Posted by JGalt on November 28, 2001, at 18:20:59
In reply to Re: amphetamine sensitization article(REBUTTLE) , posted by benzapp on November 25, 2001, at 20:59:21
You're certainly right on the fact that it was produced by the NIDA w/ their own agenda that by no means has any correlation with the truth. I was worried about that too... anyway, I think you misunderstood one thing, that is that sensitization means to be sensitized, which means that at least some of the effects (usually the undesireable ones) become more potent with time (especially during intermittant dosing).
>Stimulants are stimulants because they affect the adrenal system or mimic its function.
For some stimulants, yes, but what about those that act primarily on the reward system? I could be wrong on this, but as far as I know amphetamine goes into the brain, and then forces some of the presynaptic vesicles to release their dopamine, and of course also it has some effect on serotonin and increasing adrenaline...the increase in adrenaline surely must be small compared to the increase in dopamine (for amphetamine).
< < The end result of any stimulant, cocaine, amphetamine or epinephrine released by your adrenal gland due to stress will raise your body temperature. Stimulants affect metabolic rate, that is your body's utilization of stored energy. Stimulants cause weight loss by increasing the metabolic rate, utilizing more stored energy (fat). > >
Actually most stimulants cause weight loss primarily by decreasing appetite. The actual effect on metabolism rarely ever exceeds 10% by stimulants. High increases in metabolism are not possible without DNP (up to 70% increase) or perhaps high doses of thyroid hormone.
> >100mg/kg? Thats insane. Maybe with a rat. But I dare you to eat 30 grams of cocaine, hyperthermia will be the least of your problems. Also, with cocaine, the dopamine reuptake affect is a THEORY, and a highly unproven one at that. Its stimulant effect actually seems to be caused due to inducing cortisol release, which causes epinephrine to be released. > >Surely you realize that the mg/kg amounts for rats are much higher than for us. Granted that's still a much higher dose than we are using for psychiatry even when you do take into account the rat-human differences...
> The drugs mentioned that supposedly protect against neuron damage and hyperthermia due so because they suppress the stress response induced by these drugs. Without getting into the physiology, natural stimulant reactions occur due to the following: antagonised GABA-A receptors cause the anterior pitutary gland in the brain to release the Adrenocorticotropic hormone, which in turn causes the adrenal gland to release corisol and epinephrine. Basically, the drugs are GABA-A antagonists, and interfere with the entire stress response. Hyperthermia doesn't occur because the body no longer thinks it needs to prepare for a life threatening battle. For the Opiate advocates out there, endorphins mediated by the hypothalamus potentiate endogenous GABA-A agonist production. Of course, cooling the ambient temperature to a level that makes it impossible for your body to increase in temperature will have the same effect. So, the article spend a great deal of time talking about how to counter act hyperthermia induced by the stress response.
>I'm sorry, I guess I don't understand where you're getting this from. If what you say is true, then it would seem all one would have to do would be to take a benzo (such as clonazepam) and we would be free of amphetamine neurotoxicity. But where you're getting that all these drugs act as GABA agonists, if that is what you're saying, I do not see...their actions on DA seem much more relevant to me.
> The primary question is this, does hyperthermia cause dopamine axon damage in general, or only when present with amphetamine? The suggestion that cocaine is not damaging to dopamine axon terminals seems to suggest this, but this distinction is not made. Of course, if the former is true it would mean every time you have a fever you are killing brain cells.
>Well obviously you are right there that it is hyperthermia from amphetamine that causes the damage. The drugs they used to counteract it seemed mostly there to prevent DA from being released in too great of quantities (with the exception of the reuptake blockers).
> Damage to neuron axons seems to occur when the axon is unoccupied for extended periods of time, allowing free radicals to damage it. When you take amphetamine, it affects your brain like epinephrine, activating the same receptors, but amphetamine does not containe the necessary hormone utilized by DNA transcriptase. So while the brain wants to produce more dopamine, it lacks the ability to read a DNA strand and thus is unable to produce the proper proteins. If any neurotoxicity results, it is due to your brain using up dopamine thinking more will be made, which never happens. The exposed axons are vacated when dopamine runs out and are damaged by free radicals.
>This is an interesting theory for sure... However, I hardly feel euphoric by taking something that causes epinephrine release, unlike AMPH which from my reading has more direct effect on dopamine release.
> Cocaine probably doesn't cause dopamine axon damage because cocaine stimulates the release of natural epinephrine, which allows the further production of dopamine and thus the neurons are not as vacant.
>This isn't making any sense, if all amphetamine is doing is releasing epinephrine, then all I have to do is take ephedrine or anything else which causes some of its release and I'll get the same effect. Not hardly.
> Just to let you know, increased body temperature occurs due to increased energy utilization, either for locomotion or cellular activity. The reason you get a fever when you are sick is not to kill invading bacteria, but because your body is producing so many new cells at a rapid rate. >
So are you saying that if we take aleve to lower the body temperature that it will slow the rate at which new cells divide?
>
> Lowering the metabolic rate by interfering with the endocrine system or by directly lowering the persons temperature only means that less cellular division will be taking place, meaning less activity in general will be taking place and dopamine won't be overutilized.
>
> But for people who take low doses of amphetamine on a daily basis, this does not happen. I take 40mg of Adderall every day, and my body temperature only exceeds 98.6 degrees when I am sick, or when I am working out. > >Of course, even the article stated that after continual use hyperthermia, if present, would level out from lowered DA levels. There's several other mechanisms I can think of that would also account for the lowered body temp...in any case with several times-daily dosing tolerance to motivating effects of amphetamine wears out quick at a given dose.
> Again, the article here is about amphetamine TOXICITY, not amphetamine in general. Everything is toxic, the only question is how? If you are taking any amphetamine as prescribed, I highly doubt you have anything to worry about. I just don't see any connection between the facts presented and the toxicity of 20mg of dextroamphetamine. Further, I don't see any logical explanation on why this would even occur. The articles failure to address the significance of hyperthermia is also troubling > >
I agree, I doubt low doses have toxicity either. When you look at serious addicts that after years of high doses have finally amassed significant amounts of damage, it is easy to believe that small doses aren't going to cause the same problems. I am simply interested in decreasing tolerance to the mood-lifting/motivating effects of amphetamine and decreasing eventual sensitization to the irritability and anxiety type effects of it. To me, amphetamine seems like borrowed energy. If you take it one day, but not the next you'll be that much more depressed and unmotivated and unfocused...after a few days of steady dosing, tolerance sets in and the bad side effects become more predominant...the increased focusing ablitiy doesn't seem to go away, or else it would be uneffective for ADD. I just am interested in finding ways around this negative feedback mechanism...probably something to do with one or two of the particular DA autorecptors.
poster:JGalt
thread:84550
URL: http://www.dr-bob.org/babble/20011123/msgs/85448.html