Opioids Why does methadone make some people with equal tolerance high and others not?
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Lorne???
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That's a complex question.
First, they're really is no 'equal' tolerance. You can inject a half a gram or more of good dope daily for awhile, yet 2 or 3 days w/ nothing will knock your tolerance down(at least temporarily; that is how some OD's happen) not to mention the WD...
You mentioned T1/2? Duration is more relevant, yet either way it also effects things, because a potent and long lasting drug(like methadone, Which builds with repeat dosing and actually becomes more potent, with longer analgesia/primary "opioid" effects after a couple of days) is going to be hitting receptors hard, for a duration.
Fast and powerful drugs wear off fast, so they can build rapid tolerance, and quick Wd's, however reversal of tolerance can also be easier
In the end though, methadone is a weird drug, which effects people differently, and at times quite drastically, especially w/ acute use or a lower tolerance.
To me, it is comparable to Clonazepam, in that they are both highly potent and long lasting, and people generally either love em or hate em(although in fairness, the nitro benzodiazepines are more prone to paradoxical effects, I think)
People on MMT with high tolerances often have trouble getting high anyway, methadone just jacks your tolerance up and the doses are high, and many people probably l aren't used to having a potent opioid they don't have to chase.
For acute users, it is less potent, and doesn't produce much of a rush when injected, so a lot of people will not favor it.
Personally it worked for me long before maintenance. It was long lasting, and functional, and just made things better.
Though enough methadone is going to get a person "high", though, if they arlready take methadone or have an absurd tolerance, it isn' going to do much, as far as "getting kicks"
First, they're really is no 'equal' tolerance. You can inject a half a gram or more of good dope daily for awhile, yet 2 or 3 days w/ nothing will knock your tolerance down(at least temporarily; that is how some OD's happen) not to mention the WD...
You mentioned T1/2? Duration is more relevant, yet either way it also effects things, because a potent and long lasting drug(like methadone, Which builds with repeat dosing and actually becomes more potent, with longer analgesia/primary "opioid" effects after a couple of days) is going to be hitting receptors hard, for a duration.
Fast and powerful drugs wear off fast, so they can build rapid tolerance, and quick Wd's, however reversal of tolerance can also be easier
In the end though, methadone is a weird drug, which effects people differently, and at times quite drastically, especially w/ acute use or a lower tolerance.
To me, it is comparable to Clonazepam, in that they are both highly potent and long lasting, and people generally either love em or hate em(although in fairness, the nitro benzodiazepines are more prone to paradoxical effects, I think)
People on MMT with high tolerances often have trouble getting high anyway, methadone just jacks your tolerance up and the doses are high, and many people probably l aren't used to having a potent opioid they don't have to chase.
For acute users, it is less potent, and doesn't produce much of a rush when injected, so a lot of people will not favor it.
Personally it worked for me long before maintenance. It was long lasting, and functional, and just made things better.
Though enough methadone is going to get a person "high", though, if they arlready take methadone or have an absurd tolerance, it isn' going to do much, as far as "getting kicks"
There also the fact it is also an nmda antagonist, which can have its' own effect that if noticable either can add or, as in my case, can create unwanted side effects that could make it so one never has real relief from it even if it can cause nodding and whatnot.
Scrofula
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Drug highs are totally subjective, don't forget. And "tolerance" means different things. If you take someone with a high tolerance for a drug, nicotine maybe, and put them in a situation that forces withdrawal, like the drunk tank, that first cigarette will remind you of your very first time, and you'll be higher than nicotine's ever gotten you in a while.
Then again, there's using nicotine gums and patches that give you the exact same drug but with different concentration curves. Even if you check published absorption curves and try to match the steady-state concentrations you had before, you are left feeling something's just missing from those replacements. (Some people say there's an extra ingredient in whole tobacco, but the vaping people would have noticded) I think it's the pulse of redosing that's been lost, the timing of a fresh drug spike hitting your brain.
Or, knowing you're being denied your previous routine pours enough bitterness over the experience that you miss any positive feeling you might have.
Point being, why a drug gets one person high, and not another, all else equal, is still mostly beyond science.
Then again, there's using nicotine gums and patches that give you the exact same drug but with different concentration curves. Even if you check published absorption curves and try to match the steady-state concentrations you had before, you are left feeling something's just missing from those replacements. (Some people say there's an extra ingredient in whole tobacco, but the vaping people would have noticded) I think it's the pulse of redosing that's been lost, the timing of a fresh drug spike hitting your brain.
Or, knowing you're being denied your previous routine pours enough bitterness over the experience that you miss any positive feeling you might have.
Point being, why a drug gets one person high, and not another, all else equal, is still mostly beyond science.
Lorne???
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Methadone is complex as said, and NMDA Antagonism is worth mentioning.
Vaping didn't cut it, though you are right about the feeling you get when going an extended period without tobacco; that first cigarette is so enjoyable, especially if quality cig or a preferred brand.
Compulsive redosing is something people struggle with, just mention it because of firsthand examples.
Everyone is different, neurochemistry and physiology play a role, though it is at some point beyond science.
Why people like Oxycodone so much, and to me it(and to a lesser extent) hydromorphone are overrated, and Morphine is amazing,(H better, still) and methadone was great, who knows why?
Really do not like Valium; there are legitimate reasons for this, as not a big fan of alprazolam either, although it is certainly "good", it wears off fast and causes rebound symptoms and a rapid wd; Clonazepam is more effective yet some people simply don't get much from it; point is, can find reasons to at least partially explain preferences/a medication that is simply more effective, though in the end it is just me and how I feel, and that can't be quantified by mere mortals
(Sorry for long post)
Vaping didn't cut it, though you are right about the feeling you get when going an extended period without tobacco; that first cigarette is so enjoyable, especially if quality cig or a preferred brand.
Compulsive redosing is something people struggle with, just mention it because of firsthand examples.
Everyone is different, neurochemistry and physiology play a role, though it is at some point beyond science.
Why people like Oxycodone so much, and to me it(and to a lesser extent) hydromorphone are overrated, and Morphine is amazing,(H better, still) and methadone was great, who knows why?
Really do not like Valium; there are legitimate reasons for this, as not a big fan of alprazolam either, although it is certainly "good", it wears off fast and causes rebound symptoms and a rapid wd; Clonazepam is more effective yet some people simply don't get much from it; point is, can find reasons to at least partially explain preferences/a medication that is simply more effective, though in the end it is just me and how I feel, and that can't be quantified by mere mortals
(Sorry for long post)
Speed King
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^ Oxymorphone ftw!
OT- People are chemically different. I actually had a drug dna test done. It gave a reading, telling the doctor what drugs I am most sensitive to, or better yet, which drugs will work better for me.
Example, out of every benzodiazepine, I tested most sensitive to Valium.
I don’t know exactly what it means, but the doctor goes by it.
Since being on Valium it has consistently worked and I have no need to ever up the dose. That would explain the test a bit.
Test seems pretty accurate for what drugs they tested with me.
OT- People are chemically different. I actually had a drug dna test done. It gave a reading, telling the doctor what drugs I am most sensitive to, or better yet, which drugs will work better for me.
Example, out of every benzodiazepine, I tested most sensitive to Valium.
I don’t know exactly what it means, but the doctor goes by it.
Since being on Valium it has consistently worked and I have no need to ever up the dose. That would explain the test a bit.
Test seems pretty accurate for what drugs they tested with me.
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I have always found methadone very pleasurable for some reason, both with barely any tolerance like being used to 5mg oxycodone a day and 200mg oxy/day then methadone for weeks, this never made sense. It was like having MMT was just helping me get high rather than kick the drugs. (Not to say it isnt a godsend if youre in withdrawal and doesnt help a lot of people treat addiction)
What also didnt make sense is that the pain relief effect always peaked around 2 hours and didnt last long after that rather than round-the-clock like OxyContin even though it has a very long half life - this made me think it would give round the clock pain relief without redosing. (Ive suffered with pain problems and this made methadone horrific when it was bad as no doctor would give me any other opiate while I was on it which is fair enough as methadone can be very deadly and seems to be losing attention of its dangers because of fentanyl reports)
What also didnt make sense is that the pain relief effect always peaked around 2 hours and didnt last long after that rather than round-the-clock like OxyContin even though it has a very long half life - this made me think it would give round the clock pain relief without redosing. (Ive suffered with pain problems and this made methadone horrific when it was bad as no doctor would give me any other opiate while I was on it which is fair enough as methadone can be very deadly and seems to be losing attention of its dangers because of fentanyl reports)
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Lorne???
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Methadone is supposed to be taken in divided doses for a chronic pain/analgesia, typically 2-3 doses per day for round the clock pain relief, and sometimes even 4 smaller doses the first couple of days to stick it in your system
Liked methadone early on, as well
Liked methadone early on, as well
Scrofula
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Might be so you don't get too much pain relieved, and cross over to enjoying yourself.
That's a sin so bad we need prison terms for those who seek it or enable it. The whole Fall of Man thing. Or it could be a case of gradually accumulating to a steady plasma concentration? An oral "slow push". Accumulation would occur to a greater extent as the half-life increases.
Maybe it's just that opiates work better at preventing pain, and you'll use less overall if you don't wait for it to start wearing off.
That's a sin so bad we need prison terms for those who seek it or enable it. The whole Fall of Man thing. Or it could be a case of gradually accumulating to a steady plasma concentration? An oral "slow push". Accumulation would occur to a greater extent as the half-life increases.
Maybe it's just that opiates work better at preventing pain, and you'll use less overall if you don't wait for it to start wearing off.
Lorne???
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^yeah, someone got 30mg TID, and they even thought it was pointless to take it that way.
Twice daily dosing is understandable, and even when once daily dosing cuts it, some pain patients may need breakthrough medication; either smaller PRN doses of methadone to spike it, or, an alternative opioid to be taken when needed, either occasionally or with some discretion(hopefully); I think an alternate medication(pretty much opioid/opiate) is a better option, as breakthrough medication should be able to provide reasonable relief without a long delay. Methadone has a delayed effect, or peak analgesia, so something fast acting would seem preferable, in most cases
Then again, we don’t want people getting too much pain relief. And enjoying yourself? Not here, sir
Once or twice per day is plenty for chronic use, even then would rather have most of the dose first, with the second being a pick me up and to stretch peak(though with inhibitors once daily is fine; woken up high, though that’s been awhile)
Twice daily dosing is understandable, and even when once daily dosing cuts it, some pain patients may need breakthrough medication; either smaller PRN doses of methadone to spike it, or, an alternative opioid to be taken when needed, either occasionally or with some discretion(hopefully); I think an alternate medication(pretty much opioid/opiate) is a better option, as breakthrough medication should be able to provide reasonable relief without a long delay. Methadone has a delayed effect, or peak analgesia, so something fast acting would seem preferable, in most cases
Then again, we don’t want people getting too much pain relief. And enjoying yourself? Not here, sir
Once or twice per day is plenty for chronic use, even then would rather have most of the dose first, with the second being a pick me up and to stretch peak(though with inhibitors once daily is fine; woken up high, though that’s been awhile)
Because while it keeps withdrawal Ms can away for 24 hours if overdosed on, but the pain relief it provides will wear off within 12 hours at best usually around 4-6 hours which will take an hour or two to reduce any pain present. Great for pain if dosed right, but a methadone clinic will not split doses like that and instead expect one to make their dependency and tolerance worse by increasing and increasing until the patient is happy or they reach the maximum daily allowed dose. It's BS
Backfromthebrink
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The ability of methadone to suppress opiate withdrawls and it's potency as an analgesic are 2 different things. While it's WD suppression can last 24 hours+, it's analgesia wears off after a few hours and hence it's prescribed usually TDS for pain relief.
I was prescribed it at 60mg TDS by a pain management clinc for several yesrs (cold turkeyed off that dose too which was fun).
But yeah, people often assume that because it lasts so long when used for ORT, it would only need to be taken once a day for pain relief but that's not the case. The plasma amount of all opiates/opiods needed to suppress opiate withdrawls is often much lower than people think. Your not supposed to feel high or experience significant analgesia on ORT
I was prescribed it at 60mg TDS by a pain management clinc for several yesrs (cold turkeyed off that dose too which was fun).
But yeah, people often assume that because it lasts so long when used for ORT, it would only need to be taken once a day for pain relief but that's not the case. The plasma amount of all opiates/opiods needed to suppress opiate withdrawls is often much lower than people think. Your not supposed to feel high or experience significant analgesia on ORT
Thanks for the explanation. Damn that cold turkey after several years would make me scream. I cold turkeyed voluntarily for a bit from methadone 80mg/day after a few weeks because I needed consistent pain relief and no doctor would give me any opioid while I was on methadone and it was days of hell in a bathtub - magnified pain, sweating, twitches, diarrhea until I managed to get oxycontin and diazepam to help. It came on a lot sooner than people said it would (20hrs rather than 3 days)
Backfromthebrink
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Yesh man it's hard isn't it? I actusllky went from 60mg 3 times a day = 180mg total per day to 20mg 3 times a day (60my total per day) in a few weeks and then jumped at that (either that or very close... the memories are a bit hazy) and it was torture.
Absolute torture and something nobody should have to go through. I'll never let myself cold turkey on anything again, that oxycontin going through methadone wds was a godsend. How long did the wd last and how quick did it come on for you if you dont mind saying?
Took last oxy pills without thinking once before flying back from US and got hit with awful wds in the middle of the flight thinking oh ***k! had to sit in my seat sweating in agony and shaking trying to hide it for hours (one of the nastiest moments in my life) and went straight to get nurofen+ after landing thinking thank heavens then got home where I had alot of oxycodone left, never felt such nice relief like that.
Took last oxy pills without thinking once before flying back from US and got hit with awful wds in the middle of the flight thinking oh ***k! had to sit in my seat sweating in agony and shaking trying to hide it for hours (one of the nastiest moments in my life) and went straight to get nurofen+ after landing thinking thank heavens then got home where I had alot of oxycodone left, never felt such nice relief like that.
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The effects of Morphine/Heroin are easier to predict that those of Methadone. Methadone possesses a more complex metabolic process that that of Heroin, which means you will be bound to experience some more variability by comparison, but I'm sure that's not the full answer.