the Naloxone in Suboxone is active!

[Hammilton]

you won't induce withdrawal if you're on suboxone and take another opiate.

god people are slow. this is so simple.

If your receptors are full of a full agonist, buprenorphine will dislodge and replace it, triggering withdrawal.

if your receptors are full of a partial agonist, taking a full agonist will result in blunted or even eliminated effect because it is unable to dislodge the buprenorphine and get to the receptor. It won't cause withdrawal, obviously.

Ask yourself next time: why would taking a pure agonist ever cause withdrawal? The answer is that it won't. Only taking a partial agonist or antagonist will induce withdrawal.

i can't believe I'm actually explaining this.

 

[oxymoron310]

Why is Naloxone in Suboxone -Period-???

 

[seep]

Why is Naloxone in Suboxone -Period-???

someone's gonna maybe write a book about this one day and sell tens of copies. It was intended by the marketer of Suboxone to give the product an IV-resistant appearance. Perhaps some of the data that got into its NDA (new drug application) was falsified, or perhaps researchers were enamored by the concept of a ROA-sensitive Narcan bomb and skewed the results in subtle ways.

Either way Hammilton makes a good point. Maybe if OP would help his impassioned cause by posting links to the PDFs he's read...

Here's an idea for a trial: randomized, double-blind, double-arm, double-crossover discrimination study of Suboxone vs. Subutex IV'd into people physically dependent on a full agonist. You'd have to make it attractive to the subjects somehow (I'd do it for a grand and you can probably bargain me down to half of that)

who the fuck am I kidding: I'd do it for a bill

btw oxymoron the NDA (24 pdfs!) is on the FDA's website here

 

[P A]

Why is Naloxone in Suboxone -Period-???

Reckitt Benckiser's [rather stupid] rationale for naloxone's inclusion in its useless, knockoff repatent 'formulation' was the deterrence of intravenous abuse by the inclusion of a potent opioid antagonist that would selectively block the action of the active compound (buprenorphine) only when injected. Of course, the drug would have to actually work when ingested orally, as was intended by the manufacturer, so rather than tossing in an orally active antagonist (e.g. naltrexone), they ingeniously added the IV-only naloxone, a drug generally reserved strictly intravenous reversal of opioid overdose in hospital settings.

Though theoretically sound and practically feasible for clinical application under other circumstances, such as in the use of lower-affinity opioids like morphine or hydrocodone, this strategy is considered laughably superfluous by anyone with preliminary knowledge of the endogenous opioid system and respective drug pharmacokinetics at the site of the Mu receptors. Buprenorphine's binding affinity for the aforementioned protein isoform is so astronomically high when compared to other commercially available oral opioids that naloxone, even when injected in massive doses, is only partially (at best) capable of reversing its action. To repeat, this issue is due solely to the comparative affinities of the drugs at the active site, and cannot be remedied by an adjustment in dose.

In summary: the Suboxone brand of buprenorphine should never have been approved in its current state, nor should it ever be prescribed over alternative, less expensive brands of bupe, as its 'innovative formulation' (read: sales pitch) is essentially worthless and based upon what amounts to idiotic pharmacologic oversight on the part of Reckitt Benckinser and, further, speciously predicated upon one can only assume to be the incompetence/ignorance of the governmental agencies that approved it and the clinicians who prescribe it.

...unless you already knew all that shit and were just asking rhetorically.

researchers were enamored by the concept of a ROA-sensitive Narcan bomb and skewed the results in subtle ways.

Or, given the track record of most pharma-funded biomedical research, not-so-subtle ways. Deliberate data falsification and shoddy methods are easy to pass off so long as the bulk of research goes unpublished whilst spinning a bullshit yarn to upper management involved in the actual process of 'drug development.'

 

[oxymoron310]

Thank you Seep and P A, both answers were very informative.

 

[Hammilton]

Maybe if OP would help his impassioned cause by posting links to the PDFs he's read...

No, I would suggest everyone who has any thoughts about this period to read them all. I've only started, but I'm not reading that naloxone is inactive or that there's no effect on preventing IV use of buprenorphine+naloxone combinations. Is it all great research? not exactly, but there's definitely something to it.

 

[Slapdragonx]

I only read one and it indicated that bupe with or without naloxone makes no difference in choosing money or drugs. But naloxone decreased the high of bupe, but not below the placebo level. Interestingly naloxone and bupe made the patient pupils more pinpoint than bupe alone.

For most intentions the naloxone can be considered inactive. Other then perhaps purely oral consumption (not sublingual).

 

[P A]

No, I would suggest everyone who has any thoughts about this period to read them all. I've only started, but I'm not reading that naloxone is inactive or that there's no effect on preventing IV use of buprenorphine+naloxone combinations. Is it all great research? not exactly, but there's definitely something to it.

I did (fulltexts for some, anyway; I'm not paying money to access every one of those unlinked documents, the titles of which he ostensibly posted in support). And even after setting all concerns regarding quality aside, none of them "clearly show" anything, as Dr. Fuckwit so adamantly assured. Apart from the first and the third of them, I gathered from what little I had available that these papers either fail to present anything particularly compelling, and/or are rendered slightly fucked by the poor conclusions of the authors. But I'm not really capable of commenting with full confidence, since the full papers were never linked.

Nevertheless, when considered in the light of other, more relevant findings from research/observation that isn't so heavily influenced by author bias and severely limited by sample size and other confounds (like, for instance, the well-known clinical issue of the often-insufficient reversal of bupe-induced respiratory depression by naloxone), the notion that the 4:1 Suboxone formulation presents any practically relevant impediment to IV abuse is still as ridiculous as it was before he posted the titles of his supposedly unassailable 'PDFs.'

I would take the time to criticize the first paper in detail, but I'm severely lacking in that resource at the moment, and can't afford to take tens of minutes out of my night to belabor what I already consider to be a moot point.

As for naloxone's sublingual bioavailability - it is, as mentioned, piss poor (and still irrelevant):

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T63-4BWFBG6-5C&_user=10&_coverDate=02/28/1990&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1560822702&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=deca1e906335fe3d87d84b34f62ff4cf&searchtype=a

 

[homeydontplaythat]

i dont think anyone meant that it was inactive, just that bupe binds more aggressivley to teh receptors than nalaxone. of course its active, just isnt competitive enough for the site.

 

[seep]

Well, for the sake of wackiness:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2094723/pdf/nihms30198.pdf/?tool=pmcentrez

(2007 full text of a study in which some of the methadone-dependent subjects tolerated 32/8 mg doses of buprenorphine/naloxone without showing signs of precipitated withdrawal!

and for equipoise, this study references a dimorphism in mu receptors:

NSFW:

Adv Exp Med Biol. 2008;605:486-91.

Naloxone reversal of opioid-induced respiratory depression with special emphasis
on the partial agonist/antagonist buprenorphine.

Sarton E, Teppema L, Dahan A.

Leiden University Medical Center, Department of Anesthesiology, 2300 RC Leiden,
The Netherlands. [email protected]

Buprenorphine is relatively resistant to reversal by naloxone. We tested the
effect of various doses and infusion schemes of naloxone on buprenorphine-induced
respiratory depression and compared the data with naloxone-reversal of morphine
and alfentanil-induced respiratory depression. Both morphine and alfentanil were
easily reversed by low doses of naloxone (0.4 mg). Increasing doses of naloxone
caused a bell-shaped reversal curve of buprenorphine with maximal reversal at
naloxone doses between 2 and 4 mg. However, reversal was short-lived. The
bell-shaped reversal curve may be related to the existence of two mu-opioid
receptor subtypes, one mediating the agonist effects of opioids at low dose, the
other mediating antagonistic effects at high dose.

I posted some case reports somewhere on Bluelight that cite continuous IV naloxone infusion (via a pump) as ER treatment for buprenorphine overdose. Can't find them now.

ps: potentially stupid question: is this thread about psychoactivity, central activity, or any detectable biological response? I mean, a kiss on the cheek from mom is active.

---

Oh yeah, in 1996 UC San Francisco did the study I suggested earlier in this thread:

Clin Pharmacol Ther. 1996 Jul;60(1):105-14.

Buprenorphine and naloxone interactions in opiate-dependent volunteers.

Mendelson J, Jones RT, Fernandez I, Welm S, Melby AK, Baggott MJ.

Drug Dependence Research Center, Langley Porter Psychiatric Institute, University
of California, San Francisco 94143-0984, USA.

OBJECTIVE: Sublingual buprenorphine appears useful in the treatment of opiate dependence. A combination sublingual dose of buprenorphine and naloxone could have less potential for parenteral use by opiate-dependent individuals. To estimate the abuse potential of a combination formulation, we assessed the parenteral effects of a buprenorphine and naloxone combination in untreated heroin addicts. METHODS: Eight healthy, opiate-dependent daily users of heroin were given, under double-blind conditions on four separate occasions, either (1) 2 mg buprenorphine, (2) 2 mg naloxone, (3) 2 mg buprenorphine and 2 mg naloxone combined, or (4) placebo as a single intravenous infusion during a 30-second interval. Opiate agonist and antagonist physiologic and subjective effects were measured. Data were analyzed by analysis of variance. RESULTS: Buprenorphine increased opiate intoxication and relieved withdrawal. The buprenorphine and naloxone combination precipitated opiate withdrawal and was unpleasant and dysphoric in all subjects. Fifty percent of the subjects were unable to distinguish between naloxone alone and the combined medications during the first hour of testing. CONCLUSIONS: The buprenorphine and naloxone combination has a low abuse potential in opiate-dependent daily heroin users.

 

[SubDude]

Geez... this has been debated and argued on just about every drug forum I've seen and thats quite a few. To say naloxone is "active" is meaningless without defining exactly what active means in practical terms among maintenance users. I've never used bupe alone... only with the naloxone 4-1 as in suboxone. Most of the people [posting] who have tried both report anecdotally... no difference. However there are some who say bupe is better w/o nal.

I was on MMT for over 15 yrs and switched to subs about 2 yrs ago and have never liked it. I don't know if it's because of length of use or whatever?? Can we get some more thoughts from those with both bupe and subs experience?

I'm currently on .5mg SL and essentially feel no different than when I was on
12mg... I tapered slowly. However, I haven't been able to quit. I simply take it to avoid WD's and get no where near the pleasure from life as I did on MMT.

 

[drminaq]

I am absolutely certain that for some people, I think we are trying to make generalizations about how a drug works when we are individual and have a subjective experience. The human body is pretty elastic, I think it safe to say.
Personally I feel quite a bit of the naloxone in suboxone. I agree that Bupe is not great for pain or euphoria. But I have been on Suboxone since it became available in Canada, Subutex is not available in this country.
I suffer from Irritable bowel and feel that Methadone was great for my persistent runsand chronic pain, while subs were as effective as Immodium (for me it is useless). I still need to take an NSAID and norflex to combat my pain when on suboxone.
I feel the Naloxone in subs in a different way as well. I take Vyvanse for ADD if I were to take my suboxone during the day it would make the Amphetamine, essentially completely inactive. But if I "remove" the naloxone using the isopro alcohol method, I can dose in the morning and even take the bupe every other day.
Personally, I will run to the toilet with 1 hr of suboxone dosing, If "remove the naloxone" I don't. I believe that for some people the naloxone in subs can be quite "active' if taken as prescribed.
I haven't the balls to bang one but I think it would be asking for a taste of hell. But that is my subjective experience as one of the first people in this country to take suboxone.

 

[Robf11]

Ask yourself next time: why would taking a pure agonist ever cause withdrawal? The answer is that it won't. Only taking a partial agonist or antagonist will induce withdrawal.

I have an answer to this question

If the agonist in question has a lower affinity(binds more readily to the receptors) but also has a much weaker activation potential than the agonist you typically use

So let's say you normally take heroin and it really activates those receptors, let's assign it a number 10 for arguments sake,

but then you take a new opioid we'll call it himoin with a much lower affinity so it beats out the heroin to the receptors however this himoin has a much weaker activity on each receptor, it's only a 1 compared to heroin's 10

Depending on where your tolerance is those 1's added up might just not bring you over your withdrawal level

I like numbers so let's say you normally need 400 units to bring you out of withdrawal, that would only require 40 receptors to be activated by the heroin but to reach the same level you'd need to activate 400 receptors with the himoin or ten times as many receptors,

so unless you have that many or more receptors available so that you can reach that level you will find yourself going into withdrawal despite having taken a full agonist, assuming such an agonist exists

*numbers used are for illustrative purposes only

 

[SpiralusSancti]

Naloxone with bupe IS active via sublingual or snorted, enough to feel difference between pure bupe and mixed with naloxone if you are opiate naive but usually not enough if you are opiate junkie starting to use text or xone.

 

[Xorkoth]

was reading over some these posts and i have a question for you all.. I saw u said its a bad idea to Sublingually take suboxone and then use any opiate. (you're supposed to wait until a full withdrawal, 24hrs correct?)... but how long after u take ur last dose of suboxone can u take an opiate without enducing a withdrawal??

Its been about 40hrs for me since the last time I took a 4mg suboxone, and im curious if eating 2, 10mg methadone and a 2mg klonopin would help me out a bit..

Ive heard from over the site people use Benzo's to get through opiate withdrawals. But im 40hrs now w/o and Suboxones , just curious. Thanks.

I know this is an old post, but I see people asking this all the time. Bupe only causes PWD if you take bupe while having a full agonist opioid in your receptors, and then only if you[re dependent on the full agonist. It does NOT work in the opposite direction, ie, if you're on bupe, and you take heroin, you will never experience precipitated withdrawal. Instead what will happen is... absolutely nothing. The heroin simply won't be able to displace the bupe, and so it will be as if you didn't take anything. You'll still be on bupe.

This is because bupe is a partial agonist, rather than a full agonist, but it has an incredibly high affinity for the receptor. This means that buprenorphine will kick just about any opioid out of your receptors, or, in the case you are already on bupe, it will not allow virtually any other opioid to displace it. So, if you're dependent on a full agonist opioid, and you take bupe, and you still have any of the full agonist occupying your receptors, it will suddenly get kicked out all at once, and the bupe will fill your receptors instead. And since bupe is a partial agonist, if you're dependent on the full agonist, you will suddenly no longer have the necessary opioid in your receptors to avoid withdrawal, since partial agonists do not produce as strong an effect as full agonists. It has nothing to do with the naloxpone. Naloxone is an antagonst, so will also cause PWD, but bupe has a higher affinity than naloxone, so if you take both at once, the naloxone will no be able to bind, and will have no effect.

The naloxone in suboxone was added, ostensibly, to make it IV resistant, but in reality, it doesn't do that. For proof of this, try IVing suboxone. It works fine (except don't do that actually, because IVing pills is dangerous, and bupe is quite damaging to the veins). My guess as to the rea reason they added naloxone twofold: it sounds good for a doctor to be able to say "you will feel like shit if you IV this, so don't", also also because they are able to patent bupe + naloxone, whereas bupe can't be patented alone (anymore).

Two other things of note. First, if you are not actually dependent on opioids, and you take bupe after taking a full agonist, you won't experience precipitated withdrawal. The bupe will still displace the full agonist, but the result will be that you will suddenly stop being high on the full agonist, and will instead be on bupe. If you wouldn't experience withdrawal once the opiate you're taking wears off, then you won't experience withdrawal from taking bupe.

The other thing is that bupe won't cause PWD if you take it while you're addicted to, and on, a partial agonist. This is because if you kick a partial agonist out and replace it with another partial agonist, you've still got a partial agonist on board and you will not be lacking what your receptors need. The most common example of this is kratom. You can take bupe before going into kratom withdrawal and you'll be fine.

 

[SpiralusSancti]

if you're on bupe, and you take heroin, you will never experience precipitated withdrawal. Instead what will happen is... absolutely nothing. The heroin simply won't be able to displace the bupe, and so it will be as if you didn't take anything. You'll still be on bupe.

Well that’s true in normal doses but given that people on opiod antagonists manage to get at least somewhat high pushing dose waaaaaaay over safe levels makes me thing same can be done with bupe.

This is purely theoretically as people “breaking block” from antagonists (and I would guess same for bupe) manage to do that only with a dose that’s on border of killing them and some people did die trying to do that while trying to cure junkies with “forced blocks” were hip in some countries. What mechanism killed em, it can be speculated, maybe effects on something other than what naloxone/naltrexone affects, maybe it’s dose where H becomes toxic to either body or brain in some other way….

 

[Fertile]

Yeah - but buprenorphine has a higher affinity for the MOR receptors than naloxone - which is why naloxone is NOT indicated for a buprenorphine overdose. It is a competitive antagonist, but I think it fair to say it HAS been trialled for a long time.

Of course drug manufacturers are keen to assert some action.... or it would make their patents totally invalid. They HAVE to claim an activity just to make a profit.
Maybe it has some action on a minority of people - but don't trust a vranyo Powerpoint over independent articles. I mean, naloxone only works for 20 minutes so don't claim some major alteration. I know enough people who shoot bup with no issue to suggest that it isn't totally accurate. But it may differ from person to person - those Ki values are close.