I was also under the impression that with meth specifically that the way it crosses the blood brain barrier allows it to avoid exposure to monoamines, which in turn increases its duration of effect. And because of how quickly and for how long it can remain in the brain, its creation of things like peroxides is part of what adds to the brain damage it can cause? I also saw somewhere that using NMDA antagonists can cause amphetamine and methamphetamine tolerance to build more slowly, due to the way it effects dopamine regulation?
Neurobiology
Methamphetamine affects the central nervous system (CNS) by releasing monoamine neurotransmitters such as dopamine, norepinephrine, and serotonin.
Administration of MA leads to many pharmacological effects due to its ability to use various molecular processes.
MA increases levels of monoamines by forcing the monoamines out of their storage vesicles and expelling them into the synaptic gap by making the dopamine transporters work in reverse.
Other mechanisms by which methamphetamine are known to increase monoamine levels are by:
-Blocking the reuptake of monoamines by inhibiting the activity of monoamine transporters
-Decreasing the expression of dopamine transporters at the cell surface
-Increasing cytosolic levels of monoamines by inhibiting the activity of monoamine oxidase (MAO)
-Increasing the activity and expression of the dopamine-synthesizing enzyme tyrosine hydroxylase (TH)
-In addition to releasing potent amounts of monoamines, MA has a high lipid solubility that leads to a relatively fast transfer of the drug across the blood brain barrier.
Metabolism
The liver is primarily responsible for the breakdown of MA. The drug undergoes oxidation and glucuronidation in the liver creating amphetamine, norephedrine, and p-hydroxynorephedrine. The oxidation of MA to amphetamine is partly done by cytochrome P-450 (CYP) isoenzyme 2D6. The elimination half-life (t-1/2) of MA is dependent on the urine pH. When urine pH is six to eight, the half-life is about 12 hours, staying constant and unaffected by the route of administration.
source:
http://methoide.fcm.arizona.edu/infocenter/index.cfm?stid=166
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^Whaaaat?! got any links on the oxytocin release from mdma/and its addiction relieving properties? Im really interested in that
The hormone oxytocin — known as the “love drug” or “cuddle chemical” — plays an important role in pair-bonding, child-rearing and social behavior. Now researchers are discovering that it could also help explain the effects of a popular party drug, and may be involved in some potential treatments for autism and addiction.
Here’s a rundown of some of the latest research findings:
1.
The ecstasy–oxytocin link. Researchers have found that the loved-up effects of ecstasy (MDMA) are due at least in part to oxytocin. “Administration of MDMA increases plasma oxytocin levels in humans,” says Gillinder Bedi, Columbia University assistant professor of clinical psychology and lead author of new research on the effects of MDMA and methamphetamine.
The oxytocin–MDMA link has also been shown in rats, according to Iain McGregor, professor of psychopharmacology at the University of Sydney. “We were able to get rid of a big part of the social behavior induced by MDMA [by blocking oxytocin],” he says. “What was striking was the big reduction in social [facilitation] — but it was not a complete abolition.”
2.
Using oxytocin to battle addiction? In Bedi’s recent study, he found that methamphetamine and MDMA were surprisingly alike in terms of their social effects (surprising, because users on meth are typically thought of as cold and compulsive, rather than warm and fuzzy like users of ecstasy), at least when the methamphetamine was given orally at low doses. It turns out, however, that oxytocin is not the common denominator between the two drugs — MDMA may increase oxytocin, while methamphetamine may not affect it directly.
In previous rat studies, researchers have found that the release of oxytocin is not involved in the high of amphetamine (whose effects are more similar to those of methamphetamine than MDMA’s are) — and that blocking the hormone had no effect on rats’ desire for the drug. Conversely, blocking oxytocin did decrease rats’ interest in MDMA, suggesting that the hormone may be involved in ecstasy’s “high.”
But, interestingly, increasing oxytocin may reduce desire for meth. McGregor found that giving rats oxytocin made them lose interest in taking methamphetamine. “Much to our surprise and delight, we were able to basically eliminate meth self-administration, which is extremely vigorous in rats,” he says. “If you don’t limit them, they can overdose. It was quite interesting.”
As a result of that research, McGregor and his colleagues are now testing intranasal oxytocin to help reduce addiction in alcoholics and heavy pot smokers. “We’re in very early stages of clinical trials,” he says.
3.
Why oxytocin may help autistic people. Unlike meth and amphetamine, MDMA isn’t particularly addictive. Over time users typically take MDMA less frequently, not more, as it tends to stop having pleasant effects. Could oxytocin be involved in the difference?
“One idea that we chucked around is that there are two parallel systems in the brain — one to do with desire for things and objects, the other tilted toward animate objects, friends, family, maybe pets,” says McGregor.
Both systems clearly involve the neurotransmitter dopamine, which has long been linked with desire — including addictive desire — and the pleasures involved in anticipation and drive.
“Maybe when you get high levels of oxytocin, plus high levels of dopamine, you have a motivational situation where you are strongly oriented toward [people],” McGregor says. “Maybe when it’s only dopamine, you’re oriented toward objects.”
The former situation would describe the MDMA user, who is not compulsively driven to take more ecstasy but who does want to cuddle and be social while high. In the latter situation, you have high-dose methamphetamine users — compulsively driven not only to take more meth, but to engage in repetitive behaviors with objects like scrubbing the floor or organizing collections.
If those characteristics sound vaguely reminiscent of autism, you’d be right. The findings on oxytocin may well lead to some new treatments for autism, McGregor suggests, given that autistic people have difficulty making the oxytocin-driven connection between people and pleasure. The drug baclofen, which is, in various forms, being tested for the treatment of alcoholism, other addictions and autism, has in fact been shown to affect oxytocin. “We published a paper last year showing that baclofen strongly activated oxytocin in the rat brain,” says McGregor. And oxytocin itself is also being studied as a treatment for autism.
Sometimes the intricate interconnections of science — in this journalist’s experience — can be overwhelming. Who knew that a new study on methamphetamine and MDMA would connect to experimental treatments for both autism and addiction?
link:
http://healthland.time.com/2010/12/...addiction-and-autism-treatments-its-oxytocin/
Oxytocin decreases methamphetamine self-administration, methamphetamine hyperactivity, and relapse to methamphetamine-seeking behaviour in rats
link:
http://www.sciencedirect.com/science/article/pii/S0028390809001750
Systemically administered oxytocin decreases methamphetamine activation of the subthalamic nucleus and accumbens core and stimulates oxytocinergic neurons in the hypothalamus.
link:
http://www.bioportfolio.com/resourc...of-the-subthalamic-nucleus-and-accumbens.html
google it. tons more info around.
