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Methamphetamine neurotoxicity overstated

RavenLoon

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In the first paragraph on the Wikipedia page for methamphetamine, it says that meth is directly toxic to dopamine cells. This, I believe is misleading. And it seems like many people and self proclaimed authorities on drugs and this topics get this wrong. While MA has been shown in vivo to be toxic to cells, use in people and in animals has not at most recreational levels. Obviously we have a hard time testing this in people because of ethical standards, but we have a lot of animal data. In studies that analyze toxicity in rats, cell death is only shown when the animal is drug naive and given large doses intravenously over what for a human would be 3 - 4 days. When the rats are given smaller doses over that same time, no toxicity is shown, or when they are given these larger doses but have developed a tolerance, no toxicity is shown. And when rats are given SINGLE doses of even large amounts, no toxicity is shown. In humans the only evidence we can see of brain changes is in heavy long term users but we are not sure if this is all from cell death. Even if it is, many factors may come into play like lack of sleep over the years, lack of nutrients and anti oxidants, etc. We could just be looking at brains that have fewer dopamine cells because the brains have adjusted to having a large artificial supply of dopamine from the drug. We just don't know. But it is definitely a misleading statement to come out and say the drug is neurotoxic, period, because we know for a fact that in most doses that people use, it is not.
 
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In the first paragraph on the Wikipedia page for methamphetamine, it says that meth is directly toxic to dopamine cells. This, I believe is misleading. And it seems like many people and self proclaimed authorities on drugs and this topics get this wrong. While MA has been shown in vivo to be toxic to cells, use in people and in animals has not at most recreational levels. Obviously we have a hard time testing this in people because of ethical standards, but we have a lot of animal data. In studies that analyze toxicity in rats, cell death is only shown when the animal is drug naive and given large doses intravenously over what for a human would be 3 - 4 days. When the rats are given smaller doses over that same time, no toxicity is shown, or when they are given these larger doses but have developed a tolerance, no toxicity is shown. And when rats are given SINGLE doses of even large amounts, no toxicity is shown. In humans the only evidence we can see of brain changes is in heavy long term users but we are not sure if this is all from cell death. Even if it is, many factors may come into play like lack of sleep over the years, lack of nutrients and anti oxidants, etc. We could just be looking at brains that have fewer dopamine cells because the brains have adjusted to having a large artificial supply of dopamine from the drug. We just don't know. But it is definitely a misleading statement to come out and say the drug is neurotoxic, period, because we know for a fact that in most doses that people use, it is not.

Toxicity is always dependent on factors such as concentration and duration of exposure. Methamphetamine isn't any different. Whether or not methamphetamine produces deleterious effects at all doses has no bearing on its classification as a neurotoxin. There are doses of cyanide that are safe to ingest, but that doesn't change the fact that it is a poison.
 
First of all, even if the changes that occur in the brain are due to the reasons you mentioned (lack of sleep, nutrients, antioxidants etc), these are still indirect consequences of methamphetamine usage. Using methamphetamine will inevitably increase the chances of those events from occurring.

Even if the observed reduced number of dopaminergic cells can be thought of as a homeostatic response to the excess dopamine methamphetamine releases from neurons, these changes could be irreversible even upon cessation of methamphetamine usage.
 
Wishful thinking springs to mind. Just because some people (generally with good intentions) exaggerate the harms, or low concentrations cause limited harm, meth is still a neurotoxic compound.
 
It's curious how the motives of everyone who dares to say methamphetamine isn't as damaging as it is made it out to be are called into question. I am just looking at the science. No wishful thinking, I don't not use the drug. I did a few lines as a teenager and have known quite a few people who have used it. I am not saying it is not neurotoxic at all, but then again if you say every chemical compound that has a potential neurotoxic effect at certain doses is a neurotoxin the list would be quite long. Nearly every study on rats analyzing the toxicity of the drug shows at pretty various levels the drug does not cause toxicity. Now if it is not causing toxicity in animals at doses most people use, is it realistic to say come out and say it is a neurotoxin right off the bat in an encyclopedia article? Wouldn't it be more accurate to say it has the potential to neurotoxic at certain levels? There was even a recent study on methamphetamine as a treatment for traumatic brain injury, in which it was shown to blunt cell death and attenuate cognitive impairment when given in small doses after the injury. If it is effectively neurotoxic at all levels, then how could these results have been seen? This is definitely not what most people would consider a possible effect of a neurotoxin. When you say something is a neurotoxin, I think most people assume the the chemical, no matter the dose, will indiscriminately have an observable toxic effect. This is not the case with this drug
 
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When you say something is a neurotoxin, I think most people assume the the chemical, no matter the dose, will indiscriminately have an observable toxic effect. This is not the case with this drug
Yes, and most people don't understand much about toxicology. All neurotoxins function as you are describing. There is always a dose that is too low to produce neurotoxic effects.

The definition of a neurotoxin is a "toxin that is poisonous or destructive to nerve tissue". Notice there is no requirement that the chemical is neurotoxic at every conceivable dose. Valium isn't anxiolytic at every possible dose, but it is still classified as an anxiolytic. Cyanide isn't toxic at every conceivable dose, but it is still considered to be a toxin. And methamphetamine isn't neurotoxic at every conceivable dose but is still classified as a neurotoxin. The classification is correct because methamphetamine can produce neurotoxic effects.
 
Even under medical supervision intravenous meth use is devastating and can cause Parkinson like shaking along with a host of other neurological impairments. Just look at our old buddy Adolph hitter, he was a wreck after 6-8 years of almost daily meth use.
 
I am under the impression there is an increased incidence of Parkinson's in chronic meth abusers.

I agree that the harm of short term recreational use can be overstated but there are probably vulnerable individuals, people with genes increasing the risk of Alzheimer's (especially with predisposition to insomnia as is seen with interleukin polymorphisms), ASD and schizophrenia for example.
 
I too believe methamphetamine's role as a neurotoxic drug is way overstated, but it is bad for your teeth and ages your face (especially with respect to dark circles and wrinkles under the eyes) with chronic administration.
 
I too believe methamphetamine's role as a neurotoxic drug is way overstated, but it is bad for your teeth and ages your face (especially with respect to dark circles and wrinkles under the eyes) with chronic administration.

and even there i'd think that some of the effects are rather due to "tweaker lifestyle" and sleep deprivation rather than the drug itself and would not occur if people consumed meth like they do amp.
 
We agree. However my issue is not wether or not the drug can be classified as a neurotxiin, it is that there is no effort to be accurate when it comes to methamphetamine and its harms. It is fair game to sensationalize its effects however one wants. MDMA can be neurotoxic, but the first paragraph about it on Wikipedia does not start out by saying it is a neurotoxin. I think it is important to not further the sensationalization of meth and the stigma attached to it and it's users. Saying it is a neurotoxin, and not saying other drugs which can potentially be neurotoxic are, gives the impression that this drug is unique, and itis toxic at all levels which is not true, and furthers contributes to its demonization and the stigma of its users.Singling out this drug as neurotoxic and giving this impression, does nothing for harm reduction, and actually probably increases harm because people will not understand there are safer levels to use the drug at.
 
It's important to minimize the number of youth using methamphetamine because it can be so deleterious upon life direction and health. If this involves classifying it as a neurotoxin in the public eye even if it's not a severe so then I'm all for it, I don't think a good message to send to the youth is "meth isn't actually that bad".
 
Even under medical supervision intravenous meth use is devastating and can cause Parkinson like shaking along with a host of other neurological impairments. Just look at our old buddy Adolph hitter, he was a wreck after 6-8 years of almost daily meth use.

This is a little off topic but I think perfectly demonstrates how misinformation and sensationalization about this drug flourishes. In 2012, a book was written by a historian and medical doctor call Was Hitler Ill? By Hans-Joachim Neumann and Henrik Eberle. In it they reviewed all of the evidence, including the records kept by Hitlers Dr. Theodore Morell of all the drugs he gave Hitler. In the book they concluded that he may have been suffering from the beginnings of Parkinson's at the end of the war, but was not necessarily sick throughout the are, and was fully culpable for his actions. They determined also that he was only administered methamphetamine on a few occasions, mostly during Hitlers last days after he had lost the war. There is another book call High Hitler, by Norman Ohler that examines drug use by the third reich and Hitler, and he also says that he was given the drug on only a few occasions after reviewing the records. He talks a lot about pervatin which was the brand name for a meth pill that was given to the Nazi soldiers, but Ohler also concluded that Morell did not give Hitler pervatin and Hitler did not take it.

This meme that Hitler was a meth addict is not supported by any evidence, it is just based on speculation by some addiction specialists, and has been allowed to flourish because it is sensational and nobody has any motive to correct it. Articles that came out in the dozens after these books were written a couple years ago would be titled like Hitlers Secret Crystal Meth Addiction, But when you actually read the articles they would go on to say that the records show he was give it a couple times, and again in his dying days.

And as far as meth causing Parkinson's like symptoms, this has only been observed in the heaviest long term addicts who are typically older. Parkins patients have a significant drop in dopamine levels and cells compare to the general population, like a 60% to 80% decrease. Heavy meth addicts have been shown to have between a 10% to 20% decrease on average. These are people who use hundreds to thousand of miligrams a day over years, and most have very little cognitive impairment when compare to non users of similar age and education. Parkinson's is only observed at decreases of dopamine cells and binding in very high levels like 50 - 60%. When meth addicts quit, after a year or so, even those who had higher decreases in dopamine binding, return to normal dopamine binding and levels. So it is only really in the heaviest older addicts do you see any symptoms resembling Parkinson's, this is extremely rare.

Now even if Hitler was given methamphetamine more often than it would seem from Morells records, the levels at which the drug was administered or given by physicians at the time were very low, like 5-15milligrams. And the doses in pervatin only contained 3 milligrams. These doses are very small and small oral doses of meth have been shown to have no distinguishable differences to the effects d-amphetamine, the drug that was given to U.S. and British soldiers during the war, also the active drug in adderal. Considering addicts use 100's of milligrams a day for decades, and don't show Parkinson's like symptoms, it would be highly unlikely that someone given levels that are prescribed to people for adhd are given, would suffer from these kind of symptoms. JFK was administered methamphetamine by his German born dr. Max Jacobson, aka Dr. Fell good for years, did he have Parkinson's like symptoms?

The point is there is no conclusive evidence that Hitler was regularly given this drug. But the sensationalism goes unchecked because who wants to take the time to correct misinformation about Hitler or meth?
 
Yes, and most people don't understand much about toxicology. All neurotoxins function as you are describing. There is always a dose that is too low to produce neurotoxic effects.

The definition of a neurotoxin is a "toxin that is poisonous or destructive to nerve tissue". Notice there is no requirement that the chemical is neurotoxic at every conceivable dose. Valium isn't anxiolytic at every possible dose, but it is still classified as an anxiolytic. Cyanide isn't toxic at every conceivable dose, but it is still considered to be a toxin. And methamphetamine isn't neurotoxic at every conceivable dose but is still classified as a neurotoxin. The classification is correct because methamphetamine can produce neurotoxic effects.

So using this line of reasoning, diazepam is also a neurotoxin because you could find a concentration at which it'd cause death of nerve tissue, whether direct or indirect. And it's also a toxin, because there is a dose at which it can be fatal - or something along those lines. Dihydrogen monoxide isn't toxic at all doses either, but there is a dose at which it can be fatal. So water's a toxin now?

The reason this is stupid is because it doesn't describe the substance appropriately, can be misleading, and as can be shown, almost any classification can be applied to almost any substance if concentration/dose is irrelevant, thus rendering the whole practice of classification of substances pointless/redundant.

My point being, this way amphetamine would have to be considered a neurotoxin as well. I don't have literature on hand, but IIRC there is dispute over which (amp or meth) is more neurotoxic (or at least that amp is of comparable neurotoxicity); you're probably more in-touch with the relevant literature, so you know better, but my point remains.

So reefer madness was appropriate to keep the kids off of weed? Let's use scare tactics, not realistic education and aim for harm reduction?

I have to agree with this. Spreading misinformation for the sake of harm reduction doesn't have a good track record of producing desirable results. I want to keep the youth off meth as much as the next guy, but scare tactics is not the way to do it.
 
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˄ This.

"Sola dosis fat venenum" might be a 500 year-old adage, but it's no less true today than it was when formed. Add in the extremely non-linear effects of some substances and the dose at which they might be encountered becomes all-important.
 
So reefer madness was appropriate to keep the kids off of weed? Let's use scare tactics, not realistic education and aim for harm reduction?

So reefer madness was appropriate to keep the kids off of weed? Let's use scare tactics, not realistic education and aim for harm reduction?

I don't think it's that important to keep kids off of weed though. Weed is not going to cause the same degree of issues as methamphetamine. It's not a stretch of the term to say meth is a neurotoxin. Convincing people that everyone who smokes weed will go completely batshit crazy isn't the same thing as saying that meth can be harmful to your brain cells.

The semantics of "meth IS a neurotoxin" vs. "meth CAN BE" a neurotoxin is important to think about but for the general public my vote is I think it's more important to have the label be "meth is a neurotoxin". I understand that it can take a while for the antioxidant defenses of the dopamine nerve terminals to get overwhelmed and for actual terminal loss to occur but because you can't know when exactly that's starting to occur in a real human it's probably better to err on the side of caution when concerning what we project to youth.
 
From what I heard and read even amphetamine is neurotoxic cause it increases oxidative stress and damages dopamine neurons if I remember it correctly. Then methamphetamine is probably even worse.
 
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. 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. Even weed has potential harms, it has been shown to increase the possibility of schizophrenia, particularly in adolescent females, although this is highly unlikely. But to define the drug as causing schizophrenia is absolutely bonkers.
 
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