10 replies to this topic

[boilerroom]

http://www.ncbi.nlm....l=pubmed_docsum

I'm actually starting to become worried about taking it (should arrive tommorow) because apparently it increases flunitrazepam binding to GABA sites. Flunitrazepam is not beneficial!

READ: http://en.wikipedia....i/Flunitrazepam

[Shepard]

Try linking to the study again, that one is dead. However, I want to think I've read something like this before....although that might have been testing the anxiolytic properties of ashwaganda against benzodiazepine.

[kottke]

Who would use Flunitrazepam in the first place? That sh*t is no joke. Do you work for the FBI boilerroom? Sounds like an interegation name if you ask me.

[mitkat]

Who would use Flunitrazepam in the first place? That sh*t is no joke. Do you work for the FBI boilerroom? Sounds like an interegation name if you ask me.

Indeed. Why is this a concern? You should be at a distance from that business.

[boilerroom]

Ha, no I am not taking Flunitrazepam. I found a study on Ashwagandha on PUBMED, which stated that Ashwagandha causes Flunitrazepam to bind at GABA receptor cites. This would explain the sedating qualities of the herb. Ashwagandha does not raise GABA levels, but appears to MIMIC he effects of GABA with Flunitrazepam.

For the article, go to PUBMED.com and do the following: search for "Flunitrazepam withania", and read it carefully.

[zoolander]

Here is the originally quoted study

Indian J Med Res. 1991 Aug;94:312-5. 

Pharmacological effects of Withania somnifera root extract on GABAA receptor complex.

Mehta AK, Binkley P, Gandhi SS, Ticku MK.

Department of Pharmacology, University of Texas Health Science Center.

    A methanolic extract of W. somnifera root inhibited the specific binding of [3H]GABA and [35S]TBPS, and enhanced the binding of [3H]flunitrazepam to their putative receptor sites. The extract (5 micrograms) inhibited [3H]GABA binding by 20 +/- 6 per cent whereas a concentration of 1 mg of the extract produced 100 per cent inhibition. The extract (5-100 micrograms) produced 20 +/- 4 to 91 +/- 16 per cent enhancement of [3H]flunitrazepam binding. In functional studies using 36Cl-influx assay in mammalian spinal cord neurons, W. somnifera root extract increased 36Cl-influx in the absence of GABA. This effect on 36Cl-influx was blocked by bicuculline and picrotoxin; and enhanced by diazepam. These results suggest that the W. somnifera extract contains an ingredient which has a GABA-mimetic activity.

    PMID: 1660034 [PubMed - indexed for MEDLINE]

also.....

Effect of Withania somnifera glycowithanolides on a rat model of tardive dyskinesia.

Bhattacharya SK, Bhattacharya D, Sairam K, Ghosal S.

Withania somnifera glycowithanolides (WSG) were investigated for their preventive effect on the animal model of tardive dyskinesia (TD), induced by once daily administration of the neuroleptic, haloperidol (1.5 mg/kg, i.p.), for 28 days. Involuntary orofacial movements (chewing movements, tongue protusion and buccal tremors) were assessed as TD parameters. WSG (100 and 200 mg, p.o.), administered concomitantly with haloperidol for 28 days, inhibited the induction of the neuroleptic TD. Haloperidol-induced TD was also attenuated by the antioxidant, vitamin E (400 and 800 mg/kg, p.o.), but remained unaffected by the GABA-mimetic antiepileptic agent, sodium valproate (200 and 400 mg/kg, p.o.), both agents being administered for 28 days like WSG. The results indicate that the reported antioxidant effect of WSG, rather than its GABA-mimetic action, may be responsible for the prevention of haloperidol-induced TD.

Publication Types:

    * Letter


PMID: 11995951 [PubMed - indexed for MEDLINE]

Systemic administration of defined extracts from Withania somnifera (Indian Ginseng) and Shilajit differentially affects cholinergic but not glutamatergic and GABAergic markers in rat brain.

Schliebs R, Liebmann A, Bhattacharya SK, Kumar A, Ghosal S, Bigl V.

Paul Flechsig Institute for Brain Research, Department of Neurochemistry, University of Leipzig, Germany.

Although some promising results have been achieved by acetylcholinesterase inhibitors, an effective therapeutic intervention in Alzheimer's disease still remains an important goal. Sitoindosides VII-X, and withaferin-A, isolated from aqueous methanol extract from the roots of cultivated varieties of Withania somnifera (known as Indian Ginseng), as well as Shilajit, a pale-brown to blackish brown exudation from steep rocks of the Himalaya mountain, are used in Indian medicine to attenuate cerebral functional deficits, including amnesia, in geriatric patients. The present investigation was conducted to assess whether the memory-enhancing effects of plant extracts from Withania somnifera and Shilajit are owing to neurochemical alterations of specific transmitter systems. Therefore, histochemistry to analyse acetylcholinesterase activity as well as receptor autoradiography to detect cholinergic, glutamatergic and GABAergic receptor subtypes were performed in brain slices from adult male Wistar rats, injected intraperitoneally daily with an equimolar mixture of sitoindosides VII-X and withaferin-A (prepared from Withania somnifera) or with Shilajit, at doses of 40 mg/kg of body weight for 7 days. Administration of Shilajit led to reduced acetylcholinesterase staining, restricted to the basal forebrain nuclei including medial septum and the vertical limb of the diagonal band. Systemic application of the defined extract from Withania somnifera, however, led to differential effects on AChE activity in basal forebrain nuclei: slightly enhanced AChE activity was found in the lateral septum and globus pallidus, whereas in the vertical diagonal band AChE activity was reduced following treatment with sitoindosides VII-X and withaferin-A. These changes were accompanied by enhanced M1-muscarinic cholinergic receptor binding in lateral and medial septum as well as in frontal cortices, whereas the M2-muscarinic receptor binding sites were increased in a number of cortical regions including cingulate, frontal, piriform, parietal and retrosplenial cortex. Treatment with Shilajit or the defined extract from Withania somnifera affected neither GABAA and benzodiazepine receptor binding nor NMDA and AMPA glutamate receptor subtypes in any of the cortical or subcortical regions studied. The data suggest that Shilajit and the defined extract from Withania somnifera affect preferentially events in the cortical and basal forebrain cholinergic signal transduction cascade. The drug-induced increase in cortical muscarinic acetylcholine receptor capacity might partly explain the cognition-enhancing and memory-improving effects of extracts from Withania somnifera observed in animals and humans.

PMID: 9017665 [PubMed - indexed for MEDLINE]

So we have the study that you (Boilerroom) quoted that only suggests GABA action and then we have the second study that suggests that W. somnifera extract is not a GABA-mimetic and finally the third study, which measured GABA receptor activity directly states that W. somnifera extract did not effect GABAA receptor binding.

My money is on W. somnifera extract as an antioxidant.

Here is a nice little review paper on Ashwagandha

Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review.

Mishra LC, Singh BB, Dagenais S.

Los Angeles College of Chiropractic (LACC), 16200 E Amber Valley Dr., Whittier, CA 90609-1166. lakshmimishra@lacc.edu

OBJECTIVE: The objective of this paper is to review the literature regarding Withania somnifera (ashwagandha, WS) a commonly used herb in Ayurvedic medicine. Specifically, the literature was reviewed for articles pertaining to chemical properties, therapeutic benefits, and toxicity. DESIGN: This review is in a narrative format and consists of all publications relevant to ashwagandha that were identified by the authors through a systematic search of major computerized medical databases; no statistical pooling of results or evaluation of the quality of the studies was performed due to the widely different methods employed by each study. RESULTS: Studies indicate ashwagandha possesses anti-inflammatory, antitumor, antistress, antioxidant, immunomodulatory, hemopoietic, and rejuvenating properties. It also appears to exert a positive influence on the endocrine, cardiopulmonary, and central nervous systems. The mechanisms of action for these properties are not fully understood. Toxicity studies reveal that ashwagandha appears to be a safe compound. CONCLUSION: Preliminary studies have found various constituents of ashwagandha exhibit a variety of therapeutic effects with little or no associated toxicity. These results are very encouraging and indicate this herb should be studied more extensively to confirm these results and reveal other potential therapeutic effects. Clinical trials using ashwagandha for a variety of conditions should also be conducted.

Publication Types:

    * Review


PMID: 10956379 [PubMed - indexed for MEDLINE]

Edited by zoolander, 26 May 2006 - 01:39 AM.

[superpooper]

So the relaxation must be from serotonin receptors?

[boilerroom]

From the German study you posted: " Systemic application of the defined extract from Withania somnifera, however, led to differential effects on AChE activity in basal forebrain nuclei: slightly enhanced AChE activity was found in the lateral septum and globus pallidus, whereas in the vertical diagonal band AChE activity was reduced following treatment with sitoindosides VII-X and withaferin-A."

What role does Acetylcholine play in the verical diagonal band?

[boilerroom]

From PUBMED: "Huperzia saururus, activity on synaptic transmission in the hippocampus.

Ortega MG, Vallejo MG, Cabrera JL, Perez MF, Almiron RS, Ramirez OA, Agnese AM.

Farmacognosia, Departamento de Farmacia, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Instituto Multidisciplinario de Biologia Vegetal, IMBIV, UNC-CONICET, Ciudad Universitaria, 5000, Cordoba, Argentina.

Huperzia saururus (Lam.) Trevis. (Lycopodiaceae) known as cola de quirquincho is used in folk medicine to improve memory. The cholinergic neurons of the basal forebrain, including those in the medial septum, and in the vertical limbs of the diagonal band of Broca and the nucleus basalis of Meynert, provide a major source of cholinergic enervation of the cortex and hippocampus.

Well, if I'm reading it right (please correct me if I'm not), Huperzine, like Ashwagandha, also has cholinesterase effects in the diagonal band as well. So, I guess it can't have memory decreasing effects.

[zoolander]

I don't know where you are coming from when mentioning memory effects. You need to put this into context as memory hasn't been discussed as yet.

You have made some nice deductions from the two quote studies as the hippocampus appears to play a fundamental role in memory. If my memory serves me right or should I say if my hippocampus serves me right, recently it was discovered that the nucleus basalis, particularly in the nucleus basalis of Meynert, is a source of acetylcholine. Additionally, there are also cholinergic projections from the adjacent medial septum and diagonal band of Broca to hippocampus. Of course inhibiting the enzyme that breaks down acetylcholine in the synapse (AChE) will increase acetylcholine an potentially improve memory function.

[boilerroom]

I'm mentioning memory effects because Ashwagandha effects Acetylcholine levels in various parts of the brain. Acetylcholinesterase was reduced in the vertical dialogue band but raised in the lateral septum and globus pallidus. If Ashwagandha is a memory enhancer, then the lateral septum and globus pallidus must not be too important for memory because acetylcholine levels were drop in those areas.