![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 7 of 7. This is the beginning of the thread.
Posted by Mrsmith on October 31, 2007, at 10:24:06
Long-term use of stimulants has become counterproductive - creating the very problems it was originally prescribed for (somnolence, depersonalization, ADD). Heard that NMDA antagonists - and in particular, the relatively new alzheimer's med Numanda - can reduce/eliminate tolerance and restore effectiveness of dexedrine and/or adderall. Any thoughts out there in babble-land? Comments regarding theory or practice would be most welcome!
Posted by Mrsmith on October 31, 2007, at 10:32:34
In reply to Numanda for Adderall/Dex tolerance?, posted by Mrsmith on October 31, 2007, at 10:24:06
Babble people: let's make that NAMANDA (memantine) as the NMDA antagonist that some suggest may help psychostimulant tolerance - not Numanda. Maybe the anti-alzheimer's effects would be helpful as well!
Posted by KayeBaby on October 31, 2007, at 22:12:43
In reply to Re: Numanda for Adderall/Dex tolerance?, posted by Mrsmith on October 31, 2007, at 10:32:34
I took it for several months-seemed to help bit after a while I suspected it was a bit "flattening" I was planning on cyclying it.
I took about 10mg on average.
Kaye
Posted by Astounder on November 1, 2007, at 22:35:55
In reply to Numanda for Adderall/Dex tolerance?, posted by Mrsmith on October 31, 2007, at 10:24:06
> Long-term use of stimulants has become counterproductive - creating the very problems it was originally prescribed for (somnolence, depersonalization, ADD). Heard that NMDA antagonists - and in particular, the relatively new alzheimer's med Numanda - can reduce/eliminate tolerance and restore effectiveness of dexedrine and/or adderall. Any thoughts out there in babble-land? Comments regarding theory or practice would be most welcome!
The studies I've read indicate that uncompetitive NMDA antagonists like memantine (Namenda) prevent plastic changes induced by psychostimulants and opiates. However, they do not reverse the effects of chronic use that are already there. To reverse the tolerance you've already built, theoretically you could stop using the stimulants until you return to baseline (that is, until you stop experiencing withdrawal effects). Or if you can handle it, you can initiate fast withdrawal by taking a high-potency antipsychotic.
You try to increase Namenda's effects by combining it with other negative modulators of the NMDA ion channel: Acamprosate binds to the polyamine site and alcohol binds to the NRB2 subunit where both act as functional antagonists. Amantadine is an uncompetitive antagonist like memantine, but it's much cheaper and has been definitively shown to upregulate postsynaptic D2 dopamine receptors with chronic use. Riluzole and probably Lamictal both inhibit the release of glutamate, which is the main agonist of the NMDA receptors. Finally, you can also try to take nightly doses of highly sedating low-potency neuroleptics like Seroquel to resensitize your D2 receptors while you sleep.
I have taken amphetamines and do currently take 10 mg/d Namenda, but I haven't taken them together. I experience chronic depersonalization as well, and I've found that memantine greatly potentiates the dissociative effects of alcohol, and in high doses is dissociative itself. This makes sense, since its drug target is the same as that of the dissociative anesthetics.
Posted by Mrsmith on November 4, 2007, at 21:18:36
In reply to Re: Numanda for Adderall/Dex tolerance? » Mrsmith, posted by Astounder on November 1, 2007, at 22:35:55
Thanks for your message. If I'm reading it right, there's a treadmill aspect to amphetamines that is difficult to avoid. Moreover, it's probably unwise to even try absent a really fabulous experience with amps. The highs were great - but a crack addict would probably say much the same thing about early experience.
Currently starting imipramine + lithium; my presenting problems were almost in remission until amps were added. Hope it works again ... but there is that early morning grogginess. Maybe adding desipramine in the a.m. may help without creating conflicts ...
> >Long-term use of stimulants has become counterproductive - creating the very problems it was originally prescribed for (somnolence, depersonalization, ADD). Heard that NMDA antagonists - and in particular, the relatively new alzheimer's med Numanda - can reduce/eliminate tolerance and restore effectiveness of dexedrine and/or adderall. Any thoughts out there in babble-land? Comments regarding theory or practice would be most welcome!
>
> The studies I've read indicate that uncompetitive NMDA antagonists like memantine (Namenda) prevent plastic changes induced by psychostimulants and opiates. However, they do not reverse the effects of chronic use that are already there. To reverse the tolerance you've already built, theoretically you could stop using the stimulants until you return to baseline (that is, until you stop experiencing withdrawal effects). Or if you can handle it, you can initiate fast withdrawal by taking a high-potency antipsychotic.
>
> You try to increase Namenda's effects by combining it with other negative modulators of the NMDA ion channel: Acamprosate binds to the polyamine site and alcohol binds to the NRB2 subunit where both act as functional antagonists. Amantadine is an uncompetitive antagonist like memantine, but it's much cheaper and has been definitively shown to upregulate postsynaptic D2 dopamine receptors with chronic use. Riluzole and probably Lamictal both inhibit the release of glutamate, which is the main agonist of the NMDA receptors. Finally, you can also try to take nightly doses of highly sedating low-potency neuroleptics like Seroquel to resensitize your D2 receptors while you sleep.
>
> I have taken amphetamines and do currently take 10 mg/d Namenda, but I haven't taken them together. I experience chronic depersonalization as well, and I've found that memantine greatly potentiates the dissociative effects of alcohol, and in high doses is dissociative itself. This makes sense, since its drug target is the same as that of the dissociative anesthetics.
Posted by Questionmark on November 11, 2007, at 23:23:24
In reply to Re: Numanda for Adderall/Dex tolerance? » Mrsmith, posted by Astounder on November 1, 2007, at 22:35:55
How likely do you think that the reason amantadine has been shown to upregulate D2 receptors is that it has some D2 agonist properties (although it's supposed to be a dopamine releaser from what i understand) and consequently causes an upregulation of D2 receptors? Why or why not?
Thanks.
> The studies I've read indicate that uncompetitive NMDA antagonists like memantine (Namenda) prevent plastic changes induced by psychostimulants and opiates. However, they do not reverse the effects of chronic use that are already there. To reverse the tolerance you've already built, theoretically you could stop using the stimulants until you return to baseline (that is, until you stop experiencing withdrawal effects). Or if you can handle it, you can initiate fast withdrawal by taking a high-potency antipsychotic.
>
> You try to increase Namenda's effects by combining it with other negative modulators of the NMDA ion channel: Acamprosate binds to the polyamine site and alcohol binds to the NRB2 subunit where both act as functional antagonists. Amantadine is an uncompetitive antagonist like memantine, but it's much cheaper and has been definitively shown to upregulate postsynaptic D2 dopamine receptors with chronic use. Riluzole and probably Lamictal both inhibit the release of glutamate, which is the main agonist of the NMDA receptors. Finally, you can also try to take nightly doses of highly sedating low-potency neuroleptics like Seroquel to resensitize your D2 receptors while you sleep.
>
> I have taken amphetamines and do currently take 10 mg/d Namenda, but I haven't taken them together. I experience chronic depersonalization as well, and I've found that memantine greatly potentiates the dissociative effects of alcohol, and in high doses is dissociative itself. This makes sense, since its drug target is the same as that of the dissociative anesthetics.
Posted by Astounder on November 15, 2007, at 19:25:05
In reply to Re: Numanda for Adderall/Dex tolerance? » Astounder, posted by Questionmark on November 11, 2007, at 23:23:24
> How likely do you think that the reason amantadine has been shown to upregulate D2 receptors is that it has some D2 agonist properties (although it's supposed to be a dopamine releaser from what i understand) and consequently causes an upregulation of D2 receptors? Why or why not?
> Thanks.The specific dopaminergic action of amantadine is not well characterized. It is referred to as a DRI, but I can't find binding data. NMDAR inhibition is 10-fold less potent than memantine, and it's action is voltage-dependant (unlike DXM and other dissociatives). Amantadine is probably a ligand like memantine is for nicotinic acetylcholine receptors, which modulate DA release.
The upregulation of postsynaptic D2 receptors is probably do to either uncompetetive NMDAR blockade and (if a ligand) nAChR blockade. Preventing excessive burst firing of DA neurons while increasing tone through DAT blockade probably accounts for its effects on reducing/preventing L-DOPA-induced dyskinesia. Note that Parkinson's patients have very low DAT levels, probably an adaptive change, so DAT blockade alone is not sufficient to explain its actions in these persons.
Normal NE/DAergic drugs, the psychostimulants, all cause postsynaptic D2 downregulation. However, they also cause rapid change in DAT expression. Amphetamines decrease DAT expression--less places for it to release DA from--while cocaine, Wellbutrin, and probably methylphenidate increase DAT expression--harder to plug all the uptake pumps. It may be actions at DAT itself that attenuates tolerance rather than the postsynaptic site. DAT expression is going to play a much larger role in people with intact DA terminals than those with Parkinsons.
This is the end of the thread.
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.