Opioids Methiodone/IC-26

[BuprenorphineBrian]

Be careful guys.

Research opioids just aren’t worth the risk in my opinion. But, that’s just me. They feel cold and they lack that warm feeling. I have my Buprenorphine. I know it doesn’t work for everyone. Just reminds me of Phreex and the other BL who have passed away. You can’t outsmart this stuff.

 

[BuprenorphineBrian]

I hate to be the bearer of bad news but people must know that even medicines that have been extremely well tested and obtain a sales licence still occassionally turn out to have a dangerous side-effects.

Of the RCs, I reckon I've looked at the GC-MS / NMR instrumentation of well over 2000 samples and the class where I noted the most impurities were the synthetic cannabinoids. I kept seeing compounds that had a MW almost exactly x2 or x3 that of the expected compound. These turned out to be dimers and trimers. The problem is that with such a high MW, they won't vapourize ahead of a flame-front i.e. in a joint. Instead they will be pyrolized and the pyrolysis products are extremely carcinogenic. I fully expect to witness a peak in cancer cases among people who used that class of RC.

But we are also seeing cathinones that are growing ever further from that which is known. It's not so much a matter of if, but simply a when one of those turns out to have an unwanted side-effect.

Even if it's only a patent, if a drug has been tested in animal models, at least we have a little information although to be clear, animal models can fail in quite spectacular ways. One is that rodents appear to be much more sensitive to opioid analgesics that humans. So when a novel opioid it claimed to have some ridiculous potency, don't forget that the original animal (rodent) studies of BDPC stated that it was >10000x more potent than morphine. In man it turns out to be x504. My best guess on that one is that rodent pain models are much more subject to NOP (norciceptin receptor) ligands than man. Certainly I know someone who made the 1,3,8-triazospiro class opioids Janssen had listed as being x450 morphine in animal models. Let's just say the truth was that in man, it wasn't inactive, but it wasn't good enough to be worth the time and effort.

To be fair, I did find and send them the later patents that demonstrated that they were in fact NOP ligands but they wanted to be certain. But as I've said, you can expect to make a dozen novel opioids before you find one that is actually 'good'. Becuase nobody really knows why one opioid is euphoric while another is not. As a rule-of-thumb, the more potent the opioid, the less euphoric it is.

Hence H, dextromoramide, dipipanone, levorphanol, oxymorphone and so forth still being sought by users. Yes, U-47700 was a lucky find, but it wasn't the first or even the tenth compound tried.

It’s interesting they say bupe has no ceiling effect on pain in humans now. They thought so b/c of the rodents. I don’t understand it. But, apparently high dose (mg) bupe for pain is a thing now

 

[notsmokeymcpot42088]

Be careful guys.

Research opioids just aren’t worth the risk in my opinion. But, that’s just me. They feel cold and they lack that warm feeling. I have my Buprenorphine. I know it doesn’t work for everyone. Just reminds me of Phreex and the other BL who have passed away. You can’t outsmart this stuff.

Generally a hard agree. I have only had one ever that even slightly tickled my fancy. piperazines and nitrizes(?) fent analogues not a lot of euphoria or warmth there.

And that is interesting I always thought there was a 24mg ceiling on it at which point "all receptors are locked" (In reality I should have known things are never that black and white -- diminishing return past about 2-4mgs IME though)

 

[4DQSAR]

BTW if you ever see something for sale that YOU don't understand - do ask. I will NEVER tell you something is 'safe' but will flag specific concerns. I'm seeing crazy potent stuff turning up for frankly unsustainable prices on clearweb sites so no way to independenly give feedback. I judge these as scams (at best) OR the vendors have other motives - like get you hopelessly hooked (see fentanyl) and jack up the price OR they are in practice selling what amounts to WMDs. Or even an terribly badly concieved entrapment attempt.

But whatever the goal(s) - I see no good ones.

If it looks too good to be true - it isn't true. Be careful folks. Nothing is worth your life or liberty,

 

[notsmokeymcpot42088]

Aye -- I would and may just as extra context but I would never choose to research something I do not (Feel like) I grasp. That nitro-benzo's possible OD thing is interesting --- Phenazolam any toxicity concerns or just potency and duration?

Right now that is the only thing I am seeing that I feel comfortable researching. (Given my healthy fear of what I dont understand). Really trips me out they got "Vouched sellers" selling a bright purple opioid called 'new proton' idk who would bight on that I really really don't. (and I have been desperate)

The goal - You may be right. The goal is to be able to move with enough of a coushin not to worry about my authoritarian-esque doctor that has had me on benzos for 20 yrs and routinely makes quasi threats such as "We have an suboxone clinic that covers insurance why don't you join that?" -- and the only realistic answer is F*CK THEY POLICIES, but I can't say that as they probably the same policies just alot more strictly enforced. The US is weird right now, my 72 yr old mother is never gunna get shit for pain so we gas station 7-oh. (Doctors have effectively become nothing more than real arrogant middlemen IMPO---- Usually --- Of course something goes sideways health wise im gunna be seein one but other than that..)

Like everyone else I want to be assured that neither I or my family (rlly just my mother Im one man) suffer at the hands of a rapidly changing (and not for the better impo) environment. May I fuck up if I try; absolutely. Am I going to be fucked just as bad if I do not try? Also probably absolutely.

***edit*** Upon second glance I dont think you were addressing me lol, ignore that if not.

 

[BuprenorphineBrian]

Aye -- I would and may just as extra context but I would never choose to research something I do not (Feel like) I grasp. That nitro-benzo's possible OD thing is interesting --- Phenazolam any toxicity concerns or just potency and duration?

Right now that is the only thing I am seeing that I feel comfortable researching. (Given my healthy fear of what I dont understand). Really trips me out they got "Vouched sellers" selling a bright purple opioid called 'new proton' idk who would bight on that I really really don't. (and I have been desperate)

The goal - You may be right. The goal is to be able to move with enough of a coushin not to worry about my authoritarian-esque doctor that has had me on benzos for 20 yrs and routinely makes quasi threats such as "We have an suboxone clinic that covers insurance why don't you join that?" -- and the only realistic answer is F*CK THEY POLICIES, but I can't say that as they probably the same policies just alot more strictly enforced. The US is weird right now, my 72 yr old mother is never gunna get shit for pain so we gas station 7-oh. (Doctors have effectively become nothing more than real arrogant middlemen IMPO---- Usually --- Of course something goes sideways health wise im gunna be seein one but other than that..)

Like everyone else I want to be assured that neither I or my family (rlly just my mother Im one man) suffer at the hands of a rapidly changing (and not for the better impo) environment. May I fuck up if I try; absolutely. Am I going to be fucked just as bad if I do not try? Also probably absolutely.

***edit*** Upon second glance I dont think you were addressing me lol, ignore that if not.

I thank God I live in Canada
My doctor has me on Suboxone, Xanax and Vyvanse or Adderall (I switch between the two). It’s also covered for free by our version of the NHS. The risks just aren’t worth the benefits anymore. If Suboxone doesn’t work they will give you methadone and if worse comes to worse they will then give you methadone and morphine and then if that doesn’t work they will give you hydromorphone. I just don’t see the appeal of research chemicals.

 

[izo]

Just testet the Waters with this novel opioid recently, a few mini doses of around 5mg, Not more. Felt like a solid opioid so far, will Go higher in some month.

 

[methylenedream]

I've had past experience with this compound. Not sure if it's just me but I feel like I'm in opi wd the day after dosing this even if it's for the first time.

I find this not very recreational but for someone like me would be more suited for a maintenance substance. My tolerance is too high like when I did manage to get "high" on this it was just itchiness and other typical opioid side effects with no euphoria.

It is definitely potent I wouldn't recommend this to the opioid naive. As far as dosing I think I went as high as 250mg but I encounter the same problem I do with real methadone there's no real dose that can have me feel good that isn't on the verge of overdosing and I doubt that would even be the type of feeling I'm looking for.

I can see some benefit in this I do wish it was around when I got cut off methadone by my Dr at 85mg I would've opted to switch to this then taper off but my route went different I went back to fent for relief from the methadone wd.

I never noticed any crazy side effects although I think I've only been through 2 grams of this in total and used it very sporadically sorry if this isn't much help but I think this can be helpful for people that were in my situation where a clinic cut them off outside of that not too much to this compound ime

 

[4DQSAR]

A common problem with many compounds in this class is unreliable pharmokinetics.

IC-26 was reported as having simplar activity to methadone in some individuals, mush less activity in others. But as far as I can tell, it was only an ACUTE activity study so who knows if, on a different day, the people who reported one potency activity to methadone would report much less activity? It's quite a well know problem with many medicines of that era. Some which reached market and harmed people for that very reason.

To paraphrase Peter McDermott 'One day you could take five and be fine, the next day take three and wind up on the bathroom turning blue. Thumbs down.'

So take that with a pinch of salt, but the fact it was developed, reached human trials only to entirely disappear might hint at issue. The fact that the 1961 UNODC list doesn't include the stuff is also one of those 'what did they know that we don't?' questions. Unreliable pharmokinetics may have meant in whatever paper they read, potency was listed as much less? But that's it, who knows?

So along with my previous concerns... proceed with caution. Maybe get an electrocardiogram?

 

[notsmokeymcpot42088]

Maybe get an electrocardiogram?

Maybe don't play with something that would require obtaining one of those? lol idk the pharmokinetics either but NEVER USE ALONE AND KEEP NARCAN NEAR. (If you can't trust the person you are still alone btw)

 

[4DQSAR]

Maybe don't play with something that would require obtaining one of those? lol idk the pharmokinetics either but NEVER USE ALONE AND KEEP NARCAN NEAR. (If you can't trust the person you are still alone btw)

It's the case that nations like Germany now only use L-Polamidon (levomethadone) because it's a metabolite of dextromethadone is known to be cardiotoxic. Likewise levacetylmethadol (OrLAAM🅪) was withdrawn from use because it also proved to be cardiotoxic. So it seems like that particular class needs extremely cafeful consideration.

The obvious answer would be to resolve the product. You throw half of it away but what remains is twice as potent. BUT if it also has issues with unreliable pharmokinietics, well, that would explain why it just disappeared. If unreliable pharmokinietics IS an issue, I stongly suspect even if you swap the N,N-dimethyl moiety for a piperidine ring (like dipipanone) or a morpholine ring (like dextromoramide or phenadoxone), you will still have that issue. My Peter McDermott quote referred to dextromoramide. If 50mg is fine one day but 30mg is an OD the next day... that's a problem.

Ceratainly I ASSUME anyone considering producing IC-26 SHOULD be aware of all those things.

For what it's worth, I used to know someone who suffered sudden cardiac death after undertaking (raecemic) methadone maintainance although to be clear, it was a high dose. There is also at least one BLer who suffered a heart attack after being given a moderate dose of (raecemic) methadone to treat severe chronic pain. So it's not without risk - but I would assume that if IC-26 solved such issues, we would be using it...

 

[notsmokeymcpot42088]

sudden cardiac death? That is different from an overdose correct -- aka the narcan aint gunna help? That is fairly scary stuff and thank you for sharing I was unaware. Remain too skeptical to fck with RC opi's except for 7 oh (Honestly not for me) and I don't want that person using it on a "regular basis" for normal addiction reasons plus incomplete knowledge.

Any particular problems with 7 oh I should be watching out for? Organs it hurts? Etc... (you told me to ask i will take ya up on it!)

 

[4DQSAR]

Yes. From a study of the literature, it appears that only a certain subgroup is subject to the cardiotoxic effects and they will tend to exhibit long-QT and other signs long before it's a serious risk. I could theorize that the subgroup is those whose bodies don't form the non-toxic cyclic imine from the cardiotoxic dextrodinormethadone to the same extent as most people - but that is just a conjecture.

Nobody appears to have identified the subgroup and so there is conflicting data with some clinicians finding no association between dose and cardiotoxicity of methadone one one hand and reports reasonably strong association. It appears that cocominent use of CYP3A4 inhibitors was considered so I wonder if the subgroup might be people with low levels of this liver enzyme. Again, insufficient data.

But since methadone treatment requires titration to an appropriate dose due to tolerance as well as the varience in oral bioavaiability and half-life, it's eminently possible to use an EC to check if long-QT is detected and if it's the result of methadone being prescribed. So we CAN see it coming and consider alternatives thus providing the best outcomes for patients. In fact identifying the subgroup might allow clinicians to choose alternative treatments before commencing treatment.

Or go down the German path of using laevomethadone. It's twice as potent as raecemic methadone so while the bulk cost is higher ($1,948/Kg) compared to raecemic methadone ($398/Kg), you can halve that former number as clinicians would prescribe half as much. By my calculation, it's still in the pennies a day range.

I apologise if I've gone into too much detail The data IS contradictory but I cannot help reflect that while it is entirely possible that clinicians may have to learn how to employ levomethadone and there must be a risk of confusion if both medications were both used, my gut feeling is that there might be a feeling that 'we have used it for so long and it's so cheap, do we care enough to go for something more expensive?' given what methadone is mostly used to treat.

My two examples have no statistical value whatsoever but in the surviver who was prescribed methadone for pain, it was immediately substituted suggesting it's a known issue. But in the case where the person died, I seem to remember them having one heart attack and ending up in hospital but as far as I know, methadone continued to be prescribed. But I feel it important to mention that in their case the person had quite a huge dependence and was under the treatment of a senior consultant. So the hospital staff may well have felt constrained to continue prescribing. After all, the outcome if methadone were to be withdrawn could have been that person having stuff smuggled in to them. We will never know since an inquest was never held.

BTW obviously all of the above refers to methadone. So my post is slightly OT. But the fact remains that the dinor metabolite of IC-26 has a reasonable chance of displaying similar issues. I checked and the human studies were acute activity. So it is entirely possible that like other compounds related to methadone, it demonstrates unpredictable pharmokinetics. I mean, it all went quiet fast for some reason and as far as I can tell, it was due to unreliable pharmokinetics.

 

[notsmokeymcpot42088]

Yea if I read that right it sounds like identifying the subgroup would certainly be good for that subgroup. The CYP3A4 liver enzyme makes some sense to me. First one hopefully I'lll grasp in a couple reads.. I have noted and warned ppl that methadone seems to hit ppl differently first time I took it I was use to like 75 mg of morphine snorted and 15mg PO lit me right up. Other people started with 2 tens and seemed fine but it seemed wreckless at best.

I speak that second to last paragraph and spend money on 'scummy junkies' never gunna happen. True story when I was at my sub clinic and mentioned to not the secretary but the nurse that suboxone had a class action lawsuit for rotting peoples teeth she very loudly announced, "Yea like you guys don't smoke meth anyways" (Pregnant pause) "Well I don't and your drugtests should be pretty good proof of that?" at which point he doctor stepped out and said "Yes they would" and kind of took control --- but yea they see us as scum in the US. If we ever start looking at it as a health issue and not a criminal matter --- But let's be honest Incarceration is BIG $$ in the US. Question, Do they have privatized prison in the UK? The incarceration rate in the US is exceptionally high (as im sure you know, hell we proud of it--I guess). Doesn't look like things are going to get more pleasant quickly either...

I have also seen one person on a heavy dose of methadone seem to have heart issues; enough he went to the hospital. Never heard how it turned out, I mean he lived but diagnosis wise. Sure when you are on that much methadone the legal alternatives are slim to none. (Which is crazy because the alternatives are damn plenty and as a doctor you gotta know that -- I guess there hands are tied legally)

I remember a time in the US (and im not THAT OLD) that priority wise it went MEDICAL than Legal, Than Financial. They would throw you in jail for not making payments but you would still get your prescription. Not anymore "Medication Free Jail" A fellow from detroit died in our county jail from malnutrition and dehydration. LOST OVER 50 LBS IN TWO WEEKS. Id post the article but I dont wanna blow myself up. Clearly sounded like severe w/ds to me. Some CO's and Nurses took charges too.

 

[4DQSAR]

I can confirm that some UK prisons are run on a for-profit basis by private companies. So crime is going down but more people end up in prison.

FYI British slang for a prison offcer is 'a screw' because in the Victorian era, hard labour could be turning a handle many thousands of times within a convicts cell and how hard it was to turn that handle was adjusted by a screw.

So private prisons are not run by members of the Prison Officers Association and are referred to as 'plastic screws'.

When prisoners can tell just how unsafe private prisons are, they do have a wonderful turn of phrase to encompass the problem in just two words.

BTW I've known people who have served prison sentences and I can't help thinking that it's an eduction in itself. If I ever needed someone who could solve problems using the tools to hand in a timely manner, I would actually consider someone who survived prison to have that skillset. I've been totally stuck with a problem only for an ex-prisoner to walk over and calmly solve the problem in a moment. It seems to teach problem solving very well.