Dexedrine Tolerance and Neurotoxicity

[Advaita]

Recently I have been using Ritalin and Dexedrine to help me study. Personally I prefer Dex - it feels cleaner, lasts longer and the comedown isn't too bad.

But anyway, I have noticed that the effects of the Dex are dramatically reduced in intensity if I do it over multiple days with no break. For example, I took 50mg nasally yesterday and had a wonderful euphoric feeling with great concentration for 5-6 hours, but the same dose today was not nearly as enjoyable or effective. I have taken moderate doses of Ritalin twice in the last week I should add.

I have heard multiple reasons explaining tolerance including:
-psychological tolerance
-depletion of stored dopamine/dopamine precursors
-reduced levels of magnesium
-neurotoxicity
-depletion of stored energy sources (such as glycogen)

Now to me, none of these are satisfactory given the moderate dose, infrequent use, and relatively healthy diet/sleeping habits I have.

So basically, why does the tolerance seem to be so pronounced?

 

[Dxmmonster]

LMFAO. your taking 50mgs(which is quite a bit) of dexamphetamine oral and snorted for many days, and you don't expect a fuckin tolerance?? dream on

and your also combining it with Ritalin which is cross tolerant with dexamp. what did you expect?

also dont say "moderate dose, infrequent use" after you said "if I do it over multiple days with no break. For example, I took 50mg nasally yesterday".
infrequent moderate use my ass. your obviously taking it for the euphoria and the motivation(which is what it's for but 50mgs is too much).

tolerance is a bitch, a cold hard bitch.

 

[MurphyClox]

...I have to agree: 50 mg is no low dose anymore, especially when used for studying.

If you want a helper for your studies, take 20 Ritalin and redose not more than 2 times a day, better less. If you're obviously feeling some euphoria, I would say that the dose is too high.

 

[Dxmmonster]

sorry i might have sounded a bit harsh in my previous post but you gotta becareful man and open your eyes. tolerance is going to rise if you abuse. even if you dont abuse and do exactly what the doctor says your still going to get some tolorance.

forgive me, I get really irritable when on tramadol.

 

[MurphyClox]

LOL! ...I get just funny...

 

[Advaita]

You are probably right, 50 is too much for study purposes, but I have to say I did study well - I never felt too overstimulated. I will admit I love the buzz I get from a large dose and I guess that's my problem. I find it hard not to take more once I feel it coming on. Also to clarify it was only 2 days in a row, and the Ritalin was a few days before that. I'm not going to do that much 2 days in a row again, mainly because I felt like a zombie at the end of the second day.

I still want to know what the mechanism of short term amphetamine tolerance is though, so if anyone could tell me or give me a link I would appreciate it.
Also anything about the neurotoxicity of amphetamines would be good too.

 

[Advaita]

...I have to agree: 50 mg is no low dose anymore, especially when used for studying.

If you want a helper for your studies, take 20 Ritalin and redose not more than 2 times a day, better less. If you're obviously feeling some euphoria, I would say that the dose is too high.

I disagree that euphoria means you've taken too much, I feel it on low doses of dex and ritalin. It's the feeling of euphoria which drives me to take more.

Also I should add that I obviously realized there was going to be some tolerance build up, just not after one day. I haven't used dex for a while before the last two days but the Ritalin probably contributed to the tolerance.

 

[Rectify]

Amphetamine causes the brain to release stores of dopamine and norepinephrine which then take a few days of normal eating and sleeping to replete.

As far as neurotoxicity goes, amphetamine is metabolized to 4-OH-AMP,
3,4-di-OH-AMP, 4-OH-3-MeO-AMP, and phenylacetone to name but four metabolites. The first three are formed via toxic arene oxide intermediates and the last gives off ammonia (NH3, which is highly toxic) as a byproduct.

None of these oxidation products are good for recovering neurons.

 

[Advaita]

Thanks for the info. My dopamine/epinephrine reserves were probably depleted, hence my lack of a buzz the next day - which is what I suspected. Hopefully at low to medium doses my neurons didn't take too much of a battering though.

 

[MurphyClox]

As far as neurotoxicity goes, amphetamine is metabolized to 4-OH-AMP, 3,4-di-OH-AMP, 4-OH-3-MeO-AMP, and phenylacetone to name but four metabolites. The first three are formed via toxic arene oxide intermediates and the last gives off ammonia (NH3, which is highly toxic) as a byproduct.

NH3 is toxic, correct. But considering the released dose in the respective time (several hours!) from metabolized amphetamine, that's negligible.

Especially the 3,4-di-OH-metabolite looks nasty. It's exactly a metabolite like this that is thought to cause a major part of MDMA's neurotoxicity.