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Way to Reduce Amphetamine Tolerance?

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Scarletta

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Joined
Nov 17, 2008
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I am wondering what anyone thinks about this. The use of Seroquel (quetiapine) at night to reduce amphetamine tolerance. I am not sure what the dosage would be, but 25 mg is enough to knock me out, even if I'm wired from my Adderall or Dex.

The theory is that Seroquel's half-life is so short (only 6 hours) so that by the time you take your next stimulant dose, it will not interfere or block the stimulant.

But at night, it will participate in upregulation of dopamine receptors because of its dopamine-blocking properties.

Then, for at least 6 hours/24hrs, your dopamine receptors are going to be free of amphetamine, thus contributing to a lessening of tolerance.

Because the reason tolerance develops is that the dopamine receptors are constantly saturated with amphetamine and then become desensitized to amphetamine, so you need more to get the same effect. Seems like Seroquel would serve to resensitize the dopamine receptors so that you wouldn't need as much amphetamine to get the same good response from it.

What does anyone think? An antipsychotic such as aripiprazole, with about a 3 day half-life, woud not work this way. It would probably lower tolerance, but with the side effect of having the amphetamine blocked for 3 days, so that someone might take more and more of the amphetamine to try to overcome that.

I see the short half-life of Seroquel as being key here.

Any thoughts?
 
Interesting that this thread came about today as I was researching exactly this (well not Seroquel specific) and was going to post about it. I read a number of studies in which patients afflicted with the Skitz and had been on Anti psychotics for five years or longer and had taken them regularly were then taken off them and given a variety of brain scans. To which they discovered the patients had I believe double the amount of D2 receptors in the brain as their brains had adapted to shortage and thus unregulated.

I feel like in theory this could perhaps work though I wonder how helpful it would actually be with consistently reintroducing amphetamines to the system daily. Any words of wisdom on this would be quite interesting. Cool topic !
 
Never heard of Seroquil being a tolerance reducer. I was going to say UTFSE about amphetamine tolerance, since there are a shitload of topics on this, but I don't remember one involving Seroquil.
 
disclaimer i am blitzed atm but i think i remember hearing about seroquel and tolerance sometime , somewhere.. at least it definitely relates to the use in general of low dose antagonists as tolerance reducers.. actually, thinking about it, seroquel could be pretty ideal actually, however does it have the lowest half life of all the atypical anti dopaminergics? what about geodon
 
I had no idea quetiapine has such a short half life. AstraZeneca is currently doing 7 different phase III trials on it. Some of these trials test it's efficacy when co-administered with antidepressants and I imagine the primary mechanism of action is indeed up-regulation of serotonin, dopamine and norepinephrine receptors. Therapeutic dose in adjunctive therapy for depression w/o psychosis is 300 mg qhs (according to AstraZeneca's trials for tx of bipolar depression). One of quetiapine's advantages over other atypical antipsychotics is that it rapidly dissociates from D2 receptors, thereby decreasing the risk of EPS.

The reason I wouldn't opt for quetiapine if I wanted to decrease amp tolerance is that quetapine is such a potent H1 antagonist; also, like most neuroleptics, it seems to want to carpet-bomb every receptor in the brain (not a good thing).
 
I need to find some research on the minimal amount of quetiapine that would work. 300 mgs would indeed be too much for most people and too sedating. If something as little as 25 mg (which I've been prescribed for sleep before) would work it would avoid the worst antipsychotic symptoms. Question is whether that is enough to upregulate the dopamine receptors while you abstain from amphetamine use and during its half-life.
 
Well I found this table: http://www.nature.com/npp/journal/v25/n5/fig_tab/1395704t1.html

It shows that the amount of dopamine D2 receptor blockade is dose dependent. Someone like me, who weighs about 125 lbs, would need to take 285 mg of Seroquel in order to get perhaps 50% of the receptors bound.

And then Seroquel is bound for such a short time and easily replaced by dopamine- so I guess this probably wouldn't be such a great drug for my idea. I cannot tolerate much more than 100 mg/day of Seroquel.

But it would be interesting if there were any studies or anyone willing to try it.
 
Pharmacokinetics is still a little arcane to me, but is bioavailability similar in rats and humans for any given substance?

This will all just be speculation and anecdote without access to PET scanners and radioactive tracers and fluorescent proteins. I can't find any studies of staggered administration of D2 antagonists and amphetamine: all the studies seem to involve co-administration, and at incredibly toxic levels, and on rats or swine.

All the companies that have patented atypical antipsychotics are in a horse-race to get their particular formulations approved for every major psychiatric disorder (many of which have no psychotic component), and the phrase that keeps popping up in the medical literature is, "The mechanism of action is unknown." I want to talk someone into doing technology-aided human studies to test for optimization of the more-promising drug combos. If you chart, as functions of time, the concentrations and distribution volumes of receptors and ligands, then a little calculus is all you need to get exact answers to these types of questions.
 
Now that I take 40mg of Geodon 2x a day, I don't feel any type of euphoria if I drink, smoke green, or take adderall, which is a good thing because I am feeling "normal" again and not talking to the tv sorda speak (LOL!) I mean, I wasn't that crazy before it BUT now feeling like I am turning into a normie. Just annoying when I want to feel a little side buzz, NOT HAPPENING. I guess, next time I want to feel "chill and euphoria" I won' t take my Geodon, I had no idea it was a BLOCKER. But hey, aint complaining, I used to get way "too toasted" in the past......guess, its time for me to grow up and get healthy so the benefits are worth it. No longer bipolar maniac.
 
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