Methadone conversion factors for morphine, oxy, dihydromorphine&its esters

[Limpet_Chicken]

Hey up folks.

I could use a little help here. Background of it is, that I am a long-term chronic pain patient, I take a mixture of morphine and oxy daily. Nominally, I'm meant to take 100mg morphine orally twice daily, but at best, I can get by on about 100, thrice daily, IM or IV, I've never been able to take the dose orally and even go without withdrawal.

Also taking, I think, 20mg 4x/d oxy, although it can be more than that, give or take a bit, usually insufflated, sometimes plugged or mixed in with the shot.

Anyhow, I received several hundred 5mg physeptone (methadone, tablet form) in full boxes, from...lets just say, somebody very helpful indeed, bought them yesterday, had them shipped so quickly that the postman came right as I dug myself out of bed, when given the docs I see don't give me enough medication to even cover my chronic pain, or go without withdrawing for the entire week (typically it means at least a night, likely a day and night of misery every week, unless I make CWEs. But I need all the DHC I can get for other purposes...so it can become...something greater..several things greater in fact)

So, I could do with conversion parameters for potency for the following:

Methadone: 10mg=Xmg morphine (sulfate salt)
Methadone: 10mg=Xmg oxycodone (hydrochloride salt)
Methadone: 10mg=Xmg dihydromorphine (freebase will be most useful here, since I'm not entirely decided on the salt)
Methadone: 10mg=Xmg dipropionylmorphine
Methadone: 10mg=Xmg 6-monoacetyldihydromorphine
Methadone: 10mg=Xmg 6-monopropionyldihydromorphine
Methadone: 10mg=Xmg dihydroheroin (and ideally, the dipropionyl analog of dihydroheroin if anybody knows)

So, well, I'll have my fun a couple of times, since I rather enjoy methadone. Beginning today with taking it orally and some plugged, going to clean it up from the pills, for a few of them in some of my microscale glassware, to provide a purified isolate that I can filter, micron filter, mix with some cyclizine after conversion of the HCl in the 50mg cyclizine tabs I have to the lactate salt, which is more water soluble and the form used for injection. This is said to resemble the near legendary diconal/dipipanone, a methadone analog that was formulated with cyclizine IIRC. I want to give the combination at least a couple of tries, done similarly to a speedball (which is another thing on my to-do list actually, the cyclizine/methadone combination mixed with some 3-fluorophenmetrazine, or one of the other phenmetrazine analogs, or perhaps either mazindol or homomazindol.

Could really use both advice as to equipotency for the opioids above, so I can calculate a taper, although I'm going to be keeping to collecting the effectively infinite pain med script, just, using them only when I must. That way I can, break the chemical handcuffs my doctors have forced upon me, and use the pain meds as and when I can't do without.

So, fire away folks. I see a benzo conversion chart but no opioid one. And if there was it probably wouldn't cover a couple of the opioids in question. Since I don't know as prope dope is particularly common, for some reason people would sooner make or use heroin rather than dipropionylmorphine, regardless of the latter having a massive IV rush, is far more potent than H, and lasts 12-15 hours, perhaps more. Stuff has a real fucking kick to it.

Especially interested in dihydromorphine, morphine, oxy and the other dihydromorphine monoesters (6-monoacetyl, 6-monopropionyl)

Thanks.

 

[Jekyl Anhydride]

Sorry LC but this seems more like NPD material. If not NPD than maybe the Merck index?

OD--->NPD

 

[sekio]

Methadone tends to be difficult to come up with accurate conversion factors because its pharmacokinetics are quite different than the much more hydrophilic phenanthrene opioids.
Namely, I've seen dose conversions for both acute and chronic dosing, but even then there are large "fudge factors". In the end it seems you really have to titrate the dose as needed.

I also know that you're going to have a hard time finding equivalencies for much save for morphine and very possibly heroin/diamorphine. Unfortunately there has not been much research on stuff like dipropionylmorphine, at least not since the Harrison Narcotic Tax Act or whatever the fuck law banned their use in the mid-1920s.

Dihydromorphine may exert analgesia via a different isoform of the mu opioid receptor and apparently only produces partial cross tolerance to morphine analgesia in rats. But if you want data on the affinities of acetylated dihydromorphine analogs, .... [ref]

 

[tacodude]

The ratio for Morphine to methadone ranges from 1:1-1:8 methadone: morphine where 1:3 is pretty much standard. A good way to think of it is that a 30 MG 12 hour SR formulation of Morphine is equivalent to 5 MG methadone while 15 mg IR morphine may activate the same level of activity for only half as long.

I know this because I'm currently in methadone and Morphine that I'm still stabilizing my script it's so fresh where I have been the one figuring out equivalency and dose where they just are trying to push every common drug down I don't need trying to replace the opioids before even treating me even diagnising what they used it for. So yeah while I don't have the reference source for that 15 mg SR Morphine = 2.5 mg methadone I've found it to be the best way to figure out equivalency.

 

[seep]

Methadone is so wacky that the American Pain Society gives this advice:

When used to treat chronic pain and switching to
methadone from higher doses of another opioid,
the panel suggests that clinicians start methadone
therapy at a dose 75 to 90% less than the calculated
equianalgesic dose and at no higher than
30 to 40 mg/d, with initial dose increases of no
more than 10 mg/d every 5 to 7 days. Methadone
should be withheld if there is evidence of
sedation.

https://www.jpain.org/article/S1526-5900(14)00522-7/pdf ---> Methadone Safety Guidelines, 2014

But you shouldn't use conversion factors for methadone.

It's kind of shitty as an analgesic because its pain-killing effect lasts between 4-8 hours, but its other effects are much more prolonged. It also has a biphasic elimination so it accumulates in tissue, making dosing even more problematic as elimination half-life steadily increases. It's possible to be sedated and bradypneic on it looong after the sedative effect has passed. It's also really good at prolonging QTc and it's a common cause of ventricular arrhythmias and Torsades. Incomplete cross-tolerance is pretty significant on it so start slow.

There are at least 8 formulas for converting opioid doses to methadone. Here are some:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936085/

edit: the Plonk formula is a simple linear equation:

(Oral morphine equivalent mg per day / 15) + 15 = Methadone mg per day.

 

[clubcard]

When given for pain, methadone is usually [TID] but even then it takes some days to reach steady state plasma concentrations. As sekio correctly stated, it takes some time to find the effective dose. I've read patents that describe analytical drugs that are substrates of several common CYP enzymes so that a simple urine test will show the isoform variance in terms of the relative amounts of each metabolite. Evidently it was ahead of it's time since I've never heard of such tests being routine. Methadone is actually a very good analgesic but 2 things are worth pointing out:

- Both isomers of methadone can cause long-QT but the (R) isomer is responsible for >96% of the analgesia so if you are in a country that uses the chiral version, it's quite considerably safer so do ask.
- The pharmacokinetics of methadone are quite complex but it's long duration mean that the effects of the first dose compared to following doses can be quite different with nausea being one common issue.

30 years ago a doctor would happily give you cyclizine for the nausea but in the UK in particular, the abuse potential of concomitant use was recognized (as were several other antihistamine/opioid mixes) so be careful because the effects can be dangerous.

Methadone has been around for 70 years so it is very well understood and is an excellent (and economic) strong opioid analgesic.

I hope it works out for you.

 

[Limpet_Chicken]

Well, this methadone is from the UK, physeptone. Don't suppose you know if this is the racemate or enantiopure material?

Methadone has all the hallmarks of a drug that feels like a tricksy little bugger to dose. Think what I should do, is wait until beginning to withdraw, before taking my next dose, find out what the minimum is to hold me, (I'll likely also use 10-20mg intranasal oxycodone, iR because methadone takes quite a while to come on and oxy doesn't last long, just to transition from withdrawing into a relief state fast enough) not sure how fast to cut it down, a titration job methinks?

I can distinctly feel the NMDA antagonist trippiness. It gives the world around a distinctly detatched, dissociated sensation about it, and a wierd anaesthetized feeling I always feel in my lips, gums and roof of my mouth.

I think it might take quite a while actually, for the initial recreational dose to wear off. Must be about 350-400mg or so, and at the level I'm at currently, it really is quite trippy, in an NMDA antagonist way, its quite...otherworldly.

Has anyone got experience with plugging it? probably more efficient on a per mg basis. And how about the cyclizine combination IV? And as for 30 years ago, doctors would happily give me the stuff? my GP scripted me cyclizine already, got loads of the stuff. A mixture of cyclizine, ondansetron and 7-8 other GI meds, as I have had some nasty stomach troubles in the past.

 

[clubcard]

The NMDA affinity values are in the hundreds of nm. It is classed as a 'very weak' NMDA ligand. Relative affinity to different (sub)types of opiate receptor can give different opioids a different field but try taking about 300mg of (S)methadone and be amazed when you feel nothing whatsoever.