people should only ever take opioids VERY TEMPORARILY to get through surgeries or other such things. Opioids are not for long term pain management.

Same thing with benzos and anxiety.

Nearly all opioids present the hazard of dose escalation over time to maintain their efficacy. Hence the dose escalation commonly seen with morphine, oxycontin, etc.

Most opioids, in addition to interacting with mu-opioid receptors (the mechanism of pain relief), also activate NMDA receptors, which enhance pain sensitivity. So for most opioids, there's an adverse dynamic in which analgesic activity competes with nociceptive activity, leading to dose escalation.

Methadone is one of two opioids that don't activate the NMDA receptor system. (The other is dextromethorphan, the OTC cough suppressant.) Methadone has been used very successfully to treat chronic pain, and does not exhibit dose escalation issues. Methadone has slow kinetics and does depress respiration, so when putting patients on it, dosages should be titrated slowly to avoid hazardous or fatal events. This is easily managed in ordinary clinical practice.

A close family member has been treated with methadone for chronic refractory migraines for >20 years. She transitioned to methadone from morphine SR after experiencing the classic need for increased dose. With methadone, she's had no dose escalation, no impairment due to psychotropic effects...it's simply given her a life to live.

(If you read my reply to the above comment, you'll note the significant rebound effect I suffered from codeine in that it significantly increased the frequency of my headaches.)

It has only just occurred to me to ask this question after reading your comment and my logic for doing so is thus:

(a) Compared to certain other opiates, codeine isn't a particularly powerful painkiller, presumably this is why it's been licensed for inclusion in weak amounts in combination with NSAID painkillers in a number of countries (although I realize that in some places the rules concerning the sale of these OTC drugs have been tightened in recent years).

(b) The codeine 'rebound problem' (presumably caused by its activation of NMDA receptors) could be eliminated if codeine were to be substituted with low-dose methadone in these combination painkillers.

(c) As it has little or no NMDA activity, substituting low-dose methadone may alleviate or reduce some of the overdose problem from paracetamol overdoses (paracetamol poisoning occurs when people overdose on it in their attempt to get a bigger hit from the codeine component - or when they find that the painkillers are no longer working effectively and increase the dose above recommended amounts).

(d) Again, as methadone doesn't have any NMDA activity, its effective level could be increased in comparison to that which has been traditionally considered safe for OTC codeine preparations. In essence, for an equivalent level of risk/narcotic side effects, OTC low-dose methadone/NSAID combination painkillers could be made more effective than their codeine equivalents.

Thinking quickly through this some objections are immedately clear, the most obvious being that (from memory) methadone has a similar analgesic threshold to morphine (albeit its overall effectiveness is somewhat less for other reasons).

As methadone's analgesic threshold much higher than that of codeine (perhaps by as much as five times) it's traditionally said to be highly addictive in its own right and thus significantly more so than codeine.

The question arises that given its lack of activation of NMDA receptors how effective would it be in low-dose preparations. If there is little NMDA response one would expect little addictive risk at these low leveks. Of course, the argument against that is that the higher analgesic threshold would negate the benefits as consumers could actually get bigger hits by taking larger amount of these painkillers (that argument is used correctly with other opiates such as heroin which has an analgesic threshold of about three times that of morphine).

However, as you point out, this shouldn't happen with methadone given its lack NMDA action (especially so in small amounts).

Even if it did, would we be faced with methadone addiction kicking in first or would abusers of these painkillers succumb and die from paracetamol poisoning (as they often do now with codeine combinations)?

There's another option that is also worth considering in this debate and that's the inclusion of a small quantity of atropine in OTC preparations that include narcotic drugs such as with the anti-diarrhea drug diphenoxylate (aka Lomotil). The inclusion of atropine has proved highly effective in discouraging deliberate overdosage of diphenoxylate, as beyond a certain threshold level it makes one feel quite I'll.

No doubt, the wider use of opiates such a methadone is both a complex and very emotive subject. Moreover, it worries me that the very mention of the word 'opiate' is enough to close down sensible debate on the subject. We need a much more sophisticated and nuanced approach to the use of opiates than we have at present and I can't help feel that we're not getting it because of a silly non rational approach to the problem. Mentioning methadone for instance has widespread connotations with drug abuse and these are usually negative - even though the drug is usually used to improve the lives of people.

BTW, let it not be said that I'm advocating a wider more laissez faire approach to opiate use, I'm certainly not. What I want to see is more science and less emotion in the debate.

Moreover, if you look back on my old HN comments about such matters, you'd find few other posters whose comments were more critical over the opioid epidemic than I have been. In my opinion, the behavior of Purdue Pharmaceuticals and the Sacklers has been nothing short of criminal and the fact that they have been let off lightly is a national disgrace.

I can only speculate at the absence of methadone as a replacement for codeine pain meds. Two things come to mind.

One is the known respiratory depression hazard presented by methadone. This is complicated by the fact that methadone's clearance rate varies by more than an order of magnitude among individuals. In clinical practice, this means that the effective analgesic methadone dose must be established slowly. This isn't a problem in controlled clinical settings with patients who comply with treatment regimens. It's another story entirely in patients who are immersed in street drug polypharmacy situations. So there may be an element of caution, well-placed or not, that biases against use of methadone in place of other opiates.

The second is what you touched on - methadone (and all opiates, really) is a complex and emotionally-laden subject. Methadone has a poor reputation from its use in detoxing opiate addicts. Mentioning that you're being treated with methadone nearly never elicits even a neutral response. I think methadone's negative reputation is a serious impediment to its use in situations where it would otherwise be the logical choice.

I don't know about addictive properties of methadone. I know that my family member, who has been treated with methadone for chronic refractory migraine for ~17 years, doesn't show withdrawal symptoms when she misses her meds. Her headaches return, but there's none of the sweating, feverish shivers that characterize withdrawal from other opioids. She doesn't experience psychotropic effects, positive or negative. The principal side effect is constipation. In at least this anecdatum, there's no evidence of addiction even after a very long term of use.

I agree there's a shortage of rational thought and a great excess of emotion around opioids. I wish the emotional charge could be more directed to Purdue Pharma, the Sacklers, and the like, who have not only killed people in multitudes, but who also have compromised progress in getting effective and safe pain relief to the very many who would benefit. Sometimes, one can only live in hope of better times.

Thanks again.

I would happily trade 10 to 20 years off of my life to live the remaining ones pain-free and functional.

Edit: One of the most frustrating things I experience are doctors who don’t understand topics that guide “no tolerance” policies; for example, they are aware they hyperalgesia exists — much like the GP — but don’t really know what it is or what it’s like for the patient.

From peronal albeit limited experience, I don't doubt that opioids can cause pain they purport to relieve.

I used to take an OTC painkiller for headaches that was a combination of 500mg acetaminophen (aka paracetamol) and 10mg codeine and whilst it was somewhat effective the frequency of my headaches actually increased.

It eventually dawned on me that the painkiller and or the frequency of taking it was causing some rebound effect and that the likely culprit was the codeine - given that it was an opiate and thus potentially addictive.

I then switched to acetaminophen-only tablets and although less effective as a painkiller than the combination, the frequency of my headaches decreased quite dramatically.

I never exceeded the recommended daily dose nor did I take the tablets every day (as I've always been aware of acetaminophen's potential to cause life threatening liver damage on overdose), so my codeine intake would have been within acceptable limits (especially given the painkiller's OTC status).

That said, I abruptly switched to the non-codeine formulation without any noticeable withdrawal symptoms.

The fact that codeine could cause headache pain when taken at dose levels below that which would be considered potentially addictive has never been lost on me. I'm very surprised that the public hasn't been warned more widely about this issue.

Or realize that people should follow their doctor's advice and realize that opioids definitely can be a part of long-term pain management. Not all long-term use is equal. You can have long-term pain and long-term use of opioids without needing to take them daily just like you can use benzos for years without needing to take them daily for that entire time.