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Why do antacids potentiate amphetamines and opiates?

CrimpJiggler

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Amphetamines and opioids both have amino groups and as a result are basic drugs. How does stomach acid lower potency though?
 

pr0d1gy

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PH in the GI and blood effects absorption and excretion. Technically increasing PH might help you absorb more and excrete it slower but I really don't think it usually makes enough of a difference to justify messing with your bodies PH levels.

I take amphetamine daily, I personally don't try to make my PH more alkaline by swallowing antacids or anything. I just try and avoid highly acidic foods for the first few hours so my 1 dose lasts me through school.
 

CrimpJiggler

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PH in the GI and blood effects absorption and excretion. Technically increasing PH might help you absorb more and excrete it slower but I really don't think it usually makes enough of a difference to justify messing with your bodies PH levels.

I take amphetamine daily, I personally don't try to make my PH more alkaline by swallowing antacids or anything. I just try and avoid highly acidic foods for the first few hours so my 1 dose lasts me through school.

Yeah I read that the pH of the urine determines the excretion rate of drugs like opioids and amphetamines. As for absorption, why does pH determine absorption rates? I know that these kinda drugs are usually prepared as salts so they are in salt form to begin with. The chloride ions may be stronger than the default counterions and consequently, replace them. I don't see how this affects absorption rates though. If charged molecules can't easily be absorbed then it makes sense because the higher the pH, the less likely the amino groups are to be neutralised.
 

sekio

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As far as I know changing pH helps mostly with amphetamines, not opiates. The amine on e.g. amphetamine can be protonated and form a charged salt that is essentialy inactive because it does not pass the BBB. Raising the pH in the stomach and blood reduces the degree of protonation, providing more free amphetamine base that can diffuse across fatty tissues and through the BBB.

The same thing happens with opiates, though to a much lesser degree because the nitrogen is tertiary. I do know that adjusting the pH of e.g. a rectal morphine solution (making it more basic) enhances absorbtion as compared to acidic morphine sulphate. This is probably because less morphine is protonated. Making the solution too basic drives morphine to a morphinate salt, though.

I don't suggest changing blood pH unless you like organ damage.
 

michael_1992

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In the case of amphetamines

In the case of amphetamines(I don't know about opiates), antacids increase absorption through the gastrointestinal tract and also slow its excretion in the urine. If you ingest sodium bicarbonate everyday and do amphetamines everyday, less of the previous dose of amphetamine will have been excreted by the time that you dose again. Amphetamine's effects do not last nearly as long as its half life in the system. For example, dextroamphetamine has a half life of
10-28 hours, yet the peak euphoric effects tend to last me only 1 hour. I read that this is due to a rapid temporary tolerance that develops. If you take
sodium bicarbonate, you may have half the ingested dosage still in your system 24 hours later , even if you no longer felt the effects of that. When you
take the next dose, you will have the new dose plus a significant portion of the previous dose. This would cause stronger effects.

Acids are known to increase the rate that amphetamine is cleared from the system. Which is why doctors often discourage drinking sodas and taking
vitamin C on adderall.
 

LSDMDMA&AMP

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basifys your stomach so amphetamine (a base) can be absorbed better. Amphetamine doesn't last near as long as its half life but its half life isn't that long iirc.
methamphetamine has a 24 hour half life in your blood and that stays in ya significantly longer.
my amp experience>yours
there's no rapid tolerance BS, ive been getting high 2-3 times a week on high doses of d-amphetamine for more than 2 years now, you do enough you get a few hours of euphoric high, thats it.
no one hour bullshit.
 

Roger&Me

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Right. It's my understanding, though, that one cannot easily manipulate blood ph (certainly not via antacids).

ebola

Yeah, IIRC blood pH stays around 7.4-7.5.

I think it has less to do with BBB permeability for this very reason, because most of the amphetamine will get deprotonated anyways in the blood's basic environment. I think raising stomach pH potentiates the amp because unprotonated amines can diffuse across lipid mucosal barriers more easily, so more of it ends up getting into your bloodstream in the first place. Just throwing that out there.
 

ebola?

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rogerandme said:
I think raising stomach pH potentiates the amp because unprotonated amines can diffuse across lipid mucosal barriers more easily, so more of it ends up getting into your bloodstream in the first place. Just throwing that out there.

Well, it's correct, so I encourage you to keep throwing. :p

ebola
 

Refluxer

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As far as I know changing pH helps mostly with amphetamines, not opiates. The amine on e.g. amphetamine can be protonated and form a charged salt that is essentialy inactive because it does not pass the BBB. Raising the pH in the stomach and blood reduces the degree of protonation, providing more free amphetamine base that can diffuse across fatty tissues and through the BBB.

This is not the reason why some basifying compounds can potentiate amphetamines. It is the pH of urine that is of importance. The pH of urine can vary quite a lot, so basifying it so some degree will ensure amph. is mainly in it's lipophilic form and increase reabsorption of amphetamine from renal tubuli. This can increase the exposure/AUC quite a lot. So in essence you get more exposure to amphetamine from the same dose.
 

Coolwhip

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Refluxer, while you may be right in theory, I am pretty sure that is wrong in practice. People aren't throwing their urine PH off that much by taking a couple tums before they dose, and the effect on absorbtion is nearly immediate. It just allows more amphetamine, than usual, to be absorbed before reaching the duodenum. Meaning a quicker onset, with a faster and higher peak.
 

CrimpJiggler

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I got a book on medicinal chemistry the other day (Medicinal Chemistry: An Introduction by Gareth Thomas, good book, I recommend it) and have been reading it lately so I have a more complete picture of all this now. Its all about whether the drug is acidic or basic. Aspirin is an acidic drug and consequently, it is absorbed effectively in the stomach because the acidity in the stomach keeps the aspirin molecule unionised and uncharged and as we know, uncharged molecules can be absorbed a lot easier than charged ones. A basic drug (i.e. amphetamines or opioids due to their amino groups) on the other hand will be ionised by the stomach acid and will have a harder time being absorbed through the membranes of the stomach. If you take an antacid and raise the pH of the stomach then there will be less acid to ionise the drug meaning more of the drug will get absorbed through the stomach. Now the same thing goes for the urine. If the urine is acidic then the aspirin will remain uncharged which means that it can be reabsorbed a lot easier and consequently, less of it gets excreted. With basic drugs, acidic urine means the drug gets ionised and ionised compounds can't be reabsorbed easily so it instead gets excreted in the urine. Thats the general idea. I recommend that book I mentioned above, I'm learning all kinds of shit from it.

Refluxer, while you may be right in theory, I am pretty sure that is wrong in practice. People aren't throwing their urine PH off that much by taking a couple tums before they dose, and the effect on absorbtion is nearly immediate. It just allows more amphetamine, than usual, to be absorbed before reaching the duodenum. Meaning a quicker onset, with a faster and higher peak.

Yep. Acid inhibitors such as ranitidine or cimetidine work better for potentiating drugs because they keep the pH of the stomach higher than usual for longer periods of time. The reason antacids aren't used to treat ulcers (although they do help) while acid inhibitors are is because acid inhibitors can keep the pH high consistently for long periods of time while antacids only have short acting effects (the reason I'm assuming is that the stomach will create more acid in response to this raising of the pH).

EDIT: Just though I should share this cool fact I just learned from this book: substances take 20 minutes to pass through the stomach but take 6 hours to pass through the small intestine.
 
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Refluxer

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Refluxer, while you may be right in theory, I am pretty sure that is wrong in practice. People aren't throwing their urine PH off that much by taking a couple tums before they dose, and the effect on absorbtion is nearly immediate. It just allows more amphetamine, than usual, to be absorbed before reaching the duodenum. Meaning a quicker onset, with a faster and higher peak.

Raising the pH of the stomach might give a faster onset. What I was commenting was primarily the statement that it was increased transport over the BBB that facilitated more subjective effect.

I believe what I'm saying it's correct in practice. I have seen the blood plasma curves of amphetamine with and without basified urine and the difference can be huge. Raising the pH of urine a little bit will probably go a lot further in potentiating amphetamine than just basifying the stomach fluids.

Here's an article anno 1965 (first hit on googling "amphetamine urine ph"):

Article

There's many more articles on this subject, including human experiments.
 
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Coolwhip

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I never doubted what you were saying is true, and could be used to potentate amphetamine(although I wouldn't want to fuck with my PH on a regular basis).

I'm just not sure that eating a couple tums would actually affect urine PH enough to matter(on their own), I don't think it is mostly responsible for what most users are experiencing, although it could definitely have an additive effect. Or greater effect if you are effectively controlling urine PH, by taking larger doses of bicarb or taking it on a regular basis.

edit: Did any studies relating amphetamine to urine ph, IV the amphetamine instead of dosing it orally? Or mention just how much bicarb it would take to get your urine ph > 8.0(I missed it if that paper did).
 
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CrimpJiggler

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Raising the pH of the stomach might give a faster onset. What I was commenting was primarily the statement that it was increased transport over the BBB that facilitated more subjective effect.

This is another gap in my knowledge. How does stomach pH relate to blood serum pH and urine pH? If I'm not mistaken, normal serum pH is 7.4 which is why basic drugs are a lot more likely to pass through the blood vessel walls via transcellular diffusion and end up being deposited in fatty tissue. I assume taking antacids isn't gonna change my serum pH because the cardiovascular systems pH is separated from the stomach. Is that correct? If so, how does one basify ones urine? Is it by taking stable basic compounds that will eventually reach the urinary tract unmetabolised (as opposed to say carbonate or hydroxide salts which will be turned into CO2 or H2O in the stomach)?

As for stomach pH increasing transport across the BBB, how is that possible? I can see how serum pH will influence what crosses the BBB but again, I thought the stomach pH was kept separate to the blood serum.
 

Refluxer

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Stomach pH = 2. Amphetamine pKa = 10. Raising the pH of stomach fluids will make a larger portion of the amph. deprotonated. So more amph. is readily absorbed (perhaps already in the stomach) when entering the duodenum. Increasing stomach pH has nothing to do with passage over the BBB.

Basifying your urine can be done by several ways. Some drugs raise pH, but more commonly you can use bicarbonate or citrate salts.

http://en.wikipedia.org/wiki/Acid-base_homeostasis
 

Refluxer

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I'm just not sure that eating a couple tums would actually affect urine PH enough to matter(on their own), I don't think it is mostly responsible for what most users are experiencing, although it could definitely have an additive effect. Or greater effect if you are effectively controlling urine PH, by taking larger doses of bicarb or taking it on a regular basis.

I'm not sure it does either. One will probably need more than a few tums. So, yeah, there might be increased absorption early on in the digestive tract.

edit: Did any studies relating amphetamine to urine ph, IV the amphetamine instead of dosing it orally? Or mention just how much bicarb it would take to get your urine ph > 8.0(I missed it if that paper did).

Concerning the decreased urinary elimination, IV/oral doesn't matter. The decrased renal elimination is primarily concerning unchanged drug. When basifying urine a lot less of the drug will be excreted unchanged and a higher portion metabolized. Concerning how much bicarb u need, I don't know. If you have pH-paper you're welcome to do some experiments. Perhaps I will do it myself some day. ;)

EDIT. IV will of course bypass first pass metabolism and all that.
 

Coolwhip

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I know IV wouldn't effect urinary elimination. But it would clarify the issue, increased absorption could throw off the rest of the numbers. Limit the variables.

But I think I might try that myself also, just out of curiosity.
 
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