Methamphetamine neurotoxicity overstated

[serotonin2A]

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.

If terminal degeneration is detected then that is definite evidence of neurotoxicity. But it is difficult to conclusively detect synaptic degeneration because terminals are so small and because conclusive evidence only exists for a short period. The most conclusive test for degeneration is an assay known as silver staining (silver ions bind to denatured cytoskeletal proteins). But to detect degenerating terminals, silver staining must be performed within 24 hours after the insult. Most studies wait longer than that because it is much more useful to look for axonal degeneration, which takes longer to develop but is much more useful for mapping degeneration.

Some people here may be familiar with silver staining because it was one of the methods used to detect Olney's lesions.

 

[Jonneh]

If terminal degeneration is detected then that is definite evidence of neurotoxicity. But it is difficult to conclusively detect synaptic degeneration because terminals are so small and because conclusive evidence only exists for a short period. The most conclusive test for degeneration is an assay known as silver staining (silver ions bind to denatured cytoskeletal proteins). But to detect degenerating terminals, silver staining must be performed within 24 hours after the insult. Most studies wait longer than that because it is much more useful to look for axonal degeneration, which takes longer to develop but is much more useful for mapping degeneration.

Some people here may be familiar with silver staining because it was one of the methods used to detect Olney's lesions.

That's interesting re axonal degradation. No doubt much drug-induced synapse loss is pathological, I just wanted to recognise that such changes can be part and parcel of the 'positive' effects of drugs, that synapse loss or LTD is not a bad thing per se, and LTP and spine growth is not necessarily a good thing. We tend to slip into dualistically viewing the mind as the 'place' where the changes take place, and the biology as a necessary substrate that above all shouldn't change (cf "will taking LSD change my brain?"), although I'm not saying you were guilty of such an attitude. Axonal degradation sounds like a good proxy for genuine damage.

I know silver staining well in its Golgi guise. It gives beautiful results for such a simple technique, and is perfect for counting spines, for example, or other applications where dynamic range of intensity is not an issue. How wonderful that it's still being used 140 years on.

 

[white55]

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.

Do note that I did not rape/torture/murder anyone... I just wanted to. But I still knew that I was (and still am not) in a position to do so successfully and so I have not done it.

However if the circumstances were right.......

(yes, I'm aware that I'm evil)

 

[xbandit07x]

Thats because we live to question and critique our moods. Ive seen people casually say they used to be a meth user and my first question to them is do you still feel the effects to this day and they shrug it off saying no. Here I am wondering if il ever be joyful again from just 40 dexedrine....

but I think regular Neurotypical people get away a lot easier with hardcore drug abuse. If you already have depression, anxiety, aspie symptoms you bet your ass Meths gonna fuck with you, or atleast your brain is already hardwired to overanlzye every single difference in how you feel that its goign to be jaw droppingly shitty.

 

[Seppi]

@OP: The lead of a Wikipedia article is supposed to summarize the content covered in the body of the article. It normally doesn't need to be, and is not, cited in most well-written Wikipedia articles; however, because I rewrote the vast majority of the methamphetamine article and since I normally cite article leads, I added a statement about that and cited a handful of the citations from the body that support that statement. If you want to read the entire body of evidence which was cited in the body of the methamphetamine article and supports the assertion that methamphetamine is neurotoxic, read the medical reviews in this section: https://en.wikipedia.org/wiki/Methamphetamine#Neurotoxicity_and_neuroimmune_response

 

[golego55]

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.

I know this is aside from neurotoxicity but as far as dosage effecting toxicity I will always remember a Katt Williams: "Aspirin is perfectly legal, but if you take 13 of them motherf***ers, it'll be your last headache.

 

[Neuroprotection]

this is a very controversial issue where for many, political opinions or semantics seems to play a bigger role than the science. personally, I believe meth is better labelled as a neurotoxin or at least a very harmful substance. I fully understand why people enjoy methamphetamine and I certainly don’t believe it kills large numbers of brain cells at typical doses in humans, even after a long time. however, it is wishful thinking to deny that it does result in large scale changes in long-term neurotransmitter balance including dopamine and glutamate receptor availability/sensitivity and neurotransmitter levels. Methamphetamine also strongly upregulates pro inflammatory cytokines, including IL-6 in the brain. some theorise this leads to cell death, but more recent studies Point out that these cytokines especially IL-6 actually dampen short-term glutamate sensitivity thus protecting against excitotoxicity. unfortunately, this also leads to greater mood instability including greater risk of depression/Anxiety.
Also, we should remember that massive dopamine release will certainly lead to long-term brain changes, not only neurological, but also in terms of our life decisions and our consciousness. some people go to extremes to demonise drugs, but we should not be hypocritical and try to pretend that Methamphetamine is A benign substance weather for children or adults. The same goes for amphetamine, weather medically prescribed or off the street, it can produce serious long-term psychiatric consequences. i’m definitely in favour of the neurotoxicity label being reviewed, but I’m totally against changing The current message sent out to the youth and even adults. some people may be OK with methamphetamine and live relatively normal lives, but unfortunately that’s not the truth for most people. unlike highly addictive opioids, amphetamines and particularly methamphetamine are rather aggressive drugs in that they are very taxing on the mind/body. they also have ridiculously long half lives which probably explains the severe insomnia scene with many abusers.