DXM & MK-801 protect against methamphetamine-induced neurotoxicity

[Wickedelic]

"MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity

Methamphetamine causes long-term toxicity to dopamine nerve endings of the striatum. Evidence is emerging that microglia can contribute to the neuronal damage associated with disease, injury, or inflammation, but their role in methamphetamine-induced neurotoxicity has received relatively little attention. Lipopolysaccharide (LPS) and the neurotoxic HIV Tat protein, which cause dopamine neuronal toxicity after direct infusion into brain, cause activation of cultured mouse microglial cells as evidenced by increased expression of intracellular cyclooxygenase-2 and elevated secretion of tumor necrosis factor-alpha. MK-801, a non-competitive NMDA receptor antagonist that is known to protect against methamphetamine neurotoxicity, prevents microglial activation by LPS and HIV Tat. Dextromethorphan, an antitussive agent with NMDA receptor blocking properties, also prevents microglial activation. In vivo, MK-801 and dextromethorphan reduce methamphetamine-induced activation of microglia in striatum and they protect dopamine nerve endings against drug-induced nerve terminal damage. The present results indicate that the ability of MK-801 and dextromethorphan to protect against methamphetamine neurotoxicity is related to their common property as blockers of microglial activation."

https://www.researchgate.net/publication/7755652_MK-801_and_dextromethorphan_block_microglial_activation_and_protect_against_methamphetamine-induced_neurotoxicity

 

[Vastness]

Very interesting indeed, have read similar studies before, although honestly I have doubts how well they translate to human beings. There's a study showing brain scans of various polydrug users who used ketamine regularly, and those who combined with stimulants (typically MDMA - a less neurotoxic drug than methamphetamine by all means) showed greater changes that did not look desirable. That was ketamine though, admittedly, maybe these ones are somehow more selective in their protective actions somehow, or perhaps the level of protection is highly dosage dependent... For sure, it's good to see this sort of stuff and very promising, but more research is needed and no-one should be lulled into a false sense of security that they can protect themselves from damage as long as they remember to take their DXM with their meth.

 

[sekio]

so does this mean meth plus pcp is safer than either drug alone?

hold on let me get my "fighting with cops" outfit on and then see what happens

 

[vecktor]

so does this mean meth plus pcp is safer than either drug alone?

hold on let me get my "fighting with cops" outfit on and then see what happens

I thought it was traditional for pcp-meth cop fighting to be done naked? or is it too cold in Canada?

 

[Tricky_toes]

I thought it was traditional for pcp-meth cop fighting to be done naked? or is it too cold in Canada?

 

[polymath]

In this video they seem to not be very far in the north:

The arctic region cop-fighting outfit consists of a kevlar vest, iron knuckles, gas mask and a metal armor plate with protruding sharp spikes dipped in HIV and hep c infected blood covering your back.

 

[Lysergaman]

"MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity

Methamphetamine causes long-term toxicity to dopamine nerve endings of the striatum. Evidence is emerging that microglia can contribute to the neuronal damage associated with disease, injury, or inflammation, but their role in methamphetamine-induced neurotoxicity has received relatively little attention. Lipopolysaccharide (LPS) and the neurotoxic HIV Tat protein, which cause dopamine neuronal toxicity after direct infusion into brain, cause activation of cultured mouse microglial cells as evidenced by increased expression of intracellular cyclooxygenase-2 and elevated secretion of tumor necrosis factor-alpha. MK-801, a non-competitive NMDA receptor antagonist that is known to protect against methamphetamine neurotoxicity, prevents microglial activation by LPS and HIV Tat. Dextromethorphan, an antitussive agent with NMDA receptor blocking properties, also prevents microglial activation. In vivo, MK-801 and dextromethorphan reduce methamphetamine-induced activation of microglia in striatum and they protect dopamine nerve endings against drug-induced nerve terminal damage. The present results indicate that the ability of MK-801 and dextromethorphan to protect against methamphetamine neurotoxicity is related to their common property as blockers of microglial activation."

https://www.researchgate.net/publication/7755652_MK-801_and_dextromethorphan_block_microglial_activation_and_protect_against_methamphetamine-induced_neurotoxicity

According to Dr. Carl Hart, the head of NIDA, the potential for neurotoxicity from Methamphetamine is overstated. I don’t have a link, but I’m sure you can find a clip of him talking about it on YouTube. According to him, the neurotoxicity shown in animal models involves doses (Mg/Kg) that are significantly higher than a person without a tolerance would use recreationally, since the doses required would cause very unpleasant effects. When an individual does build a tolerance they also become more tolerant to the neurotoxic effects, and therefore can tolerate a higher dose. He also has a lot to say about the inaccuracies of brain scans comparing an addict with a control, but he can explain it much better than I can. I believe his conclusion was that although Methamphetamine has the potential to cause damage, the likelihood of it occurring and the severity of Neurotoxicity is exaggerated. And that more data is needed to make a definitive statement

 

[vecktor]

According to Dr. Carl Hart, the head of NIDA, the potential for neurotoxicity from Methamphetamine is overstated. I don’t have a link, but I’m sure you can find a clip of him talking about it on YouTube. According to him, the neurotoxicity shown in animal models involves doses (Mg/Kg) that are significantly higher than a person without a tolerance would use recreationally, since the doses required would cause very unpleasant effects. When an individual does build a tolerance they also become more tolerant to the neurotoxic effects, and therefore can tolerate a higher dose. He also has a lot to say about the inaccuracies of brain scans comparing an addict with a control, but he can explain it much better than I can. I believe his conclusion was that although Methamphetamine has the potential to cause damage, the likelihood of it occurring and the severity of Neurotoxicity is exaggerated. And that more data is needed to make a definitive statement

The trouble is that there is enough circumstantial evidence to warrant caution and moderation.
There is no reason why tolerance to the psychoactive effects should linked to tolerance to the neurotoxic effects so that is not a very sound basis to start from.
The more sensible approach is to take less methamphetamine rather than taking combos to try and mitigate the adverse effects of methamphetamine.

 

[Lysergaman]

The trouble is that there is enough circumstantial evidence to warrant caution and moderation.
There is no reason why tolerance to the psychoactive effects should linked to tolerance to the neurotoxic effects so that is not a very sound basis to start from.
The more sensible approach is to take less methamphetamine rather than taking combos to try and mitigate the adverse effects of methamphetamine.

This is a short segment of one of Dr. Harts lectures, and he starts talking about Brain Scans and Neurotoxicity around the 7:30 minute mark. He has another lecture where he goes into greater detail explaining the inaccuracies of brain scans, while also explaining the misuse of animal models, and the way tolerance to neurotoxic effects develop. But I’m pretty sure the lecture I’m thinking of is an hour+, and I havent had the time to watch through it to find the time stamps. I’m definitely no expert but it’s hard to find people who are more qualified than Dr. Hart, and I’m just going off of what he said. I completely agree that using a safe dose of Methamphetamine is safer than trying to mix drugs to mitigate potential harms. I also agree that caution is warranted, and I did say that Meth has the ability to cause damage. I’m not arguing that it doesn’t. Just that according to an international authority on that subject, the risk of brain damage is exaggerated by Law Enforcement and the Media.

 

[vecktor]

This is a short segment of one of Dr. Harts lectures, and he starts talking about Brain Scans and Neurotoxicity around the 7:30 minute mark. He has another lecture where he goes into greater detail explaining the inaccuracies of brain scans, while also explaining the misuse of animal models, and the way tolerance to neurotoxic effects develop. But I’m pretty sure the lecture I’m thinking of is an hour+, and I havent had the time to watch through it to find the time stamps. I’m definitely no expert but it’s hard to find people who are more qualified than Dr. Hart, and I’m just going off of what he said. I completely agree that using a safe dose of Methamphetamine is safer than trying to mix drugs to mitigate potential harms. I also agree that caution is warranted, and I did say that Meth has the ability to cause damage. I’m not arguing that it doesn’t. Just that according to an international authority on that subject, the risk of brain damage is exaggerated by Law Enforcement and the Media.

I don't think we disagree and I don't need to watch Dr Hart as I am more than capable of examining the evidence for myself.

 

[dopamimetic]

Physical brain safety != mental health

But well I remember my teenage years when I still was into booze, that DXM above a certain threshold (2nd plateau+ ?) was able to completely inhibit hangover... so there certainly is something about DXO and neuroprotection ...