Non-existent info on how methadone works as a mediciine -- hoping to find insights

[Wishdoctor79]

I can't find any psychopharmacology sources which are helpful in explaining the hows and whys of the magical effect that daily bolus dosing of 80+ mg oral methadone has on many in the clinic system, those lucky individuals who feel happier and healthier on MMT than they've ever felt.

The anti-drug proponents are very vocal and it seems to be that the stigma which results from that viewpoint might be suppressing research into how exactly methadone heals whatever it was that made MMT patients seek out opiates in what is always eventually a failed self-prescription that did more harm to them than good. Not so for methadone, for which many of those people choose to endure the indignities of the clinic system sometimes for the rest of their natural lives. Sure, many drop out because they gain weight or can't handle the constipation and sweating, or it's just too much of an incovenience or indignity, but methadone itself for those in whom it works is a very good medicine. It's especially so for the many people with the so-called treatment-resistant depression because methadone if I'm given a choice between periodic ECT sessions a few times a year whenever it gets really bad, or enrolling in MMT and getting as much as I want of methadone and preventing the suicidal depression, guess which one I picked. Maybe if there had been a book such as I want to write it would have not taken me so long to get into a treatment that worked instead of continuing my misusing opiates and benzos and whatever for the entire 8 years I was enrolled in the Suboxone clinic run by aprofessor at a medical school who was teaching addiction medicine at the time. Suboxone is not the same as methadone, no matter how loudly the Suboxone chauvinists will proclaim it. After I went on methadone all of that previous drug collecting and drug misusing came to a complete and almost immediate stop.

I have benefited tremendously from my past four years on methadone, but I can't find one book written in a memoir style where the author paints a positive picture of MMT. Fifty years of strong data on safety and effectiveness after Dole & Nyswander and over 100,000 patients at any time enrolled in US clinic system based on their model and set up per the 1970 Drug Abuse Treatment Act there is not even one such published memoir that I can find in the English language.

I can't tell this story in a book worthy of publication unless I can cite some scientific bases for my observations.

I have basically two theories about why methadone is fundamentally superior to other opioids: 1) it has something to do with the NMDA antagonism some have attributed to methadone, and 2) it has something to do with a biologically active metabolite of methadone which somehow or other has beneficial effects on the human body.

I can't find any research on inter-individual variations in methadone metabolism and the impact of active metabolites on treatment retention, etc. All they seem to say is that some metabolize it faster and may require twice-daily ("split") dosing, but nobody has looked into the details besides coming up with a blood test protocol to decide if the person is lying when they come in and ask for splt dosing or say they need a daily dose greater than a very arbitrary limit e.g. 150 or 200 mg.

Please try to prove me wrong by pointing me towards things I've been unable to find on my own.

 

[Coolwhip]

I have basically two theories about why methadone is fundamentally superior to other opioids: 1) it has something to do with the NMDA antagonism some have attributed to methadone, and 2) it has something to do with a biologically active metabolite of methadone which somehow or other has beneficial effects on the human body.

I wouldn't be surprised if the NMDA antagoism did play some not-insignificant role in methadones utility for ORT and its pain killing effects. Although, I think if there were some active metabolite responsible for many of the effects we would probably know it by now.

But I am not sure you're premise is exactly right in the first place, that being that methadone is fundamentally superior to other opioids because of its pharmacodynamics, where in most people's minds methadone is superior because of its pharmacokinetics e.g. long half-life, no benefit to shooting/snorting, blocking effect at high enough doses, etc.

And while you should be able to find plenty of peer-reviewed research supporting ORT and methadone in general, and even contrasting methadone to buprenorphine. It's no surprise you can't find much supporting the idea that methadone is empirically the best substance to use for ORT as very few have ever even been considered; even though there is plenty of evidence that just giving addicts diamorphine in a supervised regimen with controlled doses can just as easily if not more effectively enable them to live happier, healthier, more productive lives as functioning members of society. The real thing being corrected is the lifestyle addicts are required to live in order to support a clandestine opioid dependency.

 

[Limpet_Chicken]

I wouldn't be at all surprised if the NMDA receptor antagonism has something to do with it.

I haven't much experience with methadone, although I just started it for a while as of today (clandestinely, bagged a few hundred physeptone tabs), I have taken it before, but not very many times or in as high of a dose. I also find that NMDA antagonists, as long as they aren't in excess, and particularly ones like memantine, they sort of level me out, and make me more motivated, its hard to describe. Other opioids tend to make me really sleepy and sap my energy (I'm a longterm chronic pain patient, kinda using these, after I've had my fun a few times on it, mixing it with cyclizine and IV'ing etc, to break the doctor's chemical handcuffs and do a taper, so I can use my own pain meds when I really have to, and not be chained to them (morphine, oxy) and of course, so I can get creative exploring where morphine and oxy can lead, in terms of....family relatives thereof..

I can definitely feel that NMDA antagonist 'signature' in the background, not strong but I know its there, I'm pretty attuned to that sort of drug, and they have a lot of benefits, when used at low doses. (current dose of methadone I'm on is a couple of hundred mg) and I feel...actually impatient, I want the family asleep and out of the way so I can go get that bromine distilled, and maybe do some experiments with what I believe to be HCl2I (yes, HCl2I is the intended formula, as written, its an oddball hydrohalic acid derived from hydrolysis of iodine monochloride. Got to find out whether a flask is full of that, or whether its ICl itself, or a mixture of ICl and ICl3)

Raring to go and just....bloody hurry up folks, get to bed so I can get busy and you won't walk into any Br2 or ICl fumes, since I've only the one gas mask with a suitable cartridge for the job

Also, the nice long half life, had my larger dose straight up on receipt, conveniently enough, my little package arrived priority mail at the very moment I wriggled out from under the bedcovers, and aside from a couple of top-ups, one of 50mg the other of 20 throughout the day, I'm feeling great.

 

[clubcard]

In Germany, the (R) enantiomer is prescribed for pain. The (S) enantiomer is some 13-48 x less potent as an analgesic. Since long-QT is an issue with both methadone isomers, optical resolution makes it a good deal safer. If you want to investigate duel opioid/NMDA antagonist analgesics, dipipanone, piritamide, levorphanol & ketobemidone are the places to look.

 

[Limpet_Chicken]

Are there major differences in the NMDA antagonist potency of (R-) vs (S)-methadone? would it be worthwhile to attempt chiral resolution of some of the methadone I have? (not that the other enantiomer would be thrown away of course).

Mmmm...definitely enjoying myself, and after a few top up doses, I can definitely feel the NMDA antagonism.

 

[Hodor]

Are there major differences in the NMDA antagonist potency of (R-) vs (S)-methadone? would it be worthwhile to attempt chiral resolution of some of the methadone I have? (not that the other enantiomer would be thrown away of course).

Mmmm...definitely enjoying myself, and after a few top up doses, I can definitely feel the NMDA antagonism.

R-methadone (= levomethadone or "L-Polamidon") is used for both pain control and opioid maintenance in Germany; racemic methadone is also available. The NMDA antagonism mainly results from the activity of the S-isomer. It is entirely possible that NMDA antagonism confers additional analgesic and anti-addictive benefits, but apparently some people still do better on the enantiopure form.

Getting back to OP's original question, one advantage(?) of methadone vs suboxone is that methadone is a full agonist whereas buprenorphine is a partial agonist, so the effects ceiling is higher. Both drugs have potential atypical antidepressant activity: buprenorphine blocks "bad endorphins" at the kappa opioid receptor, whereas methadone has the NMDA antagonism.

Speaking of full agonism, here's a question of mine: I often hear people talking about a "blocking dose" of methadone; however, unlike the high-affinity/low-efficacy partial agonist buprenorphine, methadone can't really be said to "block" other opioids when it is itself capable of fully activating any mu receptor it binds to. So is the "blocking effect" simply a euphemistic way of saying that you're using high-dose methadone to give people such an insanely high opioid tolerance that the amount of heroin needed to provide them with an euphoric "rush" would simply be way too expensive for them to afford?

 

[Wishdoctor79]

Howdy. I haven't been back here since that OP and am glad to see helpful replies but there was nothing surprising. I won't post a hyperlink but I've been writing about my TRD and its successful self-treatment with MMT on Reddit at /methadone as /wishdoctor79 about my recent experiences in gradually adapting to a life without daily opioids.

Pharmacodynamics? No, being long-acting is not what makes it such a valuable medicine for me and many others. Back in 2004-2005 Reckitt-Benckiser had website with a huge treasure trove of academic science to support their large number of patents for use of buprenorphine for many maladies including depression. Since they were trying to come up with an alternative to methadone, just someone at Reckitt, out of all the scientists in the world, could probably answer my OP queries better than anyone.

Nyswander & Dole I think were just extremely lucky in choosing to use methadone as they used it in the 1960s to treat "opiate addicts." But Reckitt would not invest all that cash and their corporate image on such a high-profile methadone replacement with all the legal changes of Drug Abuse Treatment Act of 2000 unless they had at least Internal-Use-Only science to back up that choice. And of course they had a unique NDA process where it was Congress who granted approval of Subutex and Suboxone, not the FDA, and so of course Reckitt didn't perform the usual two Phase 3 double-blind RCTs to prove safety and efficacy and submit such with NDA because it was all worked out behind closed doors with politicians and lobbyists, a subject I've never seen mentioned by anyone but me.

In an effort to try to get relief from this crushing lethargy I have tried taking three kinds of kratom, tramadol, and also some codeine, all of which consistently make me feel even more lethargic because of an additive sedative effect from all of them regardless of dose level. And tramadol used to be quite energizing for me but not any more it seems. Methadone would lift me immediately out of the lethargy like nothing else I had available and I'm quite a collector.

I've tried many "non-standard" things such as pharmceutical Vasopressin, bromocriptine, memantine, Deprenyl, Dilantin, and too many others, plus of course ketamine but could never find tiletamine, and way way in the past have had "full-nine-yards" Hormone Replacement Therapy with TEST-CYP, HGH, HCG, estrogen blockers, etc., and that androgen/GH therapy really worked to boost me out a terrible slump after I first quit using opiates back around 2004.

I need something to help me have my energy back because methadone was my one and only antidepressant which ever really worked for me day in and day out. When I take methadone it boosts my energy levels to such a marked extent that I'd say it's comparable to the old Dexedrine Spansules time release beads all different colors.

It was a few years after the book Smart Drugs and Nutrients by Morgenthau and Dean came out so I'm thinking early 1990s that I got my hands on a very new antidepressant made and marketed in France which made me feel fantastic but it was taken off the market soon thereafter. The name of it was minaprine. https://www.ncbi.nlm.nih.gov/pubmed/3836113 That drug I had in the early 1990s which soon became unavailable as a "smart drug" was a blue tablet in an unusual shape, not round or oval.

Maybe I could get similar effects from tianeptine or amineptine, which I've never tried to obtain. But my first choice out of all the drugs in the world right now would be minaprine because it worked so well for me, but if there's a hormonal cause, then even the minaprine would be harmful if it kept me from looking at possible hormonal causes such as unexplained transient/transitory hypogonadism and/or hypothyroidism associated with a very protracted methadone abstinence syndrome. Hormones, anyone?

 

[Wishdoctor79]

...
Speaking of full agonism, here's a question of mine: I often hear people talking about a "blocking dose" of methadone; however, unlike the high-affinity/low-efficacy partial agonist buprenorphine, methadone can't really be said to "block" other opioids when it is itself capable of fully activating any mu receptor it binds to. So is the "blocking effect" simply a euphemistic way of saying that you're using high-dose methadone to give people such an insanely high opioid tolerance that the amount of heroin needed to provide them with an euphoric "rush" would simply be way too expensive for them to afford?

That term "blocking" has long been used in the sense of blocking the "high" sought by this treatment population, but heroin is not the only drug previously used or misused as the case may be. In the US at least, all that is required for MMT is present opiate dependency which has existed for at least the prior 12 months. Any opiate qualifies. There are clinics in the US now accepting people dependent on kratom even if kratom might not be a locally-declared controlled substance; the decision to take on such a client could be made by clinic management and the clinic MD and here at least the only entity which could review such a decision and tell them it was a mistake to do might be the health insurance program paying the bill, but for self-pay as I was, it'd be strictly between client and clinic unless the clinic was being audited for some type of accreditation.

The lowest methadone dose level at which that so-called blocking occurs is commonly given as 80 mg, which is by no means "insanely high," because methadone tablets in quantities of up to 80 mg per day are routinely prescribed (by pain doctors) to outpatients in the US to control chronic pain. A person maintained on methadone is ordinarily allowed to request dose increases based simply on a personal desire for a higher dose. Methadone "blocks" their drug cravings and reduces the desire to get high. A habitual opiate user for whom the medicine is "working" is on a sufficiently high dose of methadone that they would have no interest in using ampoules of even say diacetylmorphine or Dilaudid ampoules or levorphanol. They would just turn away and feel no desire to get high no matter what is offered.

When I requested dose increases, I gave the reason that I felt lethargic and believed a higher dose would give me relief from that lethargy. Sure, that was something not frequently heard by my clinic's doctor, but they raised my dose just the same as as they do for the majority who say it's needed to combat drug cravings. Some clinics require the "peak & trough" blood tests to go above 150 mg but my clinic allowed up to 200 mg without any blood tests.

The term "blocking" was coined in the original papers from Dole & Nyswander in the 1960s long before there was the present fascination with a deterministic model of neurobiological mechanicalism based on the concept of circulating keys competing for locks into which they can fit. The purpose of MMT is to have the clients cease and desist from using the controlled substances tested for with random UAs unless there is a recent doctor's Rx for such substance. At a minimum they test for amphetamines, cocaine, benzodiazepines, "opiates," and PCP per federal regulations with SAMHSA cutoffs in most cases, and then they also measure creatinine, methadone, and "methadone metabolites," to guard against dilution and also sample substitution with synthetic or urine from non-enrolled others. When methadone was legally established as a treatment in 1970 they tested for barbiturates but this has been replaced almost everywhere with benzodiazepine testing. Because PCP is so rarely found here while ketamine is now widely used for self-prescribed pain relief, it would be logical for them to test for ketamine instead, but most still test for PCP and not for ketamine.

Treatment is considered successful when client consistently presents with healthy appearance, has clean UAs, follows all rules, and makes tangible improvements to their social life. Well-behaving clients with clean UAs can earn the right to receive takehome bottles and make fewer visits to the clinic. Federal regulations allow clients to receive a maximum of 27 takehome bottles and visit every four weeks, though some clinics have expanded that to a full month. But just one case instance of illegal drug use admitted by the client can put them all the way back at the beginning and they'd then have to be visiting the clinic 6 days a week. The earning and retaining of takehomes is a huge incentive for following clinic rules and abstaining from the proscribed substances.

I'm just throwing the above info at you because most of what the ordinary person thinks they know of methadone clinics and their clients is not true, and it's almost always full of prejudicial bias and misinformation. I'm not here to find new friends, only to find answers to my question about the mystery of methadone's tremendous efficacy for me as a so-called antidepressant and so will check back here in a few weeks to see if there is any helpful info posted as replies. I use the term TRD to focus attention on the treatment-resistant aspect of my condition with none of the currently available medications besides methadone ever providing any significant benefit for me, but at least now it's not classic Melancholia because there is no sadness. (Melancholia of course has long been treated successfully with opium and other derivatives of papaver sominferum.) Other names for it could be narcolepsy or chronic fatigue syndrome. Further details of my experiences with methadone and my recent detox are to be found at Reddit at /methadone by /wishdoctor79.

 

[adder]

Correct me if I missed it somewhere, but I see no one has mentioned one very important factor making ORT in general so efficient for many people - stabilization it gives to people. It doesn't matter if it's methadone or buprenorphine that does it for you, but if you've spent years on heroin or morphine/oxycodone/any other opioid acquired in shady ways, then so-called detoxification with methadone or buprenorphine and maintenance that follows makes your life a lot different. Leaving all the psychological stuff aside, the stuff you have to deal with when you become more sober at the beginning of maintenance, your life gets much easier on your nerves. On maintenance you don't have to worry about availability and quality of the drug, this will vary locally of course, but I live in Poland and when I took heroin, Warsaw was the only city brown sugar heroin was available in, I had to travel around 200 kilometres to get there, I had no other choice (other than quitting of course) because I got dependent on morphine and my source got dry, and if some larger batch got busted, sometimes weeks of drought followed and what was available was heavily cut and more expensive than the usual price of otherwise high purity material was. In times like those having to travel throughout the whole city already in mild withdrawal to buy only 7 quarters which were more like 150's and I knew would not last me a week as they should was really stressing and tiresome with the school going on in the background, as if getting heroin alone when it was abundant and pouring from everywhere wasn't stressing enough. Depending on where you live, there's also the money factor, in Poland being on maintenance, be it methadone or buprenorphine, you don't pay any extra money for it, insurance covers it all, even if you don't work, you get insurance from a job centre when you register as unemployed. The mere fear of being in withdrawal soon is enough to drive your survival instinct after you become addicted. IMO the feeling of not having to cope with getting heroin is enough to lift your mood, suddenly there's plenty of time for a lot of stuff non-addicts do. As a side note this fear of being unable to get the drug does come back to me at times, every time I wake up on the day I collect buprenorphine from the program, I can feel it somewhere in the background, it's the thought "what if they ran out of it? how am I going to get up for work or labs tomorrow? how am I going to do a report/homework?" etc.

As for methadone being superior to buprenorphine, well, I realize Reckitt Benckiser makes a lot of money on Suboxone in the U.S. thanks to how buprenorphine can be prescribed by doctors who did an online training taking them several hours to get a license, but I'm no RB representative, I don't even take Suboxone or Subutex any more but a generic buprenorphine medicine. For me buprenorphine is superior to methadone in many ways and I had taken the latter for 2.5 years before I started buprenorphine maintenance on which I've been on for over 5 years now. My methadone doses weren't high, I never took more than 60mg a day regularly, most of the time I took 40mg a day, though my weight was 55kg at that time, and still after a year on it, I was more or less a zombie, I couldn't think clearly, my mind was cloudy all the time, I dropped out of university because I couldn't process information. Things changed drastically after I quit methadone, even though I was still on 2mg of clonazepam a day when I was discharged from hospital after being started on buprenorphine, my mind got much clearer. I am not the only person to notice this major difference between methadone and buprenorphine, I talked to a guy taking buprenorphine on my program who had also taken methadone before and he said he could think more clearly on bupe as well. On the other hand there are also people on methadone who tried buprenorphine but either were started on it improperly and experienced precipitated withdrawal or can't get stable on a low enough dose of methadone to be able to feel all right on buprenorphine which has a ceiling dose. I haven't seen any study discussing NMDA antagonism of methadone as a property having some specific purpose in opioid maintenance, but it certainly plays a big role in how methadone works, the mere fact that methadone is effective for certain types of pain for which classic opioids like morphine are not shows that, the same is true for levorphanol for example. At the same time I believe NMDA antagonism of methadone is a double-edged sword, at first it may add to the stabilizing effect of methadone, but long-term it's possibly what makes methadone so dulling cognitively. With buprenorphine I don't experience. On methadone I was aware that I'm on an opioid all the time, I was high in a way, on buprenorphine, even though the effect is obviously there and I took more than my dose many times which led to me running out early, I feel I live like a non-addict who has to take their pills. Of course I am dependent on it but it leaves me much more space. In my particular case I wish I had had a chance of jumping on buprenorphine at the time when I knew I had a problem with heroin, wanted out, and got into methadone, but what's done is done.

By what I will say now I don't mean to undermine the role of methadone in saving many people's lives and allowing them to live a better life, but methadone is certainly not an ideal maintenance drug, I don't say buprenorphine is either. Pharmaceutical companies seek to earn money by introducing new drugs in a certain class like it was with buprenorphine as an opioid replacement therapy drug, but there are also scientists who above anything else strive to improve on things to make life better for everyone and because they derive satisfaction from conducting research. When I read this story how Bentley started his research on orvinans, that's how I feel about it. I'm a chemist myself and I do organic chemistry mainly for the fun it gives me and I'd be happier inventing something unique of use for the whole society than earning millions, money is a secondary if not a tertiary factor as long as I don't have to worry about surviving financially and my family feels financially safe as well.

 

[Wishdoctor79]

Correct me if I missed it somewhere, but I see no one has mentioned one very important factor making ORT in general so efficient for many people - stabilization it gives to people. It doesn't matter if it's methadone or buprenorphine that does it for you, but if you've spent years on heroin or morphine/oxycodone/any other opioid acquired in shady ways, then so-called detoxification with methadone or buprenorphine and maintenance that follows makes your life a lot different. Leaving all the psychological stuff aside, the stuff you have to deal with when you become more sober at the beginning of maintenance, your life gets much easier on your nerves. On maintenance you don't have to worry about availability and quality of the drug, this will vary locally of course, but I live in Poland and when I took heroin, Warsaw was the only city brown sugar heroin was available in, I had to travel around 200 kilometres to get there, I had no other choice (other than quitting of course) because I got dependent on morphine and my source got dry, and if some larger batch got busted, sometimes weeks of drought followed and what was available was heavily cut and more expensive than the usual price of otherwise high purity material was. In times like those having to travel throughout the whole city already in mild withdrawal to buy only 7 quarters which were more like 150's and I knew would not last me a week as they should was really stressing and tiresome with the school going on in the background, as if getting heroin alone when it was abundant and pouring from everywhere wasn't stressing enough. Depending on where you live, there's also the money factor, in Poland being on maintenance, be it methadone or buprenorphine, you don't pay any extra money for it, insurance covers it all, even if you don't work, you get insurance from a job centre when you register as unemployed. The mere fear of being in withdrawal soon is enough to drive your survival instinct after you become addicted. IMO the feeling of not having to cope with getting heroin is enough to lift your mood, suddenly there's plenty of time for a lot of stuff non-addicts do. As a side note this fear of being unable to get the drug does come back to me at times, every time I wake up on the day I collect buprenorphine from the program, I can feel it somewhere in the background, it's the thought "what if they ran out of it? how am I going to get up for work or labs tomorrow? how am I going to do a report/homework?" etc.

As for methadone being superior to buprenorphine, well, I realize Reckitt Benckiser makes a lot of money on Suboxone in the U.S. thanks to how buprenorphine can be prescribed by doctors who did an online training taking them several hours to get a license, but I'm no RB representative, I don't even take Suboxone or Subutex any more but a generic buprenorphine medicine. For me buprenorphine is superior to methadone in many ways and I had taken the latter for 2.5 years before I started buprenorphine maintenance on which I've been on for over 5 years now. My methadone doses weren't high, I never took more than 60mg a day regularly, most of the time I took 40mg a day, though my weight was 55kg at that time, and still after a year on it, I was more or less a zombie, I couldn't think clearly, my mind was cloudy all the time, I dropped out of university because I couldn't process information. Things changed drastically after I quit methadone, even though I was still on 2mg of clonazepam a day when I was discharged from hospital after being started on buprenorphine, my mind got much clearer. I am not the only person to notice this major difference between methadone and buprenorphine, I talked to a guy taking buprenorphine on my program who had also taken methadone before and he said he could think more clearly on bupe as well. On the other hand there are also people on methadone who tried buprenorphine but either were started on it improperly and experienced precipitated withdrawal or can't get stable on a low enough dose of methadone to be able to feel all right on buprenorphine which has a ceiling dose. I haven't seen any study discussing NMDA antagonism of methadone as a property having some specific purpose in opioid maintenance, but it certainly plays a big role in how methadone works, the mere fact that methadone is effective for certain types of pain for which classic opioids like morphine are not shows that, the same is true for levorphanol for example. At the same time I believe NMDA antagonism of methadone is a double-edged sword, at first it may add to the stabilizing effect of methadone, but long-term it's possibly what makes methadone so dulling cognitively. With buprenorphine I don't experience. On methadone I was aware that I'm on an opioid all the time, I was high in a way, on buprenorphine, even though the effect is obviously there and I took more than my dose many times which led to me running out early, I feel I live like a non-addict who has to take their pills. Of course I am dependent on it but it leaves me much more space. In my particular case I wish I had had a chance of jumping on buprenorphine at the time when I knew I had a problem with heroin, wanted out, and got into methadone, but what's done is done.

By what I will say now I don't mean to undermine the role of methadone in saving many people's lives and allowing them to live a better life, but methadone is certainly not an ideal maintenance drug, I don't say buprenorphine is either. Pharmaceutical companies seek to earn money by introducing new drugs in a certain class like it was with buprenorphine as an opioid replacement therapy drug, but there are also scientists who above anything else strive to improve on things to make life better for everyone and because they derive satisfaction from conducting research. When I read this story how Bentley started his research on orvinans, that's how I feel about it. I'm a chemist myself and I do organic chemistry mainly for the fun it gives me and I'd be happier inventing something unique of use for the whole society than earning millions, money is a secondary if not a tertiary factor as long as I don't have to worry about surviving financially and my family feels financially safe as well.

Wow! It's really weird to be back here after five years away. I'm glad to see @adder in Poland is still here and posted today. Glad my old user ID connected to an email still accessible.

There's so much that happened it's a wonder I'm still alive, though suffering from my usual summer torpor from a record heat-wave.

@adder said there's a beneficial stabilizing social aspect to ORT in general but for me it was the daily clinic visits for observed dosing and random urinalysis, with rewards of earned take-homes reinforcing good behaviors.

At present, my daily opioid use includes ~1 gram kratom and ~1 gram dried poppy pods taken with protein powder, etc. in a Vitamix smoothie. Plus usually 100-300 mg tramadol. And smoking a few of my beloved kreteks from Indonesia seems to round it all out.

 

[AlsoTapered]

Bolus? That would imply parenteral administration? I presume you are actually referring to oral as when given parenteral methadone are given smaller doses 2-3 times a day.

Methadone has huge problems - oral bioavailability varies from 48% to 78% and so it WILL work better for someone.

Someone on Opiophile designed a simple method to extract the pure methadone powder which when cleaned and dried, can be given via other routes with close to 100% bioavailability.

Don't forget methadone only has a T1/2 of 19.5 hours which is why it simply doesn't last for some people - this is excactly WHY the person did it. Snorting 15mg/day kept them well - 30mg oral once a day did not.

Be warned - if you suddenly increase that bioavailability, you need to take LESS. They were on 80mg/day and 30mg [BID{ snorted was as potent.

Messing with medicines is, I hasten to add, a BAD idea unless you know what you are doing and have self-control. Medically methadone tablets are given twice a day. 30mg would still be considered a LOT so if you go that way, go down as far as you can.

I would also argues that it's a MUCH better way if you seek to stop (they did). They just turned up at the MMT place and said 'no more' and those people freaked.

 

[Wishdoctor79]

Bolus? That would imply parenteral administration? I presume you are actually referring to oral as when given parenteral methadone are given smaller doses 2-3 times a day.

Methadone has huge problems - oral bioavailability varies from 48% to 78% and so it WILL work better for someone.

Someone on Opiophile designed a simple method to extract the pure methadone powder which when cleaned and dried, can be given via other routes with close to 100% bioavailability.

Don't forget methadone only has a T1/2 of 19.5 hours which is why it simply doesn't last for some people - this is excactly WHY the person did it. Snorting 15mg/day kept them well - 30mg oral once a day did not.

Be warned - if you suddenly increase that bioavailability, you need to take LESS. They were on 80mg/day and 30mg [BID{ snorted was as potent.

Messing with medicines is, I hasten to add, a BAD idea unless you know what you are doing and have self-control. Medically methadone tablets are given twice a day. 30mg would still be considered a LOT so if you go that way, go down as far as you can.

I would also argues that it's a MUCH better way if you seek to stop (they did). They just turned up at the MMT place and said 'no more' and those people freaked.

No. This thread is about methadone maintenance ORT with observed oral dosing of liquid once a day. Bolus in dictionary is a medical term for single dose of a drug or other medicinal preparation given all at once.

 

[Rectify]

Bolus also means ball.

 

[AlsoTapered]

Bolus also means ball.

Well done on reading the etymology, but I'm presuming in this case the OP was referring to the medical term... unless methadone comes in balls.

 

[sekio]

Rectify is the resident special needs student, you'll have to excuse him.

I'm actually on 80mg methadone orally a day and can neither confirm nor deny any sort of miraculous effects. I actually got on methadone for pain relief from healing 3rd degree burns. It turns out when you have no solid housing and are in your early 20's Canadian doctors (at the time) would laugh me out of the clinic if I asked for opioids. "Try taking Tylenol and Advil together" kind of shit. But if you eat a few Tylenol 3s and piss positive and give a sob story, methadone is handed out freely. So I got my painkiller one way or another.

Also, after some time, the doctors here allow home delivery and even up to weekly carries. So it becomes just another prescription, really, instead of a daily chore venturing to the pharmacy every damn day, rain or shine, and be a functional slave, unable to escape the chains of the one place to get your daily meds dispensed.

Now, as a paraplegic, it sure helps the aches and pains.

For reference, assuming a rough 10:1 oral morphine:methadone conversion,
80mg of oral methadone is equivalent to daily doses of...

• 800mg oral morphine
• 240mg IM/IV morphine
• 180mg oral hydromorphone
• 36mg IM/IV hydromorphone
• 3mg IM/IV fentanyl
  and just for laughs
• 8000mg of codeine, in 267 Tylenol 3 tablets, containing about 87 grams of APAP or roughly 9 times the oral maximum dose of 10g... everyday.

 

[AlsoTapered]

That is quite a lot of methadone. Do you take it all at once, BID or TID? In the UK, for pain, BID or TID is usual.

I also hope you get regular heart checks. The last thing we need is to lose YOU.

Yes - special needs is a reasonable term. Try as I might, I cannot teach them anything. Offer links to databases, software, datasets or whatever and it's ignored. So I just gave up and usually just leave them blocked. The exception is when they are giving people incorrect technical information - someone could get hurt. But what can you do?

 

[sekio]

That is quite a lot of methadone.

My friend, I live in the centre of a fucking opioid abuse hotspot, where carfentanil is in our "down". A friend of mine is on something like 115mg a day, and I know individuals that take up to 200mg daily.
Several of my doctors, including the methadone doctor who initially prescribed it, are OK with it.

It's given once daily, but bid would be more effective as I can tell it is not quite as effective in the morning.
Specifically, I have this strange nerve pain in my right (dominant) arm, that presents almost as a crushing or burning sensation at various muscles. Methadone helps, but also: topical diclofenac, heavy oral doses of naproxen (1000mg), cannabinoids, and (strangest of all) viewing pornography. (I can't feel below my chest so I can't, uh, do anything, but it's the strangest shit... must be endorphin release?)

It could relate to a large syrinx that apparently occupies most of my cervical spine... I forgot the measurements but it's something like 10cm x 12mm. By rights I ought to be a quadriplegic, or dead....

I also hope you get regular heart checks.

I'm a paraplegic. I basically live in a hospital. I'm not worried.

 

[AlsoTapered]

My friend, I live in the centre of a fucking opioid abuse hotspot, where carfentanil is in our "down". A friend of mine is on something like 115mg a day, and I know individuals that take up to 200mg daily.
Several of my doctors, including the methadone doctor who initially prescribed it, are OK with it.

It's given once daily, but bid would be more effective as I can tell it is not quite as effective in the morning.
Specifically, I have this strange nerve pain in my right (dominant) arm, that presents almost as a crushing or burning sensation at various muscles. Methadone helps, but also: topical diclofenac, heavy oral doses of naproxen (1000mg), cannabinoids, and (strangest of all) viewing pornography. (I can't feel below my chest so I can't, uh, do anything, but it's the strangest shit... must be endorphin release?)

It could relate to a large syrinx that apparently occupies most of my cervical spine... I forgot the measurements but it's something like 10cm x 12mm. By rights I ought to be a quadriplegic, or dead....


I'm a paraplegic. I basically live in a hospital. I'm not worried.

I meant quite a lot of methadone for pain... but when you reveal just how MUCH pain you suffer and how seriously it limits you, it suddenly seems like quite a moderate dose.

But while sources give WILDLY different values for the T½ of methadone (not it's metabolites, not it's detection time, it's half life in the plasma), the BNF lists 19 hours ± 11 hours.
That is why BID is by far the most common, a few patients benefit from TID. I might add that when given for pain, UK patients don't have to drink that green (1mg/ml) or blue (10mg/ml) syrup (which has SUCH an unpredictable peak plasma time) but rather it's tiny white pills brand name Physeptone.

Now doctors absolutely ABHOR giving opioid addicts Physeptone because it's readily crushed and injected. I've never tried it (I've never injected any drug ever) BUT I am informed of 2 things. Firstly it's upto twice as potent (orally methadone is 49-78% available) AND it's euphoric and what is more, euphoric for 12 hours. So in the 1980s every single person who asked for methadone therapy (even though SOME didn't need it - they just sold it on) got ever so inventive when it came to why they couldn't POSSIBLY manage with the linctus. Most common was if/when someone was finally trusted with a 7-day pickup schedule, they would claim they worked part time in the building trade and glass bottles often get broken. Some faked myoclonus for similar reasons but those little while pills are what they ALL wanted.

As you know, I did obtain 1000mL of methadone linctus and successfully freebase it and extract the pure freebase. Typically stupid thing of me to do as on-line people telescoped down the route and in NZ they were adding methadone to 'home bake'.

Really sekio, I simply had no idea how badly dysfunctional your body is. I can walk short distances on crutches and even with clobazam I get myoclonic jerks (so I fall OFF said crutches) BUT I can walk a bit.

Have you mentioned this before and I just missed it? I feel really bad for not understanding the difficulties you are going through.

That your organic chemistry is of such a high standard really is quite astounding.