Amphetamine neurotoxicity (of a former chronic high-dose user)

[dopamimetic]

A friend of mine with severe mental symptoms and (probably) ADHD somehow managed to get a prescription for the crazy dosage of up to 150mg dexamphetamine per day, and was on this for at least three years or so. There were other meds involved from time to time like bupropion and buprenorphine, but from what I know I think the effects of these are more or less negligible in the whole picture.

Well, she has had a hell of restlessness before, tried the usual neuroleptics and such and then thought to find relief in the amphetamine. This seemingly worked, but only acutely of course - she re-dosed every few hours and became hypertensive and aggressive if not. Needless to say, things worsened over time.

I've lost contact for two years or so, now she's off the amphetamine and appears to be fucked up. No concentration, cognitive problems, restless legs, sleep disturbances etc. but mainly she's literally disabled cognitively now. I know that it's impossible to make any diagnosis over the net and this is neither the place for, or the reason why I'm writing.

Just that I've learned much 'with' her, the story made me to delve deeper into some areas of neuroscience etc. and helped myself a lot- now I see this, and am thinking about what one could do. I believe that neurotoxicity isn't as irreversible as one might think, but recovery needs to be guided in the right directions. And most professionals lack the time to be up to date unfortunately.

What are the currently assumed mechanisms for chronic, high dose amphetamine neurotoxicity?

 

[Seppi]

I think you're confusing neurotoxicity with the more general concept of neuroplasticitiy. You have to really OD on amphetamine for it to cause acute damage to neurons. Consistently using 150 mg/day is very likely not going to generate the concentrations necessary for producing an excessive amount reactive oxygen species in otherwise healthy people.

That said, very few studies have examined the effects of long-term high dose (never seen one with users below 500mg+/day) amphetamine use without polydrug use, although I'd imagine it borks the PFC and the dorsal/ventral striatum somehow.

 

[Cotcha Yankinov]

Honestly I think the biggest harm of amphetamines is the not sleeping, you do pretty much all your brain repair in sleep and you detox from harmful oxygen species. Chronic insomnia can have really bad effects on the mind, combined with sustaining more damage from the stress of the amphetamine.

Chronic sympathetic activation is known to cause deficits of neurons in the hippocampus, ECT/SSRIs are known to help with this.

http://www.bluelight.org/vb/threads...xicity-and-Tolerance-Reduction-Prevention-III Here is the official amphetamine neurotoxicity thread but basically some of it is dopamine auto oxidative damage. There are many mechanisms though. I think the biggest one the studies miss is the factor of not sleeping or eating much for years.

 

[Captain.Heroin]

Honestly I think the biggest harm of amphetamines is the not sleeping

Absolutely not true and I would stake my life on it.

The biggest harm is, by far, stroke, heart failure, arrythmia, hypertension, addiction, temporary and/or lasting psychosis.

Sleep deprivation in itself isn't that big of deal and again, I would stake my life on it. (in b4 premature death)

 

[belligerent drunk]

I have to agree with Cotcha. Sleep is very important, and so is a proper diet. Just a thought experiment: imagine how an average heavy amphetamine user's lifestyle changes after they start using, then take amphetamine out of the equation (with all the changes, e.g sleep deprivation and poor diet still there) and think how that will impact their mental and/or physical health.

That is not to say that heavy amphetamine use in itself can't induce some damage, I guess especially on the cardiovascular system (?).

 

[Cotcha Yankinov]

I agree that the aforementioned cardiovascular disease and such is a big killer of amphetamine addicts but I think we're discussing more neurodegenerative concepts that could lead to the cognitive decline that this girl might be experiencing. And not to split hairs but I believe insomnia leads to many of those things that you listed as harms. At least people with insomnia have majorly increased risk for all sorts of cardio vascular disease.

 

[Captain.Heroin]

The cognitive decline isn't universal, and is likely due to genes becoming activated, etc.

You can put people through sleep deprivation, without drugs, and it's not torture. I don't agree with sleep deprivation being labeled "torture".

I stand by my statements. If missing sleep was that big of a deal I'd be in a mental hospital. I would regularly do 6 to 7 days without any sleep. I'm not alone. Just because everyone else like this lost their minds doesn't mean it's due to a lack of sleep.

Just my 2c.

And yes, your heart will suffer from a lack of sleep. Of course. But the heart will give out from an acute OD first; which is much, much more likely with addicts.

 

[Beings]

I don't agree with sleep deprivation being labeled "torture".

I stand by my statements. If missing sleep was that big of a deal I'd be in a mental hospital. I would regularly do 6 to 7 days without any sleep. I'm not alone. Just because everyone else like this lost their minds doesn't mean it's due to a lack of sleep.

Your statement reeks of someone saying "phobias are stupid, since I don't have them, no one does."
It is a known fact that you will die if you stop sleeping. Most people cannot achieve this, since your brain will go into microsleeps https://en.wikipedia.org/wiki/Fatal_familial_insomnia

Without drug use after 48 hours of no sleep, I can barely speak, let alone function. I don't ever want to find out what will happen after 7 days of no sleep.

 

[belligerent drunk]

I remember reading about the prion-induced fatal insomnia a while back and it struck me as incredibly horrendous. I would never want to die that way.

 

[Cotcha Yankinov]

People in the mania/ADHD spectrum can do a lot better than most people with out sleep for a long time, but eventually, especially if you've been going without sleep since your were a baby, it will catch up to you in the form of things in the Alzheimer's/Dementia spectrum.

Me thinks when some people are truly sleep deprived for years (and don't have periods where they catch up on their sleep debt) have really increased risk of excess amyloid beta build and other plaque build up, they also have decreased neurogenesis (associated with depression) something like this could be causing this woman's cognitive decline.

I will also say that if this woman's cognitive decline is not from sleep deprivation then it must be entirely explainable by either her drug use (insomnia aside) or her specific vulnerability to this type of cognitive decline, where she might be showing signs even if she had never taken drugs, but maybe drugs amplified things.

Maybe some people fold their plaques poorly and are more vulnerable to the effects of chronic sleep deprivation/amyloid beta buildup.

There is a small possibility that this woman's receptors are long term downregulated and that she might recover with time and healthy living.

 

[deadendgame]

yeah. i'm going through the same thing as well. no more of the illegal stuff. i'm getting my caffeine from 711. but i too worry about what the hell is going to happen to me? Am I gonna become stupid or vegetable? Someone please tell me!