Methamphetamine neurotoxicity overstated

[Cotcha Yankinov]

I think they key point is that THC is probably not directly neurotoxic to neurons at physiologic levels while methamphetamine itself can enter the nerve terminal and cause damage, so if THC causes reduction of neurogenesis just because of CB1 signaling consequences then that doesn't classify it as a neurotoxin (and this applies to other drugs of course).

So for example I think MDMA should be classified as a neurotoxin as well (even though there are prerequisites for it to be neurotoxic such as elevated temperature and serotonin depletion) if it or its metabolites are directly causing the damage to the serotonin nerve terminals that we see in animals and might possibly be seeing some tentative evidence of in humans.

The issue with declaring most drugs neurotoxins (i.e antipsychotics, which genuinely do help many people) in the public scope is that we need to emphasize to the public the drugs that have more consequences and not scare them away from drugs that might be classified as neurotoxic academically but maybe their neurotoxicity is not too relevant to human users. So it's a boy who cried wolf scenario. It's great that you have self control as far as your usage patterns/lifestyle but a lot of people aren't like that and it's best that meth is viewed as a serious drug to keep people from ever starting down that road. This isn't the type of situation where the government is trying to keep people off psychedelics because they're causing people to "wake up".

Has it occurred to you that as a meth user you might be somewhat in denial of the potential for meth to cause some degree of harm even at your current usage level? The whole point of having many study participants and carefully sifting through the data is to find minute differences, so even if the participants themselves can't tell that they've suffered from consequences of drug use, the study can try to pick up on it. Especially if we're talking about how this will affect you in your old age. I think there are many diseases and processes that take a long time to progress to the point of presentation.

Maybe you will pay for your meth use with earlier presentation of neurodegenerative disease for example, but that's not something you will know now. You are a consenting adult and I believe you should be able to do whatever you like drug ingesting wise, but for now I stand fast behind my opinion that the minors need to get a message that says meth is no bueno. Labeling meth a neurotoxin in the public sphere is not an inappropriate way to achieve delivering that message.

 

[Black]

I think they key point is that THC is probably not directly neurotoxic to neurons at physiologic levels while methamphetamine itself can enter the nerve terminal and cause damage, so if THC causes reduction of neurogenesis just because of CB1 signaling consequences then that doesn't classify it as a neurotoxin (and this applies to other drugs of course).

So for example I think MDMA should be classified as a neurotoxin as well (even though there are prerequisites for it to be neurotoxic such as elevated temperature and serotonin depletion) if it or its metabolites are directly causing the damage to the serotonin nerve terminals that we see in animals and might possibly be seeing some tentative evidence of in humans.

you mean because there is some neurotoxicity when giving animals ten times the dose needed to show signs comparable to humans? doses that in fact are just a little below the lethal dose? (and even then you need the animals to be hyperthermic to observe any damage)
because other than that, the evidence for mdma's neurotoxicity is roughly as good as the evidence for cannabis' neurotoxicity

 

[CFC]

you mean because there is some neurotoxicity when giving animals ten times the dose needed to show signs comparable to humans? doses that in fact are just a little below the lethal dose? (and even then you need the animals to be hyperthermic to observe any damage)
because other than that, the evidence for mdma's neurotoxicity is roughly as good as the evidence for cannabis' neurotoxicity

Rodents need to be given ten times the dose because their metabolisms are much faster.

 

[serotonin2A]

Then say all drugs are neurotoxins, outside of a select few,(such as weed) because most of them can be toxic to certain types of brain cells in some way.

There are semantic issues here -- whether or not all drugs act as neurotoxins depends on how neurotoxicity is defined. If we limit the definition to structural damage to neurons, then most drugs are not neurotoxic. But if we use a looser definition that includes temporary derangement of normal neural functioning, then many drugs are neurotoxic. But the latter type of neurotoxicity is reversible and not necessarily dangerous.

We should be accurate about the effects of all drugs so that all of those who are going to use them, use them safely. If someone is going to use meth, they should know not to use at certain levels, for certain durations. It doesn't help to say it is just toxic, because they they might use at levels that are toxic thinking,"well it's toxic at all levels anyway" Or when they use it and nothing bad happens think, "all this toxic talk is bullshit, nothing happened so I'll just use it however I want" and end up using it at toxic levels. People should know how to use this drug safely, and this is possible. The realistic harms are cardiovascular issues, amphetamine psychosis, and yes toxicity , all of which come from use in very high levels over extended periods of time and binge use.

It is not possible to predict the exact conditions that will lead to toxicity across the entire population. We don't really have any type of model that can be used to predict methamphetamine-induced neurotoxicity in humans -- the types of studies required to develop models of methamphetamine neurotoxicity violate medical ethics.

 

[Black]

Rodents need to be given ten times the dose because their metabolisms are much faster.

interspecies scaling doesn't work the same for all substances. it fails dramatically for drugs that have markedly nonlinear pharmacokinetics such as mdma. you only achieve comparable concentrations of mdma and its metabolites as well as comparable effects of the drug when you give comparable doses. rats and humans react to the same mg/kg dosages in drug discrimination studies.
source.

 

[Jonneh]

...if we use a looser definition that includes temporary derangement of normal neural functioning, then many drugs are neurotoxic. But the latter type of neurotoxicity is reversible and not necessarily dangerous.

What constitutes 'structural' damage? Much of that will be reversible too.

It's like the 'China study' in epidemiology - if broccoli turns out to be cancerous, too bad for the theory.

 

[Dresden]

A recent study showed that heavy weed use reduces vocabulary and cognition and that the longer you smoke it and kore of it, the more noticeable are these effects.

I like thc as much as the next guy, but get real, all drugs are neurotoxic at the wrong dose, and weed is a drug.

I don't understand how daily weed smokers can be so oblivious to any suggestion that it can have deleterious effects but oh lord meth is pure evil!!! Meth is actually not that bad if you only dose once or twice and then comedown, taking an antipsychotic and some benadryl or benzos for the comedown.

Moderation! But seriously, my point is that weed IS a drug, all drugs that get you high are basically bad for you if misused at too high a dosage level, and that methamphetamine's reputation is way worse than its reality, either acute of an overdose or chronically.

Like I said, it's not good for your teeth and will age you faster if you don't get your beauty rest, but overall methamphetamine is a damn good, relatively safe drug that will keep you high for a long time. All drugs--including weed--should be respected!!!

 

[white55]

>The issue with declaring most drugs neurotoxins (i.e antipsychotics, which genuinely do help many people) in the public scope is that we need to emphasize to the public the drugs that have more consequences and not scare them away from drugs that might be classified as neurotoxic academically but maybe their neurotoxicity is not too relevant to human users.

Except that antipsychotics are pure poison. A supposedly low dose intended to calm me down made me extremely aggressive (I basically wanted torture/rape/kill everyone who was part of the hospital staff) for a few hours (until they gave me even more of them + benzos and knocked me out), unable to pronounce words (I could form a complete sentence in my head but when I tried to say anything nothing would come out of my mouth.... writing and understanding others was unaffected) for a few days and barely able to walk for a few more days (at first I basically had to be carried since my limbs would not obey me, later I just walked really funny and couldn't look down while walking since my head was constantly being pulled up... if I stopped walking I could move my head normally... in the end I used my arms to point my head straight forward while walking) . All of that from a few supposedly low doses of risperidone. So fuck antipsyhotics and the doctors/nurses who gave them to me, if I could do it without getting caught I would gladly do some very bad things to them and their loved ones.

 

[Ligaturd]

Our subjective experiences are not scientifically valid facts. Neuroleptics can be toxic and have been for a great many people but the newer atypical anti-psychotics used responsibly and for short periods aren't "pure poison" and help many people, myself included. Many people can have adverse reactions to any given drug, that only proves that isn't a good drug for them individually. No drug can make someone rape or torture someone, those would be impulses innate within the user beforehand.

 

[serotonin2A]

What constitutes 'structural' damage? Much of that will be reversible too.

Loss of synapses, fiber degeneration, or cell death. Often these changes are not completely reversible. There may be some compensation, but that isn't always the case.

 

[CFC]

I'm not pretending this is an exhaustive search by any means, I just flicked through paper titles on my HD. But these mostly analyse meth toxicity/harms in actual human users/ex-users rather than theorised via lab animals or in vitro cell models:


Neurotoxicity of drugs of abuse - the case of methylenedioxy amphetamines (MDMA, ecstasy ), and amphetamines
Euphrosyne Gouzoulis-Mayfrank (2009)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181923/

*Acknowledges dangers of using purely lab studies, attempts to summarise from mostly human studies, also MDMA.



Neurologic manifestations of chronic methamphetamine abuse
Daniel E. Rusyniak (2012)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148451/

*Summary, mostly from human studies.



Increased risk of Parkinson's disease in individuals hospitalized with conditions related to the use of methamphetamine or other amphetamine-type drugs
Russell C. Callaghan, James K. Cunningham, Jenna Sykes, Stephen J. Kish (2012)

http://www.drugandalcoholdependence.com/article/S0376-8716(11)00276-6/abstract



Incidence of Parkinson's disease among hospital patients with methamphetamine-use disorders
Callaghan, R. C., Cunningham, J. K., Sajeev, G. and Kish, S. J. (2010)

http://onlinelibrary.wiley.com/doi/10.1002/mds.23263/full



Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers
Johanson, C., Frey, K.A., Lundahl, L.H. et al. (2006)

http://link.springer.com/article/10.1007/s00213-006-0330-6



Association of Dopamine Transporter Reduction With Psychomotor Impairment in Methamphetamine Abusers
Nora D. Volkow, M.D., Linda Chang, M.D., Gene-Jack Wang, M.D., Joanna S. Fowler, Ph.D., Maria Leonido-Yee, M.D., Dinko Franceschi, M.D., Mark J. Sedler, M.D., S. John Gatley, Ph.D., Robert Hitzemann, Ph.D., Yu-Shin Ding, Ph.D., Jean Logan, Ph.D., Christopher Wong, M.S., and Eric N. Miller, Ph.D. (2001)

http://ajp.psychiatryonline.org/doi/abs/10.1176/appi.ajp.158.3.377



Cognitive Performance of Current Methamphetamine and Cocaine Abusers
Sara L. Simon PhD , Catherine P. Domier BA , Tiffanie Sim BA , Kimberly Richardson BS , Richard A. Rawson PhD & Walter Ling MD (2008 )

http://www.tandfonline.com/doi/abs/10.1300/J069v21n01_06

 

[Cotcha Yankinov]

^I believe those were some of the studies I was recalling when I mentioned increased incidence of Parkinson's in meth users - I imagine the observational issue there is that most severe meth users aren't going to live long enough for Parkinson's disease to reach critical mass and become symptomatic (I believe you have to lose about 80% of the relative dopaminergic cells before you become symptomatic).

So the destructive effects to dopamine could be occurring in most addicts given the proper length of binges but are just not able to be identified very often by virtue of Parkinson's symptoms before the meth addict dies of other causes.

 

[Jonneh]

Loss of synapses, fiber degeneration, or cell death. Often these changes are not completely reversible. There may be some compensation, but that isn't always the case.

Surely. There's plenty of nuance to be had though. We lose a ton of synapses during sleep for normalisation purposes - if a drug enhances or mimics this process, is it to be considered a neurotoxin? How are we to know if synapse loss is non-specific or otherwise by chucking some on some primary neurons and checking their morphology?

 

[AlphaMethylPhenyl]

I think that it's not always entirely bad, but only in the extremely treatment-resistant narcoleptic/adhd cases. Even then, the max recommended dose is like 25mg.

There are a lot of factors that go into if a drug is neurotoxic, a lot of factors that overlap, but which nevertheless contirbute to neurotoxicity.

For instance, if meth has significant impurities, is expensive, and the user has a demanding work/academic life, it will ipso facto be less toxic. But we rarely see these things.

 

[CFC]

^I believe those were some of the studies I was recalling when I mentioned increased incidence of Parkinson's in meth users - I imagine the observational issue there is that most severe meth users aren't going to live long enough for Parkinson's disease to reach critical mass and become symptomatic (I believe you have to lose about 80% of the relative dopaminergic cells before you become symptomatic).

So the destructive effects to dopamine could be occurring in most addicts given the proper length of binges but are just not able to be identified very often by virtue of Parkinson's symptoms before the meth addict dies of other causes.

A lot of these people had symptoms, it didn't require them to be near death before effects were noticed. The brain has amazing plasticity, so you can be certain that by the time you're experiencing PD-type symptoms, a hell of a lot of damage has been caused.

The first two papers (which are free) also provide a decent, non-sensationalist summary of long-term damage (in various facets) in frequent meth users in different countries.

I actually think the problem with meth is that it doesn't appear to be overly harmful in the short-term. Most people recover (superficially at least) from moderate abuse after 3-6 months. Leading people to assume that it's much less harmful than the horror stories would have you believe.

This is, of course, one of the major criticisms of showing pictures of people with rotten teeth and mangled faces from meth addiction - it's so extreme it bears no resemblance to the 'average' meth abuser. And if this is what OP means by neurotoxicity being overstated, then yes I agree.

But then you unfortunately create a seemingly legitimate arena for contrary (and perhaps self-serving) voices standing up for their drug of choice, claiming it causes insignificant long-term harm, despite the weight of research.

Lots of people use anecdote to argue meth doesn't cause much harm. So my own anecdote would be the almost 2 years I spent volunteering to help recovering addicts, about half of whom were from meth. All had some degree of memory problem and chronic anhedonia, most had some kind of aphasia (basically word loss), and most complained they couldn't 'think' or articulate as before (were 'dumb'). Some felt like their brains were now just a shell of their former selves.

However physically, many looked just fine - skin usually ok, teeth actually no worse than most, some slim, some fat - nothing out of the ordinary really...

 

[RavenLoon]

It is not possible to predict the exact conditions that will lead to toxicity across the entire population. We don't really have any type of model that can be used to predict methamphetamine-induced neurotoxicity in humans -- the types of studies required to develop models of methamphetamine neurotoxicity violate medical ethics.

I agree, but we do have a lot of info to go on. For example, as I have stated, in nearly every rodent model that studies methamphetamine toxicity shows that toxicity only appears after extended dosing periods of doses higher than 2 mg/kg introveneously. Specifically 4 doses 2 hours apart. For an 150 lb person, when adjusting for human metabolism compared to rodent and converting dosages based on weight, this would be equivalent to around 140 mg's introveneously every 20 hours, 4 times. (MA half life being 1 hour for rodents, about 12 for humans) So the person would be likely staying awake for nearly 80 hours, and have used over 500 mg's in less than 4 days. An important factor in this is that the rat cannot have been given meth before. If the rat has tolerance, the toxicity is minimal to non existent, and if the rat has been pretreated in the past, the toxicity is is completely attenuated. So really, it would be a human using at these levels the first time he used the drug to reach this kind of toxicity. How many people are going to shoot up this drug in large doses and stay up for this long without having used the drug a few times before? And if you consider most people smoke or snort this drug, the biovailability of these routes of administration are much lower 90% and 80% respectively, so one would have use much more of the drug to get this amount in there bloodstream. Also, they can only achieve toxicity if the rat is hyperthermic for so long, hence the repetitive doses over extended periods of time. We can give rodents huge doses, like something that would be comparable to 500 mg's introveneously for a 150 lb person, if it is just a single dose, and they will not experience toxicity.

Now of course there is species variation but if anything, it is likely that humans don't suffer toxicity from meth as easily and severely as rodents. Consider the heaviest addicts who use introveneously for more than 10 years at 100's to 1000's of mg's a day, show about a 20 - 25% drop in dopamine binding (which we are not really sure why). A rat, not pretreated or with tolerance,given the 4 times 2 mg/kg dosing every 2 hours, will suffer a nearly 30% drop in dopamine binding from just these 4 doses.

Obviously it is cause for concern that an addict who uses this much sufferesthis much of a brain change, which is why education is important. There are a lot of dangers that come with meth use, potential for amphetamine psychosis when used in high levels for extended periods of time, cardiovascular issues, the potential for toxicity, but there is no evidence that using the the drug say in small to moderate recreational levels say a few times a month would have any kind of neurotoxic effect. And there is actually evidence that normal doses are NOT causing toxicity. The dangers of neurotoxicity comes from binge like use when the user does not have a tolerance, using in very high amounts, or from prolonged chronic use. We should highlight this to reduce harm. If we taboo using the drug irresponsibly and in dangerous levels, instead of demonizing the drug altogether,( like alcohol) we will be better off.

And I don't want anyone to take this as me endorsing meth use or saying it is ok, it is an illegal substance, again with real dangers, and any drug off the street can be dangerous. I am just trying to highlight how we sensationalize its effects and the negatives that emerge from this.

 

[RavenLoon]

I'm not pretending this is an exhaustive search by any means, I just flicked through paper titles on my HD. But these mostly analyse meth toxicity/harms in actual human users/ex-users rather than theorised via lab animals or in vitro cell models:


Neurotoxicity of drugs of abuse - the case of methylenedioxy amphetamines (MDMA, ecstasy ), and amphetamines
Euphrosyne Gouzoulis-Mayfrank (2009)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181923/

*Acknowledges dangers of using purely lab studies, attempts to summarise from mostly human studies, also MDMA.



Neurologic manifestations of chronic methamphetamine abuse
Daniel E. Rusyniak (2012)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148451/

*Summary, mostly from human studies.



Increased risk of Parkinson's disease in individuals hospitalized with conditions related to the use of methamphetamine or other amphetamine-type drugs
Russell C. Callaghan, James K. Cunningham, Jenna Sykes, Stephen J. Kish (2012)

http://www.drugandalcoholdependence.com/article/S0376-8716(11)00276-6/abstract



Incidence of Parkinson's disease among hospital patients with methamphetamine-use disorders
Callaghan, R. C., Cunningham, J. K., Sajeev, G. and Kish, S. J. (2010)

http://onlinelibrary.wiley.com/doi/10.1002/mds.23263/full



Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers
Johanson, C., Frey, K.A., Lundahl, L.H. et al. (2006)

http://link.springer.com/article/10.1007/s00213-006-0330-6



Association of Dopamine Transporter Reduction With Psychomotor Impairment in Methamphetamine Abusers
Nora D. Volkow, M.D., Linda Chang, M.D., Gene-Jack Wang, M.D., Joanna S. Fowler, Ph.D., Maria Leonido-Yee, M.D., Dinko Franceschi, M.D., Mark J. Sedler, M.D., S. John Gatley, Ph.D., Robert Hitzemann, Ph.D., Yu-Shin Ding, Ph.D., Jean Logan, Ph.D., Christopher Wong, M.S., and Eric N. Miller, Ph.D. (2001)

http://ajp.psychiatryonline.org/doi/abs/10.1176/appi.ajp.158.3.377



Cognitive Performance of Current Methamphetamine and Cocaine Abusers
Sara L. Simon PhD , Catherine P. Domier BA , Tiffanie Sim BA , Kimberly Richardson BS , Richard A. Rawson PhD & Walter Ling MD (2008 )

http://www.tandfonline.com/doi/abs/10.1300/J069v21n01_06

Yeah, there have been a lot of studies on chronic users of the drug and I am aware that most of them conclude that there is congnitive decline associated with chronic uses. These studies can point to toxicity,but again, only in heavy long term addicts, which account for only about 15% of users. There are some comprehensive studies showing that a lot of these researchers don't account for important facotors like age and education level, and when they facotors are accounted for the methamphetamine users score in normal ranges. But I don't think there is really any kind of surprise that people with the lifestyle of a heavy addict of any drug, would score worse in cognitive tests. The Parkinson's stuff is interesting, but I have read evidence to the contrary, and again only heavy long term addicts, and I am not arguing that this isn't harmful in some way. I and specifically talking about how 85% of the population uses the drug, and if there are levels that can be used that are not neurotoxic, when clearly there are. There are no studies on people who do a couple lines a few times a month over a couple years. If you look at studies on cognitive decline and conditions of heavy long term alcoholics, you will get a pretty skewed perspective on alcohol.

 

[serotonin2A]

Surely. There's plenty of nuance to be had though. We lose a ton of synapses during sleep for normalisation purposes - if a drug enhances or mimics this process, is it to be considered a neurotoxin?

I'm not talking about the loss of just a synapse, I'm talking about loss of a synapse and all of its associated axons back to the cell body, or even loss of the neuron. Synaptic pruning happens all the time but degeneration of axons is not a normal process in the adult brain. In normal pruning, the synapses and axons don't die but rather "re-grow" in a different shape/physical orentation. By contrast, when synapses/axons degenerate, they swell up, many of the proteins become denatured, and normal biochemical function ceases. The process of degeneration leaves evidence in the form of markers that can detected, so it is possible to differentiate degeneration from normal pruning..

How are we to know if synapse loss is non-specific or otherwise by chucking some on some primary neurons and checking their morphology?

You can stain for a specific marker of degeneration and/or check the morphology of the cell and its processes.

I agree, but we do have a lot of info to go on. For example, as I have stated, in nearly every rodent model that studies methamphetamine toxicity shows that toxicity only appears after extended dosing periods of doses higher than 2 mg/kg introveneously. Specifically 4 doses 2 hours apart. For an 150 lb person, when adjusting for human metabolism compared to rodent and converting dosages based on weight, this would be equivalent to around 140 mg's introveneously every 20 hours, 4 times. (MA half life being 1 hour for rodents, about 12 for humans) So the person would be likely staying awake for nearly 80 hours, and have used over 500 mg's in less than 4 days. An important factor in this is that the rat cannot have been given meth before. If the rat has tolerance, the toxicity is minimal to non existent, and if the rat has been pretreated in the past, the toxicity is is completely attenuated. So really, it would be a human using at these levels the first time he used the drug to reach this kind of toxicity. How many people are going to shoot up this drug in large doses and stay up for this long without having used the drug a few times before? And if you consider most people smoke or snort this drug, the biovailability of these routes of administration are much lower 90% and 80% respectively, so one would have use much more of the drug to get this amount in there bloodstream. Also, they can only achieve toxicity if the rat is hyperthermic for so long, hence the repetitive doses over extended periods of time. We can give rodents huge doses, like something that would be comparable to 500 mg's introveneously for a 150 lb person, if it is just a single dose, and they will not experience toxicity.

You can't directly compare rat and human doses like you are trying to do. Interspecies scaling exists to correct for cross-species PK differences, but doesn't account for pharmacodynamic differences. There are often differences in binding affinity and efficacy across species, meaning that rats may require higher methamphetamine blood levels than humans to produce equivalent effects in the CNS. Rats also have stronger detoxification mechanisms than humans. It is very possible that the rat doses you described are perfectly relevant to humans.

Now of course there is species variation but if anything, it is likely that humans don't suffer toxicity from meth as easily and severely as rodents. Consider the heaviest addicts who use introveneously for more than 10 years at 100's to 1000's of mg's a day, show about a 20 - 25% drop in dopamine binding (which we are not really sure why). A rat, not pretreated or with tolerance,given the 4 times 2 mg/kg dosing every 2 hours, will suffer a nearly 30% drop in dopamine binding from just these 4 doses.

There isn't really any point to try to compare the % change in humans and rats because the functional implications are likely to be far different. A 25% drop in dopamine binding may be enough to produce functional impairments. It also could hasten the onset of Parkinson's disease in someone predisposed.

Obviously it is cause for concern that an addict who uses this much sufferesthis much of a brain change, which is why education is important. There are a lot of dangers that come with meth use, potential for amphetamine psychosis when used in high levels for extended periods of time, cardiovascular issues, the potential for toxicity, but there is no evidence that using the the drug say in small to moderate recreational levels say a few times a month would have any kind of neurotoxic effect. And there is actually evidence that normal doses are NOT causing toxicity. The dangers of neurotoxicity comes from binge like use when the user does not have a tolerance, using in very high amounts, or from prolonged chronic use. We should highlight this to reduce harm. If we taboo using the drug irresponsibly and in dangerous levels, instead of demonizing the drug altogether,( like alcohol) we will be better off.

And I don't want anyone to take this as me endorsing meth use or saying it is ok, it is an illegal substance, again with real dangers, and any drug off the street can be dangerous. I am just trying to highlight how we sensationalize its effects and the negatives that emerge from this.

I think you are generalizing way too much. First, we as a society tolerate some potential risk from amphetamines since they are prescribed drugs. So it's not like these drugs are absolutely and completely demonized by medical professionals. Most people who work in the field do focus on addicts since they are the ones likely to sustain harms, and they by far use the bulk of the amphetamine sold. But it is important to also focus on recreational use because that is where the pool of addicts is derived from. The message has to be addressed to recreational users because that population needs to be warned about the potential dangers associated with excessive use.

 

[Jonneh]

I'm not talking about the loss of just a synapse, I'm talking about loss of a synapse and all of its associated axons back to the cell body, or even loss of the neuron. Synaptic pruning happens all the time but degeneration of axons is not a normal process in the adult brain.

It absolutely isn't, of course. Axonal swelling and blebbing (and incident destruction of synapses) usually leads to cell death, so it's like citing loss of capillaries with death of a salesman! I thought synapse loss alone was used as evidence of neurotoxicity. Good to have the record set straight.

 

[CFC]

Yeah, there have been a lot of studies on chronic users of the drug and I am aware that most of them conclude that there is congnitive decline associated with chronic uses. These studies can point to toxicity,but again, only in heavy long term addicts, which account for only about 15% of users. There are some comprehensive studies showing that a lot of these researchers don't account for important facotors like age and education level, and when they facotors are accounted for the methamphetamine users score in normal ranges. But I don't think there is really any kind of surprise that people with the lifestyle of a heavy addict of any drug, would score worse in cognitive tests. The Parkinson's stuff is interesting, but I have read evidence to the contrary, and again only heavy long term addicts, and I am not arguing that this isn't harmful in some way. I and specifically talking about how 85% of the population uses the drug, and if there are levels that can be used that are not neurotoxic, when clearly there are. There are no studies on people who do a couple lines a few times a month over a couple years. If you look at studies on cognitive decline and conditions of heavy long term alcoholics, you will get a pretty skewed perspective on alcohol.

You've made a few claims but provided no evidence. I do accept that research on light recreational users isn't adequate, but how do you come to your 15% heavy users vs 85% "two-lines a few times a month" ratio?

If you're going by anecdote, you're being a bit disingenuous: even the most conservative often end up doing weekend party binges, it's the addictive nature of the drug.

If your argument is simply that therapeutic doses don't appear to cause much harm, that's not really disputed. But that's also not supporting your speculation that neurotoxicity is overstated, since few recreational users follow therapeutic dosing patterns.