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Methamphetamine ageing and neurotoxicity

Sorry I forgot about your vision! It appears this is the study http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324822/ "Methamphetamine Accelerates Cellular Senescence through Stimulation of De Novo Ceramide Biosynthesis", and that the harm is ultimately through NF-KB to some degree, though I still question the role of Tau and amyloid beta in some patient populations.

"We report now that methamphetamine accelerates cellular senescence and activates transcription of genes involved in cell-cycle control and inflammation by stimulating production of the sphingolipid messenger ceramide. This pathogenic cascade is triggered by reactive oxygen species, likely generated through methamphetamine metabolism via cytochrome P450, and involves the recruitment of nuclear factor-κB (NF-κB) to induce expression of enzymes in the de novo pathway of ceramide biosynthesis. Inhibitors of NF-κB signaling and ceramide formation prevent methamphetamine-induced senescence and systemic inflammation in rats self-administering the drug, attenuating their health deterioration. The results suggest new therapeutic strategies to reduce the adverse consequences of methamphetamine abuse and improve effectiveness of abstinence treatments."

Is it curcumin too or just Coenzyme q10 that is a NF-KB inhibitor? I'm not aware of any pharmaceutical NF-KB inhibitors besides minocycline, which I'm not sure of it's potency - I think it's more of a microglial inhibitor but I'm still no sure if I would want to chance it seeing as I believe ALS patients declined faster on it and that if there is a relationship between ceramides and plaques then you would want your microglia up and running.
 
Cotcha Yankinov said:
Sorry I forgot about your vision! It appears this is the study http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324822/ "Methamphetamine Accelerates Cellular Senescence through Stimulation of De Novo Ceramide Biosynthesis", and that the harm is ultimately through NF-KB to some degree, though I still question the role of Tau and amyloid beta in some patient populations.

"We report now that methamphetamine accelerates cellular senescence and activates transcription of genes involved in cell-cycle control and inflammation by stimulating production of the sphingolipid messenger ceramide. This pathogenic cascade is triggered by reactive oxygen species, likely generated through methamphetamine metabolism via cytochrome P450, and involves the recruitment of nuclear factor-κB (NF-κB) to induce expression of enzymes in the de novo pathway of ceramide biosynthesis. Inhibitors of NF-κB signaling and ceramide formation prevent methamphetamine-induced senescence and systemic inflammation in rats self-administering the drug, attenuating their health deterioration. The results suggest new therapeutic strategies to reduce the adverse consequences of methamphetamine abuse and improve effectiveness of abstinence treatments."

Is it curcumin too or just Coenzyme q10 that is a NF-KB inhibitor? I'm not aware of any pharmaceutical NF-KB inhibitors besides minocycline, which I'm not sure of it's potency - I think it's more of a microglial inhibitor but I'm still no sure if I would want to chance it seeing as I believe ALS patients declined faster on it and that if there is a relationship between ceramides and plaques then you would want your microglia up and running.
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I would imagine that both curcumin and coenzyme Q 10 would inhibit this signalling pathway by acting as antioxidants and removing the reactive oxygen species and other toxic byproducts that would otherwise activate the pathway.
It may be that despite the many pathways involved in methamphetamine neurotoxicity, free radicals appear to come up repeatedly in investigations and are possibly the root cause of most or all pathways leading to neurotoxicity of stimulant drugss. If a small molecule, lipophilic, non toxic cell permeable antioxidant could be developed, we could see the back of methamphetamine neurotoxicity or at least the worst of it.
That's just my opinion on free radicals, I developed this opinion from reading about the various mechanisms of programmed cell death, where free radicals act as both the trigger for cell death and the bullet or means of execution of the cell.
 
shugenja said:
Actually -- IT DOES

Apparently Methamphetamine induces accelerated Cellular Senescence

http://www.ncbi.nlm.nih.gov/pubmed/25671639

It is caused by increased NFkB signalling -- NFkB blockade reduced the ceramide synthesis and accelerated senescense

NFkB is one of the MAJOR pro-inflammatory signalling pathways
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Most people here are probably concerned with effects on humans. There is certainly evidence indicating that such effects probably occur in humans, but as yet there has been no direct confirmation.

The effects noted in rats were at least partially dependent on metabolism by CYP. There are large species differences with CYP and some drug effects noted in rats do not occur in humans.
 
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I think Minocycline is definitely neuroprotective in a wide range of circumstances including amphetamine neurotoxicity. The main mechanism is thought to be suppression of microglia activation. However minocycline is not well understood and is an extremely powerful antibiotic, so needs to be taken with caution. I believe a few studies have used it as an add-on therapy for psychosis and schizophrenia, where it is believed to improve both positive and negative symptoms.
Amphetamine psychosis mimics the positive symptoms of schizophrenia The drug May be beneficial to stimulant users.
I wonder whether the drug di methyl fumarate would be a good neuroprotective. This compound is widely used to treat severe Multiple Sclerosis, it's mechanism of action is as an NRF2 activator. This causes drastically increased expression of antioxidant enzymes such as superoxide dismutase and catalase. In many studies amphetamine and related drugs have been shown to markedly reduced expression of antioxidant enzymes, and since endogenous antioxidant defence systems are by far the most powerful and accurate antioxidants known, increasing their expression in neurons via a small molecule may be a great idea.
 
serotonin2A said:
Most people here are probably concerned with effects on humans. There is certainly evidence indicating that such effects probably occur in humans, but as yet there has been no direct confirmation.

The effects noted in rats were at least partially dependent on metabolism by CYP. There are large species differences with CYP and some drug effects noted in rats do not occur in humans.
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Stress Induced Premature Senescence (SIPS) is a known process, caused by high levels of oxidative stress.

Ethanol induces Premature Senescence also mediated by NFkB. -- Alcoholics that do not combat the oxidative stress caused by ethanol are cellularly "older" than non-alcoholics, visibly look older, and are many times more likely to develop cancer.

Methamphetamine addicts that do not take high levels of antioxidants are likely -- cellularly "older"
 
Since meth speeds up the heart, I don't think there is a debate whether or not it ages you. You only get so many heartbeats during your life :)
 
shugenja said:
I hope that was an attempt at humor.
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There is an element of truth in this, in that the number of heartbeats across not only humans but all mammals in biology is roughly invariant (in the order of 10^9 heartbeats). This is a consequence of lifespan being proportional to the mass of an organism raised to a quarter power (lifespan=kM^0.25) and heart rate being proportional to mass of the organism raised to -0.25.

http://www.cs.cornell.edu/~ginsparg/physics/Phys446-546/gbwscl99.pdf
 
aced126 said:
There is an element of truth in this, in that the number of heartbeats across not only humans but all mammals in biology is roughly invariant (in the order of 10^9 heartbeats). This is a consequence of lifespan being proportional to the mass of an organism raised to a quarter power (lifespan=kM^0.25) and heart rate being proportional to mass of the organism raised to -0.25.

http://www.cs.cornell.edu/~ginsparg/physics/Phys446-546/gbwscl99.pdf
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Complete and utter bullshit. First of all the average human falsifies your theory -- at 70 Bpm (average) and 75 years of age = 2.7 Billion beats

Marie Calment, even if her average heart rate from infancy to death was only 50 bpm (like an elite athlete) had a heart that beat 3.2 Billion times -- as she live past 120 years.
 
shugenja said:
Complete and utter bullshit. First of all the average human falsifies your theory -- at 70 Bpm (average) and 75 years of age = 2.7 Billion beats

Marie Calment, even if her average heart rate from infancy to death was only 50 bpm (like an elite athlete) had a heart that beat 3.2 Billion times -- as she live past 120 years.
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Lmao, ever heard of standard deviation within populations?

I did specifically mention "in the order of 10^9".
 
aced126 said:
There is an element of truth in this, in that the number of heartbeats across not only humans but all mammals in biology is roughly invariant (in the order of 10^9 heartbeats). This is a consequence of lifespan being proportional to the mass of an organism raised to a quarter power (lifespan=kM^0.25) and heart rate being proportional to mass of the organism raised to -0.25.

http://www.cs.cornell.edu/~ginsparg/physics/Phys446-546/gbwscl99.pdf
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Yeah, TAKE THAT! lol
 
Meth only ages you if you don't take care of yourself. This shit y'all have been posting is scary smart.
 
aced126 said:
Lmao, ever heard of standard deviation within populations?

I did specifically mention "in the order of 10^9".
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Dude -- you were wrong.

So if I say around $100 - $300 falls in the bounds -- Nope! 110, 95 -- sure , but not 270, and not 320

2.7 Billion is not on the order of 10E+09 -- it's just NOT

3.2 is halfway to the next power of 10

BTW, Blue Whales are mammals -- at 8-10 beats a minute and a 90 year lifespan -- we only get 470 Million -- again nowhere near a billion
 
The sleep deprivation is what you guys should be worried about in my opinion... Both for brain and bodily health.
 
I could envisage a whole host of ways in which oxidative damage >> reduced telomerase activity >> mitochondrial/cell senescence may occur with meth. Lack of sleep and poor nutrition will obviously aggravate this but even with both optimal, you'd expect some harm at high(er) doses...
 
Dry mouth -> oral decay I think would happen regardless of ceramide stuff.

Excess adrenaline/stress hormones would probably exert their deleterious effects regardless as well, with disruption of anabolic hormones as another factor?
 
shugenja said:
Dude -- you were wrong.

So if I say around $100 - $300 falls in the bounds -- Nope! 110, 95 -- sure , but not 270, and not 320

2.7 Billion is not on the order of 10E+09 -- it's just NOT

3.2 is halfway to the next power of 10

BTW, Blue Whales are mammals -- at 8-10 beats a minute and a 90 year lifespan -- we only get 470 Million -- again nowhere near a billion
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2.7 Billion has an order of magnitude of 10^9. That is basic maths knowledge. Let's see your sources for your blue whale data. Also, there's no point trying to scan the animal kingdom searching for exceptions. It is well known that lifespan scales approximately to M^0.25, and heart rate scales approximately to M^-0.25, hence heart beats in a life time is roughly invariant.

http://www.ncbi.nlm.nih.gov/pubmed/15855389

Read that (the full article is free). If you don't want to then here is an important quote from the paper: "Another simple characteristic of these scaling laws is the emergence of invariant quantities (Charnov, 1993). For example, mammalian lifespan increases approximately as Mb^1/4, whereas heart-rate decreases as Mb^-1/4, so the number of heart-beats per lifetime is approximately invariant (∼1.5 ×10^9), independent of size."
 
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ShardHUNTER420 said:
Meth is bad but I have good shit so I don't feel nearly as beaf from than using dirty as crank there really is a difference lol you'd be suprised some ppl around here think cranks better I'm more twichy and more on edge when using crank but good ice is great I can smoke again now cuz used ti smoke crank but talk about chemical burns from impurities n shit I only buy ice now and it's not rare but most ice is hella cut but I know whats in this shit just a wee bit msm also hate ppm that rape batches with too much. The cuts are doing more damage than anything if u have shitty meth only snort or eat I prefer smoking but only smoke good ice dirty ass crank gave me psychosis when I smoked it but I did alot cuz I had a lil over a ball but when it shitty u keep going anyways parents thought I was crazy hearing voices n shit but was fine soon after was 15 at the time a lil after I started yes I was young but I've grown up alot from that bs. Anyways 18 now and since my shits very clean I have 0 to none cons and many pros most of that shit everyone says about meth bugs and hallucinations goin crazy basically always has been from really cut dirty meth seen the bugs once a buddy was trippin but he was up for over a week and was smoking alot he put. Half g ina light bulb and smomed that over the hour or so this was downtown tho always shitty crank dowb there usually all shake n bake batches too so fuck that meth is bad for ya but I consider crack and herion way worse crack cuz of how addictive it was man like I walk away from ice all the time now I'm a addict I have a addictive personality so everything is my addiction but ice is used in moderation with me not rec even tho I seen it a dude did ice like every 2 years or so did a big binge then said fuck it I walk away too all the time months a year at a time I didn't quit just a break and it's funny my friends hate how well I handle ice but i've dealt with crack which is so bad for ya jesus never stole on shard but sure did for my next rock like fuxk love coke but cracks not cool destroyed me my friends don't get it through they say I must not get withdrawls I do trust me I just don't bitch like most addicts just keeps bitching to make ya more sour when you can just suck it up and smile like me I'm not weak minded and ice is all mental addiction so it's easy and all that shit u see about ppl dojng crazy shit it's all dirty meth or baddd bad cut never had bugs wanna see a real addiction do oxys or h did oxys with the old trick all play on ourself saying it's prescription pill not literally h i've done h alot of times the oxy is better
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Good quality meth also makes you omit full-stops/periods when typing.

with cocaine, you have to quit writing for re-dosing, and so therefore you always then remember to type your periods.
 
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