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Amphetamine Neurotoxicity and Tolerance Reduction/Prevention III

HoChiMin said:
I'm assuming alcohol has the potential to reduce amphetamine tolerance due to slight nmda antagonism?
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Well, alcohol's nmda agonism is very weak, and it is a rather short-acting compound. I wouldn't expect much. Hell, I wouldn't expect more than reduced tolerance accrual with use of NMDA antagonists.

ebola
 
Ho-Chi-Minh said:
I'm assuming alcohol has the potential to reduce amphetamine tolerance due to slight nmda antagonism?
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Anything you would gain in regards to NMDA antagonism would be lost to cross-tolerance to the dopamineric effects.

Ho-Chi-Minh said:
but so is magnesiums and it veritably reduces tolerance to an extent
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Enh, not really. It can definitely improve your health though. Even 40 mg of memantine a day can't stop tolerance in its place.
 
Youd need memantine or dxm for tolerance reduction, all the rest or things having nmda antagonism as a side effect will be too weak.
 
MeDieViL said:
Youd need memantine or dxm for tolerance reduction, all the rest or things having nmda antagonism as a side effect will be too weak.
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Too weak... DXM... MeD have you ever looked at the IC50 for DXM at the NMDA site? It's 7.2mM and memantine is 0.5mM. Pretty much anything that binds to NMDA channels will bind to pretty much anything else under the sun before it even inhibits half the NMDA receptors. With that said, ketamine, ethanol, and any of the other ketamine related drugs will likely not have a beneficial effect due to their short durations and other mechanisms of action.
 
Hmm what are the affinity's for dxm's metabolite, could find it myself too, but dxm is an odd one i dunno what causes the most beneficial effects with regards to this subject.

Anecdotally it seems mxe and co are far more potent for tolerance reversal but tolerance to this effect occurs rather quickly. I was experimenting with low daily doses of mxe but lost it, but alot happened the last weeks too.

Currently using low daily doses of DXM for tolerance.

Dipyridamole and losartan/candesartan
will post more but in case epsilon has more info how this is relevant, dipyridamole is a non selective PDE inhibitor and increases cyclic amp and cgmp and also is a adenosine reuptake inhbitior, this can be antagonised with cafeine tough.
 
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Which metabolite? DXO, 3-meO-morphinan (N-desmethyl-DXM), or 3-HO-morphinan (N-desmethyl-DXO)

If you are on low doses of DXM, it's unlikely metabolites are playing a major role.
 
MeDieViL said:
Dipyridamole and losartan/candesartan
will post more but in case epsilon has more info how this is relevant, dipyridamole is a non selective PDE inhibitor and increases cyclic amp and cgmp and also is a adenosine reuptake inhbitior, this can be antagonised with cafeine tough.
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Have you been using that for tolerance reduction? What are your results so far?
 
I cant say mate i take several things wich can potentially help tolerance, also since today added in minocycline.
 
After a quick look on PubMed, i only found studies showing minocycline attenuating rewarding effects of amphetamine. I also saw it affects cAMP, not sure to which extent, though.
 
It depletes glutamate and nitric oxide will work for amp tolerance theoretically, its been shown to work for morphone tolerance if im correct.

If your addicted the reduced euphoria is agood as it eliminates bad decission making and also reduces drug intake.
 
my guess to reduce modafinil tolerance is gap junction antagonists at night as modafinil exerts itself such a long time the user can sleep, but modafinil stays around for incredibly long in the brain.

for minocycline i feel as if it shares a common pathway via cAMP that a few other antibiotics I have dealt with share, namely the quinoline antibiotics, which are horrible for memory. however the inverse of that being their opposites, cAMP promoters--> forskolin, artichoke extract, quercetin, rolipram.

I feel as if minocycline functions as quercetin does, but to those who want to reduce amph tolerance--> sublingual uridine monophosphate and quercetin will be your gods, theres always random superiornutraceutical sites that can help you find the uridine at a cheaper cost but it works beautifully.
 
So medieval what is your regimen? Have you had success with zinc?

There should be a poll or something as to what works and what doesn't. We could even collect almost all anecdotal reports and studies from the internet, putting them in one place. I'm busy as fuck though.
 
May I ask if there is any chance of Seroquel reducing methamp tolerance in the short term or with some effect when used during short breaks between methamp usage for example.

I do notice that dosing again after taking a 24 hour break by using Seroquel to avoid the comedown and sleep after a 2-3 binge, results in stronger effects, close to those after a week break, much more then without using Seroquel, passing out in another way, and redosing amps again after 24 hours later.

My uneducated thought process here is that the antagonistic effect for that break period may allow the effective resupply of dopamine which will be available for the next session?

I ask simply as my experience indicates some sort of noticeable action here then without the Seroquel, but i may be very wrong here so feel free to wack this post if its not true and might be misleading. I know this thread needs careful management of the facts. Cheers.
 
This study - "Minocycline attenuates subjective rewarding effects of dextroamphetamine in humans" says, that among those attenuated effects were "High", "Drug Sgtrength" and "Good effect". Not sure what is left. Improved focus/concentration? The study didn't measure it.


blight12, what dose of Seroquel are you taking that results in this kind of effect?
 
^^ Quite low relative to the dose range. I usually take it daily for sleep at 300mg since I have reasons to avoid the usual addictive sleep aids but still needed a strong one.

For those methamp break days I usually only need 150mg since by that point your body is so drained and tired, this dose is enough to kill the amps and bring on sleep. Higher doses i found to strong causing an uncomfortable scary sensation of falling unconscious in a bad way and you tend to fight it out of fear.
 
Whoah, both are high to my standards. Never had this drug prescribed so i don't know the typical dose ranges, but even 25-50 gives me a solid hang-over feeling next morning if i take it for sleep. And 12.5mg is enough for a mild sleep inducing effect.

There was some speculation on using Seroquel on nights before amphetamine. The logic was to 'give receptors some rest' bu blocking them and was quickly refuted by forum members. But i still keep seeing those anecdotes of potentiated effects of amphetamines after a night on Seroquel. So, who knows?
 
StrikeMe said:
Whoah, both are high to my standards. Never had this drug prescribed so i don't know the typical dose ranges, but even 25-50 gives me a solid hang-over feeling next morning if i take it for sleep. And 12.5mg is enough for a mild sleep inducing effect.

There was some speculation on using Seroquel on nights before amphetamine. The logic was to 'give receptors some rest' bu blocking them and was quickly refuted by forum members. But i still keep seeing those anecdotes of potentiated effects of amphetamines after a night on Seroquel. So, who knows?
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It's possible those reports stem simply from the contrast enhanced effect of transitioning from an anti-psychotic to a stimulated state.
 
StrikeMe said:
Whoah, both are high to my standards. Never had this drug prescribed so i don't know the typical dose ranges, but even 25-50 gives me a solid hang-over feeling next morning if i take it for sleep. And 12.5mg is enough for a mild sleep inducing effect.

There was some speculation on using Seroquel on nights before amphetamine. The logic was to 'give receptors some rest' bu blocking them and was quickly refuted by forum members. But i still keep seeing those anecdotes of potentiated effects of amphetamines after a night on Seroquel. So, who knows?
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Yeah i have often need higher doses for effect with most drugs. From 50mg was tested and didn't do a thing for me until about 150 or so. I know many others get strong effects at those low doses for sleep. Also since only antihystamine action is taking place at those doses and the antipshychotic blockade action at higher doses like my own, may mean that its that action that helps me the most to sleep, possibly due to the SNS blockade since I have anxiety issues thus the sleep problems.

Well thats very interesting as i did not know others have mentioned or experienced this positive effect. Based on my experience the "'give receptors some rest'" was pretty much the logic i thought as the way to explain this.

The contrast as mentioned above also makes sense. I however usually sleep until the Seroquel no longer has any effect and dont feel any of the usually reported downsides or negatives during the day after awaking. I would then redose methamp about 9 hours after the Seroquel was no longer in effect and still experience the increased effects.
 
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