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

Monkey Mantra concluded everything relevant to answer the question in post #7.

I'd like to add just a detail: One reason that you can't get high forever is the limited number or receptors. Even without downregulation (pure theory) you will build up a tolerance to the compounds that you're using (receptor downregulation is not the only mechanism of opioid tolerance). But as the number of receptors is limited, you will sooner or later reach a level where you won't feel an increase of the desired effects.

- Murphy
 
as what post 21 said...

Wouldnt you in theory hit the limit when your tolerence was so high, that although you've occupied every mu receptor with an agonist ligand, you still dont get high? at that point, no matter how much more you took, it wouldnt matter.

Not sure if this works out in real life...I'm extrapolating from receptor overload as it applies to cannabinoids (you get as high as you can get, and more THC then just extends the high not makes it mroe intense) and neuroleptics when you obtain like 99% blockaide of the D2 receptor with an antagonist and thus can no longer neurolepticize the person anymore.
 
Not sure if this works out in real life...I'm extrapolating from receptor overload as it applies to cannabinoids (you get as high as you can get, and more THC then just extends the high not makes it mroe intense
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This is because it's a partial agonist.

neuroleptics when you obtain like 99% blockaide of the D2 receptor with an antagonist and thus can no longer neurolepticize the person anymore.
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This is because with an antagonist all you're doing is blocking agonists, so of course there's a limit. When you have agonists, they're binding, releasing, binding releasing constantly, having more and more agonist molecules present can fill in the gap time.
 
Yeah Hammilton, but in general rangrz is right:
There is a point of saturation, from which on one can not get any higher. Please note that when this point is reached with almost all opioids, you are already dead from the respiratory depression and who knows which else side-effects. But in theory it's correct.
Another 'problem' with opioids is that tolerance towards the analgetic (and euphoric) effects is built up much faster and more effective than towards undesirable side-effects. But I think that was already pointed out before.

The fact that one can reach such a saturation with cannabinoids is due the fortunate situation that cannbinoids do not interfere in an acute fashion with life-supporting functions of the body (respiratory, body temperature, blood pressure, etc.). Even full agonists will provide a point of saturation (---which is actually said to be absolutely unpleasant with full and potent CB1-agonists, so kidz, please don't try at home!).

Murphy
 
With all the science put aside, speaking from personal experience, I remember building myself up to a 100 dollar a day H habit. When I got to this point I couldn't get the long-lasting intense high that I would get with 1 bag and no tolerance. I'd be shooting up 5 times a day or so, and the high and rush would be greatly diminished and short-lasting. I also had the feeling that no matter how much more I used, I would still never get the same feeling I would if I had no tolerance. Add to this the undesirable side effects of constipation and lung mucus buildup it just wasn't worth it anymore. Also it made sense in my head that the more and more I use the worse it's gonna be when I come off of it and I start withdrawling. So yeah there comes a point where it just becomes pointless.
 
In addition to the other notices posted, it is my personal experience that with both psychostimulants and opioids, side effects regarded as negative do not accrue tolerance/resistance as quickly as sought-after effects such as mood-increase, or pain-relief. As one raises their dose to chase these effects, negative side effects increase in magnitude. Eventually the drug becomes inefficient, then unusable (when depends on one's personal chemistry, tastes, desperation, and degree of 'tardation I suppose).

My strategy of memantine is possibly a helpful ally here for some; it is certainly not a complete solution however.

(with psychostimulants this includes for example blood pressure and heart rate increases, as well as problematic psychic tendencies like OCD or 'tweaky' behavior; with opioids this includes for example excessive somnolence, constipation, and indeed blunted affect, apathy, etc.)
 
The original question was "...for the rest of your life?" I'm not sure this is necessarily true: that it is impossible for any person to remain high on opioids for, say, 3 or 4 decades. The problem is not that the high subsides, but that it ceases to be a novel experience. Once an opioid habit is kicked, the withdrawing mind realizes that it had never ceased to be high: that it mistook the stabilized opioid experience for sobriety. Same principle as in married couples who mistake less sex for less love.

I've seen enough cases of people who've maintained a fairly consistent habit for decades to conclude that it isn't impossible to stay high on opioids indefinitely, so long as one not ask too much of the drug. This is very common in methadone clinics. The high can't always be "a spreading wave of relaxation slackening the muscles away from the bones so that you seem to float without outlines, like lying in warm salt water." (Burroughs)

Did someone say nociception? Consider that organisms capable of feeling pain have enormous evolutionary advantages over organisms that are relatively numbed. There's a reason the gene for CIPA is recessive.
 
>I've seen enough cases of people who've maintained a fairly consistent habit for decades to conclude that it isn't impossible to stay high on opioids indefinitely, so long as one not ask too much of the drug.

Well, depends on what you mean by high, yea. For me, (without something like memantine, perhaps) the pleasant effects of opioids fade quickly with tolerance -- a sedative, numbing effect lingers, but I dislike it.

And, generally speaking, I also value the mood-elevating, calm stimulation that I get from opioids much more than analgesia.
 
While my knowledge of extended use of opiates is limited only to some recent, unpleasant dental work... I do know that amphetamine use for extended periods (say 1-2 weeks) results in a plateau at which the user can no longer achieve the satisfying "high" he/she deserves. After this plateau is reached, no amount of the drug will satisfy the craving, nor will it result in significant release of dopamine or inhibition of its re-uptake. Or, as Slay so simply put it: "Good things don't last forever".

It is likely that opiates react in a similar way with the brain's serotonin pathways, and there is possibly a peak which results in nullification of the drugs effects for enough time beyond the plateau to allow the body to return to its base state.

While I am not a proper chemist, this seems to be a reasonable explanation as to why one may not be able to stay "high" for the rest of their life. It is true however, that opiates are able to be administered for much longer and with a much higher level of effectiveness than in our example case of the 1-2 week methamphetamine user. Analgesia, sedation, and euphoria seem to be achievable some weeks and even months after the course is initiated. If anyone has anything more to offer on the topic, I would be glad to learn more about it. But that's my $0.02.
 
Tolerance to different effects occur at different rates. Respiratory depression, I've read before (though the source isn't necessarily 100% accurate) does increase in tolerance more slowly than euphoria. But that doesn't necessarily mean it reaches a ceiling at the same point (maybe earlier than euphoria), nor does it mean that respiratory depression tolerance can't catch up to a stable dose level. I have read of cases of an addict taking up to 2 grams of pure in a clinical setting "without any ill effects", though these may be exceptions to a rule.

Prescription of Narcotics for Heroin Addicts: Main Results of the Swiss National Cohort Study
Volume One. Uchtenhagen, A;Dobler-Mikola, A.; Steffen, T; Gutzwiller, F.; Blattler, R; Pfeifer, S. Karger; Basel; 1999

Page 20 states that the mean daily dose of heroin IV ( when used alone, without methadone on the side) was 491.7mg.

Page 22 states "A stable dose was achieved after 6 months at most; beyond this point, almost no further increases in dose were required."

Later in the volume, the authors state that most users tend to gradually reduce their dosages after achieving a peak.
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from erowid: http://www.erowid.org/chemicals/heroin/heroin_dose1.shtml

So I'm guessing that the euphoria tolerance reaches a ceiling rather than reaching a point where you would be overdosing to catch a buzz.

I wonder... how does it feel to be at the euphoria tolerance ceiling? Does the typical user feel just a little high when shooting, and a little sick for most of the day? The author of the "Heroin User's Handbook" wrote (IIRC) that he mostly felt slightly ill, rather than always slightly high. ("why addiction sucks" ... he suggested that chipping was a more effective way of being high on heroin on a regular basis)

I wonder if a maxed tolerance still has any other potential mental effects, such as reduced anxiety, OCD, or depression? Part of what I love about opioids is that for a couple days after a single dose, I feel a little calmer and relaxed, physically and mentally. It's a very small effect, but useful in my case... a medicating effect beyond pain relief and euphoria.

I wonder if it's possible to indefinitely be high every day, or every other day for instance. By having a maintaining dose most of the time, to keep sickness at bay, while taking a strong dose just once every 24/48/72 hours to get high.

What might be theoretically possible is being high twice a week, for the rest of your life. Waiting at least 3 days between doses might be just about enough time for the drug to totally leave the system and the brain to re-adjust without it. A person would have to go by how their body felt... if they get a mini withdrawal (barely noticeable, for example), wait until it has fully passed until using again. Or just use every weekend... though maybe that would create an unpleasant mid week!
 
Dolomiti said:
I wonder if it's possible to indefinitely be high every day, or every other day for instance. By having a maintaining dose most of the time, to keep sickness at bay, while taking a strong dose just once every 24/48/72 hours to get high.

What might be theoretically possible is being high twice a week, for the rest of your life. Waiting at least 3 days between doses might be just about enough time for the drug to totally leave the system and the brain to re-adjust without it. A person would have to go by how their body felt... if they get a mini withdrawal (barely noticeable, for example), wait until it has fully passed until using again. Or just use every weekend... though maybe that would create an unpleasant mid week!
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Something along the lines of what you describe was tried with the Palfium + Methadone trials in Sweden. Low doses of oral Methadone taken once a day, with oral Dextromoramide basically for craving control (providing a short Heroin-like high). Some people in Britain are maintained on low doses of Methadone with IV Methadone or IV Heroin prescriptions for the same purpose. Just from the few studies I've seen this only seems to work when one or both short and long acting narcotics are given IV. The oral Methadone/oral Palfium trial didn't go well.
 
While I don't know the precise molecular mechanism, I can attest to the ceiling on oxycodone. A few people have access to massive quantities, mainly through doctor shopping to get hundreds of 30s and 80s from several (or 10+) doctors (and selling some to pay for your own). Tolerance tops out at about 1200-1800mg/day (in that those amounts seem to keep you from being sick regardless of how much more you have been taking lately); at those levels the side effects and drowsiness just start increasing while euphoria actually decreases and this doesn't go away with time. Despite access, I cannot raise my tolerance above that level. For the getting high part, euphoria is already gone above the 1000mg at once level, increasing doses do increase the side effects, so you feel bad and tired, no matter how much you take, even taking 2400mg at once. I know several other people with this kind of access and we all top out at the same levels; and all these numbers are with IV use; I don't know what they would be for other ROA's.
It takes years to get to that level however, and it can be mitigated by rotating opiates- while at my current levels an actual euphoric high is impossible with oxycodone, heroin does the trick, although quite a large amount is still needed.
I post this mainly as a warning of what will happen if you really consider continuing to use enough to get high every day or every other day, and access isn't a wall.
 
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So I'm guessing that the euphoria tolerance reaches a ceiling rather than reaching a point where you would be overdosing to catch a buzz.
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I don't think it's a question of exact "ceilings", but rather a multitude of factors (for one example, lifestyle) playing intricately into tolerance mechanisms, which differ (to an extent) for different effects.

W/R/T the intricate effects of a certain strategy of methadone combination, it is interesting to note at this point that it is a mild NMDA antagonist.
 
So am I right in saying that patients on diamorphine maintenance in the UK, Switzerland and Canada don't actually get high on their medication? I would have thought that they must get some sort of high, otherwise there wouldn't be any point?
 
"High" comes in shades and degrees, eh? An' tastes and shapes and various metrics an' textures an' positioning and humour and architecture and architectonics and more too but I'll cut it out.

I def. think that for some or many (and not all) people, some effect can be maintained over time, though for example there may be ups and downs, or maybe not, depending. And some, perhaps, will not find that diamorphine maintenance at a certain dose works for them, will find that the program does not work for them, will seek other avenues in tandem to medicate themselves. Maybe they should try methadone maintenance instead (diff'rent molecule, diff'rent affinities, diff'rent considerations), or maybe not. Others perhaps could lose the euphoria and pain relief but keep a numb feeling, which they seek so they continue with it. Like I said, there are a lot of factors involved. The vagaries of individual neurochemistry is one. And, lifestyle is one. I've studied stronger/weakened tone of nucleus acccumbens dopamine transmission (including both receptor density and release) as a basic site for a certain 'family' of effects (e.g. mood improvement; a high -- dose-dependently; and, yes, some component of pain relief) from opioids, and, in the theory, also for psychostimulants like amphetamine. The thought is that (part of?) memantine's studied mechanism in buffering opioid tolerance -- which is going to occur to a variable extent -- is due to actions at buffering glutamate at the NaCC (and the speculation is that this does something for amphetamine too, but anyways). And there is real research to this end. There is also solid research on, say, chronic elevated stress hormone decreasing both dopamine release and receptor density in specifically the NaCC but NOT the prefrontal cortex. Very interesting. And there is the family of research and theory suggesting that much (most?) of excess cortisol's neurotoxicity owes to triggered glutamate excess ... see where I'm going with that? I dunno, these are just thoughts. Beware of too much abstraction from receptors&cit, as always.

;)

This is fucking money:
http://cat.inist.fr/?aModele=afficheN&cpsidt=14855749
 
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My understanding of this from personal experience of over a year at 150 milligrams (not mikes) of fent HCl IV a day is that at this level there is NO effect not even the rush. I know one who went to literally half a gram cuz he had an infection trying to beat the ceiling effect and he got nowhere. I think this is part of the whole concept that tolerance is modulated by the down regulation or degredation of the MORs and at a certain point the brain probably reaches a point at which there are so few, and likely won't go below this, that nothing will do anything but maintain.

Not likely to ever OD at this level, or feel any opiate effects. The withdrawal was hell to say the least. Similar withdrawal is what drove Tom Highsmith to suicide, I had about 300 mgs done when it fell apart and this couldn't hold a candle to the loss of that level of opioids in one's system.
 
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