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Why is it impossible to stay high on opioids for the rest of your life?

kratom luver

kratom luver

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Hypothetically speaking, if you had an unlimited amount of an opioid that had an acceptible profile of side effects, such as Oxycontin, why would you not be able to keep increasing the dose indefinitely up to a point where you still get high all the time?

When animals are given an unlimited access to (dia)morphine, why do they choose to stabilise at a certain dose? Is this because the side effects caused by higher doses outweight the added euphoria given by increased doses beyond a certain point or is it simply because the euphoria stops beyond a certain point?

What is there to stop you from just from increasing the dose whenever tolerance prevents it from inducing euphoria?
 
Yes, but why can you not overcome this tolerance by increasing the dose? I want to know the scientific answer why you cannot overcome this tolerance that ultimately stops you from getting high by increasing the dose.
 
Wouldn't the tolerance eventually build up so high that you wind up overdosing and dying just trying to get high?
 
kratom luver said:
What is there to stop you from just from increasing the dose whenever tolerance prevents it from inducing euphoria?
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Hypothetically it works fine. IRL money is the brick wall most people hit with opiates.

EDIT : After reading other theories on the OP's question of "why.....". I still say its the down regulation of the additcts wallet, NOT the down regulation of opiate receptors, that stops most folks from chasing the high.
 
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I'm willing to bet that at certain levels liver load DOES become significant, even with the relatively harmless opioids. Also, some effects gain tolerance quicker than others - you may still have significant respiratory depression, nausea, etc. even though you're not getting nearly as high. Plus, novelty wears off. Maybe you just get fucking bored of it because you're not such a loser that you think your life is measured only by how high you are.
 
^ I think Monkey Mantra hit it. Tolerance to the euphoria happens much quicker than tolerance to the other effects. So you would reach a ceiling effects, probably why the animals level off their self-administration at a certain point. They simply get more of the bad effects.
 
In my case, when I got to high doses of Oxy and Hydro mixed i wouldn't really get high and at the same time i was afraid of adding a bunch more to an already rediculous amount so i would only add in small quantities which wouldn't help. Its always my anxiety that stops me, thats the only good thing it does, without it I'd never stop ingesting a few drugs i get prescribed and paid fully by my insurance.
 
This has been replicated with humans; the original Swiss studies in the '90s showed chronic Heroin addicts, when given access to unlimited amounts of pure Diacetylmorphine to shoot 3 times a day, will eventually settle on a dose, and stay there, rather than upping it constantly.

There are people all over the globe who consume suprarecreational / heroic doses of different opioids several times a day. Rach has posted about people in NYC MMT programs who take several grams of Methadone a day. A guy who posts here wrote about using 40 bags of Heroin at one time. If you develop the tolerance, there is no limit to how high you can go.
 
What if you were to circulate different kinds of opioids daily? ones that don't have any cross tolerance. Like one day morphine, then methadone, then heroin, then fentanyl, then pentazocine... On top of that you can use nociceptin antagonists, NMDA antagonists, oxytocin, and other things to tolerance from building and potentiate. Then opiate antagonists at night so your receptors get upregulated as you sleep.
 
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^^ That may work slightly better in the short term but doubtfully in the long.

The reason we don't stay high forever is that we'd be very ineffective organisms if we felt no need to do anything because we were too high to care all the time. Hence, our bodies are designed to metabolise, eliminate and develop a tolerance to such compounds because they represent nutritional and reproductive toxins by causing us to abstain from eating and having sex.
 
nuke said:
^^ That may work slightly better in the short term but doubtfully in the long.

The reason we don't stay high forever is that we'd be very ineffective organisms if we felt no need to do anything because we were too high to care all the time. Hence, our bodies are designed to metabolise, eliminate and develop a tolerance to such compounds because they represent nutritional and reproductive toxins by causing us to abstain from eating and having sex.
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You don't have to abstain from those things though. When I'm high on opioids, amphetamines or whatever I remember to eat and stay hydrated. Sex is a little difficult on opiates can still be accomplished. As long as you do those things you're body will still get the message, though I don't think would have much do to do with preventing tolerance... One can also naturally feel no desire to eat or have sex. Celibate monks, guru's, and yogi's are especially good at this, but their neurotransmitters just keep building up.

Another problem I think that could be posed is the receptors might be damaged or burnt out from overstimulation. Anyone know what could remedy this?
 
Their looking into NMDA antagonists to combat opiate tolerance since it disrupts memory but i don't think it would help if their burnt out, I suppose they can get burnt out, look what meth does to dopamine receptors. fucking curls them back.
 
^ well, but that's a clear case of dopamine destruction. I think what we're looking at here is an extreme case of down-regulation for the receptors being 'burnt out'. And i dont think that anything could help damaged neurons. you might be able to make some new neuronal connections and recover a little, like stroke victims, but i'm sure you wouldn't be the same afterwards.

And again, NMDA antagonists help combat tolerance, but they are not the hail mary everyone thinks they are. they will only slow the development of tolerance.
 
^ what about nociceptin antagonists? isn't nociceptin partially responsible for development of tolerance to mu-receptor agonists?
 
I like the sound or ORL-1 over NOP1. Eventually I'll have to convert, I suppose...
 
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