a potential agent in treating oxidative damage and physiological abnormalities seen in a mouse model of Parkinson's disease.

Rajasankar S, Manivasagam T, Surendran S.

Department of Anatomy, Melmaruvathur Adhi Parasakthi Institute of Medical Sciences, Tamil Nadu, India.
Abstract

Parkinson's disease (PD) is a neurodegenerative disorder that leads to impairment of balance and coordination. Therapy for the disease is still under investigation. Withania somnifera (A-Extract), a herbal medicine, has been known for a spectrum of health-promoting effects including activation of immune, muscle and neuronal systems. Therefore effect of A-Extract in the mouse model of PD was examined. The midbrain and corpus striatum of PD mouse showed increased levels of superoxide dismutase, catalase and malondialdehyde; and reduced levels of glutathione and glutathione peroxidase compared to the control. Treatment with A-Extract 100mg/kg for 7 days significantly improved all these enzyme levels compared to A-Extract untreated PD mouse brain. In the PD mouse grooming, stride length, movement, rearing were found to be decreased compared to the control. In addition, narrow beam walk and foot slippery errors were increased. Treatment with A-Extract improved all these physiological abnormalities. These data suggests that A-Extract is a potential drug in treating oxidative damage and physiological abnormalities seen in the PD mouse, if documented also in patients with PD.

This study is interesting to me because it makes use of an extract derived from a different part of the WS plant, the leaves. Most WS extract is made from the root of the plant. This study surmises the same as the previous study but investigates dismutase, catalase and malondialdehyde levels.

From Pub Med:

J Med Food. 2009 Jun;12(3):591-600.
Possible neuroprotective effect of Withania somnifera root extract against 3-nitropropionic acid-induced behavioral, biochemical, and mitochondrial dysfunction in an animal model of Huntington's disease.

Kumar P, Kumar A.

University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Abstract

Huntington's disease (HD) is a neurodegenerative disorder that results from the destruction of neurons in the basal ganglia, and oxidative stress has been implicated in its pathogenesis. 3-Nitropropionic acid (3-NP), a potent neurotoxin, has been reported to induce oxidative/nitrosative stress and causes neurobehavioral and biochemical changes that mimic HD in humans. It also inhibits complex II of the mitochondrial electron transport chain, thereby causing cellular energy deficit. In the present work, we evaluated the effects of a well-known antioxidant on behavioral, biochemical, and mitochondrial dysfunction induced by 3-NP. The study was designed to investigate the effects of Withania somnifera root extract against 3-NP-induced gait abnormalities, oxidative stress, and mitochondrial dysfunction in striatum and cortex of rat brain. Intraperitoneal administration of 3-NP (10 mg/kg for 14 days) caused a loss in body weight and a decline in motor function (locomotor activity and impaired rotarod activity). Chronic treatment with W. somnifera root extracts (100 and 200 mg/kg) for a period of 2 weeks dose-dependently improved 3-NP-induced behavioral, biochemical, and enzymatic changes (P < .05). Biochemical analysis revealed that systemic 3-NP administration significantly increased lipid peroxidation and nitrite and lactate dehydrogenase enzyme levels, depleted antioxidant enzyme (superoxide dismutase and catalase) levels, and blocked ATP synthesis by inhibiting the mitochondrial complex activity in the different regions (striatum and cortex) of the brain. Chronic administration of W. somnifera root extract (100 and 200 mg/kg) dose-dependently restored biochemical alterations induced by chronic 3-NP treatment (P < .05). These findings suggest that neuroprotective actions of W. somnifera are mediated via its antioxidant activity. However, further studies are required to elucidate the molecular mechanisms involved in order to support the clinical use of the plant extract as a therapeutic agent for the treatment of HD.

This study links the benefits of WS to it's potent anti-oxidant activity, like so many others do. There are quite a few studies that cite WS as a potent treatment for oxidative stress in other regions of the body. Unfortunately, very few studies attempt to understand the mechanism of action behind WS beyond this level.

Neural Regrowth:

These were the only two studies I found for suggesting WS has an effect on neural regrowth. The first study is very comprehensive and covers a good number of the active constituents of WS and is also free online...if you can read Japanese. The second study is about WS's effect on the neutrophic factor receptor RET.

From Pub Med:

[Overcoming several neurodegenerative diseases by traditional medicines: the development of therapeutic medicines and unraveling pathophysiological mechanisms]

[Article in Japanese]

Tohda C.

Division of Biofunctional Evaluation, Research Center for Ethnomedicine, Insitute of Natural Medicine, University of Toyama, Toyama City, Japan. chihiro@inm.u-toyama.ac.jp
Abstract

Ashwagandha (root of Withania somnifera) has been used for many purposes, it is mainly considered a tonic in traditional Ayurvedic medicine. This review focuses on the effects of compounds isolated from Ashwagandha on dementia models and on the spinal cord injury model. Our study demonstrated that the active constituents, withanolide A, withanoside IV, and withanoside VI, restored presynapses and postsynapses, in addition to both axons and dendrites in cortical neurons after Abeta(25-35)-induced injury. In vivo, oral withanolide A, withanoside IV, and withanoside VI (10 micromol/kg/day for 12 days) improved Abeta(25-35)-induced memory impairment, neurite atrophy, and synaptic loss in the cerebral cortex and hippocampus in mice. Since spinal cord injury (SCI) is also difficult to treat, and therefore practical and curable strategies for SCI are desired. Oral treatment with withanoside IV improved locomotor functions in mice with SCI. In mice treated with withanoside IV (10 micromol/kg/day for 21 days), the axonal density and peripheral nervous system myelin level increased. The loss of CNS myelin and increase in reactive gliosis were not affected by withanoside IV. Additionally, sominone, an aglycone of withanoside IV, was identified as the main metabolite after oral administration of withanoside IV in mice. Withanolide A, withanoside IV, and withanoside VI are therefore important candidates for the therapeutic treatment of neurodegenerative diseases. In particular, withanoside IV was shown to control neurons as well as glial cells for reconstruction neuronal networks. To clarify key events in overcoming neurodegeneration, we are now studying the molecular targets and signal cascades of sominone.

This abstract is a pretty straightforward read so I'll spare myself the pain of summary. One thing to take away from this is the discussion of sominone which is the constituent under inspection in the next abstract.

From Pub Med:

Br J Pharmacol. 2009 Aug;157(8):1427-40. Epub 2009 Jul 8.
Sominone enhances neurite outgrowth and spatial memory mediated by the neurotrophic factor receptor, RET.

Tohda C, Joyashiki E.

Division of Biofunctional Evaluation, Research Center for Ethnomedicine, Institute of Natural Medicine, University of Toyama, Toyama, Japan. chihiro@inm.u-toyama.ac.jp
Abstract

BACKGROUND AND PURPOSE: Orally administered withanoside IV (a compound isolated from the roots of Withania somnifera) improved memory deficits in mice with a model of Alzheimer's disease induced by the amyloid peptide Abeta(25-35). Sominone, an aglycone of withanoside IV, was identified as an active metabolite after oral administration of withanoside IV. We aimed to identify receptors or associated molecules of sominone, and to investigate the effects of sominone on memory in normal mice. EXPERIMENTAL APPROACH: Phosphorylation levels of 71 molecules were compared between control and sominone-stimulated cortical cultured cells to search for target molecules of sominone. Object location memory and neurite density in the brain were evaluated in sominone-injected mice. KEY RESULTS: Phosphorylation of RET (a receptor for the glial cell line-derived neurotrophic factor, GDNF) was increased in neurons by sominone, without affecting the synthesis and secretion of GDNF. Knockdown of RET prevented sominone-induced outgrowths of axons and dendrites. After a single i.p. injection of sominone into normal mice, they could better memorize scenery information than control mice. Sixty minutes after sominone injection, RET phosphorylation was increased, particularly in the hippocampus of mice. After the memory tests, the densities of axons and dendrites were increased in the hippocampus by sominone administration. CONCLUSIONS AND IMPLICATIONS: Sominone could reinforce the morphological plasticity of neurons by activation of the RET pathway and thus enhance memory. Sominone, a compound with low molecular weight, may be a GDNF-independent stimulator of the RET pathway and/or a novel modulator of RET signalling.

This was probably the most interesting study to me as it might point to a GDNF-independent (wiki) stimulator of the RET pathway. GDNF possibly promotes the survival and growth of many neurons through RET signaling.

I'm kicking off this thread after reading about many people's stack that include WS without ever really citing and research as to why they take it. I also notice that many people take WS before bed (perhaps because it's that sedating?) but from the first studies I posted it appears WS may be helpful in controlling stress which would lead one to believe it should be taken during waking hours. Well hopefully this will kick off some discussion about WS and it potential benefits/negatives. Just wanted to research it a bit before I jumped on board.

To get the negatives going here are two studies I came across in my searching, one is on the heavy metal buildup contained in Ashwagandha and the other is on cytotoxicity.

From Pub Med:

J Environ Sci Health B. 2010 Feb;45(2):174-81.
Heavy metal bioaccumulation in selected medicinal plants collected from Khetri copper mines and comparison with those collected from fertile soil in Haridwar, India.

Maharia RS, Dutta RK, Acharya R, Reddy AV.

Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee, India.
Abstract

Heavy metal distribution in medicinal plants is gaining importance not only as an alternative medicine, but also for possible concern due to effects of metal toxicity. The present study has been focused on emphasizing the heavy metal status and bioaccumulation factors of V, Mn, Fe, Co, Cu, Zn, Se (essential metals) and Cr, Ni, Cd, As and Pb (potentially toxic metals) in medicinal plants grown under two different environmental conditions e.g., near to Khetri copper mine and those in fertile soils of Haridwar, both in India, using Instrumental Neutron Activation Analysis (relative method) and Atomic Absorption Spectrometry. The copper levels in the medicinal plants from Khetri were found to be 3-4 folds higher (31.6-76.5 mg kg(-1)) than those from Haridwar samples (7.40-15.3 mg kg(-1)), which is correlated with very high copper levels (763 mg kg(-1)) in Khetri soil. Among various heavy metals, Cr (2.60-5.92 mg kg(-1)), Cd (1.47-2.97 mg kg(-1)) and Pb (3.97-6.63 mg kg(-1)) are also higher in concentration in the medicinal plants from Khetri. The essential metals like Mn (36.4-69.3 mg kg(-1)), Fe (192-601 mg kg(-1)), Zn (24.9-49.9 mg kg(-1)) and Se (0.13-0.91 mg kg(-1)) and potentially toxic metals like Ni (3.09-9.01 mg kg(-1)) and As (0.41-2.09 mg kg(-1)) did not show much variations in concentration in the medicinal plants from both Khetri and Haridwar. The medicinal plants from Khetri, e.g., Ocimum sanctum, Cassia fistula, Withania somnifera and Azadirachta Indica were found rich in Ca and Mg contents while Aloe barbadensis showed moderately high Ca and Mg. Higher levels of Ca-Mg were found to correlate with Zn (except Azadirachta Indica). The bioaccumulation factors (BAFS) of the heavy metals were estimated to understand the soil-to-plant transfer pattern of the heavy metals. Significantly lower BAF values of Cu and Cr were found in the medicinal plants from Khetri, indicating majority fraction of these metals are precipitated and were immobilized species unsuitable for plant uptake. Overall, Withania somnifera (Ashwagandha) showed very high metal bioaccumulation.

Take this with a grain of salt as samples were pulled from a copper mine so IMO the results are fairly skewed. But the important thing to take away is the last line. WS has a high metal absorption which would make one want to make sure the quality of their WS supplements were high. I would imagine one would want to verify where their WS was being grown especially if consuming the plant itself.

From Pub Med:

Afr J Tradit Complement Altern Med. 2009 May 7;6(3):275-80.
Comparing the cytotoxic potential of Withania somnifera water and methanol extracts.

Pretorius E, Oberholzer HM, Becker PJ.

Department of Anatomy, School of Health Sciences, Faculty of Health Sciences, University of Pretoria, South Africa. resia.pretorius@up.ac.za
Abstract

The plant Withania somnifera (Linn.) (Solanacea) is a well-known herbal medicine used in many parts of the world. It has anti-inflammatory, antioxidant, and antitumor as well as neural protective properties. It seems as if the two most active withanolide components, namely withaferin A and withanolide D, found in methanol (MeOH) extracts, are responsible for the anti-inflammatory and antioxidant properties of the plant. The current research evaluated and compared the cytotoxic potential of water and methanol extracts of W. somnifera using a combined crystal violet MTT and Neutral Red assay. MRC-5 cells, a human embryonic lung-derived diploid fibroblast cell line, were the cells of choice. We found that the three lowest concentrations (0.007, 0.042, 0.250 microg/ml) of the plant material extracted in double distilled H(2)O and MeOH do not differ significantly in any of the assays. We therefore suggest that low concentrations of MeOH extracts (up to 0.250 microg/ml plant material) do not cause cell damage to the MRC-5 cells, however, higher levels should be avoided as cell viability and cell numbers are negatively influenced.

Take away from this is "everything in moderation."

Hope this will shed some light on Ashwagandha's actions.

Edited by Athanasios, 24 June 2010 - 10:06 PM.

[Mindweaver]

The metal issue.. what kind of adverse effects can that have?

[e Volution]

Thanks for this babcock, a great overview I have learned much from despite reading much about Ahwagandha on this forum for some time... You did leave out one important piece of information though; based on your review of the evidence what position are you personally taking regarding consumption?

[The Likud Is Behind It]

Great thread. Thanks.

[babcock]

The metal issue.. what kind of adverse effects can that have?

The issue with metal absorption relates to the body not being able to expel heavy metals (wiki). So over time heavy metals accumulate in the body potentially resulting in harmful if not fatal levels. For example take Mercury, which is currently a big problem with consuming Tuna. People who regularly eat tuna are at a high risk of developing Mercury poisoning because mercury exists at high levels in the fish since the tuna is almost at the top of the food chain (It absorbs all the substances found in the fish it eats). The same could be applied to Ashwagandha it looks like as the plant naturally absorbs many metals found in the soil it grows in.

@e Volution - I haven't taken a stance yet but I personally don't see myself supplementing with this in the near future. Unless I hear more about studies GDNF and WS being done with positive results I think I'll save my money. But hopefully some people will further this discussion and possibly persuade me otherwise.

Sorry about misspelling Ashwagandha in the title. Now I feel like an idiot. Too late to edit too. sad panda

Edit: And misspelling research too, wow go me.

Edited by babcock, 24 June 2010 - 04:32 PM.

[Mindweaver]

I've been taking ~440mg a night before bed, do you recommend a different dose?

[babcock]

I've been taking ~440mg a night before bed, do you recommend a different dose?

ATM I don't recommend anything as I have no experience with it. From what I've read over the past days I have no reason to believe this will hurt you in anyway. I'm just saying that I don't foresee myself using it in the near future because there are only a few studies suggesting it repairs/regrows damaged neural networks. If research on it explodes in the next year and a lot of studies are confirming what the two I posted about neural regeneration/growth claim then I will definitely be hopping on the band wagon. Do you notice any effects from the WS? Have you tired taking it during waking hours?

I was really surprised to find all the studies about anxiety/stress relief because I know so many people take it at night before bed.

[health_nutty]

I've been taking ~440mg a night before bed, do you recommend a different dose?

I was really surprised to find all the studies about anxiety/stress relief because I know so many people take it at night before bed.

The same is true for Bacopa and anxiety. Once things settle a bit, I may try some Bacopa in the morning.

[Thorsten3]

I've started experimenting with it sporadically, it's quite a benign drug from what I've experienced so far, much like gingko. Maybe I'm not giving it a fair go. I feel so very little from that morning dose (3 tabs @900mg of extract) that it doesn't motivate me at all to take anything in the afternoon. Maybe I'm missing out? Anyone take this herb consistently and get great results?? Because everything looks great on paper, ash included.

[babcock]

I've started experimenting with it sporadically, it's quite a benign drug from what I've experienced so far, much like gingko. Maybe I'm not giving it a fair go. I feel so very little from that morning dose (3 tabs @900mg of extract) that it doesn't motivate me at all to take anything in the afternoon. Maybe I'm missing out? Anyone take this herb consistently and get great results?? Because everything looks great on paper, ash included.

From what I've read it doesn't sound like the results are aren't that noticeable (like many noots) unless maybe you are an anxious/stressed person and taking it for stress relief. What are you taking it for?

Edit: I'm really out of it today. My apologies.

Edited by babcock, 24 June 2010 - 07:53 PM.

[aLurker]

Great article, I'll up-vote it later when I can, effort and quoted research (or should I say reasearch ) should always be rewarded. I'd give you a cookie if it wasn't for the shipping cost.

One of many herbs I'd at least try if my budget allowed me to experiment more freely.

The studies show that the effects are probably statistically significant but are they noticeable? What about side effects from Ash? Anyone had any bad experiences with this?

Edited by aLurker, 24 June 2010 - 07:38 PM.

[Thorsten3]

I've started experimenting with it sporadically, it's quite a benign drug from what I've experienced so far, much like gingko. Maybe I'm not giving it a fair go. I feel so very little from that morning dose (3 tabs @900mg of extract) that it doesn't motivate me at all to take anything in the afternoon. Maybe I'm missing out? Anyone take this herb consistently and get great results?? Because everything looks great on paper, ash included.

From what I've read it doesn't sound like the results are that noticeable (like many noots) unless maybe you are an anxious/stressed person and taking it for stress relief. What are you taking it for?

I've suffered with stress and anxiety but at this current moment I have zero stress/anxiety (in life stage terms).
I suppose experimenting with these herbs are just a phase I am going through. I want to see if they are really capable of doing what they claim. So to cut a long story short it's mainly nootropic interest for me (although from my perspective nootropic effects should include mood enahncing qualities anyway becasue I naturally perform better when I feel better excluding most recreational highs of course).
So I'd be very interested in hearing from others and their progress as well as citing my own if it's of any benefit.

[Athanasios]

Here is a general non-neuro-specific review, in PDF, that has good information but it is from 2000 so dated a bit:
Ashwagandha Review

I personally find the heavy metal issue to be a non-issue at the dosages needed for effect, especially extracts from decent companies.

It is currently my adaptogen of choice, bacopa would be the other. After that, rhodiola. Then, maca. Just my personal taste. I still take maca sometimes but find that bacopa and rhodiola overlap enough with ashwagandha that I do not feel the need for them.

P.S.: I fixed up the title for you.

Edited by Athanasios, 25 June 2010 - 01:35 PM.

[NDM]

One important neuroprotective mechanism is the inhibition of the pro-inflammatory NF-KB; In the study below, Withania somnifera ranked as the strongest NF-KB inhibitor, in a competition with 23 other medicinal plants. People with brain infections (Lyme, HIV, HSV, etc) are particularly likely to benefit from working on this NF-kB mechanism. However, inflammation is also involved in depression, so there's even more scope for Withania...


Organic extracts of 24 selected plant species, used by Palestinian traditional healers to treat different illnesses and diseases, were tested for their anti-inflammatory and anti-tumoral activities. The plant selection was based on existing ethnobotanic information and interviews with local healers. The extracts of the plants under investigation were tested for their potential anti-tumor (cytotoxic) effect on the murine fibrosarcoma L929sA cells, and on the human breast cancer cells MDA-MB231 and MCF7. Cytotoxicity screening models provide important preliminary data to select plant extracts with potential antineoplastic properties. MTT (Tetrazolium blue) colorimetric assay was used to evaluate the reduction of viability of cell cultures in the presence or absence of the extracts. The extract from Withania somnifera, L. Dunal (Solanaceae) presented an IC(50) value at 24h of 150 and 60 microg/ml, on L929sA and MCF7 cells, respectively, while the extract from Psidium guajava L. (Myrtaceae) presented an IC(50) value at 24h of 55 microg/ml on MCF7 cells. Other extracts examined, like Laurus nobilis L. (Lauraceae) and Salvia fruticosa M. (Labiatae), also displayed a remarkable activity. Additionally, as the nuclear transcription factor NFkappaB regulates the expression of various genes that play critical roles in apoptosis and immunomodulation, we further investigated the effect of nine promising plant extracts, withheld from the first cell viability screening on NFkappaB activation. The extracts showed variable degrees of NFkappaB-inhibitory activity. Whereas Withania somnifera extract demonstrated the strongest NFkappaB-inhibitory activity, other extracts derived from Laurus nobilis, Psidium guajava and Foeniculum vulgare M. (Umbiliferrae) also revealed immunomodulatory NFkappaB activities. These species are good candidates for further activity-monitored fractionation to identify active constituents.

PMID: 17716845 [PubMed - indexed for MEDLINE]

[babcock]

P.S.: I fixed up the title for you.

Thank you, I'm much obliged. Felt like an idiot after coming back from lunch today and seeing that as the topic title.

[unregistered_user]

I've been taking it for a few days. I suspect it's helping to ameliorate my social anxiety. I'm in a high stress position where I oversee a team of people and am constantly mitigating conflicts and dealing with the public. This seems to help take the edge off. Take my opinion with a grain of salt though as I've only been using it a few days.

Edited by semi-retarded-individual, 25 June 2010 - 03:37 AM.

[chrono]

Great thread. These particular effects should be gathered together in one place, as right now only a few of these abstracts are scattered all over the board. I feel like ashwagandha is probably the other best candidate besides lion's mane for a practical substance to encourage neurotrophic growth enhancement. And it took me like a year of research before I could even wrap my brain around that wacky word

Here's a few more abstracts. This first one studies stress-induced damage to hippocampal areas. The proposed neuroprotective mechanism (reduction in glucocorticoid levels), though not studied comprehensively, is supported by the second abstract babcock posted:

Neuroprotective effects of Withania somnifera Dunn. in hippocampal sub-regions of female albino rat.
Jain S, Shukla SD, Sharma K, Bhatnagar M.
Department of Zoology, University College of Science, M.L. Sukhadia University, Udaipur

The neuroprotective effects of W. somnifera were studied on stressed adult female Swiss albino rats. Experimental rats were subjected to immobilization stress for 14 h and were treated with a root powder extract of W. somnifera available as Stresscom capsules (Dabur India Ltd). Control rats were maintained in completely, non stressed conditions. Thionin stained serial coronal sections (7 microm) of brain passing through the hippocampal region of stressed rats (E(1) group) demonstrated 85% degenerating cells (dark cells and pyknotic cells) in the CA(2) and CA(3) sub-areas. Treatment with W. somnifera root powder extract significantly reduced (80%) the number of degenerating cells in both the areas. The study thus demonstrates the antistress neuroprotective effects of W. somnifera.

PMID: 11536389 [PubMed - indexed for MEDLINE]

Interestingly animals of group E3 (drug treatment for at least 30 days given prior to subjecting to stress) showed more cytoprotective effects than the post or simultaneous treatment.

Although the mechanism of degeneration and cytoprotective effects of the drug can not be explained on basis of these experiments it is possible that an increase in corticosteroid level during stress might be associated with the cell degeneration...A significant decrease in the ascorbic acid level in the brain homogenate of the stressed group and restoration to the normal level after treatment with the herbal drug substantiate our observation.

And here's a series of excellent papers from Kuboyama, Tohda, and Komatsu at the Research Center for Ethnomedicine, University of Toyama. Their science is pretty tight. Taken sequentially, they pursue and explain some of the important questions about how this stuff works.

The first paper finds significant dendrite outgrowth and interaction, but no axonal construction.

Dendrite extension by methanol extract of Ashwagandha (roots of Withania somnifera) in SK-N-SH cells.
Tohda C, Kuboyama T, Komatsu K.

Extension of dendrites and axons in neurons may compensate for and repair damaged neuronal circuits in the dementia brain. Our aim in the present study was to explore drugs activating neurite outgrowth and regenerating the neuronal network. We found that the methanol extract of Ashwagandha (roots of Withania somnifera; 5 microg/ml) significantly increased the percentage of cells with neurites in human neuroblastoma SK-N-SH cells. The effect of the extract was dose- and time-dependent mRNA levels of the dendritic markers MAP2 and PSD-95 by RT-PCR were found to be markedly increased by treatment with the extract, whereas those of the axonal marker Tau were not. Immunocytochemistry demonstrated the specific expression of MAP2 in neurites extended by the extract. These results suggest that the methanol extract of Ashwagandha promotes the formation of dendrites.

PMID: 10884056 [PubMed - indexed for MEDLINE]

In case of Ashwagandha, the methanol extract exhibited significant neurite outgrowth activity, whereas the water extract did not. Neither the methanol nor water extracts of Mandookaparni, which is also Ayurvedic medicine and considered to promote intellect, had an effect on neurite outgrowth.
...
SK-N-SH cells treated with Ashwagandha extract extended the neurites multipolarly, and these neurites seemed to interact with each other. A quantitative measurement of neurites indicated that the Ashwagandha extract caused significant multipolar (>2 neurites per cell) neurite outgrowth. In the control, there were no cells with multipolar neurites, and bipolar neurites were also hardly seen (0.18%), whereas in the Ashwagandha extract-treated cells, the percentage of cells with multipolar neurites was 38.0%...
...
Although the expression of MAP2 protein was increased 4 days after treatment with Ashwagandha extract, intense upregulation of MAP2 and PSD-95 mRNAs was seen even 6 days after treatment. The mechanisms of transcriptional regulation for both MAP2 and PSD-95 are not known...MAP2 is a structural dendritic marker of microtubule stabilization, whereas PSD-95 is a signal-mediating postsynaptic marker in dendrites...In addition, the turnover of PSD-95 is closely related to synaptic transmission in cultured hippocampal neurons. The above suggest that increases in PSD-95 provide an index of postsynaptic excitation. Because NMDA receptors exist in SK-N-SH cells, the increase in PSD-95 shown in the present experiment may be involved in the activation of signal transmission through NMDA receptors. The upregulation of MAP2 and PSD-95 may indicate not only structural dendritic formation but also an enhancement of synaptic function by Ashwagandha extract.

This study clarifies composition, and identifies which compounds are probably active. Mostly a chemical paper, with no info on neurogenesis beyond what is included in the abstract:

Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities. [free full text]
Zhao J, Nakamura N, Hattori M, Kuboyama T, Tohda C, Komatsu K.

Five new withanolide derivatives (1, 9-12) were isolated from the roots of Withania somnifera together with fourteen known compounds (2-8, 13-19)...Of the isolated compounds, 1, withanolide A (2), (20S,22R)-4 beta,5 beta,6 alpha,27-tetrahydroxy-1-oxowitha-2,24-dienolide (6), withanoside IV (14), withanoside VI (15) and coagulin Q (16) showed significant neurite outgrowth activity at a concentration of 1 microM on a human neuroblastoma SH-SY5Y cell line.

PMID: 12045329 [PubMed - indexed for MEDLINE]

This paper builds on the new chemical knowledge, and performs detailed tests to show which ones promote neurite outgrowth. They look for a different marker (NF-H) which shows that several withanolides do indeed promote axonal extension, which they did not find using the Tau marker in the 2000 Neuroreport paper above. NGF is co-studied, and found to have different properties (doesn't grow axons). Also of note is the finding that several of these molecules are neurotoxic at a certain concentration; 50mg/mL of cell culture sounds like a pretty huge amount, compared to 1micromole needed to promote neurite outgrowth. But a closer examination of these numbers is warranted.

Axon- or dendrite-predominant outgrowth induced by constituents from Ashwagandha.
Kuboyama T, Tohda C, Zhao J, Nakamura N, Hattori M, Komatsu K.

We previously reported that the methanol extract of Ashwagandha (roots of Dunal) induced dendrite extension in a human neuroblastoma cell line. In this study, we found that six of the 18 compounds isolated from the methanol extract enhanced neurite outgrowth in human neuroblastoma SH-SY5Y cells. Double immunostaining was performed in rat cortical neurons using antibodies to phosphorylated NF-H as an axonal marker, and to MAP2 as a dendritic marker. In withanolide A-treated cells, the length of NF-H-positive processes was significantly increased compared with vehicle-treated cells, whereas, the length of MAP2-positive processes was increased by withanosides IV and VI. These results suggest that axons are predominantly extended by withanolide A, and dendrites by withanosides IV and VI.

PMID: 12395110 [PubMed - indexed for MEDLINE]

However, withanolide A-treated cells unexpectedly extended axons. Namely, the treatment with withanolide A at 1 mM induced phosphorylated NF-H-positive neurites in rat cortical neurons. Our preliminary experiment showed that oral administration of withanolide A increased the axon extension in the mouse cerebral cortex (data not shown), suggesting that withanolide A may induce axonal formation in vivo as well as in vitro.

In the present study, we used NGF as a positive control for the neurite outgrowth effect on cortical neurons, since it has been reported that NGF induced axons and dendrites in CNS neurons, and TrkA, a high affinity NGF receptor, is expressed in the cerebral cortex. In the present experiment, however, NGF significantly induced dendrites in cortical neurons, but not axons. Withanolide A is the unique compound that predominantly induced axons...The damaged brain contains a variety of neurons that are sensitive or insensitive to NGF. Considering that withanolide A, and withanosides IV and VI induced outgrowth of axons and dendrites, respectively without NGF addition, the formation of both axons and dendrites in a damaged brain may be efficiently controlled by a mixed cocktail of these compounds in various ratios.

Traditionally, Ashwagandha has been considered to have no side effects. However, the methanol extract of Ashwagandha showed neurotoxicity at high doses (>50 mg/ml) in our experiments (data not shown). This neurotoxicity of the extract may have been caused by the neurotoxic constituents withaferin A and withanolide D at least in part. Therefore, isolated active compounds but not the extract form should be used for the purpose of facilitating neurite maturity.

Here, they examine withanolide A in a more complex cortical neuron model, and using even more activity markers. Amyloid-β (one of the compounds thought to cause Alzheimer's) is used to damage a neural network, and withanolide A shows significant success in reconstruction. This process is also tested in actual mice, ameliorating behavioral/memory deficits.

This paper is also profoundly significant in that it shows not only neurite outgrowth in both dendrites and axons, but actual synaptic reconstruction. That is to say, neurites aren't just protected and branched outward, but are much more likely to be (re-)incorporated into the neural network in a useful way. The authors speculate a little more about the mechanism for this, and again contrast the results in several ways to NGF/BDNF in the same model, concluding that the mechanism is likely distinct from that of these endogenous growth factors.

Neuritic regeneration and synaptic reconstruction induced by withanolide A. [free full text]
Kuboyama T, Tohda C, Komatsu K.
Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630

We investigated whether withanolide A (WL-A), isolated from the Indian herbal drug Ashwagandha (root of Withania somnifera), could regenerate neurites and reconstruct synapses in severely damaged neurons. We also investigated the effect of WL-A on memory-deficient mice showing neuronal atrophy and synaptic loss in the brain. Axons, dendrites, presynapses, and postsynapses were visualized by immunostaining for phosphorylated neurofilament-H (NF-H), microtubule-associated protein 2 (MAP2), synaptophysin, and postsynaptic density-95 (PSD-95), respectively. Treatment with A beta(25-35) (10 microM) induced axonal and dendritic atrophy, and pre- and postsynaptic loss in cultured rat cortical neurons. Subsequent treatment with WL-A (1 microM) induced significant regeneration of both axons and dendrites, in addition to the reconstruction of pre- and postsynapses in the neurons. WL-A (10 micromol kg(-1) day(-1), for 13 days, p.o.) recovered A beta(25-35)-induced memory deficit in mice. At that time, the decline of axons, dendrites, and synapses in the cerebral cortex and hippocampus was almost recovered. WL-A is therefore an important candidate for the therapeutic treatment of neurodegenerative diseases, as it is able to reconstruct neuronal networks.

PMID: 15711595 [PubMed - indexed for MEDLINE]

We demonstrated for the first time in vitro and in vivo that WLA was able to recover both neuritic atrophy and synaptic loss...In this study, we demonstrated that the remarkable enhancement of axonal and dendritic regeneration and synaptic reconstruction was induced by WL-A in the damaged mouse brain as well as in the damaged cultured neurons. In addition, p.o. administration of WL-A improved the Ab(25–35)-induced memory deficit of mice. This impairment of the memory disorder may result from the reconstruction of neuronal networks by WL-A.

Although the signal transduction mechanisms of WL-A remained unknown, one possibility was that WL-A stimulated signal cascades similar to β-estradiol. WL-A has a steroidal structure. β-Estradiol is an endogenous factor that induces neurite arborization via extracellular signal-regulated kinase (ERK), and enhances synaptophysin expression via membrane ER and p44 MAP kinase (Yokomaku et al., 2003). It is also reported that b-estradiol enhances PSD-95 transcription via the PI3-K following Akt pathway. We are now analyzing the mechanism of WL-A compared with the signal cascade of b-estradiol.

In this study, NGF induced neuritic regeneration, but did not lead to the reconstruction of synapses. These findings may indicate that NGF can induce the regeneration of neurites, but not that of synapses. BDNF is another important neurotrophin that leads to neurite extension and increases the number of synaptophysin-immunoreactive puncta, whereas BDNF (100ng ml/m1) did not induce neurite outgrowth in our study (data not shown). We are unable to account for the failure of BDNF to lead to neurite extension in cultured cortical neurons. However, we suggest that WL-A induced the growth of neurites and synapses via different mechanisms from those associated with BDNF or NGF.

Another test using the amyloid-β model, this time on WL-IV. Its active metabolite sominone was identified, which also showed potent axonal, dendritic and synaptic reconstruction, as well as neuroprotection. See babcock's abstract #7 for an examination of sominone by itself.

Withanoside IV and its active metabolite, sominone, attenuate Abeta(25-35)-induced neurodegeneration.
Kuboyama T, Tohda C, Komatsu K.

At the present, medication of dementia is limited to symptomatic treatments such as the use of cholinesterase inhibitors. To cure dementia completely, that is regaining neuronal function, reconstruction of neuronal networks is necessary. Therefore, we have been exploring antidementia drugs based on reconstructing neuronal networks in the damaged brain and found that withanoside IV (a constituent of Ashwagandha; the root of Withania somnifera) induced neurite outgrowth in cultured rat cortical neurons. Oral administration of withanoside IV (10 micromol/kg/day) significantly improved memory deficits in Abeta(25-35)-injected (25 nmol, i.c.v.) mice and prevented loss of axons, dendrites, and synapses. Sominone, an aglycone of withanoside IV, was identified as the main metabolite after oral administration of withanoside IV. Sominone (1 microM) induced axonal and dendritic regeneration and synaptic reconstruction significantly in cultured rat cortical neurons damaged by 10 microM Abeta(25-35). These data suggest that orally administrated withanoside IV may ameliorate neuronal dysfunction in Alzheimer's disease and that the active principle after metabolism is sominone.

PMID: 16553605 [PubMed - indexed for MEDLINE]

Withanolide A has no glycoside whereas withanoside IV and withanoside VI have ones in thestructure. We speculated that withanolide compounds that have no glucose residue enhance more presynaptic formation...presynaptic numbers were increased more by treatment with sominone than by withanoside IV at the same dose. This suggests that structural changes during deglycosylation may affect the potency of synaptogenesis.

And here, WL-IV is shown to prompt neuronal reconstruction in the PNS. Much of the research seems substantially similar to the 6th paper babcock posted (by Tohda alone).

Withanoside IV improves hindlimb function by facilitating axonal growth and increase in peripheral nervous system myelin level after spinal cord injury.
Nakayama N, Tohda C.

Although methylprednisolone is the clinically standard medication and almost the only therapy for spinal cord injury (SCI), its effect on functional recovery remains questionable. Transplantation strategies using sources such as neural stem cells and embryonic spinal cord still have some hurdles to overcome before practical applications become available. We therefore aimed to develop a practical medication for SCI. Per oral treatment with withanoside IV, which was previously shown to regenerate neuronal networks in the brain, improved locomotor functions in mice with SCI. In the spinal cord after SCI, axons were crushed in the white matter and gray matter, and central nervous system (CNS) myelin level decreased. In mice treated with withanoside IV (10micromol/kg body weight/day, for 21 days), axonal density and peripheral nervous system (PNS) myelin level increased. The loss of CNS myelin and increase in reactive gliosis were not affected by withanoside IV. These results suggest that oral administration of withanoside IV may ameliorate locomotor functions by facilitating both axonal regrowth and increase in PNS myelin level.

PMID: 17386954 [PubMed - indexed for MEDLINE]

Edited by chrono, 25 June 2010 - 04:39 AM.

[babcock]

Wow, great research chrono. These papers you have are a lot better than the ones I found. I'm definitely more convinced now to add WS to my stack. Thanks for all the info.

[Mindweaver]

I've been taking it before bed, I figure that it's best time to take it because your neurons are the least active in a sense that they aren't AS exposed to environmental stimuli as you would be if you were awake, giving them time to implement NGF. I'm sure it's more complicated than that, but that's my take in it

[chrono]

I've been taking it before bed, I figure that it's best time to take it because your neurons are the least active in a sense that they aren't AS exposed to environmental stimuli as you would be if you were awake, giving them time to implement NGF. I'm sure it's more complicated than that, but that's my take in it

I would say the exact opposite; neural activity and learning seems to play a role in the ability of growth factors to build neural networks:

Gene-experience interaction alters the cholinergic septohippocampal pathway of mice.
Brooks AI, Cory-Slechta DA, Federoff HJ.

Spatial learning requires the septohippocampal pathway. The interaction of learning experience with gene products to modulate the function of a pathway may underlie use-dependent plasticity. The regulated release of nerve growth factor (NGF) from hippocampal cultures and hippocampus, as well as its actions on cholinergic septal neurons, suggest it as a candidate protein to interact with a learning experience. A method was used to evaluate NGF gene-experience interaction on the septohippocampal neural circuitry in mice. The method permits brain region-specific expression of a new gene by using a two-component approach: a virus vector directing expression of cre recombinase; and transgenic mice carrying genomic recombination substrates rendered transcriptionally inactive by a "floxed" stop cassette. Cre recombinase vector delivery into transgenic mouse hippocampus resulted in recombination in 30% of infected cells and the expression of a new gene in those cells. To examine the interaction of the NGF gene and experience, adult mice carrying a NGF transgene with a floxed stop cassette (NGFXAT) received a cre recombinase vector to produce localized unilateral hippocampal NGF gene expression, so-called "activated" mice. Activated and control nonactivated NGFXAT mice were subjected to different experiences: repeated spatial learning, repeated rote performance, or standard vivarium housing. Latency, the time to complete the learning task, declined in the repeated spatial learning groups. The measurement of interaction between NGF gene expression and experience on the septohippocampal circuitry was assessed by counting retrogradely labeled basal forebrain cholinergic neurons projecting to the hippocampal site of NGF gene activation. Comparison of all NGF activated groups revealed a graded effect of experience on the septohippocampal pathway, with the largest change occurring in activated mice provided with repeated learning experience. These data demonstrate that plasticity of the adult spatial learning circuitry can be robustly modulated by experience-dependent interactions with a specific hippocampal gene product.

PMID: 11078505 [PubMed - indexed for MEDLINE]

Though I'll also point out for technical correctness (the best kind of correctness) that ashwagandha doesn't seem to act via NGF. But this principle might still reasonably apply.

Though a couple of those papers I posted suggest that the neurotrophic effect of ashwagandha lasts quite a while, even after cessation of usage (this may well apply to the anxiolytic effect that babcock mentioned in his post). I think a lot of people take it at night because they find it sedating.

Edited by chrono, 26 June 2010 - 07:48 PM.

[aLurker]

Is the anxiolytic effect something that is quickly on-setting and goes away after a few hours?

The reason I'm asking is that I'm always wide awake between 10 p.m. and 2 a.m. and find it hard to get to sleep on time. Something which could make me relax earlier and yet not make me even more impossible to wake up in the morning would be great. The opposite of this for me was Bacopa, which didn't make me noticeably more tired after taking it yet accumulatively made me sedated 24/7 and ultimately made me have no energy at all.

So basically my question is, can I use this as a "sleeping pill" in the evening and yet wake up refreshed in the morning?

[chrono]

I definitely relate to your bacopa experience. Turned me into a zombie from like 6-20 hours after I took it, and made it almost impossible to get less than 12 hours of sleep if I took it before bed. So I'm worried about this possibility as well.

Hopefully someone will weigh in (though I suspect effects can vary, like with bacopa). The only mention of this I could find was from Vamplyer, though in the next post it sounds like it was the Mentat mix (with bacopa) after all. Fatigue was also discussed in this thread, though it sounds much more like an immediate effect.

I have that same kind of insomnia. Ever since I was a child, I could never feel tired at a normal time of day...always felt like it should be about 6 hours longer. Taking 1g of taurine a few hours before bed helped a lot with this. Adding 5mg of lithium got rid of it entirely. Taurine might make it hard to get up for a day or two, lithium for probably a couple of weeks before you get used to it (slow titration is a good idea if you have things to do).

[aLurker]

Thanks chrono.

In the second thread you linked to someone quotes info which says that Ash could mess with your thyroid levels which means I'll probably stay clear of Ash. I've managed to normalize my thyroid values now and I don't want to risk ANYTHING messing them up again. The risk/reward profile is obviously different for those who aren't in my situation.

I haven't really yet done much research about NightOwlism or whatever you want to call it, perhaps it's evolutionary or others claim that it's linked to adrenal fatigue (if there is such a thing). I'll probably look into it later, much much later since those are the hours where I feel truly awake.

Taurine sounds really nice after glancing at wikipedia, I couldn't find much about its side effects or how chronic use could affect you though but maybe I'll look it up after I chug down a couple of Redbulls for dinner.

I've actually been reading a few threads here about Lithium. Whether its supplementation is helpful or harmful isn't really clear to me yet. Too much is definitely harmful to your intellect unless you have a diagnosed mental decease but a very low dose could be helpful. I however do not really feel qualified to know what dosage might be beneficial for me personally and it seems dangerous to experiment with but maybe 0-5 mg could be worth trying if I can find it cheap. I saw that the preliminary Imminst multivitamin design had 1 mg of Lithium in it. That makes me feel a little better about Lithium... well that and Nirvana.

Also... it would be awesome to mess with people by starting insane comments with "This might just be the Lithium talking but..."

[meursault]

Is the anxiolytic effect something that is quickly on-setting and goes away after a few hours?

The reason I'm asking is that I'm always wide awake between 10 p.m. and 2 a.m. and find it hard to get to sleep on time. Something which could make me relax earlier and yet not make me even more impossible to wake up in the morning would be great. The opposite of this for me was Bacopa, which didn't make me noticeably more tired after taking it yet accumulatively made me sedated 24/7 and ultimately made me have no energy at all.

So basically my question is, can I use this as a "sleeping pill" in the evening and yet wake up refreshed in the morning?

On two occasions, I experienced significant nightmares after taking Ashwagandha at night.

[meursault]

Thanks chrono.

In the second thread you linked to someone quotes info which says that Ash could mess with your thyroid levels which means I'll probably stay clear of Ash. I've managed to normalize my thyroid values now and I don't want to risk ANYTHING messing them up again. The risk/reward profile is obviously different for those who aren't in my situation.

I haven't really yet done much research about NightOwlism or whatever you want to call it, perhaps it's evolutionary or others claim that it's linked to adrenal fatigue (if there is such a thing). I'll probably look into it later, much much later since those are the hours where I feel truly awake.

Taurine sounds really nice after glancing at wikipedia, I couldn't find much about its side effects or how chronic use could affect you though but maybe I'll look it up after I chug down a couple of Redbulls for dinner.

I've actually been reading a few threads here about Lithium. Whether its supplementation is helpful or harmful isn't really clear to me yet. Too much is definitely harmful to your intellect unless you have a diagnosed mental decease but a very low dose could be helpful. I however do not really feel qualified to know what dosage might be beneficial for me personally and it seems dangerous to experiment with but maybe 0-5 mg could be worth trying if I can find it cheap. I saw that the preliminary Imminst multivitamin design had 1 mg of Lithium in it. That makes me feel a little better about Lithium... well that and Nirvana.

Also... it would be awesome to mess with people by starting insane comments with "This might just be the Lithium talking but..."

I would also suggest trying these for sleeplessness: Zinc Picolinate or Opti-zinc (see first if you have a deficiency), L-Glycine, Magnesium (Glycinate or Citrate), or Pomegranate Extract. Of all these, Zinc and Pomegranate have worked the best for me.

[FunkOdyssey]

I would also suggest trying these for sleeplessness: Zinc Picolinate or Opti-zinc (see first if you have a deficiency), L-Glycine, Magnesium (Glycinate or Citrate), or Pomegranate Extract. Of all these, Zinc and Pomegranate have worked the best for me.

Not that I'm doubting your experience but do you have any idea why pomegranate would help (mechanism of action)?

[chrono]

Thought I'd post these here, as the thyroid info is sort of buried in some older threads.

There seems to be some confusion as to whether it increases T3 and T4, or just T4 (even though both studies were by the same authors). I don't know why, if you're a scientist and you have the experiment all set up, you wouldn't just include both male and female mice to remove that as a confounding factor.

These first two papers also demonstrate some anti-oxidant activity.

Changes in thyroid hormone concentrations after administration of ashwagandha root extract to adult male mice.
Panda S, Kar A.
School of Life Sciences, D.A. University, Indore, India.

The importance of ashwagandha root extract in the regulation of thyroid function with special reference to type-I iodothyronine 5'-monodeiodinase activity in mice liver has been investigated. Although the root extract (1.4 g kg(-1)) administered daily for 20 days by gastric intubation increased serum 3,3',5-triiodothyronine (T3) and tetraiodothyronine (T4) concentrations and hepatic glucose-6-phosphatase activity, hepatic iodothyronine 5'-monodeiodinase activity did not change significantly. Furthermore, ashwagandha root extract significantly reduced hepatic lipid peroxidation, whereas the activity of antioxidant enzymes such as superoxide dismutase and catalase were increased. These findings reveal that the ashwagandha root extract stimulates thyroidal activity and also enhances the antiperoxidation of hepatic tissue.

PMID: 9811169 [PubMed - indexed for MEDLINE]

Withania somnifera and Bauhinia purpurea in the regulation of circulating thyroid hormone concentrations in female mice.
Panda S, Kar A.
School of Life Sciences, Devi Ahilya University, Vigyan Bhavan, Indore, India.

The effects of daily administration of Withania somnifera root extract (1.4 g/kg body wt.) and Bauhinia purpurea bark extract (2.5 mg/kg body wt.) for 20 days on thyroid function in female mice were investigated. While serum triiodothyronine (T3) and thyroxine (T4) concentrations were increased significantly by Bauhinia, Withania could enhance only serum T4 concentration. Both the plant extracts showed an increase in hepatic glucose-6-phosphatase (G-6-Pase) activity and antiperoxidative effects as indicated either by a decrease in hepatic lipid peroxidation (LPO) and/or by an increase in the activity of antioxidant enzyme(s). It appears that these plant extracts are capable of stimulating thyroid function in female mice.

PMID: 10619390 [PubMed - indexed for MEDLINE]

And here, a case report:

[Thyrotoxicosis following the use of ashwagandha]
van der Hooft CS, Hoekstra A, Winter A, de Smet PA, Stricker BH.
Inspectie voor de Gezondheidszorg, Den Haag.

A 32-year-old healthy woman developed thyrotoxicosis while taking capsules that contained ashwagandha herbal extract for symptoms of chronic fatigue. She was not taking any other remedies or medications. During the first few weeks, she took the capsules only occasionally without any symptoms, but after increasing the dose, she experienced clinical symptoms indicative of thyrotoxicosis. This was confirmed by laboratory assessment. The symptoms resolved spontaneously after discontinuation of the ashwagandha capsules and laboratory values normalised. To our knowledge, this relationship has not been reported previously in humans. Data from animal studies, however, have suggested that ashwagandha can increase serum concentrations of thyroid hormones. This case study suggests that thyrotoxicosis is a potentially serious side effect of ashwagandha.

PMID: 16355578 [PubMed - indexed for MEDLINE]

So yeah. If you have thyroid issues, ashwagandha may not be for you. Although I don't know if it might be helpful in treating hypothroidism. And for anyone taking it, getting your thyroid levels checked periodically is probably an excellent idea.

[meursault]

I would also suggest trying these for sleeplessness: Zinc Picolinate or Opti-zinc (see first if you have a deficiency), L-Glycine, Magnesium (Glycinate or Citrate), or Pomegranate Extract. Of all these, Zinc and Pomegranate have worked the best for me.

Not that I'm doubting your experience but do you have any idea why pomegranate would help (mechanism of action)?

I hypothesize that it's due to the reduction of systolic blood pressure.

[unregistered_user]

I take 675mg of Ash in the morning with Rhodiola, Piracetam and Choline Bitartrate and feel just fine. My dreams have become much more realistic but I can scarcely recall them after waking.

[Steve_86]

Is there any evidence to suggest that Ashwagandha should be cycled?