Amphetamine Neurotoxicity and Tolerance Reduction/Prevention

[Ex Dubio]

vvViolet on this thread wrote up a report claiming that he felt a distinct difference from adding ubiquinol and PQQ to his amphetamine. That was what got my attention. I am not much interested in taking supplements just to reduce neurotoxicity, because the neurotoxicity itself is not well documented in humans, so you are piling speculation upon speculation by trying to defeat it. It's not worth the cost of the supplements.

I see; I did not know about the report of perceptible effects. I rather doubt that is the norm, though.

That said, while I agree that taking supplements exclusively to offset theoretical neurotoxicity is unwise, there are other reasons to take a supplement like ubiquinol, including heart health and likely protection from Parkinson's disease.

I am sure that's true. But, by and large, JAMA doesn't publish studies on dietary supplements unless they are of high quality. "It is wise to trust more respected journals more than less respected journals" -- that's all I'm trying to say.

Well, I don't think we disagree too much here, but in the particular case of ginkgo, there is an enormous amount of conflicting evidence, and there are some very high-quality studies that have found positive results. With herbs, it's always a bit tricky, as there can be a lot of dependence on which extract is used. I was mostly just trying to drive home the point that, despite the article in JAMA, the issue may be a bit more complex.

I think we pretty much agree. I don't put much stock in epidemiological-type studies, regardless of where they are published.

Indeed, I think we do.

The bias is often in the interpretation. The numbers don't lie, but results of weak studies get blown out of proportion and used to support wished-for conclusions. The same kinds of errors are made over and over, so that it starts to become predictable.

This is true.

Again, it's not so much where the study is published, but the fact that its a double-blind, placebo-controlled experiment that has been subjected to peer review.

Couldn't agree more.

 

[EcHo EcHo]

I never planned on using phentermine as a substitute, just to let ya know, but that doesn't matter now. Events over the past 7 days have left me with a great big question mark as to what I'm going to take medicinally and where I now stand on the topic of methamphetamine, and close to the topic of amphetamine as well. Aside from d-amphetamine, l-amphetamine, methamphetamine, paramethoxyamphetamine, methylenedioxymethamphetamine, methylenedioxyethelamphetamine, and racemic mixtures what are the other chemical compounds that so closely resemble these amphetamines that they give the same, or nearly the same, effect? Or where can I find a list of them? If no one knows of one then I suppose I'll just have to make one, huh?

 

[Epsilon Alpha]

Well methylphenidate is pretty much the safest bet but it might not work for you, and honestly low dose amphetamine isn't too toxic.

What kind of events did you experience?

 

[yaesutom]

What is the best kind of curcumin to order? It looks like there are several versions/suppliers/etc. I would like to try it for amph tolerance/enhancement. I read the wikipedia page, said its barely bio available and goes on to mention several variations that were a lot more active.

 

[MeDieViL]

Jarrows variation with 500mg is usually recommend, other formulations are in most cases excessive.

 

[whippa craka]

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

If I may ask, why so much Vyvanse? That's ridiculous.

 

[Epsilon Alpha]

If I may ask, why so much Vyvanse? That's ridiculous.

To get really really high.

 

[bben]

Jarrows variation with 500mg is usually recommend, other formulations are in most cases excessive.

thats actually not one of the better brands at all....

in general avoid the brands that have to use piperine to increase bioavailability. The one with the best absorption and with the longest retention is the bcm 95 formula which has been selected for a current prestigious alzheimers trial IIRC. Doses under 8g are fine with the normal stuff, and with bcm 95 you wont need more than 1g, it feels much more like a potent drug than normal curcumin. Jarrow formula at 500mg has poor absorption and retention.

 

[bben]

http://www.jneurosci.org/content/16/13/4231.short
Why won't you let me be lazy

haha what do you want explained..

 

[Epsilon Alpha]

haha what do you want explained..

I'm kind of hoping for a good introduction to the mechanisms for laypeople and then a little bit more on the relevant intracellular pathways for the ADD'ers. I'm kind of wondering how much it has to do with intracellular calcium concentrations vs other pathways involved.

I'm working on a few posts that cover a few novel targets (metabotropic glutamate receptors, epigenetics, and if I can make sense of them TAAR and NAChR) if this semester leaves me with enough time.

 

[Epsilon Alpha]

So long and thanks for all the fish

Hey,

I'm leaving this topic for the time being, while I enjoy my intellectual masturbation as much as the next guy I have a whole dorm full of hot and horny first years and a 3.7 GPA to improve on right now. I hope I've provided a increased interest and understanding of the topic to the community and that this thread remains a solid reference to those who choose to further the discussion.

If I have time in the future I may comment on further discussion but I won't be doing my usual posts.

Best of luck from the frat boy, gentleman, community leader, insomniac, and all around eclectic hipster.
-Epsilon Alpha

 

[nj754]

Out of curiosity -- what is your major? Congrats on the GPA.

 

[Epsilon Alpha]

Thanks man, I'm in honours pharmacology.

 

[Fyasko.]

havent checked this thread for awhile

Hey,

I'm leaving this topic for the time being, while I enjoy my intellectual masturbation as much as the next guy I have a whole dorm full of hot and horny first years and a 3.7 GPA to improve on right now. I hope I've provided a increased interest and understanding of the topic to the community and that this thread remains a solid reference to those who choose to further the discussion.

If I have time in the future I may comment on further discussion but I won't be doing my usual posts.

Best of luck from the frat boy, gentleman, community leader, insomniac, and all around eclectic hipster.
-Epsilon Alpha

thanks so much for the contribution Epilson, i know abunch of amph users (including myself) appreciate it greatly.
ill do some research in my spare time and try to keep this thread alive but i doubt it'll be as helpful as your input :D

have fun bro!

 

[Epsilon Alpha]

Hey, just wondering if there are any questions on the topic and if anyone has tried using the curcumin method to lower tolerance.

As a side note, 500mg a day of softgel curcumin during a week of abstinence was effective in reducing a friend's methylphenidate tolerance from 90mg a day to 54mg a day. Its worth noting that his tolerance has stayed stable at 90mg a day for ADHD for about 4 years and that this is in the concerta formulation.

 

[Biovail]

When you say stayed stable, do you mean that tolerance breaks were taken but had no effect? Or was this was the first time he had attempted one? Has his tolerance since the curcumin trial gone back up?

 

[Epsilon Alpha]

He's taken most weekends and summer off every year of schooling he's had since he's been like 12 (he's 20 now) and his tolerance has never really dropped below 72mg even with week or two breaks during the summer.

Just saw him in class today and its been day 3 at his 54mg dose.

Also, a update on a different friend who consumed possibly tainted URB597: still getting dialysis but his doctor says he might be able to get off it in a month or two depending on how fast his kidneys adapt. However, they're guessing he has lost 5-20% functionality of his kidneys judging by what he's seen so far. His liver is looking like it will make a full recovery however which is a welcome bit of news.

 

[Epsilon Alpha]

Big and Dandy Amphetamine Epigenetics post:

-First off a decent introduction to epigenetics for those with at least a first year university understanding of biology: http://www.sciencedirect.com/science/article/pii/S0896627311004338#sec1.2

-DeltaFosB, which is strongly associated with tolerance to several classes of dopagenic drugs recruits histone deacetylase 1(HDAC1) to reduce the expression of cFos. Long term amphetamine dosage appears to lead to long lasting changes in methylation of H3. http://neuro.cjb.net/content/28/29/7344.short

-Co-treatment with HDAC inhibitors and amphetamine produces a increased response in rodents, yet prolonged pretreatment with HDAC inhibitors inhibits further sensitization of response. This may be related to prevention of amphetamine induced epigenetic changes, which assuming it transfers directly over to humans would mean that inhibiting HDAC would be a way to inhibit the development of amphetamine tolerance. The effects on associative learning might have some more to do with the processes of psychological addiction, but I’m not going to touch that subject.
http://www.sciencedirect.com/science/article/pii/S0166432807001878#sec4.2.1

-As far as the exact mechanisms go, it’s still fuzzy as far as what I’ve read concerns. But, histone acetyltrasferase (HAT) and HDAC inhibition seem to enhance amphetamine’s effects in rats and mice. http://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2010.03321.x/full
As a side not curcumin appears to inhibit both of them at concentrations which could be reached with less than 3g/day dosing.

-HDAC inhibitor pretreatment seems to increase levels of histone phosphorylation on cfos promoters, hinting at a relationship between the two forms of modification. Histone phosphorylation increases binding of HAT. I am currently working on the actions of histone phosphorylation and methylation as they seem to produce more variable effects on transcription from preliminary readings. However, methylation produces longer term effects than changes in histone acetylation
http://www.sciencedirect.com/science/article/pii/S1471491408001354#sec3.3

-Curcumin seems to have ridiculous effects on pretty much every epigenetic mechanism, so I thought I’d link dump some reading for those who are interested.
http://www.sciencedirect.com/science/article/pii/S0960894X08015515 (induces hypomethylation)
http://www.springerlink.com/content/c0521v04l4549x25/ (review)
http://onlinelibrary.wiley.com/doi/10.1002/cncr.25414/full (review)
-Big blurb on more amphetamine epigenetic changes
http://www.ingentaconnect.com/content/ben/cmc/2011/00000018/00000012/art00006

I'll post more when I have the time, but gotta love the boredom of the night shift.

 

[Epsilon Alpha]

Just a quick update on the 90mg to 54mg concerta friend, he just upped his dosage to 72mg today. Be it midterms or tolerance coming back I don't know.

 

[Epsilon Alpha]

Here's the regimes for those who did experience a tolerance reduction:

Quote:
Subject 1:
-90mg concerta/day + multivitamin for about 4 years prior.
-Abstinent for 1 week, dosing 500mg a day softgel curcumin.
-Was able to go down to 54mg concerta a day, hasn't been able to go down past 72 and function academically for a few years now. Back up to 72mg in about 2 weeks though.

Subject 2:
-abuse level dosage of d-amphetamine (dosage undetermined) for a few weeks before, minimum of ~30mg/day to function
-1g curcumin a day for 2 weeks while taking 15mg/day
-After trial was able to function at 20mg/day

Subject 3:
-30mg methylphenidate (generic IR)+CoQ10+200mg Mg +multivitamin+fish oil
-2 weeks using 20mg MPH/week, ~500mg-1g curcumin/day. One week abstinence +~500mg-1g curcumin/day.
-After trial was able to go down to 20mg/day with no difference in effects from 30mg

Subject 4:
-Had massive meth tolerance from months ago, no mention of what he was taking now aside from 40mg Adderall/day
-2g curcumin a day for a month + 20-40mg Adderall/day (tending towards 20)
-Down to 30mg/day after trial for ADHD

Subject 5:
-Took tons of random supplements and herbs + 20mg amphetamine (unspecified generic)
-Detox for 2 weeks just taking curcumin at 500mg to 2.5g doses + milk thistle 3 or 4 random 10mg doses thrown in there for school.
-Down to 10mg amphetamine a week
The people who didn't experience any tolerance reduction did note potentiation, but no effects on doses needed after. There were no common supplements to any of them aside from multivitamins and fish oil for 3. Most of them did one week trials, and only one was using MPH.

There were also 4 or 5 people who just couldn't stomach curcumin and did less than a week with it.
There were 8 people who trialed it for 1-2 weeks and did not experience any lasting tolerance reduction, however exercise seemed to be the strongest predicting factor in who experienced positive results.

If you'd like to trial this method please submit a report.

Best,
-Epsilon Alpha