Opioids Tramadol & suboxone/naltrexone...Precipitated Withdrawal?

[Shant]

The idea behind adding naloxone to opioids is to make them less attractive to inject.

Basically, naloxone's oral bioavailability is like 1%, while IV bioavailability is by definition 100%. So if you eat your pills as intended, virtually none of the naloxone will make it past the liver, and the only thing you'll feel is the opioid agonist. If you inject it, you'll suffer precipitated withdrawal because the naloxone's antagonism will overpower the active opioid's agonism.

While the practice does not seem to be commonplace in the US (with the exception of the blockbuster drug suboxone), in Germany the popular opioid tilidine is usually sold as a combination drug with naloxone ("Valoron N") to decrease abuse. Ditto for oxycodone, which is available in a naloxone combo called "Targin". I believe in North America, it is mostly done with pentazocine ("Talwin NX").

In all these cases, the combination makes perfect sense, because the naloxone can easily kick the tilidine/oxy/pentazocine off the receptors. With suboxone, the issue is a little more iffy - buprenorphine itself binds to the receptors just as strongly as naloxone, so the naloxone can mayyybe blunt the initial euphoria of a bupe injection to some extent by competing for the same receptors, but not send you into withdrawal. That's why a lot of people are saying that the primary reason for adding the naloxone was less about deterring people from injecting it, and mostly about having a patentable "new" drug.

This was amazing info. Thank you. I do have some questions though. If I understand you correctly, the reason so many of the more educated people in here seem to believe that the naloxone component is virtually inconsequential is because the oral bioavailability (post first pass obviously) is virtually nill ( 1% )

1 - Fine, makes sense if you're taking naloxone as a pill. But suboxone is administered as an intra-mucosal strip that dissolves. Or a sublingual version called Zubzolve (sp?) which is much better because it comes in like 1mg (possibly smaller) increments. Either version skips first pass. So what's the bioavailability of naloxone then? And what about the buprenorphine?

2 - And why in God's name would they combine an antagonist and a full agonist Targon, Valoron)? Is there a reason beyond preventing injection? Do you happen to know how much naloxone they put in each?

3 - You mentioned the naloxone perhaps blunting the initial euphoria of the bupe administration. For the life of me I've never detected even the slightest hint of euphoria on it. Not even a little mood elevation...or the initial energy boost like you get with, say, methadone. Nothing! I also believe that's at least 75% of the reason it's more effective than methadone at achieving long term sobriety. I literally dropped from 24mg of suboxone to 4mg in under a month. I dropped from 24mg to 16mg overnight, a weak later, dropped another 8mg, and roughly 2 weeks later I dropped to 4mg. Those are big drops that are usually not recommended but I gotta tell you, I literally felt nothing. No difference. When I got down to 4mg there were literally days where I'd simply forget to take it. Do a lot of people claim they get a sense of euphoria from suboxone?

 

[Hodor]

3 - You mentioned the naloxone perhaps blunting the initial euphoria of the bupe administration. For the life of me I've never detected even the slightest hint of euphoria on it. Not even a little mood elevation...or the initial energy boost like you get with, say, methadone. Nothing! I also believe that's at least 75% of the reason it's more effective than methadone at achieving long term sobriety. I literally dropped from 24mg of suboxone to 4mg in under a month. I dropped from 24mg to 16mg overnight, a weak later, dropped another 8mg, and roughly 2 weeks later I dropped to 4mg. Those are big drops that are usually not recommended but I gotta tell you, I literally felt nothing. No difference. When I got down to 4mg there were literally days where I'd simply forget to take it. Do a lot of people claim they get a sense of euphoria from suboxone?

That might also be the partial agonism talking.

Buprenorphine is actually pretty shit at activating your opiod receptors, it's just extremely good at getting into them in the first place.

So at low doses, when there's still plenty of receptors to go around? The high binding affinity more than makes up for the low efficacy, resulting in ~40 times the analgesic potency of morphine.

But as you increase the dose, you start approaching a point where the buprenorphine molecules start competing against each other for the receptors. Even if every opioid receptor in your body had a molecule of bupe stuck to it, it might not actually kill you, because buprenorphine's intrinsic activity is just that low. Typically, this point of diminishing returns seems to be reached past 4mg; there seems to be little difference between how much mu opioid receptor agonism you'd get from 8, 16 and even a 24mg dose.

(note that ultra-high doses of buprenorphine can nonetheless be valuable beyond their activity as partial mu agonists, as the compound is thought to act as an antidepressant by blocking "bad endorphins" at the kappa opioid receptors).

 

[Hodor]

This was amazing info. Thank you. I do have some questions though. If I understand you correctly, the reason so many of the more educated people in here seem to believe that the naloxone component is virtually inconsequential is because the oral bioavailability (post first pass obviously) is virtually nill ( 1% )

1 - Fine, makes sense if you're taking naloxone as a pill. But suboxone is administered as an intra-mucosal strip that dissolves. Or a sublingual version called Zubzolve (sp?) which is much better because it comes in like 1mg (possibly smaller) increments. Either version skips first pass. So what's the bioavailability of naloxone then? And what about the buprenorphine?

Sublingual doesn't exactly shoot the drug directly into your brain either. While the bioavailability of the naloxone is increased, it is still nothing to write home about. At least when what little naloxone arrives at the receptors has to compete with buprenorphine. But yeah, the whole thing being sublingual does kind of hammer home the point that the addition of naloxone to the formula was mostly about patent extension.

2 - And why in God's name would they combine an antagonist and a full agonist Targon, Valoron)? Is there a reason beyond preventing injection? Do you happen to know how much naloxone they put in each?

Valoron N is 8 mg of naloxone per 100 mg of tilidine.
100 mg of tilidine is equivalent to roughly 20 mg oral morphine.
For Targin, the ratio is 2:1, ex. 10 mg of oxycodone to 5 mg of naloxone.

As you can see, *those* are naloxone dosages you definitely wouldn't want in your bloodstream.

Anyway, your are of course right in that abuse prevention is not the only reason to do it - the naloxone is also supposed to compensate for the chronic constipation that often comes with high-dose opioid pain management, as the opioid antagonist effects stay confined to the bowels - think "reverse imodium" - without interfering with the pain-killing efficacy of the tilidine or oxycodone.
In the US, this might be accomplished by using polymer-bound naloxol ("naloxegol") or by the quaternary ammonium salt of naltrexone (which cannot penetrate the blood brain barrier due to its charged nature).

 

[Fuckupnomo]

Great question. I have a bit to say about this so I'll try to keep it pithy

Because, as a general rule, it's always better to be on fewer drugs than absolutely necessary. Suboxone has the buprenorphine and the naloxone. The Bup being the far more concerning of the two (long term at least) in terms of side effect profiles and even psychological state (mood level fluctuations by way of opiates' effect on neurotransmitters). I wish more people...no...more DOCTORS understood that you don't want to be on suboxone long term. Google the horror stories. My recommendation is to do suboxone for a couple weeks,, maybe a month. However long it takes before you can finally sleep decent again at night. THen switch to vivitrol to ensure you don't break and call your dealer for those fragile next few months. Maybe up to 6 months. By then, you're as clean as you're ever gonna get. You honestly won't need the buprenorphine after that anyway, and because you're on it such a short time you can walk off from 4mg and barely feel a thing in my experience. Long term bup users, on the other hand, have a horrendous time kicking it in my experience.

So you've been on suboxone 6 years? What's your dose? Has it been fluctuating much or decreasing over time or have you been on the same dose the whole time?

I consider myself clean now that sub has allowed me to come off and stay off everything I was doing. It’s the only thing i take and I have no side effects other than being able to live a clean life. After two months or so I no longer felt the bup at all- it was and continues to Be/feel like any other sober/clean person. I drive and work like every other ‘normal person’. I don’t know about vivitrol so I can’t speak to it unfortunately. I actually never heard of it until spending time on the site yesterday. It may have to do with what city you’re in and what’s being used etc. I live in Toronto.
I was using 50mg tram tabs taking around 30 pills a day so that’s 1,500mg- I never had a seizure but tbh I wouldn’t have chosen to be using tramadol, I came off 2 years of high dose morphine and tramadol was what I happened upon cuz of access.

I started on 8mg sub- but a different doc, who is just an amazing being and who i obviously switched clinics for and Is still my doctor - recognized I was still experiencing withdrawal, so I went up to 12mg and I felt better than I had in a very long time.
Long term- I don’t worry about being on sub and I don’t think or worry about coming off it because for the past six years it’s stabilized my life back to a normal state. Actually, I don’t see why I need to come off it at all tbh. For every google horror story there is an opposite, beautiful, life saving and life affirming story. But one aspect of my ability to not worry about it long term is that my work insurance covered sub (after much persuading from my doc) because sub is EXTREMELY expensive, like ridiculously expensive.
Over the years I naturally decreased to 8mg without feeling a thing, and that’s where I am now.
I get frustrated when people say ‘your just shifting your addiction from one thing to another’.......but for me and many others It’s everything surrounding and attached to the drug (whether it be morphine or tramadol) that causes all the fucking problems- the lifestyle, the lying and hiding and stealing and manipulating, the ups and downs of not only stability of relationships (obvi caused by me) but physiologically constantly going through withdrawal when I ran out and then overloading my body when I had tons- usually a biweekly cycle and it was hell. Bup does not ravage your body, mind, and everything attached. So I have zero reason to ‘kick it’ - I love that no matter what opiate I take, and trust me I’ve tried, I don’t feel it at all! It’s like armour for me. For me to feel a high I would have to be off of sub for at least 4 days to a week and by then the craving and/or opportunity is long gone.

The problems that were there before the tramadol and morphine from which I relapsed on (10 years of consecutive clean time) were still there once I transitioned and stabilized on sub but I was able to try and deal with them with a mind that was cleanly mending.

I may sound like an advocate for sub lol but truthfully it’s just because I get defensive- it saved my life n all. And I happily stay addicted to bup because it’s the only thing that’s allowed me to live without all other opiates that ruined my life a hundred times over.

Okay now that I’ve basically written an essay I should finish, also because my alone/chill time has been disrupted by my kid

Goodluck!

 

[Shant]

I consider myself clean now that sub has allowed me to come off and stay off everything I was doing. It’s the only thing i take and I have no side effects other than being able to live a clean life. After two months or so I no longer felt the bup at all- it was and continues to Be/feel like any other sober/clean person. I drive and work like every other ‘normal person’. I don’t know about vivitrol so I can’t speak to it unfortunately. I actually never heard of it until spending time on the site yesterday. It may have to do with what city you’re in and what’s being used etc. I live in Toronto.
I was using 50mg tram tabs taking around 30 pills a day so that’s 1,500mg- I never had a seizure but tbh I wouldn’t have chosen to be using tramadol, I came off 2 years of high dose morphine and tramadol was what I happened upon cuz of access.

I started on 8mg sub- but a different doc, who is just an amazing being and who i obviously switched clinics for and Is still my doctor - recognized I was still experiencing withdrawal, so I went up to 12mg and I felt better than I had in a very long time.
Long term- I don’t worry about being on sub and I don’t think or worry about coming off it because for the past six years it’s stabilized my life back to a normal state. Actually, I don’t see why I need to come off it at all tbh. For every google horror story there is an opposite, beautiful, life saving and life affirming story. But one aspect of my ability to not worry about it long term is that my work insurance covered sub (after much persuading from my doc) because sub is EXTREMELY expensive, like ridiculously expensive.
Over the years I naturally decreased to 8mg without feeling a thing, and that’s where I am now.
I get frustrated when people say ‘your just shifting your addiction from one thing to another’.......but for me and many others It’s everything surrounding and attached to the drug (whether it be morphine or tramadol) that causes all the fucking problems- the lifestyle, the lying and hiding and stealing and manipulating, the ups and downs of not only stability of relationships (obvi caused by me) but physiologically constantly going through withdrawal when I ran out and then overloading my body when I had tons- usually a biweekly cycle and it was hell. Bup does not ravage your body, mind, and everything attached. So I have zero reason to ‘kick it’ - I love that no matter what opiate I take, and trust me I’ve tried, I don’t feel it at all! It’s like armour for me. For me to feel a high I would have to be off of sub for at least 4 days to a week and by then the craving and/or opportunity is long gone.

The problems that were there before the tramadol and morphine from which I relapsed on (10 years of consecutive clean time) were still there once I transitioned and stabilized on sub but I was able to try and deal with them with a mind that was cleanly mending.

I may sound like an advocate for sub lol but truthfully it’s just because I get defensive- it saved my life n all. And I happily stay addicted to bup because it’s the only thing that’s allowed me to live without all other opiates that ruined my life a hundred times over.

Okay now that I’ve basically written an essay I should finish, also because my alone/chill time has been disrupted by my kid

Goodluck!

Hey listen, I'm with you on subs 100%. I was on methadone and heroin every single day for nearly 15 years now. NOTHING has worked until suboxone came along. It's a miracle drug in many ways. I also agree with you that the whole "you're trading one addiction for another" argument doesn't really apply to your case. WIth every other opiate, you're not clean until you're actually off all opiates. IE for methadone, I don't care if you're only on 1mg, you ain't clean til you're down to zero. But with suboxone it's a little different. It's almost like you're clean as soon as you start taking it. It literally gives you none of the things you want as a drug addict. There's no high, buzz, euphoria, nothing at all. So it's VERY easy to walk off suboxone if you don't use it for more than a month or two.

Look, if it's working for you, who the hell am I to tell you what to do? You got your life back, I assume you work for a living, maybe even have a wife/girlfriend. etc...why risk all that? I get it. I'm just saying, you might not need the bupe as much as you think. Consider straight naltrexone, whether it's Vivitrol (a once a month injection) or the 50mg pills. I'm glad you haven't experienced any major issues healthwise in 6 years. Have your doc check out your stomach lining though, just to be sure. If you have acid reflux, or really any stomach issues, the bup is a prime candidate. I just wanna see you and all of us do well, friend.

 

[Shant]

Oh btw, I inducted onto the suboxone yesterday. I had taken 100mg of tramadol 6 hours earlier, and heroin appx 24 hours earlier. Absolutely no PWD. Well...I felt shitty for about 45 minutes, had a bout of diarrhea (sorry) and boom it was gone. Does that mean tramadol doesn't cause PWD? No, I think 100mg is too small a dose to be able to say that. I will say that at 16mg of suboxone, I pop 3 tramadol (150mg) and honestly do feel em. What do we make of that?

Anyhow, feeling good on day 2. My legs ache for some reason, but no real symptoms beyond that. On my way to true sobriety, and the vivitrol shot is exactly 12 days from today. All I have to do is stay clean between now and then. Wish me luck