64 replies to this topic

[doug123]

National Geographic produced a special on Methamphetamine as well.

Click here to watch Meth: The Worlds Most Dangerous Drug on Google Video. They spend some time in Thailand investigating its use there. Take a look if you have 51 minutes.

And here's a sad update; the friend of mine that I mentioned earlier in this topic was discharged from the locked down mental facility about a month ago to a board and care facility, not a sober living program as I hoped his family would make him go to (he's a 27 year old whose mother is his conservator; so if she wanted she could have forced him to a sober living facility). He's already relapsed (he's all, "dude, I did a couple of grams, it was so good..."). Sad, that's all I've got to say.

Take care.

[doug123]

Another herb that might have some potential to repair (or protect) damaged neural networks in mice and rats is Centella asiatica (Gotu Kola).

In vivo evidence:

Physiol Behav. 2005 Nov 15;86(4):449-57. Epub 2005 Oct 6.

Centella asiatica treatment during postnatal period enhances learning and memory in mice.

Rao SB, Chetana M, Uma Devi P.
Department of Radiobiology, Kasturba Medical College, Manipal 576104, India.

Present investigation was planned to evaluate the nootropic effect of Centella asiatica. Three months old male Swiss albino mice were injected orally with graded doses (200, 500, 700, 1000 mg/kg body weight) of C. asiatica aqueous extract for 15 days to select an effective dose for nootropic studies. Animals were tested in radial arm maze to assess the learning and memory performance. Based on these results, mice were treated orally with 200 mg/kg of C. asiatica for 15 days from day 15 to day 30 post partum (p.p.) and the nootropic effect was evaluated on the 31st day and 6 months p.p. The behavioral (open field, dark/bright arena, hole board and radial arm maze tests), biochemical (acetylcholine esterase activity) and histological studies (dendritic arborization) were carried out. Performance of juvenile and young adult mice was significantly improved in radial arm maze and hole board tests, but locomotor activity did not show any change compared to control. Treatment resulted in increased acetylcholine esterase activity in the hippocampus. Dendritic arborization of hippocampal CA3 neurons was also increased in terms of intersections and branching points, both at one month and 6 months. Results of the present investigation show that treatment during postnatal developmental stage with C. asiatica extract can influence the neuronal morphology and promote the higher brain function of juvenile and young adult mice.

PMID: 16214185 [PubMed - in process]

Evid Based Complement Alternat Med. 2006 Sep;3(3):349-57. 

Centella asiatica (L.) Leaf Extract Treatment During the Growth Spurt Period Enhances Hippocampal CA3 Neuronal Dendritic Arborization in Rats.Mohandas Rao KG, Muddanna Rao S, Gurumadhva Rao S.

Centella asiatica (CeA) is a creeping plant growing in damp places in India and other Asian countries. The leaves of CeA are used for memory enhancement in the Ayurvedic system of medicine, an alternative system of medicine in India. In this study, we have investigated the effect during the rat growth spurt period of CeA fresh leaf extract treatment on the dendritic morphology of hippocampal CA3 neurons, one of the regions of the brain concerned with learning and memory. Neonatal rat pups (7 days old) were fed with 2, 4 or 6 ml kg(-1) body weight of fresh leaf extract of CeA for 2, 4 or 6 weeks. After the treatment period the rats were killed, their brains were removed and the hippocampal neurons were impregnated with silver nitrate (Golgi staining). Hippocampal CA3 neurons were traced using a camera lucida, and dendritic branching points (a measure of dendritic arborization) and intersections (a measure of dendritic length) were quantified. These data were compared with data for age-matched control rats. The results showed a significant increase in the dendritic length (intersections) and dendritic branching points along the length of both apical and basal dendrites in rats treated with 4 and 6 ml kg(-1) body weight per day of CeA for longer periods of time (i.e. 4 and 6 weeks). We conclude that the constituents/active principles present in CeA fresh leaf extract have a neuronal dendritic growth stimulating property; hence, the extract can be used for enhancing neuronal dendrites in stress and neurodegenerative and memory disorders.

PMID: 16951719 [PubMed - in process]

In vitro evidence:

J Pharm Pharmacol. 2005 Sep;57(9):1221-9.

Centella asiatica accelerates nerve regeneration upon oral administration and contains multiple active fractions increasing neurite elongation in-vitro.

Soumyanath A, Zhong YP, Gold SA, Yu X, Koop DR, Bourdette D, Gold BG.

Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland OR 97239, USA.

Axonal regeneration is important for functional recovery following nerve damage. Centella asiatica Urban herb, also known as Hydrocotyle asiatica L., has been used in Ayurvedic medicine for centuries as a nerve tonic. Here, we show that Centella asiatica ethanolic extract (100 microg mL-1) elicits a marked increase in neurite outgrowth in human SH-SY5Y cells in the presence of nerve growth factor (NGF). However, a water extract of Centella was ineffective at 100 microg mL-1. Sub-fractions of Centella ethanolic extract, obtained through silica-gel chromatography, were tested (100 microg mL-1) for neurite elongation in the presence of NGF. Greatest activity was found with a non-polar fraction (GKF4). Relatively polar fractions (GKF10 to GKF13) also showed activity, albeit less than GKF4. Thus, Centella contains more than one active component. Asiatic acid (AA), a triterpenoid compound found in Centella ethanolic extract and GKF4, showed marked activity at 1 microM (microg mL-1). AA was not present in GKF10 to GKF13, further indicating that other active components must be present. Neurite elongation by AA was completely blocked by the extracellular-signal-regulated kinase (ERK) pathway inhibitor PD 098059 (10 microM). Male Sprague-Dawley rats given Centella ethanolic extract in their drinking water (300-330 mg kg-1 daily) demonstrated more rapid functional recovery and increased axonal regeneration (larger calibre axons and greater numbers of myelinated axons) compared with controls, indicating that the axons grew at a faster rate. Taken together, our findings indicate that components in Centella ethanolic extract may be useful for accelerating repair of damaged neurons.

PMID: 16105244 [PubMed - in process]

Potential neuron protection properties:

Res Commun Mol Pathol Pharmacol. 2000 Jul-Aug;108(1-2):75-86.

Asiatic acid derivatives protect cultured cortical neurons from glutamate-induced excitotoxicity.

Lee MK, Kim SR, Sung SH, Lim D, Kim H, Choi H, Park HK, Je S, Ki YC.

College of Pharmacy, Seoul National University, Korea.

Asiatic acid, a triterpene of Centella asiatica (L.) Urban (Umbelliferae), has been patented as a treatment for dementia and an enhancer of cognition by the Hoechst Aktiengesellschaft (EP 0 383 171 A2). We modified the chemical structure of asiatic acid and obtained 36 derivatives of asiatic acid in an attempt to prepare neuroprotective compounds that were more efficacious than asiatic acid itself. The neuroprotective activities of these derivatives were evaluated using primary cultures of rat cortical neurons insulted with the neurotoxin, glutamate, as an in vitro screening system. Among the semi-synthesized derivatives, three derivatives significantly mitigated the neurotoxicity induced by glutamate in this screening system. The neuroprotective activities of these 3 derivatives appeared to be more powerful than that of asiatic acid itself. These 3 derivatives significantly attenuated decreases in the levels of glutathione, glutathione peroxidase and other enzymes, which participate in the cellular defense mechanisms blunting oxidative stress. Furthermore, they significantly reduced the overproduction of NO induced by glutamate. These results showed that these derivatives of asiatic acid exerted significant neuroprotective effects on cultured cortical cells by their potentiation of the cellular oxidative defense mechanism. Therefore, these agents may prove to be efficacious in protecting neurons from the oxidative damage caused by exposure to excess glutamate.

PMID: 11758977 [PubMed - indexed for MEDLINE]

...just catching up on some of the latest research on Centella asiatica (Gotu Kola or Linn) -- here's another piece of in vivo evidence that seems to further demonstrate neuronal dendritic growth stimulating properties.

I hope this encourages further research into the matter...and maybe soon a study in humans.

Let me please introduce the journal: Evidence-based Complementary and Alternative Medicine; some general background information:

About the Journal: Evidence-based Complementary and Alternative Medicine (eCAM) is an international, peer-reviewed journal that seeks to understand the sources and to encourage rigorous research in this new, yet ancient world of complementary and alternative medicine.

The Journal seeks to apply scientific rigor to the study of complementary and alternative medicine (CAM) modalities, particularly traditional Asian healing systems. eCAM emphasizes health outcome, while documenting biological mechanisms of action. The journal is devoted to the advancement of science in the field of basic research, clinical studies, methodology or scientific theory in diverse areas of Biomedical Sciences.

Here is the abstract:

eCAM Advance Access published online on August 13, 2007
eCAM, doi:10.1093/ecam/nem079

© 2007 The Author(s).

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommo...s/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Enhancement of Amygdaloid Neuronal Dendritic Arborization by Fresh Leaf Juice of Centella asiatica (Linn) During Growth Spurt Period in Rats
K. G. Mohandas Rao1, S. Muddanna Rao2 and S. Gurumadhva Rao3
1Department of Anatomy, Melaka Manipal Medical College, 2Department of Anatomy, Kasturba Medical College, 3Department of Pharmacology, Melaka Manipal Medical College, Manipal 576 104, India

Centella asiatica (CeA) is a creeping herb, growing in moist places in India and other Asian Countries. Ayurvedic system of medicine, an alternate system of medicine in India, uses leaves of CeA for memory enhancement. Here, we have investigated the role of CeA fresh leaf juice treatment during growth spurt period of rats on dendritic morphology of amygdaloid neurons, one of the regions concerned with learning and memory. The present study was conducted on neonatal rat pups. The rat pups (7-days-old) were fed with 2, 4 and 6 ml/kg body of fresh leaf juice of CeA for 2, 4 and 6 weeks. After the treatment period, the rats were killed, brains removed and amygdaloid neurons impregnated with Silver nitrate (Golgi staining). Amygdaloid neurons were traced using camera lucida and dendritic branching points (a measure of dendritic arborization) and intersections (a measure dendritic length) quantified. These data were compared with those of age-matched control rats. The results showed a significant increase in dendritic length (intersections) and dendritic branching points along the length of dendrites of the amygdaloid neurons of rats treated with 4 and 6 ml/kg body weight/day of CeA for longer periods of time (i.e. 4 and 6 weeks).  We conclude that constituents/active principles present in CeA fresh leaf juice has neuronal dendritic growth stimulating property; hence it can be used for enhancing neuronal dendrites in stress and other neurodegenerative and memory disorders.

Keywords: amygdaloid neurons – dendritic branches – dendritic intersections – neonatal rat pups – camera lucida

--------------------------------------------------------------------------------
For reprints and all correspondence: Dr Mohandas Rao K. G., Assistant Professor of Anatomy, Melaka Manipal Medical College, Manipal 576 104, India. Tel: 91 820 2922568 +919844007023; Fax: 91-820-2571905; E-mail: mohandaskg@gmail.com or mohandas.rao@manipal.edu
Received March 7, 2007; accepted June 12, 2007

I attached an image I found at Wikipedia as well.

Thoughts and comments are welcomed.

Take care.

Attached Files

•  BRAIN2.JPG   153.52KB   3 downloads

[cmorera]

Hi Adam

I went to check this thread for updates, and also to drop off a recent, not good study relating to meth and adolescents and young adults.

http://www.ncbi.nlm....Pubmed_RVDocSum

Long-term consequences of methamphetamine exposure in young adults are exacerbated in glial cell line-derived neurotrophic factor heterozygous mice.
Boger HA, Middaugh LD, Patrick KS, Ramamoorthy S, Denehy ED, Zhu H, Pacchioni AM, Granholm AC, McGinty JF.

Department of Neurosciences and Center on Aging, Medical University of South Carolina, South Carolina 29425, USA.

Methamphetamine abuse in young adults has long-term deleterious effects on brain function that are associated with damage to monoaminergic neurons. Administration of glial cell line-derived neurotrophic factor (GDNF) protects dopamine neurons from the toxic effects of methamphetamine in animal models. Therefore, we hypothesized that a partial GDNF gene deletion would increase the susceptibility of mice to methamphetamine neurotoxicity during young adulthood and possibly increase age-related deterioration of behavior and dopamine function. Two weeks after a methamphetamine binge (4 x 10 mg/kg, i.p., at 2 h intervals), GDNF(+/-) mice had a significantly greater reduction of tyrosine hydroxylase immunoreactivity in the medial striatum, a proportionally greater depletion of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the striatum, and a greater increase in activated microglia in the substantia nigra than wild-type mice. At 12 months of age, methamphetamine-treated GDNF(+/-) mice exhibited less motor activity and lower levels of tyrosine hydroxylase-immunoreactivity, dopamine, DOPAC, and serotonin than wild-type mice. Greater striatal dopamine transporter activity in GDNF(+/-) mice may underlie their differential response to methamphetamine. These data suggest the possibility that methamphetamine use in young adults, when combined with lower levels of GDNF throughout life, may precipitate the appearance of parkinsonian-like behaviors during aging.

PMID: 17699663 [PubMed - indexed for MEDLINE]

So, GDNF is protective, and also hindered in relation to meth use in mice. Interesting as just now the first meth generation is getting older, and we will see long term damages come to light, such as possible relation to neuro-degenerative diseases.




Also, I liked your posting on Centella asiatica, it looks like a good prospect, do you reccomend any brand or source for this? Would you reccomend Gotu Kola or pure Centella, as I notice they are different products. Thanks, and ttyl.

Edited by cmorera, 28 September 2007 - 04:13 AM.

[doug123]

Hi Adam

I went to check this thread for updates, and also to drop off a recent, not good study relating to meth and adolescents and young adults.

http://www.ncbi.nlm....Pubmed_RVDocSum

Long-term consequences of methamphetamine exposure in young adults are exacerbated in glial cell line-derived neurotrophic factor heterozygous mice.
Boger HA, Middaugh LD, Patrick KS, Ramamoorthy S, Denehy ED, Zhu H, Pacchioni AM, Granholm AC, McGinty JF.

Department of Neurosciences and Center on Aging, Medical University of South Carolina, South Carolina 29425, USA.
Methamphetamine abuse in young adults has long-term deleterious effects on brain function that are associated with damage to monoaminergic neurons. Administration of glial cell line-derived neurotrophic factor (GDNF) protects dopamine neurons from the toxic effects of methamphetamine in animal models. Therefore, we hypothesized that a partial GDNF gene deletion would increase the susceptibility of mice to methamphetamine neurotoxicity during young adulthood and possibly increase age-related deterioration of behavior and dopamine function. Two weeks after a methamphetamine binge (4 x 10 mg/kg, i.p., at 2 h intervals), GDNF(+/-) mice had a significantly greater reduction of tyrosine hydroxylase immunoreactivity in the medial striatum, a proportionally greater depletion of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the striatum, and a greater increase in activated microglia in the substantia nigra than wild-type mice. At 12 months of age, methamphetamine-treated GDNF(+/-) mice exhibited less motor activity and lower levels of tyrosine hydroxylase-immunoreactivity, dopamine, DOPAC, and serotonin than wild-type mice. Greater striatal dopamine transporter activity in GDNF(+/-) mice may underlie their differential response to methamphetamine. These data suggest the possibility that methamphetamine use in young adults, when combined with lower levels of GDNF throughout life, may precipitate the appearance of parkinsonian-like behaviors during aging.

PMID: 17699663 [PubMed - indexed for MEDLINE]

So, GDNF is protective, and also hindered in relation to meth use in mice. Interesting as just now the first meth generation is getting older, and we will see long term damages come to light, such as possible relation to neuro-degenerative diseases.




Also, I liked your posting on Centella asiatica, it looks like a good prospect, do you reccomend any brand or source for this? Would you reccomend Gotu Kola or pure Centella, as I notice they are different products. Thanks, and ttyl.

Dear cmorera,

Thank you for dropping by with this study. If you examine this post, you'll find the abstract of a meta-analysis that compared results in animals (e.g. a mice) to results in humans.

This page has an excellent definition of meta analysis. Here's an excerpt:

Summary points

o Meta-analysis should be as carefully planned as any other research project, with a detailed written protocol being prepared in advance

o The a priori definition of eligibility criteria for studies to be included and a comprehensive search for such studies are central to high quality meta-analysis

o The graphical display of results from individual studies on a common scale is an important intermediate step, which allows a visual examination of the degree of heterogeneity between studies

o Different statistical methods exist for combining the data, but there is no single "correct" method

o A thorough sensitivity analysis is essential to assess the robustness of combined estimates to different assumptions and inclusion criteria

What's so great about meta-analysis? I like them because they tend to take the "guesswork" out of scientific findings and are capable of eliminating (more or less) most biases. Modern health policy now is often dictated by findings of meta analyzes rather than by expert opinion or clinical experience. Click here to read: "Systems to Rate the Strength of Scientific Evidence: Summary; Evidence Report/Technology Assessment: Number 47."

While the study you presented may present a single example of a result of a study on mice, I do not think this to be conclusive enough evidence to assume we can always expect the same result in other studies on mice, or perhaps other organisms; such as rats, beetle grubs, or perhaps orangutans. Or humans.

The evidence with respect to Centella asiatica (Gotu Kola or Linn) seems promising and I hope encourages further research in human subjects. Without human testing, it seems still a sketchy prescription (we don't know what doses are required). It would be great to see evidence in humans from high resolution MRIs demonstrating increased dendritic growth after application of Centella asiatica. Until then, I would suggest sticking with what we know already induces neurogenesis -- good ol' fashioned exercise. Speaking of which, I'm off to the gym in a minute, I like that school has just resumed, there's lots of cool UCSD students for me to mingle with between sets. Do you carry out an exercise program, cmorera?

Take care.

[cmorera]

Hi again. Thanks for the well thought out response, you have provided a vast amount of information which all looks interesting (haven't read the studies/links yet). Also I appreciate that you have given a fair warning about the Centella, how its potential warrants further study in human trials, but it may be too early to judge effectiveness/saftey.

Also I think its a good judgment to not draw strong conclusions from one study on mice in relation to humans, but it is also a good idea in general to participate in an exercise program as that has been shown tried and tested for positive benefits. I do have an exercise program, its a type of interval training I recently found out which seems to be working pretty well for me. The program claims to have the advantage to strengthen your heart, increase lung capacity and lower whole body fat while gaining muscle. Sound too good to be true? Maybe it is, but it seems to be at least a good routine thats fun to do and easy to stick with.

On a separate note, I wanted to ask about exercise and vegetarianism, but ill make another post about that somewhere else and keep this thread on topic.