Opioids How does analgesia beat tolerance over the long term?

was discussing tolerance/adaptation with someone and realized i'm at a complete loss for how a stable daily dosage of opiates can provide analgesia once enough time has elapsed and tolerance to said dose has been maximized.

NMDA antagonists seem to work for some people in preventing tolerance to many beneficial drugs, opiate analgesics and amphetamine stimulants included.

I'll try and find a link to the thread in ADD.

thnx but don't worry about it i've read quite a bit on nmda (when i was still using / trying to get higher w/ same dosages).

I'm actually talking about legit, non-abused, taken-as-directed regimens. If a dr scribed someone an 80 a day, and the person took it as directed for years, how on earth would it still have effect? I was under the impression the body would balance it out (tolerance), just like it does to those who're using for euphoria (actually from what i understand, euphoria and analgesia are extremely tied together/correlated in opiate/oids)

(and re amphetamines, i know from my college days that i could retain most of their <therapeutic> effects by using <20mg/day during the week w/ weekends off. but for opiate addicts this would be undesirable, and for opiate-scribed patients it's not something i'd ever seen recommended)

well, when it comes to opioids the euphoric effects will fade much, much faster than the pain killing properties.

xxxyyy said:

well, when it comes to opioids the euphoric effects will fade much, much faster than the pain killing properties.

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I second this. I found that the euphoria from my chronic pain meds left long ago, but the pain relief is still very much and play. if physically dependent, this would be the point where 1 becomes sick without their regular does. I have a feeling this isn't what you're looking for, though??

that is what i'm looking for, though i'm trying to understand *why* analgesia doesn't get lost, eventually, due to tolerance.
/no, i'm not curious for any personal/practical purposes. while the thought of it can still make me salivate, i much, much prefer being off dope. been clean* for quite some time

(*clean = not a junkie. i've prolly used almost 10X since i got off, but each and every one of those were nice one-time experiences, no twice in a week or any shit like that. they were fully "responsible" uses. I don't endorse straight-edge/abstinence any more than being a junkie; all things in moderation, and while that's generally impossible for most with opiates i think i'm able to do it now because of how badly my junkie phase was. it's been the better part of 2yrs since i had tolerance, or used with any regularity.
wrt this thread tho, no, i'd have no need to enhance things, when i use the occasional ope nowadays a blue or two, or a dillie, are quite sufficient for the experience ;PP)

opiods actually increased my pain over time...

^do please explain that. Do you mean because they helped reduce pain while on them, after stopping your pain was more? Cuz I hear that happens.

Hiltoniano said:

^do please explain that. Do you mean because they helped reduce pain while on them, after stopping your pain was more? Cuz I hear that happens.

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I'm not sure and I'm certainly not speaking for the person who posted this, but there is something called hyperalgesia ( or something like that) and I'm thinking maybe this is what they were referring to?

bmxxx said:

that is what i'm looking for, though i'm trying to understand *why* analgesia doesn't get lost, eventually, due to tolerance.

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It does diminish due to tolerance albeit at a much slower pace. Typically pain patients with stable-levels of pain will require increases every 2 years or so (some sooner, some much quicker but if ANYONE requires more and more in a short period, they are seeking something more than analgesia).

Some lifelong pain patients will pass what is required/reasonable for oral doses and require intrathecal patient-controlled analgesia and so forth after a very long time but there isn't a ceiling on the analgesic effect, tolerance just builds more slowly to that effect than to 'side effects' such as euphoria and sedation and the more frequently you increase your doses, as recreational users do, the faster you increase your tolerance to ALL effects.

I am not sure of a physiological explanation of this phenomenon but it's seen in most drugs of abuse that are used therapeutically - when used appropriately, the side effects recreational users desire quickly disappear due to tolerance while the therapeutic effects remain much longer before tolerance catches up. I suspect this is the reason they are willing to use certain recreational substances therapeutically and not others

belfort said:

opiods actually increased my pain over time...

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macd610 said:

I'm not sure and I'm certainly not speaking for the person who posted this, but there is something called hyperalgesia ( or something like that) and I'm thinking maybe this is what they were referring to?

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Hyperalgesia is a different beast altogether and statistically quite rare in those who use pain medications appropriately.

cane- thank you lemme ask- do benzo's behave similarly? I've always kinda believed (w/o knowing for sure) that benzo's became completely neutral (like zero anxiolytic effect) after being taken regularly.

^ I'm not sure but I suspect you are right, or at minimum, larger/more frequent increases in dosages are required and this has substantial drawbacks in terms of increased physical dependency/abstinence syndrome and prolonging Post-Acute Withdrawal Syndrome to durations beyond what is seen in any other substances.

I have spoken with people who have remained on stable, low-doses of benzodiazepines for prolonged periods of time (several years or more) but they seem to be the exception and while in the past, physicians viewed this class of drug as rather benign, few are willing to maintain patients on them for prolonged periods anymore. It's also disputable whether those who stay on low-doses for years are still getting therapeutic benefit from them.

Most long-term benzo users I've known, spoken with or read about here seem to require substantial dose increases over the years and if they try to come off them, experience symptoms worse than what initially lead to the first prescription (and for very long periods). This would seem to lend some evidence to your theory that eventually they lose all (or a substantial amount) of therapuetic efficacy but users still experiencing the anxiety (or worse as a result of their prolonged use) keep trying to increase the dose to feel better.

benzos will remain therapeutic for extended periods (possibly indefinitely) if they are not abused at all. I think a mod on BL posted a source for this somewhere, i can dig it up if anyone wants to see it. There's also plenty of anecdotal evidence of people needing a set dose of a benzo and then being able to maintain on it for years and years. The thing is that you cannot abuse your meds at all or it will ruin the therapeutic effects. I think opiates are more forgiving in this manner.

There also seem to be cases where benzos worsen people's anxiety (similar to pain levels with opiate users) but it's just so variable that it's hard to figure out what's happening.

Cane2theLeft said:

^ I'm not sure but I suspect you are right, or at minimum, larger/more frequent increases in dosages are required and this has substantial drawbacks in terms of increased physical dependency/abstinence syndrome and prolonging Post-Acute Withdrawal Syndrome to durations beyond what is seen in any other substances.

I have spoken with people who have remained on stable, low-doses of benzodiazepines for prolonged periods of time (several years or more) but they seem to be the exception and while in the past, physicians viewed this class of drug as rather benign, few are willing to maintain patients on them for prolonged periods anymore. It's also disputable whether those who stay on low-doses for years are still getting therapeutic benefit from them.

Most long-term benzo users I've known, spoken with or read about here seem to require substantial dose increases over the years and if they try to come off them, experience symptoms worse than what initially lead to the first prescription (and for very long periods). This would seem to lend some evidence to your theory that eventually they lose all (or a substantial amount) of therapuetic efficacy but users still experiencing the anxiety (or worse as a result of their prolonged use) keep trying to increase the dose to feel better.

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i agree with all of that. i've actually never really known anyone, besides my mother, who's taken a steady-dose for years (and in her case, 3mg/day alprzlm seems to do jack-shit - any time i see her she seems same as she has my whole life, including before she started taking it.)

from what i understand, most countries' physicians (besides the US) do not view benzo's as ANY kind of long-term medication, but rather see it as a tool for extreme scenarios (coping with death; acclimating to an SSRI; etc etc).

RobotRipping said:

benzos will remain therapeutic for extended periods (possibly indefinitely) if they are not abused at all. I think a mod on BL posted a source for this somewhere, i can dig it up if anyone wants to see it. There's also plenty of anecdotal evidence of people needing a set dose of a benzo and then being able to maintain on it for years and years. The thing is that you cannot abuse your meds at all or it will ruin the therapeutic effects. I think opiates are more forgiving in this manner.

There also seem to be cases where benzos worsen people's anxiety (similar to pain levels with opiate users) but it's just so variable that it's hard to figure out what's happening.

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don't worry about it if pita, but would be interested in seeing that. and re making anxiety worse, that's how i usually see it happen with people (my past usage - therapeutic/rx'd and recreational - support this). seems like at best you're just gonna take steady-dosages and be neutral, at worse you're on some short one like xanax and you've got anxiety cuz your g'damn blood levels are bouncing all the time. blows my mind that my mother has an rx for 3mg daily of that, and her+her doctor approach it like it's prilosec or flexerall(sp?)

Cane2theLeft said:

^ I'm not sure but I suspect you are right, or at minimum, larger/more frequent increases in dosages are required and this has substantial drawbacks in terms of increased physical dependency/abstinence syndrome and prolonging Post-Acute Withdrawal Syndrome to durations beyond what is seen in any other substances.

I have spoken with people who have remained on stable, low-doses of benzodiazepines for prolonged periods of time (several years or more) but they seem to be the exception and while in the past, physicians viewed this class of drug as rather benign, few are willing to maintain patients on them for prolonged periods anymore. It's also disputable whether those who stay on low-doses for years are still getting therapeutic benefit from them.

Most long-term benzo users I've known, spoken with or read about here seem to require substantial dose increases over the years and if they try to come off them, experience symptoms worse than what initially lead to the first prescription (and for very long periods). This would seem to lend some evidence to your theory that eventually they lose all (or a substantial amount) of therapuetic efficacy but users still experiencing the anxiety (or worse as a result of their prolonged use) keep trying to increase the dose to feel better.

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Cane, thanks for your input on hyperalgesia (sp?). I had only heard of it, and definitely (and obviously) wasn't sure if it was an appropriate subject to bring up.
As far as benzos go... I have been taking alprazolam for about 3 years now. I take one at bedtime, and on most days I take a half a milligram at some point. I've not found it to lose its effectiveness thus far, but you never know...

I for some reason find that alprazolam, when taken once or twice a day at a low consistent dose will retain its therapeutic effects for a surprisingly long time, especially when compared to a longer acting benzo like clonazepam, which IMO looses all therapeutic effectiveness after a week, and IME even plateaued after a certain dosage increase (I.e. 6mg will feel just the same as 12mg). However, the problem is that it's very hard to maintain a consistent dose with such short acting benzo's as inter-dose withdrawal syndrome will pretty much force anyone Dependent to either increase the dose, or increase the frequency of using.

And yeah, not much of an addition, but methadone has surprisingly effectively long term analgesia. I'm not a chronic pain patient by any means, but I've come down with a really bad flare up of asthma (I am asthmatic) which after fourty eight hours will cause a tremendous strain on the lungs, and really my whole abdomen in general. It got to the point yesterday where I could hardly even make it to the clinic because walking up a flight of stairs made me feel as though I might simultaneously drown in my own mucous and suffer cardiac arrest. Ten minutes after being 'medicated', I felt the tension and pain begin to fade and within fourty minutes, I was back to normal. Of course this did fade after five hours, but I was impressed. However it's also a bit frightening as opiates can sometimes just mask an illness, and one could be really sick without experiencing the symptoms.

I am a pain patient, I take Norco 7.5 and see different things out of my medicine. I have taken more than the "prescribed dose" in the form of just adding a dose on the day (and I tell my doctor about that), and it has a direct effect on a tolerance issue.
I am prescribed up to four doses a day, but, if I am hurting really bad and can't get to sleep I will need a fifth one. Now, on the following morning when I take my first prescribed dose it does not have as good pain relieving properties. It is as if I haven't given my body the break it usually gets to process out. If I try to take doses on my regular schedule all day that following day, it will just compound the issue.

I have been on the same dosing since 2008. I try things to make sure my meds work well, and other pain relieving sources. I still even feel "head" effects from my regular medicine most of the time. Without a little of the euphoria I have a hard time dealing with the pain. I accept that I will be in some pain regardless of medications, and that is the way it has always been.

I don't know if it is because I have always been strict on myself about things like not dosing through the night (even dealing with insomnia, because I refuse to take anything between 11 PM and 5 AM) or because I have a mind set of expecting my medicine to do it's job, but tolerance hasn't been an issue for me insomuch as my regular pain needs. In fact, I still cannot tolerate a higher dose of the same medicine for more than a day (like if I have something increase my pain.. think kidney stones).

This subject interests me tremendously, especially because I myself take opiates every day for chronic pain.

I'll try and find a few good journal articles/studies, and try to put my own experience of this phenomenon into words, in the meantime.