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Opioids Instant withdrawal in the opiate tolerant. Why?

Muzda Jonxx

Muzda Jonxx

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Joined
Jan 14, 2014
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Upside down.
Hi all,

So - I've got a question I was hoping one of you folk could answer.

Back in the day, when I was opiate niave, I could at first take opiates and never feel any kind of withdrawal. This was small time stuff like codeine CWE's and kratom FST liquid. I went on like this for a year or two, before climbing up the ladder to things like oxy, bupe, then later pods and H. Once I climbed that ladder, it didn't take too long for things to unravel, and I learnt what withdrawal was like.

We know that acute withdrawal is caused by the fact that the body becomes habituated to opiates being present in the system, and it adjusts its homeostatis accordingly (and grows lots of new opiate receptors, which is why people become more and more tolerant). Once the opiates are removed, the body needs to readjust back to the original homeostasis. This takes time, and results in all the sucky acute wd sickness we all know and love.

Fast forward to today, and I'm extremely opiate tolerant after 12-15 years of hammering opiates. And here's the thing - if I were to get a nice taste of opiates now, as soon as they wore off I'd be flung into acute withdrawal. It doesn't matter if I've been sober for 2 years, that's what's going to happen. And that's the thing that confuses me. It takes time for the body's homeostasis to adjust, a very long time for the opiate niave. But certainly longer than 12 hours high on pods.

So - what's occuring there, then? It's almost as if the body throws itself into withdrawal if more opiates are not supplied. Sort of like cutting your nose off to spite your face. Or a toddler throwing a fit in the middle of aisle 3 because mum won't buy sweets.

Anyone got any theories?
 
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Well, I haven't stopped for 2 years so, I can't reply directly on that matter. But, I have a theory... Is it possible that the acute withdrawal after one 12hr pod trip, after 2 years of abstinence, you going into withdrawal was just the way that your mind processed what was happening to you - i.e., the vomiting and hot flashes and all the rest, were actually very similar symptoms that an opiate niave person would have if they used the same thing? They'd start throwing up and feeling very ill, probably much sooner than you, but the symptoms would be quite similar. Could it be that you are just totally familiar with each and every withdrawal symptom - after so many years of experience?

I too have to take a prescribed dosage of pain medication every day. I have been on for many years too, but have yet to take many consecutive months off. I will do 30 days of detoxing myself, to see if I really need the meds, and I end up not able to walk and bed-ridden. So, I get back on 'em. But, I understand your question and I have experienced similar phenomena. But, I don't have any specific answers, just more questions....sorry Jack, my bad.

Good question, Muzda Jonxx.
Good luck, hope something I said helps...

Peace out, gotta go water!!!!!!

-CBDizzle
 
That's the thing - I used to take 60mg oxy in one go when I was first getting into it, probably once a week at first. Of course that soon escalated to 80-100mg a day, and that's where the real problems started. But at the beginning, I'd take that 60mg in one go on the weekend, and the worst thing that would happen would be that I would feel a bit tired for a couple of days. If I were to try the same trick now, I'd be aching, shitting through the eye of a needle and all that other lovely stuff. Just seems to me like my body throwing a paddy just because I won't feed it more.

Of course it probably isn't that, I'd love to know what it is that changes about the way the nervous system works that means one taste of a good thing throws it right out of whack. I mean - the withdrawal for a one-off wouldn't be as bad as if I were downing oxy daily for 3 months, but it wouldn't be too far off.
 
It's possible the pod had such an acute content of narcotics that he suffered enough downregulation to experience the symptoms.

I've experienced withdrawals syndromes from one-time uses of quite massive dosages of dextromethorphan - enough to destroy enough NMDA receptors to feel it the next day, and​ then some.

This is possible.
 
Fair play BlueHair, so what you're saying is that maybe one proper dose of opiates is enough to downregulate and switch homeostasis? Sort of like a wrecking ball taking out a wall. Takes seconds to wreck it, days to rebuild. I suppose that could be it, I do need a huge dose to feel anything these days. The lower opiates (codeine / kratom) I simply do not feel at all anymore, whatever the dose.

The question with that is, why doesn't that happen with the opiate niave? I suppose maybe it would happen, except it wouldn't be possible because my dose would be an overdose for someone not used to it.
 
Muzda Jonxx said:
Fair play BlueHair, so what you're saying is that maybe one proper dose of opiates is enough to downregulate and switch homeostasis? Sort of like a wrecking ball taking out a wall. Takes seconds to wreck it, days to rebuild. I suppose that could be it, I do need a huge dose to feel anything these days. The lower opiates (codeine / kratom) I simply do not feel at all anymore, whatever the dose.

The question with that is, why doesn't that happen with the opiate niave? I suppose maybe it would happen, except it wouldn't be possible because my dose would be an overdose for someone not used to it.
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I've had it happen from a massive dose of baclofen as well, but that was an overdose. Thew me into EXTREME withdrawals. So sufficient dosages can do it. I think it's because the brain's mu, delta, and kappa receptors in the opoid-tolerant are really sensitive to any exogenous agonist and are in a sense "trained" to detect them and downregulate more quickly upon binding and activation.

Which is why when you are used to a drug you get less effects from it and they wear off more quickly, regardless of abstinence. Your body is more prepared to deal with it, which includes downregulation.

The opiate-naive would have sufficient receptors and would be very resilient to the exogenous agonist, but it would be just as possible in them in my opinion, in sufficient dosages. Which would explains hangovers and whatnot. They would just be more resilient, as I stated.

You never know after chronic administration of agonists if full receptor density is ever once again achieved, as well.
 
theGirlWithBlueHair said:
I've had it happen from a massive dose of baclofen as well, but that was an overdose. Thew me into EXTREME withdrawals. So sufficient dosages can do it. I think it's because the brain's mu, delta, and kappa receptors in the opoid-tolerant are really sensitive to any exogenous agonist and are in a sense "trained" to detect them and downregulate more quickly upon binding and activation.

Which is why when you are used to a drug you get less effects from it and they wear off more quickly, regardless of abstinence. Your body is more prepared to deal with it, which includes downregulation.

The opiate-naive would have sufficient receptors and would be very resilient to the exogenous agonist, but it would be just as possible in them in my opinion, in sufficient dosages. Which would explains hangovers and whatnot. They would just be more resilient, as I stated.

You never know after chronic administration of agonists if full receptor density is ever once again achieved, as well.
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Interesting, that makes a lot of sense, many thanks! :)

Regarding receptor density - I was under the impression that where opiates are concerned, the body actually increases the receptor density, rather than reducing it. Which is partially why people get more and more tolerant to those drugs over time, because it takes a higher dose to activate all the extra receptors. I've no idea whether the body removes those extra receptors over time, once the opiates are removed from the equation?
 
Nope, drug tolerance is due to desensitization and downregulation (there are less sites to elicit biological responses as opposed to a full density where many biological responses can be produced):

https://en.wikipedia.org/wiki/Drug_tolerance

Which is why antagonists are used to reverse tolerance (flumazenil in the case of benzodiazepines). They rapidly induce upregulation and restore a somewhat normal receptor density. Antagonists - in the presence of already-normal receptor density - will also induce upregulation, which will cause a drug to have intensified effects, due to the increased receptor presence.

Drugs have less effects in tolerant people because there are less receptors to activate and you need a higher dose to hit them. With high receptor densities, just a small amount can elicit a biological response.

Tolerance

A person may develop tolerance to a drug when the drug is used repeatedly. For instance, when morphine or alcohol is used for a long time, larger and larger doses must be taken to produce the same effect. Usually, tolerance develops because metabolism of the drug speeds up (often because the liver enzymes involved in metabolizing drugs become more active) and because the number of sites (cell receptors) that the drug attaches to or the strength of the bond (affinity) between the receptor and drug decreases (see Site Selectivity : Receptors on Cells).

It has to deal with metabolism too, as the article above states. (I have no idea why I'm still in the same font :/ lol) But I've read somewhere that your body develops some sort of "antibody" system against certain drugs once they are introduced and this is involved as well.


And yes, the body does attempt to restore homeostasis.
 
Are you currently using opioids regularly so that when you do use, your body would have reason to go into withdrawal?

But you stated that if you were sober it would happen too...

So the alcohol article... He wouldn't really be having "subsequent withdrawal reactions" if he gets them when using opioids even when sober... Right?

Because that is going on the basis that the person is regularly using alcohol before each subsequent withdrawal begins, and that is long enough to form a dependence and downregulate GABAAR , NMDAR, AMPAR, nAChR, and to cause negative regulation of high voltage-gated calcium as well as GIRK channels...
 
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No, I got clean about 5 and a half weeks ago, so not using anything other than a little alcohol right now. Every so often the temptation hits me though, so I keep reminding myself about the instant withdrawal problem when the cravings hit. :)
 
Congratulations on that! :) Keep it up.

Yeah... That's odd... Let's steer away from pods for a sec, as you can't guage the dosage. Say you were to take a recreational dosage of an opioid right now - one that would send you into instant withdrawal, what dosage would you take?

I'm only asking because I want to see how much downregulation might occur because of your dose.

Man, I can't find any lit on this...
 
Muzda Jonxx said:
No, I got clean about 5 and a half weeks ago, so not using anything other than a little alcohol right now. Every so often the temptation hits me though, so I keep reminding myself about the instant withdrawal problem when the cravings hit. :)
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Have you actually had this same type of experience after being off opiates for two years not just 5 weeks? It is common I believe for this to happen if you are in your first three months or so of recovery from a longer habit.

One time after being clean for 4 weeks off suboxone and a short term benzo addiction I relapsed in treatment on 2 mg of bupe. After a few more days I went back into WD's which then slowly caused a case of sleep deprivation. The WD's from the 2 mg of bupe only lasted a few days but it made me think about the kindling process. This small dose caused havoc on my brain as I had been kicking 24 mg of bupe and a 5 mg ativan habit essentially cold turkey. So I had not been sleeping so well before relapsing 4 weeks in.
 
It's certainly true to say that my tolerance drops with time, but this I've gone six months clean in the past and then resumed at a similar dose. I didn't take opiates to nod though, I prefer to feel great whilst still being able to go about my day. I did notice that the side effects like itching ramp up after a long break.

But no - I've not gone years without and then resumed, so that's a very good point.
 
This is just a theory, but maybe what you are interpreting as "acute withdrawal" is more of that hangover sickness you get when you do too much opiates like for the first time after a break, or if you tolerance is low at the time. For the better part of a year I would take a 30-35 day break in between one day of use every month. Nearly every day I ended up getting that hangover nausea and all that.
 
^ I tend to agree on this one. With that long of a tolerance break you wouldn't want to resume at the dose you left off doing. Usually after a month I can get the same effect from about half my usual DOC. Granted my tolerance increases at a more rapid pace but I think what you're describing as wd may be side effects and the subsequent comedown.
 
I feel you...I've written this before, my thought with kindling is that if you've gone through enough binge/withdrawal cycles and you've been clean for a while, when you do opiates your brain basically goes "oh, I remember this stuff, I better quickly rearrange myself to compensate" and voila, you're right back to square one...high tolerance, worse withdrawals, all that fun ass shit I've been through too many times...

It's like once you've been addicted to opiates your brain is already wired to immediately change when it feels a high dose come on....supposedly this is even worse with high dose benzo addiction which thank Gawd I've never and will never have to go through as benzos do nothing for me recreationally...
 
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