Oh, wise ones in ADD! (And I mean that sincerely!)
I hate to post someone else's theories, but on the other forum it has sat dead for several months now and I want to get someone's take who is more knowledgeable.
This is the article in question:
VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse
http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05906.x/full
And here is the text of member "holdout", his interpretation of the article:
"Intimidating read?
The nutshell: when you first took a stimulant such as methylone or butylone or MDMA or mephedrone, etc. your susceptibility to neurotoxicity was extremely high due to high incidences of neuroexcitation because your neurons' little storage pockets, (which hold spare neurotransmitters for future use), had large "storage bins" the VMAT2 transporter is what that is. it has storage membranes that pump out the neurotransmitters forcibly by the stimulant you take.
so at first you EASILY got an overabundance of them being released because it was your first time. over time as you repeatedly did more stims, your VMAT2 stores became smaller because you have metabolized lots of ur neurotransmitters from pumping them out all over the place. so now you have your tolerance and also causing less neurotoxicity when doing stims because you have less neuroexcitation. after the VMAT2 stores become smaller from prolonged use of stimulants, they dont get big again. overall your brain/body is storing less neurotransmitters even if you take a 1-year abstinence!
some of you may now be picturing how it makes perfect sense if you chart the level of "magic" from before, where it would instantly spike super high, and compared to now, where the peak is not even CAPABLE of reaching the same peak as it reached before because you dont have enough neurotransmitters stored to enable that to happen when the stimulant comes and forces the VMAT2 to secrete.
as a compensatory change towards homeostasis like their publshing touches on, prolonged use of stimulants results in hypersensitivity of receptors that respond to the affected neurotransmitters because the overall volatility of acute neuroexcitability is "permanently" low due to the small VMAT2 stores. so to react to the small acute spikes/secretions, you need to be hypersensitive to them. that is why you are able to function normally again while sober: moved by things, good times / bad times, etc., rather than being a brain-dead zombie. that is also why you can get stressed out easily while coming down off stims and for the few days after that.
"So wait-- if i'm hypersensitive, why do i not have the magic?" dont forget you still have receptor downregulation from prolonged use of stims, so that's another factor that reduces the peak on that chart i visualized above. therefore you can only excite the entire neuron to a certain extent, much lower than before, causing weaker firings to other neurons, and therefore a cascading overall impression of just "blaaah". those who take periods of sobriety have some upregulation of receptors which is why the euphoria is slightly more profound when starting to take stimulants again, but still, your VMAT2 stores are too small to store as much neurotransmitters as before for the peak to reach the "magic" level. your hypersensitivity is pretty much secondary to the fact that your VMAT2 stores are minimal, so being hypersensitive does not mean you are profoundly so -- just a tad.
"so can't i load up on 5-HTP and tyrosine?" FOOL! don't be stupid. you'd be refueling a fire your body put out and maybe kill yourself, but in any case, it's not gonna work cuz the biosynthesis of serotonin and dopamine from availability of precursors/amino acids does not "shove them in all the right places" right off the bat. not all neuronal regions of the brain will be saturated with even distribution and the surplus would just get metabolized quickly without helping much anyway.
so... funny how things work out and give this overall impression of "adaptation" like your body adapted to stims to become unaffected and protect your health by "softening the blow" of acute spikes of neuroexcitation this way and that, but just as a natural failsafe quality of the "architecture". there was no deliberate intention to manipulate changes for your safety
moving along, i'm sure the question on everyone's mind is: "how do we get the vesicles big again?" well blocking influences on VMAT2 for a while does not seem to help much, so ... *shrugs*. no one knows of a way (yet?). if a way is found, tjhen i hypothesize that with so much neurotoxicity from stims use and changing the VMAT2 back to normal, you would be chronically inducing a state of psychosis with your perceptions of reality. as in chronic hallucinations galore."
So do you think he is on target with his interpretation? Is there anything that can be done?
I hate to post someone else's theories, but on the other forum it has sat dead for several months now and I want to get someone's take who is more knowledgeable.
This is the article in question:
VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse
http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05906.x/full
And here is the text of member "holdout", his interpretation of the article:
"Intimidating read?
The nutshell: when you first took a stimulant such as methylone or butylone or MDMA or mephedrone, etc. your susceptibility to neurotoxicity was extremely high due to high incidences of neuroexcitation because your neurons' little storage pockets, (which hold spare neurotransmitters for future use), had large "storage bins" the VMAT2 transporter is what that is. it has storage membranes that pump out the neurotransmitters forcibly by the stimulant you take. so at first you EASILY got an overabundance of them being released because it was your first time. over time as you repeatedly did more stims, your VMAT2 stores became smaller because you have metabolized lots of ur neurotransmitters from pumping them out all over the place. so now you have your tolerance and also causing less neurotoxicity when doing stims because you have less neuroexcitation. after the VMAT2 stores become smaller from prolonged use of stimulants, they dont get big again. overall your brain/body is storing less neurotransmitters even if you take a 1-year abstinence!
some of you may now be picturing how it makes perfect sense if you chart the level of "magic" from before, where it would instantly spike super high, and compared to now, where the peak is not even CAPABLE of reaching the same peak as it reached before because you dont have enough neurotransmitters stored to enable that to happen when the stimulant comes and forces the VMAT2 to secrete.
as a compensatory change towards homeostasis like their publshing touches on, prolonged use of stimulants results in hypersensitivity of receptors that respond to the affected neurotransmitters because the overall volatility of acute neuroexcitability is "permanently" low due to the small VMAT2 stores. so to react to the small acute spikes/secretions, you need to be hypersensitive to them. that is why you are able to function normally again while sober: moved by things, good times / bad times, etc., rather than being a brain-dead zombie. that is also why you can get stressed out easily while coming down off stims and for the few days after that.
"So wait-- if i'm hypersensitive, why do i not have the magic?" dont forget you still have receptor downregulation from prolonged use of stims, so that's another factor that reduces the peak on that chart i visualized above. therefore you can only excite the entire neuron to a certain extent, much lower than before, causing weaker firings to other neurons, and therefore a cascading overall impression of just "blaaah". those who take periods of sobriety have some upregulation of receptors which is why the euphoria is slightly more profound when starting to take stimulants again, but still, your VMAT2 stores are too small to store as much neurotransmitters as before for the peak to reach the "magic" level. your hypersensitivity is pretty much secondary to the fact that your VMAT2 stores are minimal, so being hypersensitive does not mean you are profoundly so -- just a tad.
"so can't i load up on 5-HTP and tyrosine?" FOOL! don't be stupid. you'd be refueling a fire your body put out and maybe kill yourself, but in any case, it's not gonna work cuz the biosynthesis of serotonin and dopamine from availability of precursors/amino acids does not "shove them in all the right places" right off the bat. not all neuronal regions of the brain will be saturated with even distribution and the surplus would just get metabolized quickly without helping much anyway.
so... funny how things work out and give this overall impression of "adaptation" like your body adapted to stims to become unaffected and protect your health by "softening the blow" of acute spikes of neuroexcitation this way and that, but just as a natural failsafe quality of the "architecture". there was no deliberate intention to manipulate changes for your safety
moving along, i'm sure the question on everyone's mind is: "how do we get the vesicles big again?" well blocking influences on VMAT2 for a while does not seem to help much, so ... *shrugs*. no one knows of a way (yet?). if a way is found, tjhen i hypothesize that with so much neurotoxicity from stims use and changing the VMAT2 back to normal, you would be chronically inducing a state of psychosis with your perceptions of reality. as in chronic hallucinations galore."
So do you think he is on target with his interpretation? Is there anything that can be done?
