Methamphetamine ageing and neurotoxicity

[Neuroprotection]

In an article by the Daily Mail titled ' why crystal meth ravages the body' scientists claim they have found out why methamphetamine addicts age so quickly. They point out that methamphetamine induced disturbances of lipid metabolism in cells throughout the body triggers the release of highly toxic substances called ceramides. They described these as toxic proteins, but according to my knowledge ceramides are lipid amides but please correct me if I'm wrong. Never the less ceramides are extremely toxic went over expressed in cells and are powerful promoters of programmed cell death. I don't think ceramides are necessarily a bad thing since in small amounts they increase the metabolic activity of cells, but in the large amounts released by methamphetamine exposure they are lethal to cells.
The article focuses on the role of ceramides in methamphetamine induced accelerated ageing, but I am more interested in where the proposed mechanism fits in with methamphetamine and regular amphetamine neurotoxicity. The article also states that scientists using an enzyme inhibitor that prevents the release of ceramides have been able to prevent the harmful effects of methamphetamine on rodents. The inhibitor is also being modified and studied as a possible treatment for human methamphetamine dependence or at least preventative against its toxicity.
What do you all think?
Should we be optimistic or could this be too good to be true?
Is it possible that a ceramide release inhibitor when taken with methamphetamine could allow users to enjoy the high without toxicity or do you think it's will interfere with and suppress the pleasurable aspects.

 

[asecin]

the whole meth causing accelerated aging is based on the drugs are bad campaigns that show videos of rednecks (who in general meth free look like they are badly aged) just get into trouble with law which accelerates the negative effects of meth even further by them being thrown in jail, all beaten up and looking filthy (hence those nasty mugshots we see on drugs are bad campaign) thus leading general public to actually do believe meth causes people to age fast when using meth.
ok, there is more to it, of course. meth causes agitation, lack of appetite, LACK OF SLEEP, all causing temporary signs of aging. those are vital side effects of meth that will make anyone look bad TEMPORARY. meth DOES NOT CAUSE ACTUAL PERMANENT ACCELERATED AGING.
so, go back to the previous statement of usually poor people with bad looks in general abusing the drug, and the indirect effect of diet and sleep patterns, you have a good campaign against meth and drugs to show to the kids and convince them too!

 

[pofacedhoe]

everyone looks shit with no sleep. thats what ages them, sun and booze dont help

 

[Burnt Offerings]

Yeah meth addicts, the serious tweakers, look that way because they pay 0 attention to the needs of their own physical health. No sleep, often little to no food, not sufficiently hydrated , living in squalor, etc.

 

[ShardHUNTER420]

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

 

[Neuroprotection]

the whole meth causing accelerated aging is based on the drugs are bad campaigns that show videos of rednecks (who in general meth free look like they are badly aged) just get into trouble with law which accelerates the negative effects of meth even further by them being thrown in jail, all beaten up and looking filthy (hence those nasty mugshots we see on drugs are bad campaign) thus leading general public to actually do believe meth causes people to age fast when using meth.
ok, there is more to it, of course. meth causes agitation, lack of appetite, LACK OF SLEEP, all causing temporary signs of aging. those are vital side effects of meth that will make anyone look bad TEMPORARY. meth DOES NOT CAUSE ACTUAL PERMANENT ACCELERATED AGING.
so, go back to the previous statement of usually poor people with bad looks in general abusing the drug, and the indirect effect of diet and sleep patterns, you have a good campaign against meth and drugs to show to the kids and convince them too!

I agree that many meth addicts acquire bad habit's including the overconsumption of unhealthy high sugar fluids or even worse a Phalia to drink enough fluid and also skipping days worth of sleep and not eating enough Will all contribute to the aged look. Also you are right in suggesting that and to drug campaigns widely utilise misinformation in order to maximise their Effectiveness at drug prevention.
Just out of interest have you ever tried methamphetamine or know someone who has. If so can you describe what it felt like particularly if the drug was relatively pure

 

[Neuroprotection]

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

Are you saying that methamphetamine is less addictive than cocaine? That seems to contradict scientific research and also that I thought I knew about meth. However I am in no way doubting what you say, rather I am fascinated by your experience and I must say Old studies on the neurotoxicity of many drugs are being criticised for use of excessive amounts in small animals leading to over exaggerated results. Also since you have experience with methamphetamine and cocaine I would like to ask you a few questions if that's okay with you.
1 do you find methamphetamine or cocaine more euphoric.
2 when using crystal meth of high purity do you use any antioxidant supplements, ensure you take in plenty of fluids and a balanced diet?
3 do you think the MSM, used to cut hi quality methamphetamine gives some kind of protection against neurotoxicity and many side-effects by acting as a biological source of sulphur, note that the bodies Master antioxidant glutathione is depleted by many drugs of abuse and is very important in protecting the brain against their toxicity, sulphur is an essential elements for the synthesis of this antioxidant.
Thanks for posting your experience, you have given me a completely different perspective of amphetamine users.

 

[Ligaturd]

Cocaine definitely is a lot more, "moreish" due to it being an NDRI, it dumps a lot of dopamine at once and causes a pretty intense rush. Meth can provide a rush but it takes a lot to even be comparable to cocaine. Meth is cheaper, lasts longer, and is a more enjoyable in my experience.

Cocaine is more impulsive and has a pretty intense and immediate craving aspect that has most people finding it more addictive than meth. As far as one actually being more addictive than the other, thats highly subjective as they function differently and different people will have unique experiences with either or.

I find meth more euphoric and useful as a drug as cocaine is mostly an initial rush and after a couple of them the euphoria is gone. With Methamphetamine being a releaser and not dumping available neurotransmitters in a relatively short amount of time, the euphoria can be constant. Plus it's not nearly as powerful of a vasoconstrictor so you can have nasty ass marathon sex on it quite easily.

Isn't N-Acetyl-Cysteine a precursor to glutathione? People could definitely benefit from being educated on how Methamphetamine impacts theit brain and how to mitigate any damage. I have also read of people using methylene blue as a neuroprotective agent in conjunction with Methamphetamine.

 

[Neuroprotection]

Cocaine definitely is a lot more, "moreish" due to it being an NDRI, it dumps a lot of dopamine at once and causes a pretty intense rush. Meth can provide a rush but it takes a lot to even be comparable to cocaine. Meth is cheaper, lasts longer, and is a more enjoyable in my experience.

Cocaine is more impulsive and has a pretty intense and immediate craving aspect that has most people finding it more addictive than meth. As far as one actually being more addictive than the other, thats highly subjective as they function differently and different people will have unique experiences with either or.

I find meth more euphoric and useful as a drug as cocaine is mostly an initial rush and after a couple of them the euphoria is gone. With Methamphetamine being a releaser and not dumping available neurotransmitters in a relatively short amount of time, the euphoria can be constant. Plus it's not nearly as powerful of a vasoconstrictor so you can have nasty ass marathon sex on it quite easily.

Isn't N-Acetyl-Cysteine a precursor to glutathione? People could definitely benefit from being educated on how Methamphetamine impacts theit brain and how to mitigate any damage. I have also read of people using methylene blue as a neuroprotective agent in conjunction with Methamphetamine.

That's interesting I've never looked at cocaine and crystal meth that way before.I have read many media reports and scientific studies claiming that methamphetamine is three times more powerful than cocaine and gives 12 hours of extreme euphoria and energy.I have also listened to testimony of users on YouTube, claiming that they were given methamphetamine instead of cocaine without knowing only to find that the experience was many times more intense and addictive. However I am starting to question the validity of such reports and wonder if there are other reasons for many peoples horrific experiences with methamphetamine and The demonisation of crystal meth as a drug far worse than cocaine.
Is it possible that inexperienced Street users could on knowingly interest toxic quantities of methamphetamine and end up suffering the consequences.
Yes Nacetyl cystine is a precursor to glutathione but also an excellent antioxidant in its own right. The use of methylene blue to prevent methamphetamine neurotoxicity relies on 2 proposedmechanisms in the body.
1 methylene blue acts as an electron carrier in the electron transport chain of the mitochondrion, theoreticaly enhancing ATP synthesis and reversing energy depletion, A factor believed to be largely responsible for methamphetamine neurotoxicity.
2 methylene blue acts as a neuronal nitric oxide Synthetase inhibitor and is only selective for this enzyme so does not interfere with nitric oxide production in blood vesselswhere it is essential for keeping blood pressure normal. In the brain nitric oxide is produced and used as a signalling molecule, often as a downstream reaction of a signalling cascade for example activation of glutamate receptors, and resorts when calcium influx activates The neuronal nitric oxide a synthetase enzyme. Being a free radical nitric oxide and damages proteins and DNA and can trigger programmed cell death

 

[Burnt Offerings]

Just out of interest have you ever tried methamphetamine or know someone who has. If so can you describe what it felt like particularly if the drug was relatively pure

I've done it. It feels incredible, especially when you shoot it. You'll feel like you're walkin' on sunshine

 

[Neuroprotection]

I've done it. It feels incredible, especially when you shoot it. You'll feel like you're walkin' on sunshine

Would you say the come down from a moderate dose is manageable, that is, do you just feel a little down and does sleeping it of work. Also is there a difference in the intensity of the come down between injecting and oral use.
Sorry if I'm asking too many questions, it's just that I struggle to find answers for more specific questions, and also the view of drug information websites seems to differ so much as compare to actual methamphetamine users. From what I have read, it looks like other drugs like opioids and cannabis get a somewhat balanced discussion in the media, while methamphetamine has been totally demonised, despite its relative toxicity when compare to other drugs, it might have been disproportionally targeted.

 

[Ligaturd]

There is a difference in how bad the come down is when comparing IV and oral use in general but then there are factors such as dosage. Someone who injects .2 of meth will probably have a comparable come down to someone who swallowed .3 or .4 but the total dosage can make one come down much worse than the other method of administration.

The come down from Methamphetamine would make me feel off and depressed for up to a week after usage, with cocaine I might get some prolonged anxiety and general malaise for a day or two after but then it's over. Methamphetamine definitely feels much more toxic on the mind and body but I would say that it is generally less cardiotoxic. I am very greatful that I haven't touched the stuff for almost a year now, it had such a massively negative impact on my mind and my behavior. I have some symptoms of psychosis possibly right now so using in the future is definitely out of the question, I'd like to retain some control of my mind. Many people can handle it and function normally for many years but I guess based on my own mental health problems that just isn't possible for me.

 

[sekio]

I think a big part of the issue is that methamphetamine is really, really potent - probably no more than 10-20mg is enough for an infrequent or first time user to be running all over the house tidying. And given that most meth users don't exactly roll around with a milligram scale... you end up with street users that eyeball doses & "start out" with 100mg smoked.... of course you're going to see side effects and mental breakdowns.

The general rule of thumb with amphetamine-type stimulants seems to be, keep your doses low as possible, and they'll treat you well. That way you don't forget to eat, sleep, bathe...

As for meth versus cocaine, well, the two are not very comparable. One has a 20 minute half life, the other has 20 hours, one is a norepinephrine-dopamine releaser, th' other is a triple-reutake inhibitor. I guess both are addictive stimulants, but I thought it was also well known that some people have a preference for one over the other. Like LSD versus shrooms.

 

[Neuroprotection]

That explains why so many people have terrible side-effects from methamphetamine. If someone was to use for example 20 mg of pure meth on one night, and they only do this once twice per month, do you think they could avoid neurotoxicity, and could you avoid a pro long depressing come down.

 

[Neuroprotection]

Does anyone have any idea where the research regarding ceramides I posted earlier fits in with halm reduction, prevention of methamphetamine toxicity and treatment of addiction and mental illnesses brought on by amphetamine. I have also read more about ceramides and discovered a rather disturbing Fact, that is ceramdes cause death of brain cells especially in the hypocampus and reward centres.

 

[aced126]

That explains why so many people have terrible side-effects from methamphetamine. If someone was to use for example 20 mg of pure meth on one night, and they only do this once twice per month, do you think they could avoid neurotoxicity, and could you avoid a pro long depressing come down.

Yes

 

[WSH]

As for meth versus cocaine, well, the two are not very comparable. One has a 20 minute half life, the other has 20 hours, one is a norepinephrine-dopamine releaser, th' other is a triple-reutake inhibitor.

Cocaine is actually an inverse agonist at the transporters (at least the dopamine one), rather than a classic reuptake inhibitor (which would be an "antagonist" at the transporters):

Dopamine reuptake transporter (DAT) "inverse agonism"--a novel hypothesis to explain the enigmatic pharmacology of cocaine

 

[Cotcha Yankinov]

Does anyone have any idea where the research regarding ceramides I posted earlier fits in with halm reduction, prevention of methamphetamine toxicity and treatment of addiction and mental illnesses brought on by amphetamine. I have also read more about ceramides and discovered a rather disturbing Fact, that is ceramdes cause death of brain cells especially in the hypocampus and reward centres.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170854/

"Ceramides, the central molecular species of the sphingolipids pathway, have important structural roles in cell membranes and function as second messengers for critical intra- and inter-cellular signaling affecting cellular growth, differentiation, proliferation, and apoptosis. While ceramides are important for cell survival, injury-induced cytokine production, and activate stress-signaling protein phosphatases and kinases (Hannun, 1996), at high levels ceramides inhibit cell division and induce cellular dysfunction and apoptosis (Goodman and Mattson, 1996).

Several lines of evidence suggest both direct and indirect associations between ceramides and Aβ levels at the cellular level (Mattson, et al., 2005; Tamboli, et al., 2011). Recent studies have also suggested that ceramides, particularly the 18-carbon acyl chain length species, modulate tau phosphorylation (Chalfant, et al., 1999; Dobrowsky, et al., 1993; Goedert, et al., 1995"

So ceramides can probably have structural consequences and more second messenger type signaling consequences; that a species of ceramides was associated with amyloid beta in the study I linked is worrisome but this is worse in people with an APOE e4 allele - reminding us that genetics play a role in how some brains cope with drugs. 200$ spent on 23andme + promethease to figure out your APOE alleles isn't a bad harm reduction practice, in the sense that you can decide to really restrict what drugs you use or how you use them if you have an APOE e4 allele etc.

I think getting good sleep would be the most important factor but that's hard to do with such a long half life of meth.

I would assume that dopamine nerve terminal injury still occurs to some degree with that enzyme inhibitor the scientists were using to decrease ceramide induced damage. If you could post that study that would be dandy

 

[CfZrx]

the whole meth causing accelerated aging is based on the drugs are bad campaigns that show videos of rednecks (who in general meth free look like they are badly aged) just get into trouble with law which accelerates the negative effects of meth even further by them being thrown in jail, all beaten up and looking filthy (hence those nasty mugshots we see on drugs are bad campaign) thus leading general public to actually do believe meth causes people to age fast when using meth.
ok, there is more to it, of course. meth causes agitation, lack of appetite, LACK OF SLEEP, all causing temporary signs of aging. those are vital side effects of meth that will make anyone look bad TEMPORARY. meth DOES NOT CAUSE ACTUAL PERMANENT ACCELERATED AGING.
so, go back to the previous statement of usually poor people with bad looks in general abusing the drug, and the indirect effect of diet and sleep patterns, you have a good campaign against meth and drugs to show to the kids and convince them too!

idk man, my granny really looks bad for 43

 

[Neuroprotection]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170854/

"Ceramides, the central molecular species of the sphingolipids pathway, have important structural roles in cell membranes and function as second messengers for critical intra- and inter-cellular signaling affecting cellular growth, differentiation, proliferation, and apoptosis. While ceramides are important for cell survival, injury-induced cytokine production, and activate stress-signaling protein phosphatases and kinases (Hannun, 1996), at high levels ceramides inhibit cell division and induce cellular dysfunction and apoptosis (Goodman and Mattson, 1996).

Several lines of evidence suggest both direct and indirect associations between ceramides and Aβ levels at the cellular level (Mattson, et al., 2005; Tamboli, et al., 2011). Recent studies have also suggested that ceramides, particularly the 18-carbon acyl chain length species, modulate tau phosphorylation (Chalfant, et al., 1999; Dobrowsky, et al., 1993; Goedert, et al., 1995"

So ceramides can probably have structural consequences and more second messenger type signaling consequences; that a species of ceramides was associated with amyloid beta in the study I linked is worrisome but this is worse in people with an APOE e4 allele - reminding us that genetics play a role in how some brains cope with drugs. 200$ spent on 23andme + promethease to figure out your APOE alleles isn't a bad harm reduction practice, in the sense that you can decide to really restrict what drugs you use or how you use them if you have an APOE e4 allele etc.

I think getting good sleep would be the most important factor but that's hard to do with such a long half life of meth.

I would assume that dopamine nerve terminal injury still occurs to some degree with that enzyme inhibitor the scientists were using to decrease ceramide induced damage. If you could post that study that would be dandy

Sorry I can't post links because I am using an iPhone and have vision problems. The article was from an online newspaper I think the Daily Mail. Just Google why crystal meth ravages the body, and I'm sure you'll find it. You can probably google role of ceramides in methamphetamine neurotoxicity to find the actual study. It would be great if scientists could selectively inhibit the neurotoxic ceramides whilst preserving the neural protective or essential ones. This breakthrough mate not stop methamphetamine neurotoxicity completely, but it would likely drastically reduce it and make methamphetamine a relatively safe drug. Also the damage may be limited to short-term reductions in striatal dopamine depletion and long term Neuron damage