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Different tolerance by methods of administration?

gher

gher

Bluelighter
Joined
Jul 9, 2004
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I recently met a guy who can get me some particular pills for pretty cheap and I suspect that they're rather average. There's a few reports up, two of them scored 8 with a lot of disagreement, a few others didn't rate them at all but that's besides the point.

Anyway, when I get them I'll probably eat one to test their strength and if they really are average, I'll take the rest of them sublingually or rectally over the summer, say every 2-3 weeks or so. This got me thinking, is tolerance affected by administration methods? Say I do follow through with it and shelf or dissolve them all, then go back to eating pills once some better ones come my way. Will I get diminished effects from the better pills than if I just ate the average ones?
 
I'm pretty sure it'd all be the same, because it all does the same thing, you're just getting it there by different means ...
 
Tolerance doesn't depend on the method of administration per se, just on how high you get.

More effects --> More tolerance.
 
More effects --> More tolerance.
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VelocideX, is this why the duration of effects is shorter when snorting pills? Because the effects are so great in such a short time?

peace,
beta theory
 
I disagree, i think im more tollerent to snorting than eating, eating a half will have greater effect than snorting, because i snort them all the time.
 
More effects --> LESS tolerance, surely?
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Velocide meant, "A pill which gives you more effects, leads to more tolerance" you mean "if you get more effects, you must have less tolerance" ...

I've been puzzeling over the maths of this for some time-
If one could introduce MDMA at a certain concentration instantaneously, and then kept it at that concentration for infinity (so the system could reach equilibrium) then the tolerance that would be induced would soley be a function of that concentration.

I'm pretty sure that the tolerance induction (or more really Ätolerance) would be a function of the Area under the curve (AUC) of the the time/plasma concentration...

No, thats not right, because a very low concentration of MDMA for an infinite time wouldn't induce an infinite tolerance...

...Its about how long it takes for the system to equilibriate...

hmmm, tolerance = ((c1 x concentration) x (time/(1 + c2 x time))

Maybe? I think that would give the amount of tolerance on the accending phase of the MDMA experience... Yeah, thats assuming that the rate of loss of tolerance is insignificant...

* bilz0rs brains melts out his ears...


The important point is that the rate of change of the MDMA plasma level has to be higher than the rate of tolerance induction, or the high will decrease.
 
BilZ0r: My brain just melted out my ears too. :|

If everything said here is true, it seems that tolerance is dependant on both physical and psychological factors. Because I've only eaten my pills to date, any increased effects from other administration methods would be a result of more drug entering my system and unfamiliarity of the method. This raises another question, could different parts of the body (i.e. stomach, intestines, lungs) develop a tolerance of sorts? For example, a person who always eats pills 'trains' his stomach to filter out more of the chemical, but his lungs are less 'trained'. He then rails a pill and gains more effects because less of the chemical would be filtered out than if he had always railed his pills. Is this a likely scenario?

Back to the real world, I'm not so sure about stocking up on these particular pills because of reports I've seen and heard. Thanks for the replies, I'll keep it all in mind in future.
 
gher - When you snort a substance it does not go into your lungs. If any does your snorting way to hard. The substance coats the mucus membranes in the sinuses and is abosorbed through the same.


Tolerance is tolerance. It doesn't matter how you get it. The fact is, they don't know enough about MDMA and the way it builds tolerance. The only thing that is known is, the more time you abstain the more of it goes way.
 
beta theory said:
VelocideX, is this why the duration of effects is shorter when snorting pills? Because the effects are so great in such a short time?

peace,
beta theory
Click to expand...

More rapid absorption, but more intense.

Here's a really lamo graph I just made with MAPLE. It's so wrong in so many ways. For starters, blood plasma levels aren't parabolas :P They asymptote to infinity, rather unlike the ones ive drawn here. It's just for illustrative purposes

differentabsorption.gif


Imagine the y axis is plasma levels (which is related to, though different from actual effects).

I've assumed here that one of the routes of absorption is significantly faster than the other... In reality you've got things like a delay when consuming orally etc... again just for comparative purposes.

The area under the curve (AUC) corresponds with the total dose. I've ensured that both these curves have the same AUC, and so correspond to (approximately) the same dose.

The faster absorber has a much higher peak than the later one.

Of course all this is highly dependent on the body's ability to remove the material. The assumption that's kindof implicit in this graph is that the body can remove material at roughly the same rate as its absorbed... so in reality the "tails" of the graph would be much longer.

One day if I can be arsed I'll make a slightly better approximation from a differential equation. If anyone happens to know an approximate formula i'd love to know, to save myself the trouble.

Incidentally one of these graphs has the formula y = x(x-5). The other has the formula y=(125/27)x(x-3). You can confirm by integration that these yield the same areas.
 
gher said:
BilZ0r: My brain just melted out my ears too. :|

If everything said here is true, it seems that tolerance is dependant on both physical and psychological factors. Because I've only eaten my pills to date, any increased effects from other administration methods would be a result of more drug entering my system and unfamiliarity of the method. This raises another question, could different parts of the body (i.e. stomach, intestines, lungs) develop a tolerance of sorts? For example, a person who always eats pills 'trains' his stomach to filter out more of the chemical, but his lungs are less 'trained'. He then rails a pill and gains more effects because less of the chemical would be filtered out than if he had always railed his pills. Is this a likely scenario?

Back to the real world, I'm not so sure about stocking up on these particular pills because of reports I've seen and heard. Thanks for the replies, I'll keep it all in mind in future.
Click to expand...

^^ all i can say is "oh dear". i just posted in another thread that i am constantly surprised...but i think this has even surpassed that...

again im not trying to be mean...but goodness.

---------------------------------------------

nice graph babes :)
 
Muhaaha I am a genius

differentabsorption2.gif


Graphs have equal area from 0-->infinity

For anyone who is really nerdy like myself, each graph is ~ (x/p)^2*exp(-x/p)

Probably not the best approximation, though to be fair its me fiddling a guess at a simple approximation to the differential equation.
 
Thanks for that last part Velocide... I was trying to work out an accurate one of those from combining all the relavent pharmacokinetic functions...

The concentration in the stomach/nose would be a function of original dose and rate of absorbtion
Rate of Absorbtion would be a function of concentration in the stomach/nose
Blood plasma would be a function of rate of absorbtion and metabolism
Metabolism would be a function of blood plasma

And whack them all together



Also, don't forget that AUCs are only equal if bioavailability is equal... oral doses are going to have smaller AUCs.
 
Mine isn't really a serious solution, it just happens to look OK in that range. I've had to alter the exponential decay constants, which means lowered clearance rates, which is clearly wrong. I just fiddled the graph to get something that looks ok.

The problem is I was only considering a first order differential equation.

The differential equation which describes that is going to be of at least degree 2.
 
Eh its not even going to have constant coefficients I dont think... --> in general no analytic solution

After my exams are over I might have a serious attempt at making a better equation, though I don't know nearly enough about differential equation construction. One thing I'd like to know more about, given that the whole world runs on the fuckers
 
Pippin said:
^^ all i can say is "oh dear". i just posted in another thread that i am constantly surprised...but i think this has even surpassed that...

again im not trying to be mean...but goodness.

---------------------------------------------

nice graph babes :)
Click to expand...

8) Well until proper studies are made, we'll just have to waste our time spouting bullshit like this. I learnt something so this thread isn't a total waste.
 
Most of this stuff is based of fact. Theres enough human pharmacokinetic data out there on MDMA that we could accurately figure all this stuff out if we knew maths and pharmacokinetics well enough...
 
Oh I agree its based on fact, I'm just good enough at constructing differential equations.

It can be done in principle. I'll have a sit down and think about it in the holidays as to what exactly the terms would be...

Aha! I think I've just realised what describes it. It's a set of coupled first order differential equations...that's not too bad to solve, you can just use matrix mathods. I'll attack it in the holidays.

I wonder if anyone around has attempted simple analytical approximations. Surely they must have...
 
gher -- I don't see how you could desensitise something with no receptors to desensitise. It's like saying you'd build up a tolerance to absorbing chocolate because that's all you ate.

I'd find it hard to believe the human body would want to maintain an absorbative tolerance to food... Back when food was scares you wanted to absorb everything you could.
 
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