Why does MDMA Tolerance occur?

MDMA tolerance occurs because of taking mdma in large doses or lots in a short space of time. Or reguarly over a long period of time But why is this? I have searched the forums and tried to come up with a reason for why this happens but have not found one
This is the best i came up with but it doesnt tell me why the tolerance occurs.
How long do tolerances last?
when you just don't want the big night to end
Braindead
Mdma feelings lasting for more than 4 hours..
anyone scared about post NYE tolerance?
The only reason i can come up with is tolerance occurs on a short term basis because of lack of seritonin. But we all know this and it isnt really tolerance cause there is no seritonin left after u have just used it all up. But when ya replenish this seritonin to full levels say with 5htp or time etc, there is a long standing tolerance that makes a person have to take more mdma on there next dose to get similar effects.
Why is this tolerance caused? Is it because the seritonin uptake receptors have been damaged by the flooding of them with seritonin or what is it that causes this exactly. If it is the seritonin uptake receptors being depleted or damaged how can this be stopped?
Any one have any idea as to why the tolerance of MDMA occurs?
[This message has been edited by shank (edited 11 July 2001).]

EDIT: D'oh.. i just read on the last slide that the 'cause of tolerance' slide is yet to be put in the slideshow... but after doing more reading on other sites, i think the reason below is right
Well the theory on the cause of tolerance, according to Dancesafe's Ecstasy Slideshow (a must read if you haven't already), is downregulation of serotonin receptors
From slide 18:
The brain is built to adapt to changing circumstances. One of the ways your brain adapts is through the up-and-down regulation of receptors. What this means is that if your serotonin receptors get hyper-activated by serotonin molecules, they may retreat into the membrane of the dendrite, essentially shutting themselves down for a while. One theory says they do this in order to avoid getting damaged from over-stimulation. Another theory says that it is just a way for your brain to maintain a balanced, normal state. Whichever one of these theories is true, it has been proven conclusively that serotonin receptors will down-regulate over time if bombarded with large amounts of serotonin.
The slide is explaining the cause of long-term ecstasy related depression, but I think it's the same theory for tolerance (either that or I've just made a fool of myself)
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"We risk sanity for moments of temporary enlightenment"
[This message has been edited by Daffy (edited 11 July 2001).]

Yeh have read that too. Is there anyway to stop the downgrading of the receptors?
Is this the only cause of MDMA tolerance or what cause there must be a way to minimise it.

If you stop the downgrading of serotonin receptors, you will probably end up with permanent tolerence and depression caused by receptors no longer functioning.

I'm going to offer my slightly untechnical point of view , just backed up from experience. I sort of believe it also has something to do with the experience. For example the first time you go and see Titanic at the movies or go on a roller coaster ride it blows you away. Go on that ride 50 times in one day and your gonna start feeling sick and never want to go on the damn ride ever again. The ride isnt getting any worse your just getting absoultely sick of it because you've been there done that.
Maybe im explaining exactly the same thing as was said above but in more everyday terms i'm not sure but i just feel that you get used to the experience and over time it grows to mean less and less. It may be the most mind blowing experience in your life the first time you have it, but if you have it every weekend after that it can't really be the most mind blowing experience every weekend can it?

that doesnt help explaining why sex is always good? (if done right of course )

Look, I think it works this way (this is SO not scientific, but explains what I think)
(example) When you weight train, weights at first seem so heavy, and your muscles grow SO quickly and it all works well for you. But eventually, your body 'adjusts' to the weights, and compensates for this. Then what happens...no more growth. So to kick your body into it again, you have to increase your weights more and more as you grow! But if you take a break from training for a few months, then jump back into it, even the light weights will make your muscles sore. This is common practice in body building, as it lets the muscles 'forget' and shocks them..
NOW... if you do this with pills, at first, YAY! but eventually, you will have to do more to get the same feeling. So, if you take a break, your body will forget, and repair and replenish seratonin and all that shit... So when you start again, BANG! your body has forgotten and your rush is FUCKING WICKED!
That's the best I could dop kiddies, hope it made sense. The break thing has ALWAYS worked for me. At on stage I was up to 4 - 5 pills a night. when I started again, it was 1 - 2 AT THE MOST to get me rockin!
ENJOY!

the best way to keep your muscles growing is confusion. Throw your routine around etc. So maybe we could somehow do 'mdma confusion?'
i.e instead of dropping at night, maybe do a day drop etc and see how it goes? Who knows, it may open a whole new world up on an otherwise seemless 'groundhog day rolling periods'

setting makes a bit of a difference, but your best bet is to try to mix the md** up. Shulgin reckons that there is very little cross tolerance between mdma and mda (no idea about mdea).
Probably why you find that alot of people who take pills often find new pills all the is better than having the same good pills constantly, because of the different chemical compositions.
Also probably explains why we like to have a different pill for the second one.
just my 2c

MDMA tolerance occurs because your receptors get downgraded. Studies on monkeys showed that after 7 years the receptors began to repair themselves (maybe someone knows where that reference is??).
The way to stop serotonin receptors from downgrading is prozac. Prozac shifts the damaging force of the mdma from the serotonin system to the dopamine system. The dopamine system is more robust than the serotonin system.
This is my understanding, if you ask this question in the medical forum you'll get a much more detailed responce.

Acid_Reign: Not sure if i understand that.
Prozac "plugs" the serotonin reuptake transporters. It is believed to work by increasing the amount of serotonin in the synapse, so there is increased binding to receptors.
Prozac does not effect the receptors directly.
Its believed it assists in prevention of neurotoxicity by preventing dopamine getting through the transporters and into the serotonin AXONs during periods of UNNATURAL serotonin depletion.
Thats the thing about MDMA and its long term effects; there is damage to the axons and serotonin producing cells as well as damage/downregulation/alteration of receptors to consider.
There doesnt seem to be anything that can be done to reduce the receptor problems. Some people have argued that as good as 5-HTP is, it may exacerbate this due to overstimulation for long periods of time.
I think the problem with MDMA is the experience is so unnatural and so magical its hard to match it with the first few times. It feels so amazing because your body has never felt like this ever before.
Thats y i think for people who have been doing this for a while, setting is the key to any subsequent MDMA experience.
It makes good things fantastic, but will never reach the same undescribable heights of the fantasy land it put u in again.
I also believe its definitely the receptors which play a part in the quality of the experiece. I can take all the HTP i want and numerous pills, and go for a long time and get very "fucked".
But the ecstasy aspect is missing and i feel thats only going to return with an extended break.

I guess this is slighttly off topic, but not sure if its worthy of its own thread.
Everybody says that you don't want to risk losing the wonderful effects that mdma has on you bo overdoing it, to the point where you do become tolerant to it (for whatever medical/scientfic reasons). What I'm curious to find out is, how long does it actually take for this to occur, is it a matter of months, years, is it inevitable?
I'm in my first 6 weeks of pilling, and I'm scared that if I keep it up like I have been, the effect will gradually decrease.
I know people say take 3-4 weeks off during pilling, but it's not that easy! Any advice would be great
[This message has been edited by CynaKill (edited 16 July 2001).]

So this annoying tolerance thing is pretty much due to downgrading of receptors hey. Besides the fact that u get used to the feeling as mentioned and it doesnt feel as good anymore because its not somthing new.
Must be someway to stop these annoying little receptors downgrading themselves. Cause prozac doesnt stop them downgrading as someone said.
cynakill. how long does it take to get a tolertance u ask. well from personal experience. It took me 3 weeks in a row (that incleded 22 sets of 2 nights in a row) since i had my first pill well over a year ago now to start droppin 2 pills a night to get the same effects and hasnt dropped back at all since. only increased i would say. I would love to go back and organise it better cause everyone seems to give it the overkill once they find these nice little pilz for the fisrt time.

Its important to note that receptor down regulation is a theory; and not a lot is known about it; esp things like how long does it take to reverse? how much is required for it to occur?
Most people say wait a month.
However i think people should be more selective of their MDMA experiences.
The worst thing that could happen whilst enjoying MDMA is realising this seems all too "normal" now. Its NOT NORMAL. You r taking your body so far from normal its a joke; possibly more than any other substance can.
So my advice would be: dont say to yourself, "its been 4 weeks, i am having a pill."
Say: "i cant wait for tonight", "my favourite DJ is in town", or "my partner and i are celebrating our anniversary", or "its my birthday", or "my friends and i want to get close and sort out our differences", or "i've worked fucking hard at uni to get HDs, its time to celebrate" etc...THEN say "i am having a pill".
Trust me when u r an old pill fart like some of the people on this site, this wonderful drug will still have significant meaning to u.
The word "normal" or "familiar" should never come up, and if it does its likely u've potentially lost something special. (or at least will do if changes arent made)

Prozac does prevent the downregulation of serotonin receptors. It "plugs" the serotonin receptors preventing dopamine from entering and causing neurotoxicity. As i was trying to say before it's hypothesised that while prozac prevents neurotoxicity of the the serotonin system it may increase neurotoxicity of the dopamine system the same way meth does.

I see what u r saying, but chemicals bind to receptors; they dont go through them.
They r two different things; RECEPTORS and REUPTAKE TRANSPORTERS.
Neurochemicals bind to receptors causing a number of responses, then are removed.
If prozac bound serotonin receptors the receptors would remain stimulated or never be stimulated; i guess depending on if prozac mimiced the action of serotonin on the receptors, which i doubt it does.
U r saying then prozac binds receptors which prevents other chemicals binding to them and subsequent downregulation? Or prozac binds before they r downregulated, by "holding" the receptor outside the cell?

Whoa dude!
You always make me use my head more then usual
Almost all my knowledge on this is from the dancesafe slideshow.
I don't have the time to look now and refresh my memory.
But prozac "plugs" *something* and prevents neurotoxicity that way.
I'll be back with the results of my research

Oh hehe, ic; i didnt want to dismiss what u were saying because, while i have some clue, i am completely ignorant when compared to people with actual neurochemical/pharmacological knowledge. Hey even those guys dont understand the majority of it!
But yeah, u r mistaken. Its the transporters, not the receptors that prozac plugs.
Prozac is a SSRI = selective serotonin reuptake inhibitor.
So its in the name; it prevents serotonin being taken FROM the synapse, leaving a greater amount in the synapse to stimulate receptors, and presumably make depressed people happy.

Posted this is medical Q&A as well and this is the response
Why does MDMA Tolerance occur

man... love that scientific jargon... oh well. my mum always said i looked like a monkey... "if ya cant beat 'em join em...."
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Mr_Clean (aka muzik_response) ... tell me is that really YOU?