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  1. #21
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    i just want to know what is recommended, i understand that for many these stimulants come with many negatives, is amp the best option for study aid/cognitive enhancer?

  2. #22
    Senior Member kassem23's Avatar
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    Quote Originally Posted by rovuex View Post
    i just want to know what is recommended, i understand that for many these stimulants come with many negatives, is amp the best option for study aid/cognitive enhancer?
    Amphetamine or modafinil. Depends on the individual.

  3. #23
    Senior Member Sanction's Avatar
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    Quote Originally Posted by rovuex View Post
    i just want to know what is recommended, i understand that for many these stimulants come with many negatives, is amp the best option for study aid/cognitive enhancer?
    It might be more productive to you start your own thread on this topic

  4. #24
    Senior Member kassem23's Avatar
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    Quote Originally Posted by Sanction View Post
    It might be more productive to you start your own thread on this topic (rather than inserting your off-topic question into multiple threads)
    I agree.

  5. #25
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    my apologies if i wasn't supposed to post in this thread, i figured that this question wouldn't really need another thread and that i would just bump this one which was related to the discussion. thanks for the info guys

  6. #26
    Senior Member Tussmann's Avatar
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    Quote Originally Posted by evanski View Post
    http://www.utoronto.ca/seeman/Philip...et%20D2Hi*.pdf

    Take a look at this. I don't use amphetamine but I know many on this site do. This study shows that amphetamine use in animals does not change actual d2 density but apparent density. This concept is explained in the abstract. Most interesting though is that the effects of amphetamine sensitization were reversed by a compound guanilylimidodiphosphate that equalized the affinity of [3H]raclopride binding for d2 between the control group and the amphetamine group.

    I certainly am no expert. Could the aforementioned compound prove useful for tolerance? Just thought it was worth posting.

    Where's MeD?

  7. #27
    Senior Member NeuralFrequency's Avatar
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    I would also be interested if perhaps some of the more knowledgeable posters here had some input on this.
    "A mind that is stretched by a new experience can never go back to its' old dimensions"

    ~Oliver Wendell Holmes, Jr.

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    Quote Originally Posted by NeuralFrequency View Post
    I would also be interested if perhaps some of the more knowledgeable posters here had some input on this.

    A couple more interesting notes. Straight NaCl has an effect, although less potent than the guanine nucleotide, on converting from high to low affinity states. Also cAMP is an activator of Guanine nucleotide exchange factors (GEFs). Forskolin has been shown to increase D2 density and stimulates cAMP. Maybe the connection there is that forskolin changes the apparent D2 density....

    Here's what i'm referencing: http://www.ncbi.nlm.nih.gov/pubmed/3157782

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  10. #29
    Senior Member kassem23's Avatar
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    Quote Originally Posted by Tussmann View Post
    Where's MeD?
    With his girlfriend in England. Nobody knows if he's alive or dead. Reminds me a bit like Schroedinger's cat, lol.

    Usually he comes back alive with another insane regimen setup.

  11. #30
    Senior Member Ex Dubio's Avatar
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    Quote Originally Posted by NeuralFrequency View Post
    I would also be interested if perhaps some of the more knowledgeable posters here had some input on this.
    What exactly do you want to know? This is a pretty well-established finding by now.

  12. #31
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    Quote Originally Posted by Ex Dubio View Post
    What exactly do you want to know? This is a pretty well-established finding by now.
    Can you maybe summarize how downregulation of dopamine receptors works? I used to think that receptors actually disappear after chronic stimulation. But according to that study it seems density is set and only the affinity state of the receptors changes.

  13. #32
    Senior Member kassem23's Avatar
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    Quote Originally Posted by evanski View Post
    Can you maybe summarize how downregulation of dopamine receptors works? I used to think that receptors actually disappear after chronic stimulation. But according to that study it seems density is set and only the affinity state of the receptors changes.
    Well, you understand this, right?

    Agonism = down-regulation (less sensitive to stimulation from agonist, and reduction of receptors on said neuron)
    Antagonism = up-regulation (more sensitive to stimulation from agonist, and increase of receptors on said neuron)

    Not sure what you're unsure about.

  14. #33
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    Quote Originally Posted by kassem23 View Post
    Well, you understand this, right?

    Agonism = down-regulation (less sensitive to stimulation from agonist, and reduction of receptors on said neuron)
    Antagonism = up-regulation (more sensitive to stimulation from agonist, and increase of receptors on said neuron)

    Not sure what you're unsure about.
    That was my original understanding. But I must be missing some fundamental concept that caused me to be thrown for a loop by that study.

    1. Why does amphetamine, basically an agonist for DA, cause a shift of receptors to high affinity state when antipsychotics also cause a shift to high affinity states?

    2. When people use memantine for tolerance, how exactly does upregulation occur? Is there an increase in DA receptors or a kind of state change of existing receptors?

  15. #34
    Senior Member Ex Dubio's Avatar
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    Quote Originally Posted by evanski View Post
    That was my original understanding. But I must be missing some fundamental concept that caused me to be thrown for a loop by that study.
    It's still true.

    1. Why does amphetamine, basically an agonist for DA, cause a shift of receptors to high affinity state when antipsychotics also cause a shift to high affinity states?
    I'm not sure this is known. You have to realize that this process occurs only in some regions on the brain (namely the nigrostriatal system); after all, repeated amphetamine treatment does not cause sensitization to the euphoria! Moreover, the shift of receptors to a high affinity state coincides with normal receptor downregulation. The total number of D2 receptors is decreased, but the remaining receptors have a higher percentage in the D2High state.

    If I had to guess, I'd suspect the mechanism involves amphetamine's secondary effects. In addition to inducing DA release, amphetamine has glutamatergic properties (though the mechanism seems unclear) and, moreover, amphetamine appears to be an alpha7 nAChR agonist.

    2. When people use memantine for tolerance, how exactly does upregulation occur? Is there an increase in DA receptors or a kind of state change of existing receptors?
    Amphetamine induces, through a number of mechanisms, increased NMDA activity in the mesolimbic system. This increase in NMDA activity leads to, among other effects, a decrease in D2 receptor density. Memantine partially blocks this NMDA activation and thus prevents, or attenuates, the reduction in D2 receptor density.

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  17. #35
    Senior Member Ubiyca's Avatar
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    Quote Originally Posted by Ex Dubio View Post
    Withdrawal from ephedrine is much, much worse than that from amphetamine, IMO.
    WTF, really?

    WD with ephedrine is, you're a bit tired for a day, and then back to normal.. IME.
    [03:14] FunkOdyssey: dude the only reason nazi's didnt put blacks in concentration camps is because there werent any in germany.
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  18. #36
    Senior Member kassem23's Avatar
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    Quote Originally Posted by Ubiyca View Post
    WTF, really?

    WD with ephedrine is, you're a bit tired for a day, and then back to normal.. IME.
    IIRC... there have been some people who when having used ephedrine chronically, and then withdraws, it can induce a certain almost CFS-like state. Maybe this is what ExD is referring to.

  19. #37
    Senior Member Ex Dubio's Avatar
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    Quote Originally Posted by Ubiyca View Post
    WTF, really?

    WD with ephedrine is, you're a bit tired for a day, and then back to normal.. IME.
    This is why I included "IMO". I don't get withdrawal from amphetamine really, just a return to ADHD symptoms and maybe a subtle hint of anhedonia. But good god, withdrawing from even low doses of ephedrine (12.5mg 3x/day) is a shit for me -- a good week of intense fatigue.

    That said, I suspect this all comes down to varying beta adrenergic receptor activity/sensitivity; ephedrine, in addition to being an NE-releaser, is a rather potent beta agonist.

  20. #38
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    On a related note... when you lower the dose, is it the same thing (just milder) ?

    How long should it take to get a reduction in dose fully stable? I know that when you reduce the dose it's a mess for a few days, and I usually go back to my old trusty dose. Maybe I should wait some more.
    [quote name='Sonic' timestamp='1300976024' post='654942']I have consumed 5 liters of diet coke per day for the last 6 years and my psychiatrist says that I am perfectly fine with my antipsychotic regime.[/quote]

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