Is Cognitive Functioning Impaired in Methamphetamine Users? A Critical Review.

[Amu]

Is Cognitive Functioning Impaired in Methamphetamine Users? A Critical Review.
http://www.ncbi.nlm.nih.gov/pubmed/22089317

I think the study does an excellent job of examining all the studies regarding ex-methamphetamine users' cognitive function and exposes some of the biases against methamphetamine even in scientific studies.

 

[airsh0w]

Seems like a valid question but by damaging DA producing neurons I couldn't imagine how it couldn't be. It increases chances of Parkinson's. Hmm it reverses some monoamine transporters and increases cAMP which could be good at first but over the long term it is toxic due in-part by oxidative stress from breaking down all of those monoamines like MMDA is. So a nice helping of anti-oxidants couldn't hurt but would a MAO-I inhibitor hurt at low doses at least or make this feat possible? I wonder how that would play out. I've heard of serotonin poisoning but not dopamine poisoning unless you would consider schizophrenia just that. But methamphetamine also increases serotonin and is a monoamine itself so its more complicating. But (ANIMAL) experimentation with meth and MAOI would be interesting. Perhaps with a serotonin partial agonist to prevent serotonin syndrome.

 

[negrogesic]

In no effort to discredit his work, Dr. Carl Hart has contributed to some admittedly curious studies in the past.....


partial list


On an unrelated note, i'd been an interested in study that would read, "While studies of the reinforcing effects of cocaine abound, few studies have investigated the acute effects of intranasal cocaine when inhaled from betwixt a prostitute's ass-cleft; in the following, we will evaluate......"

 

[cryptix420]

Dude, you don't need a study. All you need to do is live with some tweakers and then we'll talk about this 'cognitive functioning' you speak of

 

[airsh0w]

Dude, you don't need a study. All you need to do is live with some tweakers and then we'll talk about this 'cognitive functioning' you speak of

haha such truth

 

[Amu]

Dude, you don't need a study. All you need to do is live with some tweakers and then we'll talk about this 'cognitive functioning' you speak of

Right, and you assume every meth user wants to tweak the shit out of their brain and at the same time deprive their brain/body of food/sleep which is necessary to recover from the possible damage, this is not "Is the meth ABUSE lifestyle harmful?" Seriously, I expect a certain level of academic discussion based on the topic of this thread, did you even bother to read any of the article?

 

[cryptix420]

^ damn have a little humor in your life amigo. i have no interest in learning more about meth. I already know if I tried it I would love it, as I have an addictive personality. I've heard it compared to MDMA except it works on dopamine instead of serotonin. It would be intense. I've already kicked a cig habit and like alcohol a bit too much, so I'm good on more vices.

I mean come on, who takes ONE hit of meth? It just doesn't happen. You never eat one chip.

When it comes down to it, meth is goddamned toxic.

effects of habitual use


fatal kidney and lung disorders
possible brain damage
permanent psychological problems
lowered resistance to illnesses
liver damage
stroke
cardiovascular crises, chest pains, heart attacks
Damage to gums, teeth, and can lead to tooth loss


come on dude, what other drugs have that kind of profile? Except for maybe most prescription drugs lol.

 

[Amu]

^ damn have a little humor in your life amigo. i have no interest in learning more about meth. I already know if I tried it I would love it, as I have an addictive personality. I've heard it compared to MDMA except it works on dopamine instead of serotonin. It would be intense. I've already kicked a cig habit and like alcohol a bit too much, so I'm good on more vices.

I mean come on, who takes ONE hit of meth? It just doesn't happen. You never eat one chip.

When it comes down to it, meth is goddamned toxic.

effects of habitual use


fatal kidney and lung disorders
possible brain damage
permanent psychological problems
lowered resistance to illnesses
liver damage
stroke
cardiovascular crises, chest pains, heart attacks
Damage to gums, teeth, and can lead to tooth loss


come on dude, what other drugs have that kind of profile? Except for maybe most prescription drugs lol.

Well, I'm not making any claims on how meth should be used, simply discussing the cognitive changes it causes in human users and abusers. None of the side effects you mention will be seen in low oral doses (i.e. 5-20 mg), and yes it can be used properly and safely, by ADHD patients or TBI (brain damaged) patients, or whatever the case may be, even used recreationally in similar oral doses for studying or staying up (duh). Not to mention the long list of agents that block and reduce the neurotoxicity by a lot, not to mention neurotoxicity is reduced in young rats anyway and is almost insignificant at room temperature. By the way this is Advanced Drug Discussion, not Drug Culture, and not "Should I tweak on meth to get high everyday?" On top of all that, exposing the brain to low doses (5-20 mg) a few times PROTECTS against future large neurotoxic doses, and has been shown to be cognitively beneficial in many studies.

I'm saying 20 mg a day orally spread out with proper sleep/nutrition is VASTLY VASTLY different than 100 mg smoked/injected by some random addicted tweaker, and by the way a single hit of meth has approximately 20+ mg of meth in it, so you can imagine how different the two cases are.

P.S. 5 mg pharmaceutical-grade dextromethamphetamine has the least side effects of any significantly psychoactive substance I've ever come across, certainly less than any other stimulant, definitely so than dissociatives, and probably even opiates, even low dose hydrocodone has annoying side effects, perhaps LSD would match the smoothness of d-meth but it's ridiculously psychedelic while that dose of d-meth does not impair functioning in any domain.

 

[persianslipper]

Unfortunately, I think one of the reasons we aren't treated to more conclusive statements on methamphetamines is due to our comparative ignorance about the human brain and the systems which work in synergy with it. However, they correlate far more often than not, and I'm definitely throwing my change behind the idea that altering any kind of neurotransmitter release mechanism will end in the long-term or permanent altering of said mechanism. Here are a couple of papers which support this:

On the Control of Control: The Role of Dopamine in Regulating Prefrontal Function and Working Memory - http://ccpweb.wustl.edu/pdfs/Chapter31.pdf

And this one, which studies chronic amphetamine use and Parkinson's: http://www.acnp.org/G4/GN401000166/CH162.htm

The persistent, sustained increase in the sensitivity to the psychosis-inducing properties of stimulants suggests that chronic consumption of central stimulants induces a permanent alteration in the functional organization of the central nervous system, especially dopaminergic systems. This hypothesis has been presented in reference to amphetamines (111, 117) and indeed similar considerations have been raised for cocaine (167, 205). Arguments for the DA nature of these chronic effects come from studies on L-dopa treatment, which is more easily studied clinically in a prospective manner. In general, psychomotor disturbances are rare in the early phases of L-dopa treatment of Parkinsonism but become increasingly frequent as treatment is continued (117). After two years of treatment, the incidence of such side effects rises to nearly 70% (118 ). It has also been noted that these side effects (relative to individual doses of L-dopa) tend to increase with chronic administration, such that lower doses are required to elicit psychosis and dyskinesia (117). Thus, a long-lasting hypersensitivity appears to develop, not only to central stimulants but also to L-dopa, such that previously well tolerated doses may later come to induce toxic symptoms.

However, I also found a study which suggests that the tolerance to neurotoxic effects and events can be mitigated through microglial activation. This seems to support your claim. Every person is wired different in little ways, though, so while 20mg a day may treat one person, that same 20mg could seriously mess with someone else's brain juice (http://www.ncbi.nlm.nih.gov/pubmed/15686480). Not only that, but hyperthermia did occur at known neurotoxic doses even with low-dose tolerance, so even though chemically your brain might be safe, you probably still run risk of frying it if you have a single abusive day. (Not to say this is going to be a problem for everyone; I just thought I'd throw it out there due to the nature of the drug.)

airsh0w made a good point - if someone does use methamphetamines, it would probably be wise to use some sort of antioxidant to try and counter any oxidative stress. I hope you like garlic.

 

[Epsilon Alpha]

One thing that we also need to take into account is how long these effects persist for, amphetamine's produce a protracted withdrawal so that could easily cause lower test scores for at least a year in my opinion.

Had a really good Thai paper on the topic, but I'll have to find it again for this thread.

 

[Amu]

persianslipper, you're forgetting the brain has a massive endogenous supply of anti-oxidants, and there are numerous studies which show it increases this supply after just two low doses of methamphetamine, and anti-oxidant supplements might be harmful to this adaptation.

Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration.
http://www.ncbi.nlm.nih.gov/pubmed/21190217

Acute, low-dose methamphetamine administration improves attention/information processing speed and working memory in methamphetamine-dependent individuals displaying poorer cognitive performance at baseline.
http://www.ncbi.nlm.nih.gov/pubmed/21122811

Tolerance to the neurotoxic effects of methamphetamine in young rats
http://www.ncbi.nlm.nih.gov/pubmed/11821024

Long-term protective effects of methamphetamine preconditioning against single-day methamphetamine toxic challenges.
http://www.ncbi.nlm.nih.gov/pubmed/21886558

Adaptative response of antioxidant enzymes in different areas of rat brain after repeated d-amphetamine administration.
http://www.ncbi.nlm.nih.gov/pubmed/11900599

Evidence against an essential role of endogenous brain dopamine in methamphetamine-induced dopaminergic neurotoxicity.
http://www.ncbi.nlm.nih.gov/pubmed/11389185

How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis).
http://www.ncbi.nlm.nih.gov/pubmed/20350594

Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis.
http://www.ncbi.nlm.nih.gov/pubmed/17327526

Sublethal mitochondrial stress with an attendant stoichiometric augmentation of reactive oxygen species may precipitate many of the beneficial alterations in cellular physiology produced by caloric restriction, intermittent fasting, exercise and dietary phytonutrients: "Mitohormesis" for health and vitality.
http://www.ncbi.nlm.nih.gov/pubmed/16242247

Effects of isradipine on methamphetamine-induced changes in attentional and perceptual-motor skills of cognition.
http://www.ncbi.nlm.nih.gov/pubmed/10731625

The acute effects of d-amphetamine and methamphetamine on attention and psychomotor performance.
http://www.ncbi.nlm.nih.gov/pubmed/16761129

Amphetamine analogs methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) differentially affect speech.
http://www.ncbi.nlm.nih.gov/pubmed/19916063

Acute physiological and behavioral effects of intranasal methamphetamine in humans.
http://www.ncbi.nlm.nih.gov/pubmed/17851535

Subjective and physiological effects of acute intranasal methamphetamine during d-amphetamine maintenance.
http://www.ncbi.nlm.nih.gov/pubmed/21072503

 

[negrogesic]

I apologize for my remark last evening (I had a little too much egg nog, which when combined with a gram of pregabalin)......

"While studies of the reinforcing effects of cocaine abound, few studies have investigated the acute effects of intranasal cocaine when inhaled from betwixt a prostitute's ass-cleft; in the following, we will evaluate......"

Look to be frank, I see no major additional deleterious health implications with a 20mg/day of d-METH (admin po and dosed as prescribed) when compared to a similarly 'effective' dose of d-AMP or mixed isomers-salts thereof (again assuming po, as prescribed). This being said, I think its somewhat clear that neither compounds are 'beneficial' from a toxicological standpoint.

 

[skillet]

Hehe, it was funny :D

 

[ebola?]

Off-topic:

I apologize for my remark last evening (I had a little too much egg nog, which when combined with a gram of pregabalin)......

It's cool. There's room for humor in here, as long as we continue to discuss specific psychopharmacology (and as long as it's funny). Besides, this is nothing compared to the time you got drunk on "technical grade ethanol" and started hitting on Jamshyd.

Look to be frank, I see no major additional deleterious health implications with a 20mg/day of d-METH (admin po and dosed as prescribed) when compared to a similarly 'effective' dose of d-AMP or mixed isomers-salts thereof (again assuming po, as prescribed).

Has anyone established a threshold for a non-neurotoxic level of meth use (as one can do in a rough sense for amphetamine)? It seems that methamphetamine causes axon pruning, neurotransmitter depletion, and cellular death at far lower doses (after controlling for potency).

So a nice helping of anti-oxidants couldn't hurt but would a MAO-I inhibitor hurt at low doses at least or make this feat possible?

l-deprenyl was found to prevent oxidative stress in rats given methamphetamine. However, due to unpredictable potentiation, this combination is not safe (or rather, you need to know exactly what the fuck you're doing to avoid a hospital visit).

ebola
ps: anyone notice that the abstract of the article ends with, "The implications of this situation are multiple..."? Who has time to say nothing when one has so few words with which to do so?

 

[Amu]

Obviously methamphetamine has a neurotoxic potential, I just think a lot of the conclusions on ex-meth users by those studies were assumptions and the article explained how, I don't think the point of starting the thread was to prove methamphetamine is "beneficial" just that there is some evidence against "neurotoxicity at all doses" which is the safe (and reasonable given almost everyone will slowly increase the dose) for harm reduction

 

[ebola?]

Right, and given this, I'm interested in what level of dosing is comparatively neurologically benign.

ebola

 

[Epsilon Alpha]

Right, and given this, I'm interested in what level of dosing is comparatively neurologically benign.

ebola

Around 0.5mg/kg is the upper limit of "safe for at least a few weeks" dosage I've seen in all my research. It could go up to as far as 0.75mg with the right supplements/environment/tolerance, but I wouldn't test my luck.

Can't for the life of me figure out if the same ratio applies to racemic or D/L mixes, but that's what I've found on D-amphetamine.

 

[shulsd33]

In no effort to discredit his work, Dr. Carl Hart has contributed to some admittedly curious studies in the past.....


partial list

Out of these studies, which do you find to be curious? I don't see anything wrong with the work he's done.

 

[Amu]

Right, and given this, I'm interested in what level of dosing is comparatively neurologically benign.

ebola

For d-methamphetamine, in situations where hyperthermia is not present and there is a fairly normal sleep/nutrition schedule, I think single doses of 10 mg for an average adult is comparatively benign, and I seriously doubt any permanent damage would occur, but from my research, there will still be some down regulation that would take a few weeks to perhaps even months to reverse, but this is seen with other stimulants too. Considering the half-life of d-meth, I think for users without tolerance, 20 mg/day d-meth is the dose you are wondering about, and perhaps up to 30-40 mg/day once tolerance has built and the brain's supply of anti-oxidants has adapted appropriately, this is all assuming hyperthermia is absent.

 

[ebola?]

but from my research, there will still be some down regulation that would take a few weeks to perhaps even months to reverse, but this is seen with other stimulants too.

Ah. Yes. I am not counting downregulation as damage, as this is the typical 'first pass' mechanism via which tolerance manifests, and one will easily observe tolerance 'even' with 10 mg / amphetamine / day. I operationalize "damage" as axon pruning or cellular death. 20-40 mg methamphetamine a day seems like a fairly forgiving upper limit, as even with solid tolerance, this would get me pretty solidly high.

ebola