• Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

  • N&PD Moderators: Skorpio | someguyontheinternet

Amphetamine Neurotoxicity and Tolerance Reduction/Prevention

Status
Not open for further replies.
nj754 said:
I don't mean to rain on anybody's parade, but how are you going to tell if this is working? I mean the neurotoxicity prevention part. This kind of brainstorming ideas is an important step toward an anti-tox cocktail, but it's only one step. Then you have to do experiments to prove that it actually works. And proving that it works in humans will be darn-near-impossible. Without the experiments, all you will be doing by taking these pills is making yourself feel better, and giving money to the supplements store. I'm not aware of any studies showing that losing those dopamine axons has any actual consequences, so I'm going to just assume you don't need them. Unless it's super-cheap and easy, I would feel too silly throwing money at supplements on the basis of a lot of conjecture and hoping to achieve a benefit that is entirely theoretical and can't be measured or detected.
Click to expand...

Like I said in the first thread, this is pretty much educated conjecture. All I do is look for treatments that may help the parameters that amphetamine changes and make sure that they have a decent safety margin.

Unfortunately amphetamine neurotoxicity is one of the skeletons in the closet of the pharmaceutical industry so there's next to no research on the topic. But, the research that does exist suggests that there is a strong possibility that even lower AD(H)D level doses produce a neurotoxic effect which may present itself as cognitive issues or Parkinson's later in life.

All the compounds I put in my suggestion box have a great margin of safety or are part of a healthy lifestyle so that the risk of anyone harming themselves through my advice is minimal (you know unless someone chokes on a Flintstone's vitamin). But, the discussion of things like PQQ and lithium are more for helping out those who are dependent on amphetamine (like AD(H)D individuals) who feel that it would be worth a shot or those who abuse it and would like to provide very probable protection for their brains.
 
Epsilon: It's worthwhile work, and I'm glad you're doing it. But I hope you go on to get a PhD and actually follow it up with real laboratory research. Anything you come up with here is too preliminary to form a recommendation.
 
nj754 said:
Epsilon: It's worthwhile work, and I'm glad you're doing it. But I hope you go on to get a PhD and actually follow it up with real laboratory research. Anything you come up with here is too preliminary to form a recommendation.
Click to expand...

I see where you're coming form, but honestly this kind of thing preliminary research can help stimulate research funding by showing concern and provide leads for proper researchers. These suggestions would primarily attract people who are worried about amphetamine induced brain damage and are intended to simply point them in a promising direction. I've stated several times in this thread that I am not a MD or Ph.D so I feel I've expressed enough for people to take everything I say with a grain of salt.

This is also why I brought this discussion from imminst to bluelight, because I feel it would attract more attention from those who would be interested. Also, anecdotal reports are the best that we can get through a medium like this, so I don't find any issue suggesting that people who are interesting in trying various approaches if it could lead to more promising leads.
 
ellekereljer said:
Uh... so yeah.. 4mg isn't going to cut it at the time being.

I took 4mg yesterday with coconut water, dmae, l-cartinine, there was no comeup but at the peak of the dose maybe beginning at 2 hours it was felt. Slight mood increase. Leg stamina increased. Music sounded better. I could bust raps with more word clarity. It didn't last very long, another hour and a half the feeling just fizzled out. ALmost unnoticeably, almost.

Today I took 4 mg with coconut water and nothing else. Impossible to really distinguish any effect. I may have felt it a tad but it was borderline placebo. I thought tolerance had won again.

What I didn't realize is coconut water has vitamin c in it!!! I didn't even think to check because the usual cheapy stuff I get doesn't list any % of vitamin c. It is a very modest amount but still it effects me.

Honestly, I am pretty disappointed with myself for being ignorant and the experiment for being a failure. I need more time, I knew that but I was really hoping that I wouldn't have to up my mementine dose to keep tolerance down. I thought that on such n such dose not a lot of it would not be needed? Wouldn't it correlate that x amount of amp needs x amount of antagonist? Otherwise there is no way 10 mg would cut it at any regular dose of amphetamine. 4mg, this is a baby dose maybe too unrealistic for me, although I have heard others are capable of doing it.

I am pondering bumping up to 15/20 mg of mementine, I should probably do it sooner than later since I need my wits about me once school is in session.
Click to expand...

I don't think the vitamin c in coconut water would be enough to really affect it, it might just be the fact that you're still tolerant to amphetamine at that dose or perhaps it was just too mild to notice.

Also, I've kind of got a feeling that mementine might block some of the subjective effects of lower dose amphetamine. I'd ask MeD if he noticed any kind of effect like that if you want to know more.
 
ellekereljer said:
I do know curcumin is a serious contender for potentiation. I totally forgot about this but the doc had to put me on welbutrin before I could be prescribed adderall. I tried it out for a month. In that same month, I heard how curcumin could be amazing for depressive individuals. I was taking a tablespoon with too much pepper , 3 times a day. Just taking the standard dose of 300mg welbutrin, half way through the month I had a hypertensive crissis? Or sertonin syndrome? Couldn't stop shaking, veins bulging out of my head, super red and hot. I didn't know what it was at the time but didn't thnk it severe enough to go to the hospital. It left me with tinnitus, ringing of the ears. I am just way too fool hardy. It may have been the pepper allowing me to absorb wayyyy to much welbutrin. Curcumin supposedly potentiates antidepressants as well.
Click to expand...

You should be careful mixing prescription drugs with herbs, especially ones with reputations as "potentiators." Curcumin is a CYP2B6 inhibitor (according to wikipedia), so it could very well have caused you to overdose on Wellbutrin. Wellbutrin is known for causing seizures at high doses.
 
Lithium is an interesting one. Maybe the effect on VMAT2 is the reason for some of lithium's dopaminergic-like side effects. You would think that there would be a lot of experience out there combining lithium with amphetamines, though. Psychiatry doesn't really have a huge number of drugs, and those two date from a time when it had even fewer. I'd be surprised if there wasn't literature on mixing them that was written in the 1970s or even earlier.
 
nj754 said:
Lithium is an interesting one. Maybe the effect on VMAT2 is the reason for some of lithium's dopaminergic-like side effects. You would think that there would be a lot of experience out there combining lithium with amphetamines, though. Psychiatry doesn't really have a huge number of drugs, and those two date from a time when it had even fewer. I'd be surprised if there wasn't literature on mixing them that was written in the 1970s or even earlier.
Click to expand...

I would argue that it would be more of the upregulation of tyrosine hydroxylase than VMAT2, but assuming increased VMAT2 was associated with greater amounts of neurotransmitter release during normal activity then probably.

interestingly enough VMAT2 isn't needed for amphetamine's mechanism of action, which appears to be primarily through DAT reversal in knockout rats.
http://www.cell.com/neuron/retrieve/pii/S0896627300804183

And lithium and amphetamine link dump:
http://www.springerlink.com/content/wgp6l0g5203n6787/
http://www.ncbi.nlm.nih.gov/pubmed/443465
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1557682/
 
Epsilon Alpha said:
I would argue that it would be more of the upregulation of tyrosine hydroxylase than VMAT2, but assuming increased VMAT2 was associated with greater amounts of neurotransmitter release during normal activity then probably.

interestingly enough VMAT2 isn't needed for amphetamine's mechanism of action, which appears to be primarily through DAT reversal in knockout rats.
http://www.cell.com/neuron/retrieve/pii/S0896627300804183

And lithium and amphetamine link dump:
http://www.springerlink.com/content/wgp6l0g5203n6787/
http://www.ncbi.nlm.nih.gov/pubmed/443465
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1557682/
Click to expand...

I can't hit the second and third link in your list of amphetamine and lithium links. I found a paper specifically on mixing the two drugs here:

http://www.springerlink.com/content/q1409567r621028u/

It's from the 1970s, so it seems my intuition was right.

That article from Neuron looks interesting from the perspective of basic science. Good find.

Edit:

There is a wealth of studies of the combined effects of lithium and amphetamine from before 1980 (which I chose as the arbitrary cutoff year for my search).

http://www.ncbi.nlm.nih.gov/pubmed/7189675

http://www.ncbi.nlm.nih.gov/pubmed/443465

http://www.ncbi.nlm.nih.gov/pubmed/100811

et cetera

Edit #2:

Here, I have constructed the search string for you: http://scholar.google.com/scholar?a...&as_sdtf=&as_sdts=5&btnG=Search+Scholar&hl=en
 
Last edited:
nj754 said:
I can't hit the second and third link in your list of amphetamine and lithium links. I found a paper specifically on mixing the two drugs here:

http://www.springerlink.com/content/q1409567r621028u/

It's from the 1970s, so it seems my intuition was right.

That article from Neuron looks interesting from the perspective of basic science. Good find.

Edit:

There is a wealth of studies of the combined effects of lithium and amphetamine from before 1980 (which I chose as the arbitrary cutoff year for my search).

http://www.ncbi.nlm.nih.gov/pubmed/7189675

http://www.ncbi.nlm.nih.gov/pubmed/443465

http://www.ncbi.nlm.nih.gov/pubmed/100811

et cetera

Edit #2:

Here, I have constructed the search string for you: http://scholar.google.com/scholar?a...&as_sdtf=&as_sdts=5&btnG=Search+Scholar&hl=en
Click to expand...

Thanks man, I'll do some reading on that. More or less these links just show attenuation of some of amphetamine's effects in rat models when pretreated with lithium. I've got a lot to do lately, so I'll try to do as much reading as I can for these threads while still getting everything done I need to.

I'm currently trying to find out the role of heat shock proteins and DNA methylation in amphetamine toxicity so if I could get some help on that it would be great :)
 
Epsilon Alpha said:
Thanks man, I'll do some reading on that. More or less these links just show attenuation of some of amphetamine's effects in rat models when pretreated with lithium. I've got a lot to do lately, so I'll try to do as much reading as I can for these threads while still getting everything done I need to.
Click to expand...

It looked like there was attenuation of the effects in humans, too. So lithium may defeat the benefits of amphetamine. Although, some of the articles seemed to indicate that the attenuation varied depending on when and for how long the lithium was given.

I'm currently trying to find out the role of heat shock proteins and DNA methylation in amphetamine toxicity so if I could get some help on that it would be great :)
Click to expand...

A paper on amphetamine and HSP. Not free.
Changes in mRNA Levels for Heat-Shock/Stress Proteins (Hsp) and a Secretory Vesicle Associated Cysteine-String Protein (Csp1) after Amphetamine (AMPH) Exposure

Have you seen this paper? It looks like a good overview of neurotoxicity mechanisms, and it's free:
Amphetamine toxicities: Classical and emerging mechanisms (full text)

This looks like it contains a good review of possible antioxidant interventions. Unfortunately, it's not free.
Neurotoxicant-Induced Oxidative Events and Antioxidative Interventions in the Central Nervous System

Another one on HSP. Free.
Expression of heat shock protein (HSP 72 kDa) during acute methamphetamine intoxication depends on brain hyperthermia: neurotoxicity or neuroprotection? (full text)

This may be a useful review (not free):
Potential adverse effects of amphetamine treatment on brain and behavior: a review

Here's one on memantine that's not free.
Memantine is a useful drug to prevent the spatial and non-spatial memory deficits induced by methamphetamine in rats

Another non-free one from a book.
Molecular Bases of Methamphetamine-Induced Neurodegeneration
 
Last edited:
nj754 said:
It looked like there was attenuation of the effects in humans, too. So lithium may defeat the benefits of amphetamine. Although, some of the articles seemed to indicate that the attenuation varied depending on when and for how long the lithium was given.



A paper on amphetamine and HSP. Not free.
Changes in mRNA Levels for Heat-Shock/Stress Proteins (Hsp) and a Secretory Vesicle Associated Cysteine-String Protein (Csp1) after Amphetamine (AMPH) Exposure

Have you seen this paper? It looks like a good overview of neurotoxicity mechanisms, and it's free:
Amphetamine toxicities: Classical and emerging mechanisms (full text)

This looks like it contains a good review of possible antioxidant interventions. Unfortunately, it's not free.
Neurotoxicant-Induced Oxidative Events and Antioxidative Interventions in the Central Nervous System

Another one on HSP. Not free.
Expression of heat shock protein (HSP 72 kDa) during acute methamphetamine intoxication depends on brain hyperthermia: neurotoxicity or neuroprotection? (full text)

This may be a useful review (not free):
Potential adverse effects of amphetamine treatment on brain and behavior: a review

Here's one on memantine that's not free.
Memantine is a useful drug to prevent the spatial and non-spatial memory deficits induced by methamphetamine in rats

Another non-free one from a book.
Molecular Bases of Methamphetamine-Induced Neurodegeneration
Click to expand...

Haha man, I was literally hunting down the first 2 papers when you posted this great work man :)
With these more recent reviews we should be able to see where the current research points us in terms of harm reduction.

I've also been looking at some of the inflammation and hyperthermia links and it appears NSAID's may play a bigger role than we expected. Feel free to try and make some suggestions based off this data, I'll be busy for a while with this gold mine.

Also, lithium in my opinion is primarily to up-regulate some of the proteins that amphetamine downregulates such as VMAT2, and DA autoreceptors. It may exert a protective role acutely, but that's not why I first looked into it.

edit: curcumin appears to provide several of the same antipyretic and anti-inflammatory effects of asprin without the COX-1 inhibition problems. I'll do more research on the enzymes in question and how curcumin inhibits them to see how likely the effect is to carry over to humans.

http://www.ncbi.nlm.nih.gov/pubmed/18664365
http://www.mdma.net/aspirin/index.html
 
Last edited:
Glad I could help. I found that Google scholar is better for searching than Pubmed. Also, if I find a paper that is on the right track, I look through its references. If a paper mentions in passing that "methamphetamine exposure has been shown to cause elevated expression of HSP 72 kDa," there is most likely a reference to a paper that deals specifically with that point. Usually, they'll reference one of the better papers.
 
Hey, I'm probably going to disappear for a while. I need to get a lot more stuff in my life worked out before I can put the time and research into these threads. With that said there are plenty of intelligent posters who could keep up this thread, and continue providing much needed research on the topic.

I'm currently training for a new job, studying for the MCAT, and have a few other commitments both personal and business/school related that need to take priority right now.

Best of luck :)
-EA
 
i purchased some Curcumin, Lithium Orotate and PQQ last month because of this thread. didn't try the Lithium Orotate yet so i've got nothing to report there. with Curcumin, i thought i'd be fun to take a 875mg. capsule (it contained 5mg. of piperine as well) ~3 hours after dosing 100mg. of Vyvanse. it didn't take any longer than 90 minutes for me to conclude that Curcumin is the strongest AMPH potentiator that i've ever tried; it felt like it potentiated it 2.5x over. it was not a pleasant surprise. that was the only time i took Curcumin though i do plan on finding a way to incorporate it in some way as there seems to be too much good stuff going on with it.

that leaves me at PQQ. it's easily the most impressive supplement i have ever used in regard to my AMPH use/abuse.
i always dosed the PQQ with Ubiquinol and either a fatty meal or 2-3 tablespoons of extra virgin olive oil.
i always supplement: 10,000IU Vitamin A, 1.0g. Vitamin C, 2,000IU Vitamin D, 400mg. Vitamin E, 200mcg. Selenium in the morning ... 533mg. Magnesium Glycinate, 60mg. Zinc, 5.0mg. Melatonin (sublingual) at night.
here's what how i dosed the Vyvanse, PQQ and Ubiquinol:


7/7 - 7/11: 100mg. Vyvanse
7/12: 150mg. Vyvanse
7/13: 200mg. Vyvanse (100mg. @ 1200pm, 100mg. @ 0330pm)
7/14: 150mg. Vyvanse
7/15: 150mg. Vyvanse
7/16: 20mg. PQQ, 200mg. Ubiquinol

7/17:
1230pm: 100mg. Vyvanse
0400pm: 20mg. PQQ, 200mg. Ubiquinol


7/18:
1215am: 100mg. Vyvanse
0230am: 50mg. Vyvanse
0600am: 30mg. PQQ, 100mg. Ubiquinol
1130am: 100mg. Vyvanse
0230pm: 30mg. PQQ, 200mg. Ubiquinol
0945pm: 20mg. PQQ, 200mg. Ubiquinol


7/19 - 7/23:
~1100am: 20mg. PQQ, 200mg. Ubiquinol
~0900pm: 20mg. PQQ, 100mg. Ubiquinol


7/24 - 7/26
~1100am: 10mg. PQQ, 100mg. Ubiquinol
~0900pm: 10mg. PQQ, 100mg. Ubiquinol


Positives: when used concurrently with AMPH, PQQ + Ubiquinol gave a much cleaner feeling to AMPH. they also seemed to moderately potentiate AMPH but in a totally good way; mainly its concentration/focus enhancement and energized feeling were what i noticed as being potentiated. i also noticed an overall sense of well-being. but again, a very clean sense of well-being,, what was odd about it (this sense of well-being) is that it had a distinct cocaine feel to it. i'm not a big cocaine guy at all but it was very pleasant. astonishing considering i had been binging for a few days, ingesting 350mg. of Vyvanse over the last 23 hours of it. what was most impressive though was,, the after-binge symptoms i always get (anhedonia, profound somnolence, low energy, return/amplification of ADHD symptoms, cognition impairment) were not only drastically reduced (i would say a ~70% reduction in severity) but recovery time was also reduced by ~75%; i was doing things within 6 days that would normally take me at least 17-21 days to do.

Negatives: around the 22nd i became itchy. dosed PQQ and Ubiquinol the same as usual on the 22nd and 23rd. by the end of the day on the 23rd, the itchiness had gotten worse. felt very much like the itchiness that opiates cause with their dang histamine-releasing BS. i did not take any anti-histamine for it, simply reduced my dosages the next day and it went away quickly. PQQ is kind of expensive too.

Comments: this has been pretty much my standard pattern of use for Vyvanse for the past 3 months and similiar to how i dosed it from Aug. 2010 - Dec. 2010. before this past month, i was supplementing ALCAR, R-ALA and high doses of Vitamin C in an effort to combat neurotoxicity and the other nasty stuff that comes along with AMPH abuse. while i still believe ALCAR and R-ALA to be worthwhile supplements, they don't touch PQQ and Ubiquinol. i just wish i would have been using both with Vyvanse the entire time. but no worries, i started back on Vyvanse 3 days ago. i'm currently dosing 10mg. of PQQ + 100mg. of Ubiquinol in the morning and taking 50mg. of Vyvanse 2-3 hours later. i plan on keeping my Vyvanse use under 100mg. daily. if i decide to take more, i will adjust my doses of PQQ and Ubiquinol accordingly. i plan on adding Curcumin soonly. if anyone has any questions, i'd be more than happy to answer them. comments and thoughts are also totally cool. i'll keep ya'll posted as i try to incorporate PQQ+Ubiquinol with therapeutic doses of Vyvanse.

thanks for reading, hope i didn't ruin your day.
 
vvViolet: Very interesting results. You never tried PQQ or ubiquinol separately to see if both are strictly necessary? I'm all about value, and I'd rather take the smallest amount of the cheapest supplement necessary for the effect. Does anyone know if PQQ or ubiquinol have any drug interactions (other than with AMP)?
 
Status
Not open for further replies.
Top