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  1. #1
    Senior Member krazyj's Avatar
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    After searching around the forums, I only found little bits of useful information regarding amphetamine tolerance/sensitization/withdrawal. I figured we could reap the most information on this topic by creating one thread for it and getting the ball rolling. With that...


    When does tolerance begin? 2 weeks? 1 month? A Year?
    When does sensitization begin? 2 weeks? 1 month? A Year?

    Which effects does tolerance develop to?
    Which effects does sensitization develop to?

    Does tolerance continue to build over time or is it reached and stays?
    Does sensitization continue to build over time or is it reached and stays?

    What are ways to combat tolerance? Extended time off? Day off/week? Supplements?

    How long is withdrawal?

    Any other pertinent information for starting/trialing amphetamine or using amphetamine as a sustained treatment?


    Let's hear it.

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    Senior Member Frangible's Avatar
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    1. Single dose
    2. Single dose
    3. Adrenergic (partial), anorexic, wakefulness
    4. Various regional DA transmission
    5. Both
    6. Both
    7. All
    8. Varies
    9. Talk to your doctor

    You don't get much sensitization in humans really though some of the beneficial effects on DA transmission persist after the drug is completely withdrawn due to plastic adaptations.

    Tolerance to euphoria / mood boosting effects is 100% with Rx dosing in ~1-2 weeks.
    Tolerance to anorexia is 100% with Rx dosing in ~4-6 weeks
    Beta receptor downregulation happens after a single dose and should be mostly suppressed after a week or so, same story as ephedrine.
    Wakefulness seems to take about 2 weeks and tolerance depends on consistent dosing.

    Most of the beneficial effects for ADD are subject to neither tolerance nor sensitization.

    Withdrawal from chronic Rx dosing is about a week of brain fog/poor mood/sleeping, a month of fatigue, and then a month of that gradually diminishing thereafter.

    Withdrawal for a month or so will reverse tolerance to most of the effects.
    <span style="color:#660000"><span style="font-size:8pt;line-height:100%"><span style="font-family:Arial Narrow">"... </span></span></span><span style="font-family:Arial Narrow"><span style="font-size:8pt;line-height:100%"><span style="color:#8b0000">fresh bread, which deforms elastically is not frangible." --Wikipedia</span></span></span>

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    Senior Member ziddy's Avatar
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    <div class='quotetop'>QUOTE ('frangible')</div><div class='quotemain'>Withdrawal from chronic Rx dosing is about a week of brain fog/poor mood/sleeping, a month of fatigue, and then a month of that gradually diminishing thereafter.</div>
    What about sporadic dosing, sometimes < Rx (60mg/day) and sometimes > Rx (I generally don't count >_>)? Have been feeling like shit, day 5 off the shit and little signs of improvement. Friends applaud for quitting but aren't too keen to spend much time around me either >_<.
    http://abolitionist-society.com
    Towards the Abolition of Suffering Through Science

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    Senior Member krazyj's Avatar
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    Frang,
    I want to start titrating Vyvanse up from the bottom starting at no prior use (well, I dropped 50mg today but I decided I want to start at 20mg and work up painfully slow).

    Any ideas on what might be a good protocol? 1 month at 20mg then +10mg every 2 weeks (2 weeks for stabilization then 2 weeks to trial the effects of each)?

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    Senior Member Frangible's Avatar
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    <div class='quotetop'>QUOTE (ziddy @ Sep 24 2008, 01:47 PM) <{POST_SNAPBACK}></div><div class='quotemain'>What about sporadic dosing, sometimes < Rx (60mg/day) and sometimes > Rx (I generally don't count >_>)? Have been feeling like shit, day 5 off the shit and little signs of improvement. Friends applaud for quitting but aren't too keen to spend much time around me either >_<.</div>

    I don't think anyone can say definitively. At the higher end, here's a study on meth abuse:

    <div class='quotetop'>QUOTE </div><div class='quotemain'>http://www3.interscience.wiley.com/journal...=1&SRETRY=0

    Findings Methamphetamine withdrawal severity declined from a high initial peak within 24 hours of the last use of amphetamines reducing to near control levels by the end of the first week of abstinence (the acute phase). The acute phase of amphetamine withdrawal was characterized by increased sleeping and eating, a cluster of depression-related symptoms and less severely, anxiety and craving-related symptoms. Following the acute withdrawal phase most withdrawal symptoms remained stable and at low levels for the remaining 2 weeks of abstinence.

    Conclusions This study has provided evidence of a methamphetamine withdrawal syndrome that can be categorized into two phases, the acute phase lasting 7–10 days during which overall symptom severity declined in a linear pattern from a high initial peak, and a subacute phase lasting at least a further 2 weeks.</div>

    Note you're likely still going to have whatever symptoms you took the drug for in the first place afterwards.

    <div class='quotetop'>QUOTE (krazyj @ Sep 24 2008, 02:03 PM) <{POST_SNAPBACK}></div><div class='quotemain'>Frang,
    I want to start titrating Vyvanse up from the bottom starting at no prior use (well, I dropped 50mg today but I decided I want to start at 20mg and work up painfully slow).

    Any ideas on what might be a good protocol? 1 month at 20mg then +10mg every 2 weeks (2 weeks for stabilization then 2 weeks to trial the effects of each)?</div>

    Coordinate this w/ your doctor and work it out with him, that way you won't have to worry about him thinking you're doing drug-seeking behavior when you're titrating your dose up on your own.
    <span style="color:#660000"><span style="font-size:8pt;line-height:100%"><span style="font-family:Arial Narrow">"... </span></span></span><span style="font-family:Arial Narrow"><span style="font-size:8pt;line-height:100%"><span style="color:#8b0000">fresh bread, which deforms elastically is not frangible." --Wikipedia</span></span></span>

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    Junior Member Allie's Avatar
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    <div class='quotetop'>QUOTE (Frangible @ Sep 24 2008, 02:53 PM) <{POST_SNAPBACK}></div><div class='quotemain'>Most of the beneficial effects for ADD are subject to neither tolerance nor sensitization.</div>

    Hmmm...maybe this is the wrong quote to use for my question, but if someone really didn't have a true, organic case of AD/HD what kind of effects and symptoms can occur with the use of dextroamph or even Adderall IR?
    <span style="font-family:Franklin Gothic Medium">the metaphysical isn't spiritual.</span>

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    Senior Member Frangible's Avatar
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    <div class='quotetop'>QUOTE (Allie @ Sep 24 2008, 04:19 PM) <{POST_SNAPBACK}></div><div class='quotemain'>Hmmm...maybe this is the wrong quote to use for my question, but if someone really didn't have a true, organic case of AD/HD what kind of effects and symptoms can occur with the use of dextroamph or even Adderall IR?</div>

    Basically the same. Adderall isn't abused for euphoria on college campuses for the most part, it's abused because it's the academic steroid for everyone.

    You can't distinguish ADD vs. non-ADD by drug response, only by the degree to which symptoms of ADD (which everyone has to some extent) adversely and pervasively affect your life in a long-term manner.
    <span style="color:#660000"><span style="font-size:8pt;line-height:100%"><span style="font-family:Arial Narrow">"... </span></span></span><span style="font-family:Arial Narrow"><span style="font-size:8pt;line-height:100%"><span style="color:#8b0000">fresh bread, which deforms elastically is not frangible." --Wikipedia</span></span></span>

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    Junior Member Allie's Avatar
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    <div class='quotetop'>QUOTE (Frangible @ Sep 24 2008, 06:24 PM) <{POST_SNAPBACK}></div><div class='quotemain'>Basically the same. Adderall isn't abused for euphoria on college campuses for the most part, it's abused because it's the academic steroid for everyone.

    You can't distinguish ADD vs. non-ADD by drug response, only by the degree to which symptoms of ADD (which everyone has to some extent) adversely and pervasively affect your life in a long-term manner.</div>

    Yeah, see, a friend of mine has for the past year and a half been using Adderall IR at therapeutic dosages and I think the diagnoses of ADD he received was one of those run-of-the-mill ones. I know he does have a couple symptoms of ADD/I that can be problematic at times, but sometimes I question if any of it is mental.

    But I know for sure he has Dysthymia, and he doesn't take that as serious as ADD/I. I actually believe his problems stem more from Dysthymia and possibly an unresolved PTSD. He had something like 3-4 immediate family members die within a few years of each other and he was in the ages of 10 or 11 - 13 then some other similarly bad crap happen after.

    Regardless, he never really had an issue with that neurotransmitter depletion and symptoms of withdrawal people usually speak of. I just presumed if someone really didn't have it they would feel the effects of such more.
    <span style="font-family:Franklin Gothic Medium">the metaphysical isn't spiritual.</span>

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    Senior Member Frangible's Avatar
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    Fortunately, amphetamines are also an effective treatment for PTSD and dysthymia.

    Even people you can show as definitively ADD as current theories allow with neuroimaging will have varied responses to the same drug.
    <span style="color:#660000"><span style="font-size:8pt;line-height:100%"><span style="font-family:Arial Narrow">"... </span></span></span><span style="font-family:Arial Narrow"><span style="font-size:8pt;line-height:100%"><span style="color:#8b0000">fresh bread, which deforms elastically is not frangible." --Wikipedia</span></span></span>

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    I feel focused but about half the time it turns into an irritable feeling. I am trying to think how to describe it but I am really not sure. I wonder if its the vyvanse wearing off or if its something else such as blood sugar or something like that.

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    What do the activating effects count as, mood effect or add therapeutic effect.

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    Senior Member Frangible's Avatar
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    <div class='quotetop'>QUOTE (oyster @ Sep 24 2008, 08:37 PM) <{POST_SNAPBACK}></div><div class='quotemain'>What do the activating effects count as, mood effect or add therapeutic effect.</div>

    Both.
    <span style="color:#660000"><span style="font-size:8pt;line-height:100%"><span style="font-family:Arial Narrow">"... </span></span></span><span style="font-family:Arial Narrow"><span style="font-size:8pt;line-height:100%"><span style="color:#8b0000">fresh bread, which deforms elastically is not frangible." --Wikipedia</span></span></span>

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    "You don't get much sensitization in humans really though some of the beneficial effects on DA transmission persist after the drug is completely withdrawn due to plastic adaptations."


    Frangible can you elaborate on this, I like what I hear.

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    Senior Member Frangible's Avatar
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    <div class='quotetop'>QUOTE (simpllyhuge @ Sep 24 2008, 11:41 PM) <{POST_SNAPBACK}></div><div class='quotemain'>"You don't get much sensitization in humans really though some of the beneficial effects on DA transmission persist after the drug is completely withdrawn due to plastic adaptations."


    Frangible can you elaborate on this, I like what I hear.</div>

    The only human data you're gonna find for that right now is children with ADHD, and adults recovering from stroke/TBI. But the animal data suggests sane/therapeutic dosing may restore hypoactive dopaminergic transmission in many various pathways.
    <span style="color:#660000"><span style="font-size:8pt;line-height:100%"><span style="font-family:Arial Narrow">"... </span></span></span><span style="font-family:Arial Narrow"><span style="font-size:8pt;line-height:100%"><span style="color:#8b0000">fresh bread, which deforms elastically is not frangible." --Wikipedia</span></span></span>

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    ok, let me ask what i really wanted to know: does it show tolerance or reverse tol. or neither?

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    <div class='quotetop'>QUOTE (Frangible @ Sep 25 2008, 12:55 AM) <{POST_SNAPBACK}></div><div class='quotemain'>The only human data you're gonna find for that right now is children with ADHD, and adults recovering from stroke/TBI. But the animal data suggests sane/therapeutic dosing may restore hypoactive dopaminergic transmission in many various pathways.</div>


    Really? How would this compare to nicotine, which is also proven to increase reward sensitivity over time?

    Also, seems to me that the irritability that many people get after using it for awhile would be stemmed from too much NE and too little DA. If one does indeed develop sensitization in many dopaminergic pathways, you would think the mood lifting effects would be MORE prevalent over time, not less.

    I'm not trying to discredit you on this, but I'm just wondering how that works out.



    EDIT: In my own experience with Vyvanse and Adderall, I haven't noticed sensitization to ANY aspects of amphetamine, only tolerance. After two years of taking Adderall in high school, a 40 mg dose was about as effective as a sugar pill for me. I could miss a dose and not notice a difference whatsoever, so I didn't even have withdrawal....

    My experience makes me wonder if the rodent studies are flawed in some way. Perhaps rodents process amphetamines and cocaine differently than humans. Anyone know of any primate studies on tolerance?

    Also, what's your experience? Have you noticed any sensitization? If so, what effects?

    <div align='left'><span style="font-family:Franklin Gothic Medium"><span style="font-size:8pt;line-height:100%"><span style="font-size:12pt;line-height:100%"><span style="font-size:12pt;line-height:100%">RIP Gaines Adams:</span>
    </span></span></span><blockquote><span style="font-family:Franklin Gothic Medium"><span style="font-size:10pt;line-height:100%">I'll never forget lowering my head and shoulder-pads and running full-speed into a head-on collision with you, only to be stopped dead in my tracks, with ears ringing, feeling slightly disoriented, like I had run into a brick wall. You, however, seemed only to react as one would to a sudden gust of wind, and continued on unabated.

    I'll also never forget the first thing you said to me. To which I responded:

    "No, Gaines, I did NOT call you a nigga."

    Rest in peace, man.</span></span> </blockquote><span style="font-size:8pt;line-height:100%">

    "C
    ombinations are the next step for drugs.
    Individual agents lose their effectiveness on the whole and to get their effectiveness up the central problem is that they go after a target too far, beyond certain homeostatic parameters. This then results in compensatory mechanisms and the drug often plataeus, or it just produces side-effects which are most probably the compensatory mechanisms. The solution will always be to go after several targets simulateneously, but less aggressively. Without research into combinatorial treatments, pharmacy hits 'the wall' and few new effective and proffitable drugs will ever be created."
    </span></div><div align='right'><span style="font-size:8pt;line-height:100%">-ATB

    <div align='left'></span><span style="font-size:8pt;line-height:100%">
    The statements made in this post are actual FACT, not simply personal subjective opinion, and they DO necessarily reflect Captain Obvious's personal views. Anything in this post that mentions or refers to, either directly or indirectly, any real person, place, product, or organization, was purposefully written, NOT simply coincidental. Moreover, any statement that appears to attempt to defame, discredit, or otherwise negatively impact the person, product, or idea to which it refers, WAS, in its entirety, intentional. Trademarked or copyrighted names were used explicitly without the consent of their owners.
    </span> </div><span style="font-size:8pt;line-height:100%"></div> </span>

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    <div class='quotetop'>QUOTE (Captain Obvious @ Sep 24 2008, 11:30 PM) <{POST_SNAPBACK}></div><div class='quotemain'>seems to me that the irritability that many people get after using it for awhile would be stemmed from too much NE and too little DA.</div>

    I've come to tihnk this is pseudoscientific brotillinigence. NE where? DA where? why would NE make you irritable when it is involved in euphoria, is uplifting, is used to battle depression vie NRIs...

    I gave the answer to the irritability part in another thread - high limbic drive(stims could do this, but many other things can too), (low blood glucose,) low mid brain DA(that is the killer).
    Man on a mission

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    <div class='quotetop'>QUOTE (liorrh @ Sep 25 2008, 05:49 AM) <{POST_SNAPBACK}></div><div class='quotemain'>I've come to tihnk this is pseudoscientific brotillinigence. NE where? DA where? why would NE make you irritable when it is involved in euphoria, is uplifting, is used to battle depression vie NRIs...

    I gave the answer to the irritability part in another thread - high limbic drive(stims could do this, but many other things can too), (low blood glucose,) low mid brain DA(that is the killer).</div>


    lol. Thanks for, uh, setting me straight. [img]style_emoticons/<#EMO_DIR#>/blink.gif[/img] I never said I'm an expert on this. [img]style_emoticons/<#EMO_DIR#>/3.gif[/img]

    But that all makes sense, the blood glucose part especially. So many variables to account for, I didn't even consider food intake, insulin, yadda yadda. I get irritable when hungry. But don't amphetamines increase blood glucose?

    Also, you DID mention low mid-brain DA. That's the part that I'm confused about. If amphetamines (at therapeutic doses) sensitize the dopaminergic system over time, what's with the low DA? Is this stemming from a shortage of amino acids to synthesize it? Or has the system somehow DEsensitized, contrary to the rat studies?
    <div align='left'><span style="font-family:Franklin Gothic Medium"><span style="font-size:8pt;line-height:100%"><span style="font-size:12pt;line-height:100%"><span style="font-size:12pt;line-height:100%">RIP Gaines Adams:</span>
    </span></span></span><blockquote><span style="font-family:Franklin Gothic Medium"><span style="font-size:10pt;line-height:100%">I'll never forget lowering my head and shoulder-pads and running full-speed into a head-on collision with you, only to be stopped dead in my tracks, with ears ringing, feeling slightly disoriented, like I had run into a brick wall. You, however, seemed only to react as one would to a sudden gust of wind, and continued on unabated.

    I'll also never forget the first thing you said to me. To which I responded:

    "No, Gaines, I did NOT call you a nigga."

    Rest in peace, man.</span></span> </blockquote><span style="font-size:8pt;line-height:100%">

    "C
    ombinations are the next step for drugs.
    Individual agents lose their effectiveness on the whole and to get their effectiveness up the central problem is that they go after a target too far, beyond certain homeostatic parameters. This then results in compensatory mechanisms and the drug often plataeus, or it just produces side-effects which are most probably the compensatory mechanisms. The solution will always be to go after several targets simulateneously, but less aggressively. Without research into combinatorial treatments, pharmacy hits 'the wall' and few new effective and proffitable drugs will ever be created."
    </span></div><div align='right'><span style="font-size:8pt;line-height:100%">-ATB

    <div align='left'></span><span style="font-size:8pt;line-height:100%">
    The statements made in this post are actual FACT, not simply personal subjective opinion, and they DO necessarily reflect Captain Obvious's personal views. Anything in this post that mentions or refers to, either directly or indirectly, any real person, place, product, or organization, was purposefully written, NOT simply coincidental. Moreover, any statement that appears to attempt to defame, discredit, or otherwise negatively impact the person, product, or idea to which it refers, WAS, in its entirety, intentional. Trademarked or copyrighted names were used explicitly without the consent of their owners.
    </span> </div><span style="font-size:8pt;line-height:100%"></div> </span>

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    Senior Member krazyj's Avatar
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    <div class='quotetop'>QUOTE (simpllyhuge @ Sep 24 2008, 10:07 PM) <{POST_SNAPBACK}></div><div class='quotemain'>I feel focused but about half the time it turns into an irritable feeling. I am trying to think how to describe it but I am really not sure. I wonder if its the vyvanse wearing off or if its something else such as blood sugar or something like that.</div>

    Try to find out the times after dosing this occurs.

    For the record, I also get a bit irritable on Vyvanse sometimes. I'm ashamed to admit I can tend to be kind of ugly on the inside (something I'm working on) and I think Vyvanse doesn't hold that back like other medicines can.

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    Senior Member krazyj's Avatar
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    <div class='quotetop'>QUOTE (liorrh @ Sep 25 2008, 06:49 AM) <{POST_SNAPBACK}></div><div class='quotemain'>\I gave the answer to the irritability part in another thread - high limbic drive(stims could do this, but many other things can too), (low blood glucose,) low mid brain DA(that is the killer).</div>

    Could you link this?

    While we're at it, what do you think can be done to quell this side effect?

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