Meth and the brain

Taken from PBS's Frontline: the Meth Epidemic

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Richard A. Rawson, Ph.D is an Adjunct Associate Professor in the Department of Psychiatry and Biobehavioral Sciences at the David Geffen School of Medicine, University of California at Los Angeles.

In this audio slideshow, Dr. Rawson explains how meth affects the brain's dopamine receptors, causing the intense pleasure associated with a meth rush and yet eventually making it impossible for the user to experiene any pleasure at all.



One of the questions we often get is, why do people take this drug? And people start taking drugs for a whole variety of reasons. Curiosity. Peer Pressure. In the case of methamphetamine some people take it because they know they can lose weight with it. But after they've taken the first dose for whatever reason, why they continue to use it is pretty common. It's because they like what it does to their brain. They like how it feels.

Methamphetamine affects the centers of the brain that control judgment, control reward, and control memory. The most important one probably are the reward centers of the brain. When, when that part of the brain is stimulated dopamine's released, and you experience that as pleasure. Under normal circumstances those responses occur for naturally occurring rewarding events.

Similarly if you put a rat, a male rate in a box and you give him access to a receptive female, and you allow them to have sex, at the point where they experience orgasm you get a huge release of dopamine. You see an increase of about 200 units. This rush is what feels good and what is experienced is pleasure. And this slide of course illustrates the principle that one orgasm equals two cheeseburgers.




Now drugs of abuse release dopamine. Alcohol, for example, produced a release of dopamine from about 100 units to about 200, You get a similar magnitude of an effect with nicotine. Cocaine produces a huge release of dopamine, from 100 units to about 350 units, however the mother of them all is methamphetamine. Methamphetamine you get a release from the base level to about 1250 units. A tremendous increase of dopamine. This produces an extreme peak of euphoria that people describe as something like they've never experienced and they probably never have experienced before because the brain really isn't made to do this. And that's why people will be attracted to it and want to take it over and over and over again. They want to produce that response.

Over time doing this to the brain and having it feel good changes the way the brain works. Part of what we've learned about addiction is that addicts, after they've used drugs, have different brains than they did before they used drugs. The units that are changed are these, the neurons. Dendrite, cell body, axon, terminal.



Dopamine has its effect here at the terminal. Dopamine is stored in the nerve terminals in these, in these little sacs called vesicles. Sit there waiting until a nerve impulse comes down from the, the neuron, causes these to move to the cell wall and release their dopamine. These little dopamine guys get released, they float across the synapse, they attach on the receptor and they cause the downstream neuron to fire. If that goes on in the reward centers of your brain that feels good They sit here for a few microseconds, they're released, and they're taken back in and recycled. That's how the pleasure system is supposed to work. You have this recycling where these mechanisms called reuptake pumps pull them out of the synapse and bring dopamine back in to be reused. When you take cocaine, the only effect cocaine has is to sit on these reuptake pumps and block them. That means that as this cell fires and releases dopamine into the synapse dopamine accumulates because this ting has been deactivated. Dopamine accumulates causing this cell to fire and fire and fire way longer than it's supposed to because the dopamine isn't being pulled out of the synapse. And in fact cocaine will sit here for an hour or two causing this big accumulation of dopamine and this extended feeling of pleasure.



Now methamphetamine takes it one step further. Methamphetamine actually will sit here for eight to 12 hours causing this build up of dopamine for a much longer period so you experience this positive feeling for a longer period of time plus methamphetamine is actually taken into the terminal and destroys the nerve terminals.

Now luckily for meth users they regrow; however the bad news is they take quite sometime and for months meth users are feeling the absence of this reward because the reward center of the brain has essentially been damaged. Other areas of the brain are also effected. This is an MRI of the human brain done here at UCLA and this shows the judgment center of the brain in the prefrontal cortex. This is the brain of a meth user who's about five days sober and this blue area represents a reduction in normal activity, a reduction in blood flow. In essence, this part of the brain is shut off and for meth users who are in early recovery, they really don't have the ability to make good decisions.



You have this sort of worst-case scenario. You have a brain that is not producing reward, you're having a lotta craving because you want to feel better, and you have the part of the brain that controls judgment not working, and so individuals do stupid things that end up with them relapsing and going back to using. It's a wonder any meth users ever get better, but in fact they do.

--Richard A. Rawson, Ph.D

Watch PBS's Frontline: The Meth Epidemic

How Meth Destroys the Body

The image below compares the brain of a control, a meth abuser after 1 and 14 months of abstinence. Still not fully recovered yet -- even after 14 months.


Brain images of a person who has never used methamphetamine (left) and of a methamphetamine user after 1 month of abstinence (center). Lighter colors show distribution of dopamine transporters (DAT) in the striatum. DAT distribution is reduced in striatum of methamphetamine user. Brain image of a methamphetamine user after 14 months' abstinence (right) shows substantial recovery of DAT in striatum. Low levels of DAT in methamphetamine users were associated with poorer performance on tests of memory and motor skills, which did not improve with DAT after lengthy abstinence.

Image above from here

Edited by nootropikamil, 10 November 2006 - 05:58 AM.

in summary, dont do meth

whats more interesting to me, considering meth is a FREKING EPIDEMIC in the United States now, not just a 'west coast' thing anymroe, its sweeping eastward, and even taking over towns in midwestern regions, is treatment/recovery options for abusers.

I used to smoke this shit off tinfoil in my later teens to early 20's.

There is a 'PROMEtA" treatment, run by Hytheim that claims to be the only treatment currently for stimulant abuse and methamphetamine. They are the #1 sponsor of ALL meth recovery discussion boards on the net, in fact its hard to not know who they are if you visit any meth related sponsorships or recovery forums.

http://www.prometain...amphetamine.jsp

The only information I was able to find out about the program was, its abuot a month long, involves an IV treatment of 3 already FDA approved medication, and was designed by one of the directors of of ... (something) ... top meth researcher. I am trying to find out WHICH exact drugs are so effective in the treatment, the only clue I was able to find it one or more of them target the GABA system.

Other than that,even with long term abstitence, seveal years +, there is strong evidence showing that certain parts of the former addicts brain will never recover, specifically dopamine related tissue in striatum, and possible several other areas.

There is some research showing many compounds can attenuate damage done by meth, such as NAC and others in vivo, but recovery of brain is another story also. Recently a study involving Seroquel, a second generation atypical antipsychoticm, was shown to possible restore memory deficit and dopamine terminal deficit in meth users

http://www.ncbi.nlm....earch&DB=pubmed

Also, Delta Opioid Peptide (DADLE) shows a complete blockade of damage caused by meth, and also possible regeneration of tissue in the striatum for former meth users AND parkinsons patients. The damage caused by meth in certain parts of the brain resembles parkinsons or huntingtons.

anyways, some interesting stuff, I think a lot of research should be put into this more, due to the epidemic of meth now (wordwide also), will be causing a lot of problems down the road for these 'zombies' walking around and everyone also =]

Edited by cmorera, 10 November 2006 - 07:15 AM.

Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

Hey dudeman,

One of my childhood friends is locked up in a sanitarium right now and has been for the past 9 months or so. He did so much meth that he thinks he's a musician...however, he's never been on a stage, played in a band, or written a song. He's been playing guitar for ten years and owns a Les Paul custom that is still in pretty good condition; however, I don't know if I expect him to ever learn how to play it -- the only way he thinks he can play when he is high on meth...I went to visit him a couple of months ago with another one of his friends, and he honestly would rather be locked up in this facility than just admit he's a dope fiend and go to a sober living program and move on. It's really sad when you see a drug take your friends away...and in some cases, there's nothing at all you can do about it.

I think that some drugs and supplements -- such as Provigil (modafinil), Hydergine, ALCAR, and possibly a few other nootropics could be potential treatments for recovering methamphetamine addicts. There is some preliminary evidence to support these hypotheses at least.

I could be wrong with my Provigil hypothesis because it rests mostly upon the role of the dopamine transporter system (which appears to be somewhat damaged by meth use):

J Clin Psychiatry. 2003;64 Suppl 14:35-9. 
Role of executive function in ADHD.Swanson JM.
Department of Pediatrics, University of California, Irvine.

Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder characterized by inattention, hyperactivity, and impulsivity. ADHD is commonly treated with behavioral therapy and noradrenergic and dopaminergic pharmacotherapy with psychostimulants such as methylphenidate and dextroamphetamine. Stimulants primarily have dopaminergic and noradrenergic mechanisms of action, with blockade at the dopamine transporter reducing reuptake, resulting in an increase in these neurotransmitters at the synapse. Theoretically, inattention, hyperactivity, and impulsivity in ADHD may be due to underlying executive functioning, alerting, and orienting deficits, and the nonstimulant modafinil could be beneficial in managing symptoms of ADHD by improving these components of attention that accompany wakefulness. Although modafinil exhibits a small degree of dopaminergic action by blocking the dopamine transporter, the major effect of modafinil may be attributable to neuronal activity in the hypothalamus, particularly pertaining to the recently discovered peptides hypocretin 1 and 2 (also known as orexin A and B). However, further placebo-controlled and flexible-dose studies are needed to determine the efficacy of modafinil in treating the symptoms of ADHD in children and adults.

PMID: 14658934 [PubMed - in process]

Modafinil already has established the best reputation as a cognitive enhancer for healthy individuals; see this topic and this topic to understand why.

However; recovering methamphetamine addicts probably don't fit the same brain criteria as a "healthy" individual -- at least for the first year or two of abstinence. I still think it might help many get a boost in any brain oriented tasks.

Personally, I am very confident that recovering methamphetamine addicts would benefit from treatment with Hydergine and ALCAR; and I think I can back this up okay. I actually came up with the Hydergine hypothesis myself; and I remember reading lynx hypothesize that ALCAR could help out too; and I checked into this and it seems to check.

First, as illustrated above by Dr. Rawson, methamphetamine damages nerve cells; in particular the dendrite, cell body, axon, and terminal.

Hydergine seems to have effects on these parts of the brain; first the rat data; Hydergine increasing the number of synapses (dendrite growth) -- here we assume an aged rat would benefit similarly to a damaged rat:

J Gerontol. 1987 Sep;42(5):482-6.

The effect of chronic hydergine treatment on the plasticity of synaptic junctions in the dentate gyrus of aged rats.

Bertoni-Freddari C, Giuli C, Pieri C, Paci D, Amadio L, Ermini M, Dravid A.

The number of synapses (Nv) , the surface density of contact zones (Sv) as well as the average size (S) of E-PTA stained synapses in the supragranular layer of the dentate gyrus from adult (12 months), old (30 month), and Hydergine-treated old (30 months) rats were measured by using quantitative morphometric techniques. In old animals, Nv and Sv were significantly reduced, whereas S was significantly increased as compared with the values in adult rats. Hydergine (Codergocrine mesylate) treatment of old animals (3 mg/Kg/day for 4 weeks) influenced these three parameters, differentially. The Sv in aged animals receiving Hydergine, relative to that in untreated old rats, was significantly increased; the number and size of synapses in the treated old rats were significantly higher and smaller, respectively, than that in old controls. We interpret the present findings to indicate a modulating effect of Hydergine on the morphological plasticity of synaptic junctions in the dentate gyrus of aged rats.

Pharmacol. 1985;16 Suppl 3:33-8.

A modulating effect of Hygergine on the synaptic plasticity of old rats.

[Article in English, French]

Bertoni-Freddari C, Giuli C, Pieri C, Paci D, Dravid A.

The morphological plasticity of E-PTA stained synaptic junctions was investigated by means of quantitative morphometry in the dentate gyrus supra-granular layer of adult, old and old-Hydergine treated rats. Numerical (Nv) and surface (Sv) density as well as average size of the synapses (S) were the three parameters considered. During aging, Nv and Sv significantly decrease whereas S increases. Hydergine treatment to old rats resulted in a significant increase of Nv and Sv and a significant decrease of S. Present findings are interpreted as a modulating effect of Hydergine on the synaptic plasticity of old rats.

PMID: 4094445 [PubMed - indexed for MEDLINE]

Arch Gerontol Geriatr. 1990 May-Jun;10(3):287-96.


Effect of long term hydergine treatment on the age-dependent loss of mossy fibers and of granule cells in the rat hippocampus.

Amenta F, Jaton AL, Ricci A.

Dipartimento di Sanita Pubblica e Biologia Cellulare, Universita 'Tor Vergata', Rome, Italy; Dipartimento di Scienze Neurologiche, Universita 'La Sapienza', Rome, Italy.

The effects of senescence and of long-term Hydergine treatment on the density and pattern of mossy fibers and on the number of granule cells of the dentate gyrus were studied in the rat hippocampus. Timm's technique for the histochemical demonstration of tissue stores of zinc, associated with quantitative image analysis and microdensitometry, was used for the study of mossy fibers. Consistent with our previous studies, we observed an age-related reduction both in the area occupied by mossy fibers and in the intensity of Timm staining in the mossy fiber area. Moreover, the density of granule cells in the dentate gyrus of hippocampus was reduced with age. Hydergine administration (1 and 3 mg/kg/day, p.o.), started when the rats were 17 months old and continued for 4 months, significantly increased the area occupied by mossy fibers and the intensity of Timm staining in the hippocampus of senescent animals. Moreover, Hydergine treatment was found to counteract the age-dependent decrease in granule cell number in the dentate gyrus of the hippocampus. These findings suggest that treatment with Hydergine is effective in counteracting or in slowing down the morphological disorganization observable in the hippocampal formation with advancing age. Moreover, it is possible that the effects of Hydergine administration in elderly patients might be related to an effect at the level of the hippocampus.
PMID: 15374504 [PubMed - in process]

So essentially, this suggests that Hydergine makes the brain of aged rats "denser" -- a denser brain = more connections = probably more dentrites, &c.

This abstract is a study that might suggest recovering meth addicts could benefit from long term Hydergine treatment; however, these results are from elderly subjects and not recovering addicts. So it's just a hypothesis for now.

Curr Med Res Opin. 1989;11(6):380-9.

Ergoloid mesylates ('Hydergine') in the treatment of mental deterioration in the elderly: a 6-month double-blind, placebo-controlled trial.

Rouy JM, Douillon AM, Compan B, Wolmark Y.

Centre de Soins, C.H.U.R., Nime, France.

A double-blind, placebo-controlled trial was carried out in 97 elderly patients with age-related mental deterioration to assess the efficacy of ergoloid mesylates in improving their symptoms. Patients were allocated at random to receive either 4.5 mg ergoloid mesylates per day or a matching placebo tablet and were followed-up for 6 months after the start of treatment. Clinical examinations were performed by the doctor, using the EACG rating scale (a French version of the Sandoz Clinical Assessment Geriatric scale), and by the nurse, using the NOSIE scale, when patients entered the trial and repeated after 2, 4 and 6 months. Changes in the factors (symptom groups) covered by these scales were subjected to statistical analysis. After 6-months' treatment, a statistically significant difference in favour of the ergoloid mesylates group was observed for cognitive deficits (p less than 0.05), anxiety and mood depression (p less than 0.01), unsociability (p less than 0.01), retardation (p less than 0.05) and irritability (p less than 0.001). Treatment was very well tolerated. It was also observed that there was a progressive increase in efficacy throughout the trial; this indicates that treatment with ergoloid mesylates in patients with mental deterioration should be long-term.
Publication Types:

* Clinical Trial
* Randomized Controlled Trial


PMID: 2651014 [PubMed - indexed for MEDLINE]

Why should an ex-drug addict take high dose ALCAR? It seems to restore the functionality of aged (or in a drug addicts case "damaged") dopamine receptor systems.

Life Sci. 1994;54(17):1205-14.

Acetyl-L-carnitine affects aged brain receptorial system in rodents.

Castorina M, Ferraris L.

Institute for Research on Senescence, Sigma-Tau, Pomezia, Rome, Italy.

Acetyl-L-carnitine (ALCAR), the acetyl ester of carnitine, is regarded as a compound of considerable interest because of its capacity to counteract several physiological and pathological modifications typical of brain ageing processes. In particular, it has been demonstrated that ALCAR can counteract the age-dependent reduction of several receptors in the central nervous system of rodents, such as the NMDA receptorial system, the Nerve Growth Factor (NGF) receptors, those of glucocorticoids, neurotransmitters and others, thereby enhancing the efficiency of synaptic transmission, which is considerably slowed down by ageing. The present review thus postulates the importance of ALCAR administration in preserving and/or facilitating the functionality of carnitines, the concentrations of which are diminished in the brain of old animals.

Publication Types:

* Review


PMID: 8164502 [PubMed - indexed for MEDLINE]

J Neurosci Res. 1991 Nov;30(3):555-9.

Effect of acetyl-L-carnitine on the dopaminergic system in aging brain.

Sershen H, Harsing LG Jr, Banay-Schwartz M, Hashim A, Ramacci MT, Lajtha A.

Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York 10962.

We studied the effect of acetyl-L-carnitine (ALCAR) on dopamine release and the effect of long-term acetyl-L-carnitine treatment on age-related changes in striatal dopamine receptors and brain amino acid levels. In striatal tissue that had been incubated with [3H]dopamine, acetyl-L-carnitine increased the release of [3H]dopamine evoked by electrical stimulation. In striatal tissue from aged mice administered acetyl-L-carnitine for 3 months, the release of [3H]dopamine evoked by electrical stimulation was higher than that of its aged control; the release after a second stimulation was similar in the two groups. There was a significant decline in the number of D1 striatal dopamine receptors with age. The Bmax was 51% lower in 1.5-year-old mice than in 4-month-old animals. Administration of acetyl-L-carnitine for 3 months diminished the reduction in the binding of [3H]SCH-23390. [3H]Spiperone binding to D2 receptors was not decreased with age and was not affected by acetyl-L-carnitine treatment. Age-related decreases in levels of several amino acids were observed in several brain regions. Acetyl-L-carnitine lessened the reduction in the level of taurine only in the striatum. The findings confirm the multiple effects of acetyl-L-carnitine in brain, and suggest that its administration can have a positive effect on age-related changes in the dopaminergic system.

PMID: 1839317 [PubMed - indexed for MEDLINE]

However, if one is taking ALCAR in high doses, it is probably smart to also take high dose R-alpha-lipoic acid to counteract the supposed increase in free radicals.

The three aforementioned compounds seem to be safe...so if I think more research should be done to assess if Provigil (modafinil), ALCAR, and Hydergine are effective at treating recovering methamphetamine addicts suffering from cognitive deficits. Some non stimulant ADD medicines also might help too.

Regardless, there are millions of abusers trying to move on with their lives after meth, and they should be be able to move on with their lives; and I think medicine could provide a solution for many of these individuals so they have better solutions than relapse.

Edited by nootropikamil, 24 March 2007 - 05:34 PM.

meth can be classified in the same category for all drugs as far as addiction and ability to ruin lives, but it is seperate from other drugs, including heroin and crack, in its destructive properties. specifically the high extent of neurotoxicity caused.

I think Modafinil could be a good use to get addicts OFF meth, as it is already shown to be effective in cocaine users, but i am not sure if it helps or harms LONG term recovery from the poison. sometimes i admit it just makes me feel cracked out and strung out and cold and like a calculating machine. considering the damage seen in primarily the right brain (limbic system), I think this may be the opposite of the desired action for recovering meth users ... considering they can kick the habit which of course is the first priority.

kidna of like giving methadone to heroin addicts perhaps ... it should be tapered down to elimination after stop using drugs ...

of course this is all speculation really and not based on any 'science'

=]

So essentially, this suggests that Hydergine makes the brain of aged rats "denser" -- a denser brain = more connections = probably more dentrites, &c.

The research papers only talk about the dentate gyrus, which limits the available positive data on hydergine to the hippocampal formation. Fixing the damaged prefrontal areas will be a whole another arena.

The research papers only talk about the dentate gyrus, which limits the available positive data on hydergine to the hippocampal formation. Fixing the damaged prefrontal areas will be a whole another arena.

good point, this is where modafinil MAY come in, as i think its shown to stimulate frontal areas ... and possibly stimulation can lead to changes .. just some rought ideas tho

meth can be classified in the same category for all drugs as far as addiction and ability to ruin lives, but it is seperate from other drugs, including heroin and crack, in its destructive properties. specifically the high extent of neurotoxicity caused.

Simply by observing the increase in dopamine levels from baseline -- 100 units to 1250 units -- this should give you a pretty good idea of the potential damage it can do considering a drug like cocaine only increases dopamine levels to 350 units meanwhile sex raises dopamine levels to about 300 units. Any drug that stimulates the reward system of your brain in such a manner is obviously throwing your brain out of spectrum.

I think Modafinil could be a good use to get addicts OFF meth, as it is already shown to be effective in cocaine users, but i am not sure if it helps or harms LONG term recovery from the poison. sometimes i admit it just makes me feel cracked out and strung out and cold and like a calculating machine. considering the damage seen in primarily the right brain (limbic system), I think this may be the opposite of the desired action for recovering meth users ... considering they can kick the habit which of course is the first priority.

kidna of like giving methadone to heroin addicts perhaps ... it should be tapered down to elimination after stop using drugs ...

I am not sure if Provigil (modafinil) could get people off meth as much as I am confident it could help recovering meth addicts perform similarly to controls in tests of cognitive performance. I am confident less meth addicts would relapse if they didn't feel brain damaged for a year or so after using the stuff.

of course this is all speculation really and not based on any 'science'

=]

This isn't called a discussion board for nothing. ;-)

The research papers only talk about the dentate gyrus, which limits the available positive data on hydergine to the hippocampal formation. Fixing the damaged prefrontal areas will be a whole another arena.

Methamphetamine affects the centers of the brain that control judgment, control reward, and control memory.

Memory damage is likely -- at least partially -- the result of some damage to the hippocampus.

The abstracts I cited above suggest the rats had increases in the number of synapses (Nv), the surface density of contact zones (Sv) as well as the average size (S) -- in the hippocampus -- which is more or less understood to be where memories are formed and then stored and retrieved from. Even if these neuron growth stimulant properties are limited to the hippocampus, if they proved to be true in humans, could demonstrate benefits from recovering addicts suffering from meth induced brain damage that adversely affects their memory performance.

The hippocampus is a part of the brain located inside the temporal lobe (humans and other mammals have two hippocampi, one in each side of the brain). It forms a part of the limbic system and plays a part in memory and spatial navigation. The name derives from its curved shape in coronal sections of the brain, which resembles a seahorse (Greek: hippo=horse, kampos=sea monster).

In Alzheimer's disease, the hippocampus becomes one of the first regions of the brain to suffer damage; memory problems and disorientation appear amongst the first symptoms. Damage to the hippocampus can also result from oxygen starvation (anoxia) and encephalitis.

In the anatomy of animals, the hippocampus is among the phylogenetically oldest parts of the brain. The hippocampal emergence from the archipallium is most pronounced in primates and Cetacean sea mammals. Nonetheless, in primates the hippocampus occupies less of the cerebrum in proportion to cerebral cortex among the youngest species, especially humans. The significant development of hippocampal volume in primates correlates more with overall increase of brain mass than with neocortical development.

Hydergine's clincal uses are currently limited to Alzheimer's like dementia, and a recent Cochrane seems to render the evidence inconclusive in this application.

Cochrane Database Syst Rev. 2001;(2):CD000359. Related Articles, Links

Update of:
Cochrane Database Syst Rev. 2000;(2):CD000359.

Hydergine for dementia.

Olin J, Schneider L, Novit A, Luczak S
Adult and Geriatric Treatment and Preventative Interventions Branch, National Institute of Mental Health, NIMH, Room 7160, MSC 9635, 6001 Executive Blvd., Bethesda, Maryland, 20892-9635, USA. jolin@mail.nih.gov

BACKGROUND: Currently hydergine is used almost exclusively for treating patients with either dementia, or 'age-related' cognitive symptoms. Since the early eighties there have been over a dozen more clinical trials, yet hydergine's efficacy remains uncertain. Although previous reviews offer generally favorable support for hydergine's efficacy, they were, however, limited by a bias with respect to the particular clinical studies chosen (eg, the inclusion of case reports, and uncontrolled trials), and by authors' impressionistic assessments of results. Not surprisingly, there has been a lack of consensus among reviewers with regard to the efficacy of hydergine. In 1994, a meta-analysis was published by the present reviewers who reported that overall, hydergine was more effective than placebo. However they also observed that the statistical evidence for efficacy in 'possible or probable Alzheimer's disease' patients was so modest that one additional statistically non-significant trial would have reduced the results to non significance. OBJECTIVES: Because of uncertainty surrounding the efficacy of hydergine, the goals of this overview were to assess its overall effect in patients with possible dementia, and to investigate potential moderators of an effect. SEARCH STRATEGY: The trials were identified from a search of the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group on 15 November 2000 using the terms hydergin*, ergoloid* and dihydroergo*. Two proprietary databases were searched also. Published reviews were inspected for further sources. SELECTION CRITERIA: Trials to be included must be randomized, double-blind, parallel-group, and unconfounded comparisons of hydergine with placebo for a treatment duration of greater than 1 week in subjects with dementia or symptoms consistent with dementia. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers, pooled where appropriate and possible, and the pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Where possible, intention-to-treat data were used. Outcomes of interest included clinical global impressions of change and comprehensive rating scales. Potential moderating variables of a treatment effect included: inpatient/outpatient status, trial duration, age, sex, medication dose, publication year, and diagnostic grouping. MAIN RESULTS: There were a total of nineteen trials that met inclusion criteria and that had data sufficient for analysis. Thirteen trials reported sufficient information to use a global rating of improvement and nine trials provided information on a comprehensive rating scale. Three trials provided both outcome measures. It was not possible to use many of the published results in a combined analysis owing to the lack of sufficient data to perform statistical analyses. For the twelve trials that used global ratings, there was a significant effect favoring hydergine (OR 3.78, 95%CI, 2.72-5.27). For the nine trials that used comprehensive ratings, there was a significant mean difference favoring hydergine (WMD 0.96, 95%CI, 0.54-1.37). Hydergine was well tolerated in these trials, with 78% of randomized subjects available for data analyses. Greater effect sizes on global ratings were associated with younger age, and possibly higher dose, although most of the subgroup analyses were statistically insignificant. REVIEWER'S CONCLUSIONS: As in an earlier systematic review, we found hydergine to show significant treatment effects when assessed by either global ratings or comprehensive rating scales (based here on a smaller set of trials than in the earlier published systematic review because trials were required to have data that could conform with MetaView, the Cochrane Collaboration statistics software) . The small number of trials available for analysis, however, limited the ability of subgroup analyses to identify statistically significant moderating effects. Unfortunately, most of the randomized, double-blind, and placebo-controlled trials of hydergine were conducted and published before the advent of consensus-based diagnostic standards of dementia in 1984; therefore diagnostic criteria were less specific. As a result, uncertainty remains regarding hydergine's efficacy in dementia.
Publication Types:
Review

PMID: 11405961 [PubMed - indexed for MEDLINE]

It seems the primary reason why prior research has focused mostly on the hippocampus is due to our understanding of its central role in forming and retrieving memories and therefore it's direct application to its role in the pathology of Alzheimer's disease. However, I wouldn't be at all surprised if the same effects that seem to occur in the hippocampus of these rats; namely, number of synapses (Nv) , the surface density of contact zones (Sv) as well as the average size (S), etc. -- also extend to in other parts of the brain. I am confident of this outcome because Hydergine seemed to demonstrate it's effects on dopamine receptors throughout the brain in vivo. Among the main reasons we haven't confirmed these results in (1) rats and (2) humans is because (1) it appears no one has done so yet, and (2), because it is considered highly unethical to administer a treatment to a human being then slice open their brains to count increases in regional brain density.

J Pharmacol. 1985;16 Suppl 3:19-24.

Ergot alkaloids and central monoaminergic receptors.[Article in English, French]

Goldstein M.

The interactions of ergolines and of ergopeptines with dopamine (DA), alpha 1 and alpha 2 central adrenoreceptors were studied. Ergolines and ergopeptines exert agonist activities at central DA receptors and exhibit antiparkinsonian activities in monkeys with unilateral ventromedial tegmental lesions of the brain stem. Both ergolines and ergopeptines are used in treatment of Parkinson's disease and their therapeutic efficacy, as well as their propensity to develop undesirable side effects is under investigation. The interactions of ergolines and of ergopeptines differ with DA receptor subtypes and states. The former are regulated by guanine nucleotides, but not the latter. Hydergine is used in treatment of disorders associated with senile dementia, and its interaction with DA, alpha 1 and alpha 2 adrenoreceptors may affect the monoaminergic imbalance in the aging brain.

PMID: 3005775 [PubMed - indexed for MEDLINE]

Eur J Pharmacol. 1982 Dec 24;86(2):145-55.

Dopamine receptor profile of co-dergocrine (Hydergine) and its components.Markstein R.

Co-dergocrine (Hydergine), an ergot preparation composed of four dihydrogenated peptide ergot alkaloids (dihydroergocornine, dihydroergocristine, dihydro-alpha-ergokryptine, dihydro-beta-ergokryptine, 3:3:2:1), has been reported to exert in vivo effects suggesting an interaction with dopaminergic systems. The present investigation provides evidence that, in the striatum of the rat, co-dergocrine and its components interact directly with D1- and D2-subtypes of dopamine receptors. In homogenates of rat striatum, co-dergocrine and three of its components (dihydroergocornine, dihydro-alpha-ergokryptine, dihydro-beta-ergokryptine) stimulate cyclic AMP formation (D1-receptor response) having similar EC50 values but different efficacies. The same compounds inhibit electrically evoked tritium overflow from rat striatal slices preincubated with [3H]choline (D2-receptor response) at about 50 times lower concentrations. Here again the compounds exhibit differential maximal effects. One component, dihydroergocristine, antagonises both receptor types. The effect of co-dergocrine in functional responses mediated by both D1- and D2-receptors seems to reflect the summation of the contribution of its components.

PMID: 6297930 [PubMed - indexed for MEDLINE]

Hydergine also seems to have other beneficial effects on the brain regardless; the following evidence may offer further support why an individual who has suffered brain damage as a result of methamphetamine abuse could benefit from long term treatment.

Hydergine stimulates glucose uptake in the human brain:

Tohoku J Exp Med. 1990 Nov;162(3):225-33.


Effects of co-dergocrine mesylate (Hydergine) in multi-infarct dementia as evaluated by positron emission tomography.

Nagasawa H, Kogure K, Kawashima K, Ido T, Itoh M, Hatazawa J.

Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.

Three female patients aged from 74 to 79 with multi-infarct dementia were studied using positron emission tomography (PET) to assess the effect of co-dergocrine mesylate (Hydergine) on cerebral glucose metabolism. The cerebral glucose utilization (CMRGlc) of each patient was evaluated by PET scan using 2-deoxy-[18F]-2-fluoro-D-glucose (FDG). Following the first PET study, 0.04 mg/kg of co-dergocrine mesylate was injected intravenously with 250 ml saline solution, and then the second PET study was performed. The CMRGlc was determined from the images of the PET scan and the radioactivity of 18F in the plasma. After the administration of co-dergocrine mesylate, the value of CMRGlc increased significantly in the cerebral cortex (p less than 0.01 and p less than 0.05) and basal ganglia (p less than 0.05) compared with values before the administration, but no significant increase was found in the centrum semiovale. These results suggest that co-dergocrine mesylate stimulates glucose metabolism of neurons in the human brain.

Dose associated decrease in lipofuscin in old rats:

Gerontology. 1988;34(5-6):250-6.

Effects of long-term Hydergine administration on lipofuscin accumulation in senescent rat brain.

Amenta D, Ferrante F, Franch F, Amenta F.

Dipartimento di Scienze Neurologiche, Universita La Sapienza, Roma, Italia.

The effects of ageing and of 6 months of Hydergine treatment on lipofuscin deposition within the cytoplasma of pyramidal neurons of rat prefrontal cortex, hippocampus (fields CA1 and CA3) and of Purkinje neurons were assessed microfluorimetrically. No lipofuscin autofluorescence was detected in the nerve cell populations of 3-month-old rats, but lipopigment had accumulated in nerve cell bodies of 16-month-old animals and increased significantly thereafter in rats of 22 months of age. In 22-month-old rats, Hydergine administration (0.6 and 1 mg/kg p.o.) started at 16 months caused a significant dose-related decrease in lipofuscin accumulation within the cytoplasm of the various kinds of nerve cells examined.

It seems that Hydergine might also increase the "firing rate" (or activity) of locus ceruleus (or LC) neurons; many of which are located in the frontal cortex.

J Neural Transm. 1982;55(2):101-9.

The effect of vincamine, hydergine and piracetam on the firing rate of locus coeruleus neurons.

Olpe HR, Steinmann MW.

Vincamine, hydergine and piracetam are used for the treatment of memory disturbances as well as for the treatment of various other brain dysfunctions seen in the elderly patient. The action of these three psychogeriatric compounds on the activity of noradrenergic neurons in the rat locus coeruleus was investigated. All three compounds, when administered intraperitoneally, increased the firing rate of noradrenergic neurons in the chloral hydrate anaesthetized animals. Vincamine and hydergine had a similar potency producing a maximal mean increase of about 70% at a dose of 1 mg/kg. Likewise, piracetam was significantly less potent eliciting a 30 to 40% increase in firing at doses of 300 and 1000 mg/kg, respectively. A role for the locus coeruleus in processes related to attention, cortical and behavioral arousal, learning and memory has been proposed on the basis of behavioral and electrophysiological experiments. In the awake rat, the firing rate of noradrenergic neurons in this brain nucleus has previously been shown to relate directly to the level of vigilance. The activating action of vincamine, hydergine and piracetam on these neurons may be linked with some of the drugs' beneficial therapeutic effects.

PMID: 7175517 [PubMed - indexed for MEDLINE]

Look dudes: I've got a midterm to study for.

Edited by nootropikamil, 10 November 2006 - 07:11 PM.

Full text available free here

[quote name='http://www.jneurosci.org/cgi/content/full/24/26/6028']We visualize, for the first time, the profile of structural deficits in the human brain associated with chronic methamphetamine (MA) abuse. Studies of human subjects who have used MA chronically have revealed deficits in dopaminergic and serotonergic systems and cerebral metabolic abnormalities. Using magnetic resonance imaging (MRI) and new computational brain-mapping techniques, we determined the pattern of structural brain alterations associated with chronic MA abuse in human subjects and related these deficits to cognitive impairment. We used high-resolution MRI and surface-based computational image analyses to map regional abnormalities in the cortex, hippocampus, white matter, and ventricles in 22 human subjects who used MA and 21 age-matched, healthy controls. Cortical maps revealed severe gray-matter deficits in the cingulate, limbic, and paralimbic cortices of MA abusers (averaging 11.3% below control; p < 0.05). On average, MA abusers had 7.8% smaller hippocampal volumes than control subjects (p < 0.01; left, p = 0.01; right, p < 0.05) and significant white-matter hypertrophy (7.0%; p < 0.01). Hippocampal deficits were mapped and correlated with memory performance on a word-recall test (p < 0.05). MRI-based maps suggest that chronic methamphetamine abuse causes a selective pattern of cerebral deterioration that contributes to impaired memory performance. MA may selectively damage the medial temporal lobe and, consistent with metabolic studies, the cingulate-limbic cortex, inducing neuroadaptation, neuropil reduction, or cell death. Prominent white-matter hypertrophy may result from altered myelination and adaptive glial changes, including gliosis secondary to neuronal damage. These brain substrates may help account for the symptoms of MA abuse, providing therapeutic targets for drug-induced brain injury.[/quote]

[quote name='http://www.loni.ucla.edu/~thompson/MEDIA/METH/tosta.htm?tacodalogin=no']SANDRA BLAKESLEE
NEW YORK TIMES

People who do not want to wait for old age to shrink their brains and bring on memory loss now have a quicker alternative — abuse methamphetamine for a decade or so and watch the brain cells vanish into the night.

The first high-resolution MRI study of methamphetamine addicts shows "a forest fire of brain damage," said Dr. Paul Thompson, an expert on brain mapping at the University of California, Los Angeles. "We expected some brain changes but didn't expect so much tissue to be destroyed."

The image, published in the June 30 issue of The Journal Of Neuroscience, shows the brain's surface and deeper limbic system. Red areas show the greatest tissue loss.

The limbic region, involved in drug craving, reward, mood and emotion, lost 11 per cent of its tissue.

"The cells are dead and gone," Thompson said.

Addicts were depressed, anxious and unable to concentrate.

The brain's centre for making new memories, the hippocampus, lost 8 per cent of its tissue, comparable to the brain deficits in early Alzheimer's. The methamphetamine addicts fared significantly worse on memory tests than healthy people the same age.

The study examined 22 people in their 30s who had used methamphetamine for 10 years, mostly by smoking it, and 21 controls matched for age.

On average, the addicts used four grams a week and said they had been high on 19 of the 30 days before the study began.

Methamphetamine is an addictive stimulant made in clandestine laboratories throughout North America. When taken by mouth, snorted, injected or smoked, it produces intense pleasure by releasing the brain's reward chemical, dopamine.

With chronic use, the brains that overstimulate dopamine and another brain chemical, serotonin, are permanently compromised.

The study held one other surprise, Thompson said.

White matter, composed of nerve fibres that connect different areas, was severely inflamed, making the addicts' brains 10 per cent larger than normal.

"This was shocking," he said.

But there was one piece of good news. The white matter was not dead. With abstinence, it might recover.[/quote]

http://www.jneurosci...0491920001.jpeg
Figure 1. Gray-matter differences on the medial brain surface. Group difference maps © show mean percentage differences in gray-matter volumes between the control group average (a) and the methamphetamine group average (b), according to the color bar. The significance of these reductions is plotted in d as a map of p values. The cingulate gyrus shows highly significant gray-matter deficits (red colors; p < 0.034, corrected), whereas other brain regions are comparatively spared (blue colors). e is from London et al. (2004) (reprinted with permission). It shows the locations of MA (n = 17) and control (n = 18) group differences in relative regional cerebral metabolic glucose rate, assessed with PET. This PET sample partially overlaps with the current sample assessed with MRI. Briefly, in e, statistical parametric maps reveal regions in which the MA group has greater (red colors) or lesser (blue colors) glucose metabolism. Colors superimposed on a gray-scale MRI template indicate areas in which the significance of the group difference was t 1.69 (p = 0.049). The region of greatest gray-matter deficit (b, d) is in the right hemisphere posterior cingulate cortex (pCING), and so is the region of greatest metabolic increase in the MA group (e). This suggests an anatomical congruence of the MRI-based deficits with metabolic differences observed with PET. igACC and pgACC denote the inferior and perigenual anterior cingulate cortex, respectively. CTL, Control; R hem, right hemisphere; L hem, left hemisphere.

http://www.jneurosci...0491920002.jpeg
Figure 2. Gray-matter differences on the lateral brain surfaces. The mean reduction in gray matter in the MA group, relative to healthy controls, is expressed as a percentage and shown color-coded (blue colors, no reduction; red colors, greater reduction). In the left medial wall (a) and right-lateral (b) and left-lateral © brain surfaces, gray-matter differences are not pronounced. The significance of these differences is plotted in d-f. Differences were not significant after correction for multiple comparisons.

http://www.jneurosci...0491920003.jpeg
Figure 3. Comparison of brain structure volumes in MA abusers and healthy controls (CTL). Means and SE measures (error bars) are shown for the volumes of the hippocampus (a), frontal horn of the lateral ventricles (b), total cerebral gray matter (GM) ©, and total cerebral white matter (WM) (d). MA abusers show reductions in hippocampal volumes without significant reductions in gray-matter volume overall ©. They also show volume expansions in some ventricular regions (b) and increases in white-matter volume (d). e shows that mean gray-matter density in the cingulate gyrus is reduced in MA abusers (by 11.3%; p < 0.034), erasing the normal right > left asymmetry in gray-matter density that is found here and has been documented previously in healthy subjects. In agreement with the maps, this deficit pattern is not found in the adjacent medial frontal cortex.

http://www.jneurosci...0491920004.jpeg
Figure 4. Hippocampal atrophy in MA abusers is linked with poorer memory performance. Each individual's hippocampus is traced in coronal MRI sections (a) and converted to a mesh surface representation (b) in which the radial size of the hippocampus is measured from a centerline and plotted in color on the surface to index radial atrophy. Arrows in b represent vectors from the centerline to various points on the hippocampal surface. These meshes are averaged across subjects ©, and atrophy relative to the control mean is computed at each surface grid point (d). Shown in millimeters in e and f, the average radial size of the hippocampus in MA abusers (e) is smaller in some regions [red colors in g] than corresponding regions in healthy controls (f). h shows hippocampal regions (in red colors) in which word-recall performance is significantly linked with radial atrophy.

[quote]Table 1. Characteristics of research participants


--------------------------------------------------------------------------------



--------------------------------------------------------------------------------
Controls (n = 21)

--------------------------------------------------------------------------------
MA abusers (n = 22)

--------------------------------------------------------------------------------

Age (years)a  31.9 (1.47)  35.3 (1.66) 
Gender (males/females)  10/11  15/7 
Education (years)a  15.2 (0.50)  12.8 (0.42)* 
Mother's education (years)a,b*  14.2 (0.48)  13.0 (0.68) 
Race   
Caucasian (non-Hispanic)  14  13 
Caucasian (Hispanic)  3  5 
African American  3  2 
Asian  1  2 
Handedness (right handed)c

--------------------------------------------------------------------------------
16

--------------------------------------------------------------------------------
17

--------------------------------------------------------------------------------




a Data shown are means (SEM); n = 21 for controls; n = 22 for MA abusers.

b n = 20 for controls.

c Handedness was determined according to the Lateral Preference Pattern Assignment subtest of the Physical and Neurological Examination for Soft Signs (Denckla, 1985). To qualify as right handed, a participant had to write and to perform all or all but 1 of 11 items other than writing with the right hand.

* Significantly different from controls; p <0.001 by Student's t test.[/quote]

[quote]Table 2. Self-reported drug usea


--------------------------------------------------------------------------------



--------------------------------------------------------------------------------
Controls (n = 21)

--------------------------------------------------------------------------------
MA abusers (n = 22)

--------------------------------------------------------------------------------

Methamphetamine use   
Duration (year)  10.5 (1.09); n = 21 
Average (gm/week)  3.44 (0.79); n = 19 
Days used in last 30 d  18.9 (1.75); n = 21 
Age of first use (year)  26.1 (1.77); n = 12 
Tobacco smokers   
(>5 cigarettes/d)  n = 2  n = 15* 
Marijuana use   
Days used in last 30 d  0.14 (0.08); n = 21  2.38 (0.91);** n = 21 
Alcohol use   
Days used in last 30 d

--------------------------------------------------------------------------------
2.38 (0.69); n = 21

--------------------------------------------------------------------------------
3.24 (0.85); n = 21

--------------------------------------------------------------------------------




a Data shown are means (SEM) of self-reported drug use from an intake questionnaire, a drug-use survey, and the Addiction Severity Index (McLellan et al., 1992).

* Significantly different from controls by Pearson 2 analysis.

** Significantly different from control group; p <0.05 by Student's t test.[/quote]

[quote]Table 3. Self reports of mood and feeling statea


--------------------------------------------------------------------------------



--------------------------------------------------------------------------------
Control subjects (n = 21)

--------------------------------------------------------------------------------
MA abusers (n = 22)

--------------------------------------------------------------------------------

Beck Depression Inventory   
Sample size  20  22 
Mean score  1.25 (1.25)  9.77 (1.89)b* 
Mean days abstinent (SD)  6.64 (5.2) 
Spielberger State-Trait Anxiety Inventory   
Sample size  15  15 
State anxiety score  31.4 (3.77)  38.67 (2.64)** 
Trait anxiety score

--------------------------------------------------------------------------------
31.9 (2.41)

--------------------------------------------------------------------------------
38.7 (2.63)***

--------------------------------------------------------------------------------




a Data are expressed as means (SEM). Beck Depression Inventory scores range from 0 to 63. Spielberger State-Trait Anxiety Inventory scores are reported as the sum of 20 questions ranking anxiety on a scale of 1-4.

b Beck Depression Inventory scores were closely correlated with the days of abstinence at time of assessment; p < 0.05 by regression.

* Significantly different from controls; p < 0.0005 by Student's t test.

** Not significantly different from controls; p = 0.0506.

*** Significantly different from controls; p < 0.001 by Student's t test.[/quote]

This might throw more weight behind the potential role of ALCAR in assisting recovering methamphetamine addicts in recovery:

Ann N Y Acad Sci. 2005 Aug;1053:183-91.
Effects of metabolic modifiers such as carnitines, coenzyme Q10, and PUFAs against different forms of neurotoxic insults: metabolic inhibitors, MPTP, and methamphetamine.
Virmani A, Gaetani F, Binienda Z.
Research and Development, Sigma-Tau Health Science, Via Treviso 4, Pomezia 00040, Italy. ashraf.virmani@st-hs.it

A number of strategies using the nutritional approach are emerging for the protection of the brain from damage caused by metabolic toxins, age, or disease. Neural dysfunction and metabolic imbalances underlie many diseases, and the inclusion of metabolic modifiers may provide an alternative and early intervention approach that may prevent further damage. Various models have been developed to study the impact of metabolism on brain function. These have also proven useful in expanding our understanding of neurodegeneration processes. For example, the metabolic compromise induced by inhibitors such as 3-nitropropionic acid (3-NPA), rotenone, and 1-methyl-4-phenylpyridinium (MPP+) can cause neurodegeneration in animal models and these models are thought to simulate the processes that may lead to diseases such as Huntington's and Parkinson's diseases. These inhibitors of metabolism are thought to selectively kill neurons by inhibiting various mitochondrial enzymes. However, the eventual cell death is attributed to oxidative stress damage of selectively vulnerable cells, especially highly differentiated neurons. Various studies indicate that the neurotoxicity resulting from these types of metabolic compromise is related to mitochondrial dysfunction and may be ameliorated by metabolic modifiers such as L-carnitine (L-C), creatine, and coenzyme Q10, as well as by antioxidants such as lipoic acid, vitamin E, and resveratrol. Mitochondrial function and cellular metabolism are also affected by the dietary intake of essential polyunsaturated fatty acids (PUFAs), which may regulate membrane composition and influence cellular processes, especially the inflammatory pathways. Cellular metabolic function may also be ameliorated by caloric restriction diets. L-C is a naturally occurring quaternary ammonium compound that is a vital cofactor for the mitochondrial entry and oxidation of fatty acids. Any factors affecting L-C levels may also affect ATP levels. This endogenous compound, L-C, together with its acetyl ester, acetyl-L-carnitine (ALC), also participates in the control of the mitochondrial acyl-CoA/CoA ratio, peroxisomal oxidation of fatty acids, and production of ketone bodies. A deficiency of carnitine is known to have major deleterious effects on the CNS. We have examined L-C and its acetylated derivative, ALC, as potential neuroprotective compounds using various known metabolic inhibitors, as well as against drugs of abuse such as methamphetamine.

PMID: 16179522 [PubMed - indexed for MEDLINE]

Ann N Y Acad Sci. 2004 Oct;1025:267-73. 
Role of mitochondrial dysfunction in neurotoxicity of MPP+: partial protection of PC12 cells by acetyl-L-carnitine.
Virmani A, Gaetani F, Binienda Z, Xu A, Duhart H, Ali SF.
Research and Development, Sigma-tau HealthScience S.p.A., Pomezia 00040, Italy. ashraf.virmani@st-hs.it

The damage to the central nervous system that is observed after administration of either methamphetamine (METH) or 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is known to be linked to dopamine (DA). The underlying neurotoxicity mechanism for both METH and MPP+ seem to involve free radical formation and impaired mitochondrial function. The MPP+ is thought to selectively kill nigrostriatal dopaminergic neurons by inhibiting mitochondrial complex I, with cell death being attributed to oxidative stress damage to these vulnerable DA neurons. In the present study, MPP+ was shown to significantly inhibit the response to MTT by cultured PC12 cells. This inhibitory action of MPP+ could be partially reversed by the co-incubation of the cells with the acetylated form of carnitine, acetyl-L-carnitine (ALC). Since at least part of the toxic action of MPP+ is related to mitochondrial inhibition, the partial reversal of the inhibition of MTT response by ALC could involve a partial restoration of mitochondrial function. The role carnitine derivatives, such as ALC, play in attenuating MPP+ and METH-evoked toxicity is still under investigation to elucidate the contribution of mitochondrial dysfunction in mechanisms of neurotoxicity.

PMID: 15542726 [PubMed - indexed for MEDLINE]

Also there are these:

Neuropsychopharmacology. 2003 Apr;28(4):683-93. Epub 2002 Oct 1.  Links
Effects of long-term acetyl-L-carnitine administration in rats--II: Protection against the disrupting effect of stress on the acquisition of appetitive behavior.
Masi F, Leggio B, Nanni G, Scheggi S, De Montis MG, Tagliamonte A, Grappi S, Gambarana C.
Department of Neuroscience, Pharmacology Unit, University of Siena, Italy.

Long-term acetyl-L-carnitine (ALCAR) administration prevents the development of escape deficit produced by acute exposure to unavoidable stress. However, it does not revert the escape deficit sustained by chronic stress exposure. Rats exposed to chronic stress show a low dopamine (DA) output in the nucleus accumbens shell (NAcS) and do not acquire an appetitive behavior sustained by the earning of vanilla sugar (VS) made contingent on the choice of one of the two divergent arms of a Y-maze (VS-sustained appetitive behavior, VAB), while control rats consistently do. The present study shows that ALCAR treatment in rats exposed to a 7-day stress protocol prevented a decrease in DA output in the NAcS and medial prefrontal cortex (mPFC) of rats, and that it strengthened the DA response to VS consummation in the same two areas. Moreover, rats treated with long-term ALCAR or exposed to chronic stress while treated with ALCAR acquired VAB as efficiently as control rats. Moreover, VAB acquisition in stressed rats treated with ALCAR coincided with the reversal of the deficits in escape and in dopaminergic transmission in the NAcS. Thus, repeated ALCAR treatment preserved the DA response to VS in chronically stressed rats and this effect appeared to be predictive of the rat's competence to acquire VAB.

PMID: 12655313 [PubMed - indexed for MEDLINE]

Eur J Neurosci. 2004 Mar;19(6):1609-20. 
Repeated acetyl-l-carnitine administration increases phospho-Thr34 DARPP-32 levels and antagonizes cocaine-induced increase in Cdk5 and phospho-Thr75 DARPP-32 levels in rat striatum.
Scheggi S, Rauggi R, Nanni G, Tagliamonte A, Gambarana C.
Department of Neuroscience, Pharmacology Unit, University of Siena, Via Moro 4, 53100 Siena, Italy.

Abstract Acute cocaine administration increases phosphorylation of dopamine and cAMP-regulated phosphoprotein (M® 32 kDa) (DARPP-32) at threonine (Thr)-34, whereas repeated cocaine administration increases DARPP-32 phosphorylation at Thr-75 in Sprague-Dawley rat striatum. Repeated acetyl-l-carnitine (ALCAR) administration persistently increases dopamine outflow in the nucleus accumbens. The present study examined the effect of repeated ALCAR administration on the DARPP-32 phosphorylation pattern in the nucleus accumbens and caudate-putamen. ALCAR increased phosphoThr-34 DARPP-32 levels and decreased phosphoThr-75 DARPP-32 levels, after 1 and 10 days of washout. We compared the effects of repeated cocaine and repeated ALCAR administrations on the behavioural response to cocaine challenge and on the DARPP-32 phosphorylation pattern and cyclin-dependent kinase 5 (Cdk5) levels in the striatum. We also studied whether ALCAR administered daily during or after cocaine sensitization procedure would interfere with the effects of cocaine. When the response to the cocaine challenge was assessed, cocaine- and ALCAR-treated rats showed a similar sensitized behavioural response, and rats receiving combined cocaine and ALCAR treatments, irrespective of treatment order, also showed a sensitized response. A week after the cocaine challenge, the two drugs had induced opposite modifications in DARPP-32 phosphorylation, as cocaine increased phosphorylation at Thr-75, while ALCAR increased phosphorylation at Thr-34. In cocaine plus ALCAR treated rats, irrespective of treatment order, ALCAR administration antagonized cocaine effects on DARPP-32 phosphorylation. Moreover, cocaine, but not ALCAR, increased DeltaFosB and Cdk5 expression, and the increase in Cdk5 was antagonized by ALCAR administration in rats receiving combined treatments. These effects were relatively persistent, as they were still present 7 days after the last treatment.

PMID: 15066157 [PubMed - indexed for MEDLINE]

Another compound (that seems to be safe -- it's been used for over 3,000 years in India) that might help recovering methamphetamine brains -- Ashwagandha (Withania somnifera). Of the posted abstracts below that demonstrate neurite outgrowth activities -- ALL appear to be in vitro (or in culture -- not in a living organism -- so that's far from being able to claim these neuron regrowth effects will occur in a human) except for one -- this one -- in mice:

[quote name='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15711595']Br J Pharmacol. 2005 Feb 14; [Epub ahead of print]

Neuritic regeneration and synaptic reconstruction induced by withanolide A.

Kuboyama T, Tohda C, Komatsu K.

[1] 1Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan [2] 221st Century COE Program, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan.

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 Abeta(25-35) (10 muM) induced axonal and dendritic atrophy, and pre- and postsynaptic loss in cultured rat cortical neurons. Subsequent treatment with WL-A (1 muM) induced significant regeneration of both axons and dendrites, in addition to the reconstruction of pre- and postsynapses in the neurons.  WL-A (10 mumol kg(-1) day(-1), for 13 days, p.o.) recovered Abeta(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.

British Journal of Pharmacology advance online publication, 14 February 2005; doi:10.1038/sj.bjp.0706122.

PMID: 15711595 [PubMed - as supplied by publisher][/quote]

These are all in vitro:

[quote name='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12395110']
Axon- or dendrite-predominant outgrowth induced by constituents from Ashwagandha.

Kuboyama T, Tohda C, Zhao J, Nakamura N, Hattori M, Komatsu K.

Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.

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.

Copyright 2002 Lippincott Williams & Wilkins[/quote]

[quote name='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10884056']Neuroreport. 2000 Jun 26;11(9):1981-5.

Dendrite extension by methanol extract of Ashwagandha (roots of Withania somnifera) in SK-N-SH cells.

Tohda C, Kuboyama T, Komatsu K.

Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Japan.

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.[/quote]

[quote name='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12045329&query_hl=1']Chem Pharm Bull (Tokyo). 2002 Jun;50(6):760-5.

Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities.

Zhao J, Nakamura N, Hattori M, Kuboyama T, Tohda C, Komatsu K.

Department of Metabolic Engineering, Toyama Medical and Pharmaceutical University, Sugitani, Japan.

Five new withanolide derivatives (1, 9-12) were isolated from the roots of Withania somnifera together with fourteen known compounds (2-8, 13-19). On the basis of spectroscopic and physiochemical evidence, compounds 1 and 9-12 were determined to be (20S,22R)-3 alpha,6 alpha-epoxy-4 beta,5 beta,27-trihydroxy-1-oxowitha-24-enolide (1), 27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside VIII, 9), 27-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside IX, 10), 27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranoside (withanoside X, 11), and (20R,22R)-1 alpha,3 beta,20,27-tetrahydroxywitha-5,24-dienolide 3-O-beta-D-glucopyranoside (withanoside XI, 12). [b]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][/quote]
More research on this compound in many colors is available here.

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:

In vitro evidence:

Potential neuron protection properties:

[quote name='cmorera']in summary, dont do meth [/quote]

A no brainer; literally.

[quote name='cmorera']whats more interesting to me, considering meth is a FREKING EPIDEMIC in the United States now, not just a 'west coast' thing anymroe, its sweeping eastward, and even taking over towns in midwestern regions, is treatment/recovery options for abusers.[/quote]

What is particularly troublesome is the fact that methamphetamine seems to induce paranoid behavior and this type of behavior seems to be correlated with higher rates of crime -- I believe theft, domestic violence, and child abuse to be some of the worst types of crimes (am I missing anything?). If you watch PBS's documentary (excellent, by the way) -- you can see how there is a correlation between higher rates of meth purity and higher rates of crime. Now children are getting exposed to this drug because their parents do it and that is a BIG problem.

[quote name='cmorera']There is a 'PROMEtA" treatment, run by Hytheim that claims to be the only treatment currently for stimulant abuse and methamphetamine.  They are the #1 sponsor of ALL meth recovery discussion boards on the net, in fact its hard to not know who they are if you visit any meth related sponsorships or recovery forums.

http://www.prometain...amphetamine.jsp

The only information I was able to find out about the program was, its abuot a month long, involves an IV treatment of 3 already FDA approved medication, and was designed by one of the directors of of ... (something) ... top meth researcher.  I am trying to find out WHICH exact drugs are so effective in the treatment, the only clue I was able to find it one or more of them target the GABA system.[/quote]

I have never really looked into the Prometa treatment and I probably shouldn't have gotten into my own hypotheses so quick...I think it is important for the doctor administering the treatment to be able to explain to the patient how the medicine works...if it is a combination of 3 FDA approved medications -- then it shouldn't be some big secret, I guess.

[quote name='cmorera']Other than that,even with long term abstitence, seveal years +, there is strong evidence showing that certain parts of the former addicts brain will never recover, specifically dopamine related tissue in striatum, and possible several other areas.[/quote]

If you view the evidence I presented -- it appears that approximately 10% of the brain can be destroyed with 10 years of use. So, in essence, every year for an addict is about a 1% loss of the brain tissue. A high price to pay for something as important as the brain. You only got one.

I think with cases presented from individuals who have abused meth for 10 years -- yes, for these patients, it seems there might be little hope. I think that the compounds I suggested might make their life easier so they don't have to go back to using. This drug destroys peoples' lives like no other I've heard of.


[quote name='cmorera']There is some research showing many compounds can attenuate damage done by meth, such as NAC and others in vivo, but recovery of brain is another story also.  Recently a study involving Seroquel, a second generation atypical antipsychoticm, was shown to possible restore memory deficit and dopamine terminal deficit in meth users

http://www.ncbi.nlm....earch&DB=pubmed[/quote]

Hey! That link does not work! Can you find the one you were referencing please?

[quote name='cmorera']Also, Delta Opioid Peptide (DADLE) shows a complete blockade of damage caused by meth, and also possible regeneration of tissue in the striatum for former meth users AND parkinsons patients.  The damage caused by meth in certain parts of the brain resembles parkinsons or huntingtons.

anyways, some interesting stuff, I think a lot of research should be put into this more, due to the epidemic of meth now (wordwide also), will be causing a lot of problems down the road for these 'zombies' walking around and everyone also =][/quote]

Regarding Delta Opioid Peptide (DADLE), you have posted before:

[quote name='http://www.nida.nih.gov/DirReports/DirRep501/DirectorReport7.html']The delta opioid peptide [D-Ala2, D-Leu5]enkephalin (DADLE) has been reported to block the neurotoxicity induced by multiple administrations of a moderate dose of methamphetamine (METH). IRP scientists examined in this study if DADLE might block the neurotoxicity caused by a single high dose of METH in CD-1 mice. The levels of dopamine transporter (DAT), tyrosine hydroxylase (TH), major biogenic amines including DA, 5-hydroxytryptamine (5-HT), and their metabolites were examined. In addition, since the tumor suppressor p53 has been implicated in the neurotoxicity of METH, this study also examined the levels of p53 mRNA and protein affected by METH and DADLE. METH (25 mg/kg, i.p.) caused significant losses of DAT, TH, DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-HT in the striatum within 72 h.  The administration of a single dose of DADLE (20 mg/kg, i.p., 30 min before METH) caused a complete blockade of all losses induced by METH except for that of the DA content (an approximately 50% blockade). DADLE did not affect the changes of rectal temperature induced by the administration of the high dose of METH. METH increased p53 mRNA in the striatum and the hippocampus of CD-1 mouse. DADLE abolished the p53 mRNA increase caused by METH. METH tended to increase the p53 protein level at earlier time points. However, METH significantly decreased the p53 protein level by about 30% at the 72-h time point. DADLE blocked both the increase of p53 mRNA and the decrease of p53 protein caused by METH. These results demonstrate a neuroprotective effect of DADLE against the neuronal damage and the alteration of p53 gene expression caused by a single high dose of METH. The results also indicate an apparent discordance between the protein level of p53 and the neurotoxicity caused by a high dose of METH. Hayashi, T., Hirata, H., Asanuma, M., Ladenheim, B., Tsao, L.I., Cadet, J.L. and Su, T.P. Synapse 39(4), pp. 305-312, 2001.[/quote]

and

[quote name='http://www.nida.nih.gov/newsroom/06/NS-2.html']Brain Protein May Elicit Neuroprotective Effects on Brain Nerve Cells
Findings from a recently published NIDA-funded study suggest a brain protein may combat nerve cell damage in the brain.

Dr. Shang-Yi Tsai and colleagues from the National Institute on Drug Abuse in Baltimore, Maryland, cultured a hybrid of mouse and rat brain cells with the delta opioid peptide enkephalin (DADLE)—a powerful brain protein with properties to prevent nerve cell damage—to examine the effects of DADLE on nerve growth factor (NGF), a biological compound that stimulates nerve cell growth and differentiation in the brain.

Researchers observed significant increases in NGF when brain cells were exposed to small amounts of DADLE. Because DADLE was found to raise NGF levels by selectively increasing transcription factors (proteins that regulate the gene expression of NGF), DADLE may be one of the most potent agents known to increase NGF in the
biological system.

* WHAT IT MEANS: DADLE has been found to mediate a host of neuroprotective and biochemical effects in the brains of mice, including protection from nerve cell damage. These research findings suggest that DADLE may be effective in the production of growth factors important for the survival of brain cells. Thus, DADLE may effectively combat methamphetamine-induced brain damage and neurodegenerative diseases such as Parkinson’s.

These research findings were published in the September 2005 issue of Synapse.[/quote]

and

[quote name='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15353366&query_hl=1&itool=pubmed_docsum']Front Biosci. 2004 Sep 1;9:3392-8.

Delta opioid peptide (D-Ala 2, D-Leu 5) enkephalin: linking hibernation and neuroprotection.

Borlongan CV, Wang Y, Su TP.

Department of Neurology and Institute of Molecular Medicine and Genetics, Medical College of Georgia, 1120 15th Street, Augusta GA 30912-3200, USA. cborlongan@mail.mcg.edu

Hibernation is a potential protective strategy for the peripheral, as well as for the central nervous system. A protein factor termed hibernation induction trigger (HIT) was found to induce hibernation in summer-active ground squirrels. Purification of HIT yielded an 88-kD peptide that is enriched in winter hibernators. Partial sequence of the 88-kD protein indicates that it may be related to the inhibitor of metalloproteinase. Using opioid receptor antagonists to elucidate the mechanisms of HIT, it was found that HIT targeted the delta opioid receptors. Indeed, delta opioid (D-Ala 2, D-Leu 5) enkephalin (DADLE) was shown to induce hibernation. Specifically, HIT and DADLE were found to prolong survival of peripheral organs, such as the lung, the heart, liver, and kidney preserved en bloc or as a single preparation. In addition, DADLE has been recently demonstrated to promote survival of neurons in the central nervous system. Exposure to DADLE dose-dependently enhanced cell viability of cultured primary rat fetal dopaminergic cells.  Subsequent transplantation of these DADLE-treated dopaminergic cells into the Parkinsonian rat brain resulted in a two-fold increase in surviving grafted cells. Interestingly, delivery of DADLE alone protected against dopaminergic depletion in a rodent model of Parkinson s disease. Similarly, DADLE blocked and reversed the dopaminergic terminal damage induced by methamphetamine (METH). Such neuroprotective effects of DADLE against METH neurotoxicity was accompanied by attenuation of mRNA expressions of a tumor necrosis factor p53 and an immediate early gene c-fos. In parallel to these beneficial effects of DADLE on the dopaminergic system, DADLE also ameliorated the neuronal damage induced by ischemia-reperfusion following a transient middle cerebral artery occlusion. In vitro replication of this ischemia cell death by serum-deprivation of PC12 cells revealed that DADLE exerted neuroprotection in a naltrexone-sensitive manner. These results taken together suggest that DADLE stands as a novel therapeutic agent. In this review paper, we present laboratory evidence supporting the use of DADLE for protection of peripheral and central nervous system.

Publication Types:
Review

PMID: 15353366 [PubMed - indexed for MEDLINE][/quote]

This compound looks promising indeed. I should look into it further. You mentioned it before and did so again here and I somehow managed to overlook it both times as I am sometimes rushing through and if I don't quote that generally means I just scanned a post and saw a word or two that jumped out at me for one reason or another.

Does this evidence suggest that this compound protects against neurotoxicity after the damage has been done or only if one takes this compound before meth administration? In my cursory read, it seemed to be unclear to me.

See you around, bro.

Oh, I almost forgot! What is probably the best thing for anyone (including recovering meth addicts!) to help restore normal brain function is exercise! There is much peer reviewed literature that suggests that exercise not only induces neurogenesis and has beneficial effects on neuroplasticity; but excercise also seems to have some antidepressant and "anti aging" effects...

The abstracts:

J Psychiatry Neurosci. 2006 Mar;31(2):84-92.

Antidepressant effects of exercise: evidence for an adult-neurogenesis hypothesis?

        * Ernst C,
        * Olson AK,
        * Pinel JP,
        * Lam RW,
        * Christie BR.

Neuroscience Program, UBC Hospital, University of British Columbia, Vancouver, BC.

It has been hypothesized that a decrease in the synthesis of new neurons in the adult hippocampus might be linked to major depressive disorder (MDD). This hypothesis arose after it was discovered that antidepressant medications increased the synthesis of new neurons in the brain, and it was noted that the therapeutic effects of antidepressants occurred over a time span that approximates the time taken for the new neurons to become functional. Like antidepressants, exercise also increases the synthesis of new neurons in the adult brain: a 2-3-fold increase in hippocampal neurogenesis has been observed in rats with regular access to a running wheel when they are compared with control animals. We hypothesized, based on the adult-neurogenesis hypothesis of MDD, that exercise should alleviate the symptoms of MDD and that potential mechanisms should exist to explain this therapeutic effect. Accordingly, we evaluated studies that suggest that exercise is an effective treatment for MDD, and we explored potential mechanisms that could link adult neurogenesis, exercise and MDD. We conclude that there is evidence to support the hypothesis that exercise alleviates MDD and that several mechanisms exist that could mediate this effect through adult neurogenesis.

PMID: 16575423 [PubMed - indexed for MEDLINE]

Curr Alzheimer Res. 2006 Feb;3(1):49-54.

Environment, physical activity, and neurogenesis: implications for prevention and treatment of Alzhemier's disease.

* Briones TL.

Department of Medical-Surgical Nursing, University of Illinois, Chicago, IL 60612, USA. tbriones@uic.edu

Age is the biggest risk factor for the development of neurodegenerative diseases. Consequently, as the population ages it becomes more critical to find ways to avoid the debilitating cost of neurodegenerative diseases such as Alzheimer's. Some of the non-invasive strategies that can potentially slow down the mental decline associated with aging are exercise and use of multi-sensory environmental stimulation. The beneficial effects of both exercise and multi-sensory environmental stimulation have been well-documented, thus it is possible that these strategies can either provide neuroprotection or increase resistance to the development of age-related cognitive problems.

PMID: 16472203 [PubMed - indexed for MEDLINE]

Neurobiol Aging. 2002 Sep-Oct;23(5):941-55

Exercise, experience and the aging brain.

        * Churchill JD,
        * Galvez R,
        * Colcombe S,
        * Swain RA,
        * Kramer AF,
        * Greenough WT.

Beckman Institute, University of Illinois at Urbana-Champaign, 405 N Mathews, Urbana, IL 61801, USA.

While limited research is available, evidence indicates that physical and mental activity influence the aging process. Human data show that executive functions of the type associated with frontal lobe and hippocampal regions of the brain may be selectively maintained or enhanced in humans with higher levels of fitness. Similarly enhanced performance is observed in aged animals exposed to elevated physical and mental demand and it appears that the vascular component of the brain response may be driven by physical activity whereas the neuronal component may reflect learning. Recent results have implicated neurogenesis, at least in the hippocampus, as a component of the brain response to exercise, with learning enhancing survival of these neurons. Non-neuronal tissues also respond to experience in the mature brain, indicating that the brain reflects both its recent and its longer history of experience. Preliminary measures of brain function hold promise of increased interaction between human and animal researchers and a better understanding of the substrates of experience effects on behavioral performance in aging. Copyright 2002 Elsevier Science Inc.

PMID: 12392797 [PubMed - indexed for MEDLINE]

Trends Neurosci. 2002 Jun;25(6):295-301
Exercise: a behavioral intervention to enhance brain health and plasticity.

    * Cotman CW,
    * Berchtold NC.

Institute for Brain Aging and Dementia, Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-4540, USA. cwcotman@uci.edu

Extensive research on humans suggests that exercise could have benefits for overall health and cognitive function, particularly in later life. Recent studies using animal models have been directed towards understanding the neurobiological bases of these benefits. It is now clear that voluntary exercise can increase levels of brain-derived neurotrophic factor (BDNF) and other growth factors, stimulate neurogenesis, increase resistance to brain insult and improve learning and mental performance. Recently, high-density oligonucleotide microarray analysis has demonstrated that, in addition to increasing levels of BDNF, exercise mobilizes gene expression profiles that would be predicted to benefit brain plasticity processes. Thus, exercise could provide a simple means to maintain brain function and promote brain plasticity.

PMID: 12086747 [PubMed - indexed for MEDLINE]

Brain Res. 2000 Dec 15;886(1-2):47-53

Neuroprotective signaling and the aging brain: take away my food and let me run.

* Mattson MP.

Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, 5600 Nathan Shock Drive, 21224-6825, Baltimore, MD, USA. mattsonm@grc.nia.nih.gov

It is remarkable that neurons are able to survive and function for a century or more in many persons that age successfully. A better understanding of the molecular signaling mechanisms that permit such cell survival and synaptic plasticity may therefore lead to the development of new preventative and therapeutic strategies for age-related neurodegenerative disorders. We all know that overeating and lack of exercise are risk factors for many different age-related diseases including cardiovascular disease, diabetes and cancers. Our recent studies have shown that dietary restriction (reduced calorie intake) can increase the resistance of neurons in the brain to dysfunction and death in experimental models of Alzheimer's disease, Parkinson's disease, Huntington's disease and stroke. The mechanism underlying the beneficial effects of dietary restriction involves stimulation of the expression of 'stress proteins' and neurotrophic factors. The neurotrophic factors induced by dietary restriction may protect neurons by inducing the production of proteins that suppress oxyradical production, stabilize cellular calcium homeostasis and inhibit apoptotic biochemical cascades. Interestingly, dietary restriction also increases numbers of newly-generated neural cells in the adult brain suggesting that this dietary manipulation can increase the brain's capacity for plasticity and self-repair. Work in other laboratories suggests that physical and intellectual activity can similarly increase neurotrophic factor production and neurogenesis. Collectively, the available data suggest the that dietary restriction, and physical and mental activity, may reduce both the incidence and severity of neurodegenerative disorders in humans. A better understanding of the cellular and molecular mechanisms underlying these effects of diet and behavior on the brain is also leading to novel therapeutic agents that mimick the beneficial effects of dietary restriction and exercise.

PMID: 11119686 [PubMed - indexed for MEDLINE]

Prog Neurobiol. 2004 Feb;72(3):167-82
Recovery from brain injury in animals: relative efficacy of environmental enrichment, physical exercise or formal training (1990-2002).

        * Will B,
        * Galani R,
        * Kelche C,
        * Rosenzweig MR.

Laboratoire de Neurosciences Comportementales et Cognitives, Institut Federatif des Neurosciences, Universite Louis Pasteur, UMR 7521, CNRS, Strasbourg, France. bruno.will@psycho-ulp.u-strasbg.fr

In the 1960s, it was shown for the first time that enriched housing enhances functional recovery after brain damage. During the 1970s and 1980s, many findings similar to this initial one have been reported, enlarging greatly its generality. Over the last 13 years, many different kinds of brain damage were modelled in animals or even directly studied in humans. Overall, these recent studies corroborated earlier findings, although occasional exceptions were reported. Other critical data, obtained mainly in intact animals, showed that enriched housing increases neurogenesis in the adult hippocampus. Recent evidence that this neurogenesis is involved in hippocampal-dependent learning supports the original interpretation of the enrichment effects as being the result of an accumulation of informal learning experiences (e.g., [. Heredity, environment, brain biochemistry, and learning. In: Current Trends in Psychological Theory. University of Pittsburgh Press, Pittsburgh, pp. 87-110;. Brain changes in response to experience. Sci. Am. 226, 22-29]). Other components of enriched environment, such as physical exercise, may have additive effects with those of training. The comparison of the relative effectiveness of enriched experience, of physical exercise and of training on structural and/or functional assessments of recovery, shows that training/learning is generally more effective than physical exercise and that enriched experience is a more potent therapy than either of these two other treatments. The combination of enriched experience with some other neurosurgical and/or neuropharmacological treatments may further improve its therapeutic effectiveness. Finally, other recent reports emphasize that the treatment parameters may be changed in order to approximate clinical/rehabilitation conditions and, nevertheless, remain effective. Copyright 2004 Elsevier Ltd.

PMID: 15130708 [PubMed - indexed for MEDLINE]

Prog Brain Res. 2000;127:35-48
Activity-dependent regulation of neuronal plasticity and self repair.

        * Kempermann G,
        * van Praag H,
        * Gage FH.

Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.

Plasticity is an essential characteristic of the brain: it is part of how the brain functions and is continuous while the brain interacts with the outer world. The state of activation and the level of activity of the entire organism affect the brain's plastic response. Brain plasticity has many substrates, ranging from synapses to neurites and entire cells. The production of new neurons is part of plasticity even in the adult and old brain, but under normal conditions neurogenesis only occurs in two privileged regions of the adult brain: hippocampus and olfactory system. At least in the hippocampus, physical activity stimulates neurogenesis by acting on the proliferation of neuronal stem cells. More specific functions such as learning may be able to recruit new neurons from the pool of cells with neurogenic potential. In a broader context neuronal stem cells can likely be found throughout the brain. Therefore, novel approaches to neuroregeneration will, when most effective, make use of the activity-related effects on neuronal stem cells in the adult brain to activate these stem cells in a targeted manner to enhance brain function.

PMID: 11142036 [PubMed - indexed for MEDLINE]

More information on possible therapeutic solutions for recovering methamphetmaine addicts:

[quote name='http://alcoholism.about.com/od/meth/a/bljama050408.htm']Brain Recovery Possible for Meth Users
From JAMA News Release

Abstinence Can Reverse Some Brain Damage
Adaptive changes in chemical activity in certain regions of the brain of former methamphetamine users who have not used the drug for a year or more suggest some recovery of neuronal structure and function, according to an article in the April 2005 issue of Archives of General Psychiatry, one of the JAMA Archives journals.
Methamphetamine use has been shown to cause abnormalities in brain regions associated with selective attention and regions associated with memory, according to background information in the article. Recent animal and human studies suggest that neuronal changes associated with long-term methamphetamine use may not be permanent but may partially recover with prolonged abstinence.

Thomas E. Nordahl, M.D., Ph.D., of the University of California, Davis, and colleagues compared eight methamphetamine users who had not used methamphetamine for one to five years and 16 recently abstinent methamphetamine users who had not used the drug for one to six months with 13 healthy, non-substance-using controls using a method of brain imaging, proton magnetic resonance spectroscopy (MRS), that allows the visualization of biochemical markers that are linked with damage and recovery to the neurons in the brain.

The researchers measured biomarkers in the anterior cingulum cortex, a region of the brain associated with selective attention.

Levels of N-acetylaspartate (NAA), which is present only in neurons, were measured as a marker of the amount of damage (neuronal loss).

Neuronal Recovery
Choline (Cho), which is generated by the creation of new membranes and, the authors write, "may be an ideal marker to track changes consistent with neuronal recovery associated with drug abstinence," was measured as a biomarker of recovery.
Levels of NAA were abnormally low in all the methamphetamine users, the authors found. Levels were lower relative to the length of methamphetamine use, but did not change relative to the amount of time that the methamphetamine users had been abstinent. The researchers found elevated Cho levels in the methamphetamine users who had not used the drug in one to six months, but normalized levels in the longer abstainers.


Normalization of Function
"In the early periods following methamphetamine exposure, the brain may undergo several processes leading to increased membrane turnover. The relative Cho normalization across periods of abstinence suggests that when drug exposure is terminated, adaptive changes occur, which may contribute to some degree of normalization of neuronal structure and function," they write.
"The understanding of how the human brain can recover or partially recover as a function of extended drug abstinence has important implications both for the neurobiology of addiction and substance abuse treatment," the authors conclude. "Additional longitudinal studies…are needed to further understand the underlying physiological changes of stimulant drugs on the human brain."


Updated: April 8, 2005[/quote]

I found the primary source of the article discussed above: the abstract is available free here.

It appears that "normalization" of creatine (which I understand may metabolise into phosphocreatine?), N-acetylaspartate, and Choline -- or whatever compounds might be best to "normalize" activity in the cholinergic system -- Alpha GPC, Citocholine (CDP Choline), Acetyl-L-carnitine (previously mentioned), other miscellaneous cholinergic agonists (such as pyritinol, the various "racetams," etc.)....might be able to allow recovering addicts to gain improved cognitive function -- I would imagine that in combination with other substances, there may be much quicker recovery to baseline mental performance that it may otherwise be possible with simple abstinence.

Here is the abstract:

[quote name='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15809412&query_hl=7&itool=pubmed_DocSum']Arch Gen Psychiatry. 2005 Apr;62(4):444-52.

Methamphetamine users in sustained abstinence: a proton magnetic resonance spectroscopy study.Nordahl TE, Salo R, Natsuaki Y, Galloway GP, Waters C, Moore CD, Kile S, Buonocore MH.

Department of Psychiatry and Behavioral Sciences, University of California Davis Medical Center, 4701 X Street, Sacramento, CA 95817, USA. tenordahl@ucdavis.edu

BACKGROUND: Abnormal patterns of metabolite levels have been detected by magnetic resonance spectroscopy in frontostriatal regions of individuals meeting DSM-IV criteria for methamphetamine dependence, but less is known about the effects of drug abstinence on metabolite levels. OBJECTIVE: To assess the effects of long-term methamphetamine use and drug abstinence on brain metabolite levels. DESIGN: To assess regional specific metabolite levels using magnetic resonance spectroscopy imaging techniques in 2 groups of currently abstinent methamphetamine users: methamphetamine users who recently initiated abstinence and methamphetamine users who had initiated abstinence more than 1 year prior to study. SETTING: Participants were recruited from outpatient substance abuse treatment centers. PARTICIPANTS: Eight methamphetamine users with sustained abstinence (1 year to 5 years) and 16 recently abstinent methamphetamine users (1 month to 6 months) were compared with 13 healthy, non-substance-using controls. MAIN OUTCOME MEASURES: Magnetic resonance spectroscopy measures of N-acetylaspartate-creatine and phosphocreatine (NAA/Cr), choline-creatine and phosphocreatine (Cho/Cr), and choline-N-acetylaspartate (Cho/NAA) ratios were obtained in the anterior cingulate cortex as well as in the primary visual cortex, which served as a control region. RESULTS: The absolute values of Cr did not differ between controls and methamphetamine users. Methamphetamine users had abnormally low NAA/Cr levels within the anterior cingulate cortex, regardless of the time spent abstinent (F(2,34) = 12.61; P<.001). No NAA/Cr group differences were observed in the primary visual cortex (F(2,33) = 0.29; P = .75). The Cho/NAA values for the anterior cingulate cortex were abnormally high in the methamphetamine users who recently initiated abstinence but followed a normal pattern in the methamphetamine users who had initiated abstinence more than 1 year prior to study (F(2,34) = 7.31; P = .002). CONCLUSIONS: The relative choline normalization across periods of abstinence suggests that following cessation of methamphetamine use, adaptive changes occur, which might contribute to some degree of normalization of neuronal structure and function in the anterior cingulum. More research is needed to elucidate the mechanisms underlying these adaptive changes.


PMID: 15809412 [PubMed - indexed for MEDLINE][/quote]

this really is an interesting thread as meth seems to be a highly damaging drug in terms of neurotoxicity ... also the addiction is a global problem, i hear in Asian countries many employers are giving this to their workers (poor) to increase productivity. If this is true, coupled with the spreading usage in the states, we will definitely need a better understanding and treatment options for users and those seeking recovery.

oh yes, heres the correct article link you requested above

http://www.ncbi.nlm....earch&DB=pubmed

    The effects of chronic administration of quetiapine on the methamphetamine-induced recognition memory impairment and dopaminergic terminal deficit in rats.

        * He J,
        * Yang Y,
        * Yu Y,
        * Li X,
        * Li XM.

    Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan, 103 Wiggins Road, Saskatoon, Sask., Canada S7N 5E4.

    Previous studies have suggested that quetiapine, a new atypical antipsychotic drug, may have beneficial effects on cognitive impairment and be a neuroprotectant in treating neurodegenerative diseases. In the present study, we investigated the therapeutic effects of chronic administration of quetiapine on methamphetamine (METH)-induced recognition memory impairment and dopaminergic terminal neurotoxicity in rats. Rats were pretreated with METH (5 mg/kg; s.c.) four times at 2-h intervals while their body temperature was monitored. Fifteen minutes after the last METH injection, rats were administered quetiapine (10 mg/kg/day; i.p.) for 28 days. One day after the last quetiapine injection, rats were trained and tested on an object recognition task on days 29 and 30. Finally, on day 31, rats were sacrificed for immunohistochemistry, 1 day after the object recognition task. METH induced hyperthermia, recognition memory impairment and a decrease of tyrosine hydroxylase immunoreactivity in the caudate putamen (CPu) of striatum. Quetiapine attenuated the METH-induced hyperthermia. Furthermore, chronic post-treatment of quetiapine reversed the METH-induced memory impairment and dopaminergic terminal deficit. These findings suggest that quetiapine may have therapeutic effects in the treatment of cognitive impairment and neurodegeneration induced by METH.

    PMID: 16712969 [PubMed - indexed for MEDLINE]

This story might seem to be related:

Scientific American: News source


Image: © SCOTT HOUSTON/SYGMA/CORBIS
STROKE FROM SMOKE: A new study provides evidence that meth use may lead to an increased risk of stroke

December 26, 2006

Strokes in Young People Could be Due to Meth

Discovery that methamphetamine and related drugs lead to tears in major arteries could change how doctors handle such cases
by Charles Q. Choi

The drug known on the streets as crystal meth could increase the risk of stroke and major tears in neck arteries, neurologists report.

With help from his colleagues, neurologist Wengui Yu, now at the University of Texas Southwestern Medical Center at Dallas, examined two women, ages 29 and 36, both of whom used methamphetamine and then suddenly experienced weakness and difficulty in speaking. Brain scans revealed both women had suffered severe strokes from tears in the inner lining of one of the major arteries in the neck, an injury known as carotid artery dissection.

On the National Institutes of Health Stroke Scale, a score over 16 suggests a high chance of death or severe disability. The 29-year-old woman received a score of 17, while the 36-year-old woman received a 21. Besides methamphetamine abuse, the women did not have any other significant risk factors for stroke. Both recovered with mild to moderate disabilities after stroke therapy.

"The work they did was beautifully done and very carefully characterized," says stroke neurologist Steven Cramer of the University of California, Irvine. "If I ever see any young person with a stroke--that is, anyone under 65--I'll be sure now to do a toxicology screen early on in the evaluation."

Methamphetamine, an addictive stimulant, is known to increase blood pressure, constrict blood vessels and inflame or damage blood vessel walls. It has previously been linked with aortic dissections, which are tears in the walls of the aorta, the largest artery in the body. Yu notes that cocaine has effects on the body similar to those of methamphetamine, and is also linked with aortic and carotid artery dissections. This suggests tears in arteries may be an effect linked to a class of drugs rather than to a specific drug.

"If larger studies confirm these findings and the suspicions of many that this is not a rare process, this could open up an avenue for intervention when it comes to methamphetamine. It could prevent a rise in frequency in the expensive and disabling condition of stroke," says Cramer. Data from such studies could "help physicians to better diagnose, treat, and prevent stroke in young adults," says Yu.

Yu and his colleagues reported their findings in the December 26 Neurology.

I happened upon an A&E show called "Intervention" this past fall. This episode documentes a 24-year-old stripper (Cristy) who has been using crystal meth for over ten years. It was a disturbing show.

Pre-meth videos of Cristy as an adolescent showed a warm and seemingly normal, happy young teenager. Comparing this with the person she'd become, it was apparent to me that heavy crystal meth usage had absolutely changed Cristy's personality. To me, her current personality, attitude and behavior were that of a psychopath. When her younger sister brings her soup, Cristy provokes a fistfight. When she runs out of alcohol and money, Cristy hangs out by a liquor store asking men to buy liquor for her (which they do). She wanders around her neighborhood naked without a care. During the intervention itself, she rolls her eyes and openly laughs at her mother's tearful request that she seek help. There was no getting through to Cristy. It seemed that she only agreed to go into detox to avoid the annoyance of her family's pestering.

Cristy was expelled after a month in the detox treatment. Later. after being arrested for outstanding criminal charges, she chose jail over court-imposed treatment. That was it. There was no happy ending.

In effect, heavy meth usage appears to alter who you are, and not for the better. I've no doubt that it alters the brain. It seems that the only time you can be sure that you'll have the ability to reject the drug is before you've actually experienced it. After that, it's a big gamble.

I have met and known plenty of people in the rave scene in the mid-late 90's who have plagued by crystal use. Girls, teenaged and very pretty, with pock marked faces and in sub-runway model weight categories. A very good friend of mine who I drove to school with everyday in grade 13 was a crystal addict - she had a four year old baby (she was 20) and had people back to the house that even I wasn't comfortable with... [mellow] It does change people.

I rarely make out to "big" parties anymore, but when I do I see some faces that I really wished had moved on. God knows how messed their brains are now (combined with the classic up all weekend, poor diet thing).

so.....

most of us here are in a position to educate and guide those in need towards a better understanding. Alot of members here have used most of these drugs mentioned above but now do not. They choose another road. One that is not plagued by such addictive substances.

Why not speak with friends that do meth and offer safer alternatives such as nootropics. Most know and a scared shitless by the negatives such as neuronal damage and so on. Most users can feel the negatives first hand.

I have some friends that I have guided away from substances. They still feel the peer pressure though. I tell them to crush up placebo pills (buy from chemist) or to simply pop placebo pills if they have to. Some now prefer to use phenibut over amphetamines.

Anyhoo......use what we know and lead by example.

By the way, Meth is not just a US thing. Methamphetamine use is out of control in Australian clubs and if you have ever tried crystal meth you should be able to sympathize with those who have become addicted. It's just not fair!

Two bbc docos title drugland

Part 1:
http://video.google....bbc documentary

Part 2:
http://video.google....bbc documentary

edit ... when i do deep meditation, i can kind of think that i have some sort of psychological problem ... and im a liar of a person

Edited by cmorera, 28 December 2006 - 07:07 PM.

I happened upon an A&E show called "Intervention" this past fall.  This episode documentes a 24-year-old stripper (Cristy) who has been using crystal meth for over ten years. It was a disturbing show. 

Pre-meth videos of Cristy as an adolescent showed a warm and seemingly normal, happy young teenager.  Comparing this with the person she'd become, it was apparent to me that heavy crystal meth usage had absolutely changed Cristy's personality.  To me, her current personality, attitude and behavior were that of a psychopath.  When her younger sister brings her soup, Cristy provokes a fistfight.  When she runs out of alcohol and money, Cristy hangs out by a liquor store asking men to buy liquor for her (which they do).  She wanders around her neighborhood naked without a care.  During the intervention itself, she rolls her eyes and openly laughs at her mother's tearful request that she seek help. There was no getting through to Cristy.  It seemed that she only agreed to go into detox to avoid the annoyance of her family's pestering.

Cristy was expelled after a month in the detox treatment.  Later. after being arrested for outstanding criminal charges, she chose jail over court-imposed treatment.  That was it. There was no happy ending.

In effect, heavy meth usage appears to alter who you are, and not for the better.  I've no doubt that it alters the brain.  It seems that the only time you can be sure that you'll have the ability to reject the drug is before you've actually experienced it.  After that, it's a big gamble.

Well I did a little bit of research on the Intervention series, and I found a link.

http://www.aetv.com/...ntion/index.jsp

This does not mean that it's only girls doing the stuff. Meth is supposedly the "moonshine" of the gay community...and I've known plenty of straight dudes who either are or were tweakers. I hope none of them get the "wise" idea that they can still tweak as long as they take hydergine or something...if only we could find compounds as effective at inducing neurogenesis as meth is at neuro-destruction...and I highly doubt that, even if such therapies exist, that they could reverse the damage done by lack of sleep or meth induced psychosis.

I just visited my friend again in the 'bin and he's still thinking it's okay to smoke that shit...sad, I tell you.

Click here to watch a little bit of the Intervention clip on Christy. To be honest, I find it hard to believe she's been tweaking for 10 years and have all of her teeth.

Intervention®
“31 - Cristy”

Rated: TV14 L
Running Time: 60 Minutes
Genre: Real Life Series
Closed Captions: Yes

Search for other upcoming episodes
Cristy was born into a tight-knit family and sought a career as a clothing designer before she became addicted to alcohol and crystal meth. Now she earns her money as a stripper, and her desperate family knows she needs an intervention.

Quote from the clip

"People can't handle crystal meth. I can handle it because I am smarter than them"

I've heard that one before. Time and time again.
Holy shit! If you have a crack pipe in one hand and a 750mL bottle of half drunk Smirnoff in the other. That's not smart. There are better quality vodkas on the market!

Some of these highly refined drugs are very addicted of course and we are going to see worse. Think scanner darkly and substance D

You are either on it or you have never tried it

hey Adam,

that was cool o visit your friend and show support for him ... it also must be prety hard I think to do ... i hope your friend can realize that this stuff is not good =]

I think on the phone, he said 'something that good can't be done all the time' so he still associate it with something 'good' which is a little troublesome ... ;p

so.....

most of us here are in a position to educate and guide those in need towards a better understanding. Alot of members here have used most of these drugs mentioned above but now do not. They choose another road. One that is not plagued by such addictive substances.

Why not speak with friends that do meth and offer safer alternatives such as nootropics.  Most know and a scared shitless by the negatives such as neuronal damage and so on. Most users can feel the negatives first hand.

I have some friends that I have guided away from substances. They still feel the peer pressure though. I tell them to crush up placebo pills (buy from chemist) or to simply pop placebo pills if they have to. Some now prefer to use phenibut over amphetamines.

Anyhoo......use what we know and lead by example.

By the way, Meth is not just a US thing. Methamphetamine use is out of control in Australian clubs and if you have ever tried crystal meth you should be able to sympathize with those who have become addicted. It's just not fair!

I hear you. I think I've stated somewhere here before that I volunteered with a harm reduction program in the past, and when I'm done this year of school, I'm thinking I may go back to such an organization for a while. The damage you can do over the teenage years is way too easy to inflict, and for the time being, seemingly impossible to repair. There's still much to do through education for a user, but a lot of it is dedicated ignorance in favour of geting high - and that is not easily tackled.

Zoo - what is this peer pressure? I remember hearing about it as a young person, and waiting for it to hit, waiting for one of my friends to offer me a cigarette, a joint, a mysterious pill....i'm still waiting....no shady pusher in the corner with a dark trenchcoat is selling me anything. In fact - hey! That guys just asked me for drugs! [wis] *ironically cuts dreads*

Some freindships are developed as a result of drug use. Bonding deeply with E. So you start using and experiment with other drugs. You build a circle of friends within the drug culture and whilst you do this your other friends fade away in the distance. Then you may find yourself wanting to move on because it's all becoming to much but everytime that you are with your (drug circle) friends, they offer drugs. You say no and they feel like you are judging them because you have decided not to take. You still want to hang with these people even though you do not want to take drugs any more but it's hard.

I think we all know the answer here. Move on. Hang in the background and wait for them to come around. Be there as support when they finally decide to call it a day.

Mitkat, I do understand one thing. Peer pressure is just another name for weak willed. The pressure is not from your peers at all is it? The pressure is for you to fit in, right?

Some freindships are developed as a result of drug use. Bonding deeply with E. So you start using and experiment with other drugs. You build a circle of friends within the drug culture and whilst you do this your other friends fade away in the distance. Then you may find yourself wanting to move on because it's all becoming to much but everytime that you are with your (drug circle) friends, they offer drugs. You say no and they feel like you are judging them because you have decided not to take. You still want to hang with these people even though you do not want to take drugs any more but it's hard.

I think we all know the answer here. Move on. Hang in the background and wait for them to come around. Be there as support when they finally decide to call it a day.

Mitkat, I do understand one thing. Peer pressure is just another name for weak willed. The pressure is not from your peers at all is it? The pressure is for you to fit in, right?

I have seen, and participated in such friendships, and I may be going out on a limb assuming many of us have in one way or another. It was at this time in my life when I fully realized the difference between a friend and an acquaintance.

Zoo, we agree on so many things, I don't want it to seem that I'm stepping on your toes. Myself, and I believe you, do not always equal "fitting in" in certain social paradigms and the peer pressure thing doesn't necessarily apply. Peer pressure is one of the many logical fallacies of the war on drugs. It's a hasty generalization, assuming all will be faced with a certain prototypical situation (are you IN or OUT, BOYEEE??) rather than an intelligent choice, well-researched opinion, or just taking a fucking chance. Maybe I'm not able to fully grasp the concept of peer pressure being the person that I am, but I've never done anything I've been uncomfortable with, and never been pressured to do otherwise.

Whoops. please delete.
Happy holidays.

Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

To be honest, I find it hard to believe she's been tweaking for 10 years and have all of her teeth.

I say this not as a challenge to Christy's integrity...I've just heard of a condition called "meth mouth" -- so when I hear anyone claim to be a meth addict for multiple years (especially 10!), I find it hard to believe they could have their teeth in as good a shape as Christy's are in the video I linked to.

Everyone should check out PBS: The Meth Epidemic.

Here is a link to the "Meth and the Mouth" segment.

hey Adam,

that was cool o visit your friend and show support for him ... it also must be prety hard I think to do ... i hope your friend can realize that this stuff is not good =]

I think on the phone, he said 'something that good can't be done all the time' so he still associate it with something 'good' which is a little troublesome ... ;p

I also went to visit this dude a few months ago. The locked down facility my friend is at is actually really close to where I stay when I am up in LA (maybe a 10 minute drive), so it wasn't too much of an issue to visit him. Another main reason I go to visit this dude is because it reinforces the importance of staying off of that stuff -- and considering I am a recovering dope fiend -- seeing a kid in as bad a shape as him is the strongest motivation I know of.

It was coincidental that you happened to call me while I was there...hope you have a good holiday with your family

Edited by nootropikamil, 24 March 2007 - 05:35 PM.