• 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

researchers discover immune system mechanism behind methamphetamine tolerance

E

excxp

Bluelighter
Joined
Mar 22, 2004
Messages
5
Location
El Cajon, ca
http://www.scripps.edu/newsandviews/e_20040927/janda.html

Antibodies are usually produced only in response to large molecule invaders such as proteins, not to small drug molecules. Glycation acts like a linker that allows [the methamphetamine] to be displayed to the immune system, triggering a vaccine-like reaction.
Click to expand...

The crux of our finding is that methamphetamine can react with glucose and proteins to form what are called a "glycated" product. Additionaly, we showed that the presence of these methamphetamine-glycated proteins in the bloodstream can lead to a response from the immune system, stimulating the production of antibodies that recognize the glycated form of methamphetamine. This immune response might be one way that the body acquires resistance and may have implications for why methamphetamine addicts go on long binges. If the antibodies prevent some of the drug from reaching its place of action in the brain, addicts might require more of the drug because some of it is bound up by antibodies. What this suggests is that since methamphetamine may react with proteins and induce an immune response; perhaps the body naturally has the ability to generate antibodies that may counteract methamphetamine. If the mechanism we are proposing is correct, then addicts are in essence vaccinating themselves against the drug when they use it and thus exposing themselves to ever-increasing amounts of methamphetamine in order to achieve a high. Amphetamines in general are capable of this type of chemistry, but not all drugs of abuse. It is the molecular structure of the drug that determines if "glycation" is possible. Our initial studies into this area were with a long-lived nicotine metabolite, nornicotine, which can also participate in protein glycation. The two compounds possess similar molecular structures. Thus, our study does not necessary provide new "cautions" as methamphetamine is already known to be highly addictive and heavy use leads to tolerance, but instead, provides a previously unrecognized mechanism for why methamphetamine users develop tolerance.
Click to expand...
 
Not thouroughly surprising
Reference
Dickerson TJ, Yamamoto N, Ruiz DI, Janda KD.
Immunological consequences of methamphetamine protein glycation.
J Am Chem Soc. 2004 Sep 22;126(37):11446-7
 
when i was using methamphetamine, i would only do a 1/4 gram at a time. that was more than enuff usually, and i wouldn't use the stuff again for several days.

i've heard ppl say they injected a gram or more at one time. now i can understand why. i always thought anyone injecting a whole gram at once was insane....

methamphetamine is very powerful and i it find interesting that the body may actually be fighting against the substance in the system while the "user" (tweaker) is high.
 
This is kinda like a study of looking at this concept from another "view" or "side" of previous knowledge/studies on the subject. which is neat.

To further support the role of Magnesium in amphetamine addiction/tolerance etc.

Along with its supporting subjects, as B12 injection at hospitals.
 
Not to sound like a broken record, but how does "this [imply] that severe receptor downregulation probably isn't as severe." They make no effort to quantify the effect of the immune response on tolerance, or even that it has one.
 
I'm saying that if the immune response is partially (to whatever degree) responsible for tolerance, then it takes some of the burden of tolerance off other mechanisms.

My brain is having issues wording things today, so apologies if that still doesn't make sense.
 
This might be of some interest

Attenuated microglial activation mediates tolerance to the
neurotoxic effects of methamphetamine

Journal of Neurochemistry, 2005, 92, 790–797

David M. Thomas and Donald M. Kuhn

Abstract

Methamphetamine causes persistent damage to dopamine nerve endings of the striatum. Repeated, intermittent treatment of mice with low doses of methamphetamine leads to the development of tolerance to its neurotoxic effects. The mechanisms underlying tolerance are not understood but clearly involve more than alterations in drug bioavailability or reductions in the hyperthermia caused by methamphetamine. Microglia have been implicated recently as mediators of methamphetamine-induced neurotoxicity.

The purpose of the present studies was to determine if a tolerance regimen of methamphetamine would attenuate the microglial response to a neurotoxic challenge. Mice treated with a low-dose methamphetamine tolerance regimen showed minor reductions in striatal dopamine content and low levels of microglial activation.

When the tolerance regimen preceded a neurotoxic challenge of methamphetamine, the depletion of dopamine normally seen was significantly attenuated. The microglial activation that occurs after a toxic methamphetamine challenge was blunted likewise. Despite the induction of tolerance against drug-induced toxicity and microglial activation, a neurotoxic challenge with methamphetamine still caused hyperthermia.

These results suggest that tolerance to methamphetamine neurotoxicity is associated with attenuated microglial activation and they further dissociate its neurotoxicity from drug-induced hyperthermia.
Click to expand...
 
So does that mean taking l-deprenyl regularly would reduce the damage d-methamphetamine does to the dopamine axons, because l-deprenyl is metabolised to l-methamphetamine?

(i hope so)
 
Has anyone thought if this could also explain 'loss of magic' type of tolerance reported by MDMA users?
 
^^^
I don't think so, simply because the two tolerances seem so different.

I lost the magic around MDMA dose 8 or 9, despite never using the drug heavily (and always spread out, 1 dose at a time, etc). I never lost the EFFECTS, the magic simply wasn't there anymore.

Meth tolerance is much more simple and all encompassing, as time goes on, you need more and more to get ANY effects.
 
I would have thought that if antibodies can be produced to this "glycated" methamphetamine then they would only inhibit the "glycated" methamphetamine as well. I have a feeling any of this glycated methamphetamine would be unable to produce its normal effects anyway so it's difficult to see how this would have an effect on tolerance.
 
^ Your absolutely right. The affinity that the glycated-meth antibody had for standard methamphetamine was very low. As I commented before, they made no attempt to quantify whether or not the antibody played any role in tolerance.
 
rather interesting.

During my methamphetamine weekly abuse i encountered a really annoying tollerance.
To be more precise...it was a psicological tollerance.
After smoking 1/4g i would feel no real tweaking in my brain and muscles, but still some other side effect where very noticeble like pupil dilatation, body decongestion, jaw clenching, sweating, oily skin,eyes wide open, dry mouth, deep breathing, wanting to smoke sigs.......like in the mirror i look really fucking tweaked, but i wasnt tweaked at all, none of that wonderfull brain effect and that comfty sensation un your skin.
Im sure it wasnt pseudoefedrine nor L-methamphetmine since the other people i smoked with where really, really tweaked after 1/8g.
I smoked some more later and there was only a slight tweak in my head, but phisically, I looked like i had an overdose...like a fucking zombie.
Btw some sort of psicological and skin tweaking (different from normal meth tweaking) showed up if i layed or sat down and started breathing energetically.

Back then i knew nothing about brain functions, neurotransmitters, and how drugs work in the body.
Later on i suggested it was due to methamphetamine neurotoxicity, that i fucked up most of my dopamine receptors.
Now, after a looong pause from meth, a healthy diet full of vitamins and especially phosphorous compouds, magnesium, zinc (which i read that may benefit brain health), i start to feel some good tweaking again, not as strong as my first times, but still i feel satisfied with 1/4g of good quality d-meth.

You guys thing my tollerance could have been (also) due
to this antibody function?

I would really apreciate a response for someone that knows more than me on the subject, so i might avoid this anoying tollerance again.

Respect - Navarone
 
http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/ja047690h
does anyone know where one can acquire a hacked logon to the American Chemical Society?
damm facists want people to pay for knowladge....

"Beware the man who tries to deny you knowladge, for he is trying to become your god"
-(unsure of originator), heard it from a person who's place i crashed at in calgary after my car got tag teamed by a patch of ice and a curb
 
^ I don't think they want you to pay for knowledge, they want you to pay for their salaries. Anyway here is the PDF.
 
Almost certainly not.

That'll just be some immune response to something else. Whether it's a direct effect of noradrenaline, or because your mouth got all dry and bactaria started growing, or something else... but it wont be that.
 
You must log in or register to reply here.
Top