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Adderall (four amphetamine salts)

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  #31  
Old 05-13-05, 03:26 PM
jerry83 jerry83 is offline
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adde
Quote:
Originally Posted by JimboOmega
taking Adderall XR in the fasted state versus the fed state bumps your Tmax up a couple hours, to something between 5 and 6 hours. This might be part of the reason people find it tapering off after 5 or 6 hours, because that's when levels would start to drop.
Isn't it the other way around? "Food does not affect the extent of absorption of ADDERALL XR capsules, but prolongs T max by 2.5 hours (from 5.2 hrs at fasted state to 7.7 hrs after a high-fat meal)."
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  #32  
Old 05-13-05, 06:09 PM
JimboOmega JimboOmega is offline
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Well okay, I guess the way I said it was misleading --
When I said it gets "bumped up" a couple hours, what I meant was that it occurs about two hours earlier. So taking medication in the fasted state makes the Tmax two hours earlier.
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  #33  
Old 05-13-05, 09:26 PM
LegallyInsane LegallyInsane is offline
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Actually, tolerance (and specifically, amphetamine tolerance) is the result of a natural phenomenon known as long-term potentiation. Basically this means that your brain "remembers" the substance and therefore rejects it as foreign. The only way to reduce this "memory" is to block NMDA-receptors from receiving transmissions. This is done through an NMDA-antagonist. There are several NMDA-antagonists available, including minerals Magnesium and Zinc, cough suppressant dextromethorphan hydrobromide, and Memantine (which is a drug generally used for Alzheimer's patients). All these antagonists have varying bioavailabilities, half-lifes, and affinities for NMDA-receptors. My pick would be Memantine due to its mean plasmid concentration (~100%) compared to that of something like Magnesium or Zinc. Taking Memantine at night would ensure a nice plasmid level for when you take your Adderall in the morning. However, this is not a long-term solution for Adderall tolerance because blocking NMDA-receptors results in memory loss and learning difficulty. For this reason, Adderall is pretty much ineffective for the long-term treatment of ADHD and should not be considered a first line of defense.
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  #34  
Old 05-13-05, 09:32 PM
brandnewvibe brandnewvibe is offline
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Ascorbic Acid versus X Ascorbates

It seems pretty clear that ascorbic acid will acidify intestinal contents. I'm not entirely clear on what effect this has on absorption--I've always heard that it decreases absorption, but a poster in this thread is claiming that the acidification will actually increase intestinal absorption, but will decrease reabsorption in the kidneys.

Vitamin C not only comes in the form of ascorbic acid, but also as "magnesium ascorbate," "sodium ascorbate," and various others. Magnesium Ascorbate is actually pH neutral. I assume this means it will not acidify intestinal contents, so therefore it shouldn't have much of an effect on intestinal absorption. But will it have an effect on kidney reabsorption? Basically I'm trying to figure out how much of what is said about 'Vitamin C' with relation to Adderall is actually relevant only to ascorbic acid, and how much is relevant to any form of Vitamin C.
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  #35  
Old 05-14-05, 12:27 AM
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Quote:
Originally Posted by LegallyInsane
Actually, tolerance (and specifically, amphetamine tolerance) ..... Adderall is pretty much ineffective for the long-term treatment of ADHD and should not be considered a first line of defense.
That is quite a mouthful, considering that Adderall is one of the most widely prescribed drugs for adhd. I'm connecting the dots here but it looks like your implying that Adderall is not good choice because tolerance would make the drug ineffective for most, over the long term. If this is what your suggesting I would like to see links please. I'm sure many on the board would be interested.
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  #36  
Old 05-14-05, 02:53 PM
LegallyInsane LegallyInsane is offline
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Quote:
Originally Posted by scuro
That is quite a mouthful, considering that Adderall is one of the most widely prescribed drugs for adhd. I'm connecting the dots here but it looks like your implying that Adderall is not good choice because tolerance would make the drug ineffective for most, over the long term. If this is what your suggesting I would like to see links please. I'm sure many on the board would be interested.
I don't have any links specifically, but you can surely look up NMDA and its effects on tolerance on any medical encyclopedia. Adderall is extremely effective (perhaps too effective) for the short-term treatment of ADHD. Every person is different though and building up tolerance may come within weeks or it may come within months. It's just like a tolerance to alcohol. It depends how much and how often you use it.

In my opinion, the medication that makes the most sense for the long-term treatment of ADHD is Wellbutrin (which is actually marketed as an anti-depressant, much the same way that Adderall is used off-label as an anti-depressant). Wellbutrin changes the way existing dopamine/norepinephrine is controlled in the brain, rather than a drug like Adderall which simply produces more dopamine/norepinephrine.
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  #37  
Old 05-14-05, 03:06 PM
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I have started a new thread because possible stimulant tolerance which would make a stimulant ineffective, is an important issue to many. It also strays from the question of whether vitamin c is helpful for those who take meds. Hope to post soon.

http://www.addforums.com/forums/showthread.php?t=17742
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  #38  
Old 05-14-05, 06:23 PM
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Quote:
Originally Posted by LegallyInsane
Wellbutrin changes the way existing dopamine/norepinephrine is controlled in the brain, rather than a drug like Adderall which simply produces more dopamine/norepinephrine.
This is incorrect.

Adderall does not "produce" more dopamine/norepinephrine, nor does it it indirectly result in increased production of either. Just like Wellbutrin, it just changes the way existing dopamine and norepinephrine are handled.

Adderall blocks the reuptake of dopamine and norepinephrine into the presynaptic neuron, and actually increases their release from the presynaptic neuron into the extraneuronal space.

The working theory of how it achieves this effect is that it "reverses" the reuptake mechanism, turning it into a "pump" instead of a vacuum.

I can see how one might hear that Adderall causes the "release" of dopamine and norepinephrine and think this means the same thing as "increasing production."

Of course, the distinction between LegallyInsane's claim and the theory currently accepted by the medical community isn't that important for anything being discussed here. My reason for posting this is both for educational value, and so that people are reminded to take with a grain of salt (maybe even amphetamine salt ) things posted here by even very knowledgable-sounding posters.

References:

Kuczenski R, Segal DS. Neurochemistry of amphetamine. In: Cho AK, Segal DS, eds. Amphetamine and Its Analogs—Psychopharmacology, Toxicology, and Abuse. San Diego, Calif:Academic Press; 1994:81-113.

Pliszka SR. Comparing the effects of stimulant and non-stimulant agents on catecholamine function: implications for theories of ADHD. In: Solanto MV, Arnsten AFT, Castellanos FX, eds. Stimulant Drugs and ADHD—Basic and Clinical Neuroscience. New York, NY: Oxford University Press; 2001:332-352.

Grace AA. Psychostimulant actions on dopamine and limbic system function: relevance to the pathophysiology and treatment of ADHD. In: Solanto MV, Arnsten AFT, Castellanos FX, eds. Stimulant Drugs and ADHD—Basic and Clinical Neuroscience. New York, NY: Oxford University Press; 2001:134-157.

Wilens TE. Faraone SV. Biederman J. Attention-deficit/hyperactivity disorder in adults. JAMA, 2004; 292(5):619-23.

Wilens TE, Spencer TJ. Pharmacology of amphetamines. In: Tarter RE, Ammerman RT, Ott PJ, eds. Handbook of Substance Abuse:Neurobehavioral Pharmacology. New York, NY:Plenum Press; 1998:501-513.
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  #39  
Old 05-14-05, 07:57 PM
LegallyInsane LegallyInsane is offline
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Yeah I figured I shouldn't have dropped out of medical school
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  #40  
Old 05-14-05, 08:13 PM
LegallyInsane LegallyInsane is offline
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Btw, you got that information from the back cover of Shire's brochure: http://www.fda.gov/cder/foi/label/20...303s005lbl.pdf

"Amphetamines are thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space."
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  #41  
Old 05-15-05, 12:31 AM
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Brandnewvibe,

This is the way that I understood it, a good post.
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  #42  
Old 05-15-05, 01:13 AM
HughEvans HughEvans is offline
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First things first: I want to clarify that I don't question whatsoever that urine pH has a direct impact on AMP excretion rates. What I meant in my earlier post is that seriously doubt any benefits from brief "medication holidays."

The LTP model has not been examined in ADHD, which is where it would be relevant for us. We have strong evidence of physiological differences in the ADHD brain. To the best of my knowledge, LTP research has thus far been limited to sea-slugs and mice (haven't looked too thoroughly into this, so if I'm off it wouldn't suprise me). Animal models are often useful as guides but are often inconsistent with humans. There's no way of knowing until more is learned about ADHD's causes.
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  #43  
Old 05-15-05, 11:31 AM
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There are many anecdotes of holidays ameliorating tolerance. What explains this? Placebo effect, mass hysteria?

There are certainly physiological differences in those with ADHD. Many structural and functional abnormalities can cause ADHD symptoms. One person's cause of ADHD may not be another's. I have a feeling this is what may determine "tolerance" in some people, and/or response short and long-term to particular types of drugs.
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  #44  
Old 05-16-05, 11:02 AM
JimboOmega JimboOmega is offline
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The "standard" holiday is around a month. HughEvans was referring to shorter holidays, of a weekend, or in the extreme case, an evening, as being ineffective.

Also, poking around what LegallyInsane posted shows a of holes. The links aren't clear and well established as he would have you believe, and his ultimate conclusion is( "For this reason, Adderall is pretty much ineffective for the long-term treatment of ADHD and should not be considered a first line of defense.") is very questionable.

As we all know, stimulant medications have been used for decades to treat ADHD symptoms, and are generally prescribed as the first-choice, and are generally held to be a lot *more* effective than slower-acting drugs (such as Strattera, Wellbutrin, etc). In fact, I *have* seen studies pitting strattera against adderall, and the result was that ritalin was clearly more effective. (You can see the discussion here though you are forewarned the site in question is pushing their own alternative treatment and is somewhat sketchy. The study was apparently done by the APA, but funded by Shire.)

Shire's research (as illustrated elsewhere) also showed long-term improvement in symptoms with adderall treatment, and even my P-Doc has spoken of patients in whom improvement was still present after 15+ years of treatment.

The implied mechanism by which tolerance develops, long-term potentiation, is totally a red herring. Long Term Potentiation is the means by which cells adapt to stimulus to "learn", this is true. And NDMA is very important in this process. What does this have to do with tolerance? Nothing! Blocking memory to prevent tolerance which doesn't exist is a completely ridiculous solution.

People don't "learn" to tolerate the drug. That's ridiculous. It's not a matter of memory. That suggests that if I didn't "know" I was taking it, I'd never develop tolerance...? Bizarre.

Don't believe me? Do a google yourself. Do "Long term potentiation tolerance" You'll get a lot of links, but if you examine them, they're nearly all unrelated things - for instance, a study of tolerance summarized on the same page as a long-term potentiation study. Or a glossary page. Sometimes they're both evaluated in the context of chronic drug use, but there is no implied link. You'd think if this was the main means by which tolerance was achieved, there'd be something more. There isn't.

Actually, I did find one study stated that "that there may be a threshold beyond which the excessive brain stimulation that probably occurs with compulsive psychostimulant use results in the occlusion of LTP[Long Term Potentiation]. " ( here) So Long term potentiation is actually OCCLUDED by serious psychostimulant use? There are a few other studies like this, indicating chronic drug use can interfere with LTP and thus that could be a cause of memory problems.

While stimulant medications can increase stimulation, and thus increase Long Term Potentiation (in moderate/light use), the link to tolerance is... non-existent.
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  #45  
Old 05-16-05, 12:16 PM
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As yet I have not developed a tolerance to stimulant medication. My psychiatrist is pretty sure this strongly confirms the diagnosis of ADHD. While I disagree that you can make that particular claim (I think even those without significant frontal lobe impairment generally benefit from stimulant therapy), I am very grateful for the continuing benefits this drug brings me.
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