Hi all,

I was asking the same question numerous times in the boards, then I realized I had the answers I needed on my bookshelf (silly me!) in one of my favorite books. Guess I was too hazy to remember. I spent last night catching up on my reading. I'm sharing it with you.

All excerpts to follow are from 'A Primer of Drug Action' by Robert M. Julien, M.D., Ph.D. It is unbiased and incredibly informative. Anything in parenthesis are my comments, not his.

Here we go:

Buprenorphine has a half life of 37 hours. (this we know...but please indulge further explanation.) Half-life is based on 6 half-lives(!).

This means that in 37 hours, 50% of the original dosage will remain in the body. In another 37 hours, 25% will remain; another 37 hours, 12.5% remains; another 37, 6.2% remains; 37 more, 3.1% remains; and finally the last 37 hours, 1.6% remains. (Wow!)

Sublingual naloxone has a half life of 1.1 hours. (So, the naloxone is negligible by comparison. It is eliminated FAR more quickly than the buprenorphine in Suboxone.) Sublingual naloxone is poorly absorbed.

(Next):

We've all heard of the partial agonist (which means 'activates'), pure antagonists (which means 'inhibits'), mixed agonist-antagonist (yuck), and (our favorites) the full agonist (morphine, H, those pills we love, etc.).

Naloxone is a pure antagonist which means it blocks the access of other opioids. (To be a bit more technical), it blocks access of both endogenous ligands (here, endorphins), or an exogenous drug (e.g., any morphine derivative -- other opioids) either present in the body -- precipitating withdrawal -- OR ADMINISTERED WITH OR AFTER THE ANTAGONIST -- RESULTING IN NO EFFECT OF THE AGONIST. (**That's what I wanted to know.**)

A partial agonist (bupe) binds to the opioid receptors but has a low intrinsic activity (low efficacy). It therefore exerts an analgesic effect, but such an effect has a ceiling at less than the maximal effect produced by a pure agonist opioid. Buprenorphine is the prototype partial agonist opioid. When administered to a "naive" individual, analgesia is observed; when administered to an addict, however, a blockade of the pure agonist can occur and withdrawal can be precipitated. Compared to a mixed agonist-antagonist, the partial agonist buprenorphine binds to all three types of opioid receptors, albeit with lower efficacy.

Buprenorphine is a newer, semisynthetic, partial agonist (at the risk of being redundant) opioid whose action is characterized by limited stimulation of mu receptors, which is responsible for its analgesic properties. As a partial agonist, however, there is a ceiling to its analgesic effectiveness, as well as to its potential for inducing euphoria (don't I know it!) and respiratory depression.

Bupe has a very long duration of action (24 hours) because it binds very strongly to mu receptors, limiting its reversibility by naloxone when reversal is considered necessary. (Naloxone can stop an overdose of opiates if caught in time.)

The drug can be given by oral, parenteral, or sublingual routes. At LOW doses, buprenorphine can substitute for morphine (in morphine-dependent individuals -- this means you --- H turns to morphine in the body) and it is analgesic (in nontolerant individuals). However, higher doses do NOT substitute well for morphine, and they can precipitate withdrawal symptoms. (So, I guess, for us, less IS more!)

(CAPS in the above writing were added by me.) Sorry for any redundant material, but I was picking and choosing from various parts of the book.

I highly recommend the above referenced book if you want a better understanding of how drugs work. Get the most recent edition.

A simpler, great book, also (another fave of mine) is called, "Buzzed: Just say Know" by Cynthia Kuhn, Scott Swartzwelder, and Wilkie Wilson, of the Duke Univ. Medical Center. It's the truth, not government propaganda and bull****.

Hope you got this far...[].

Hope you dont mind me stepping in on your info posts...just want to make sure we are posting correct information..

TWO questions about the paragraph below...It says the drug can be given "orally"?? Dont know if they are speaking of the naloxone or the bupe? As far as I know, neither one of them are effective at all if taken orally.

Other question...if someone were to take too much bupe. Would giving an injection of Narcan(Naloxone) knock the bupe off the receptors? My guess is there is probably no such thing as an OD on bupe because in high doses it becomes an antagonist. Right or wrong?

~~~Do the right thing and risk the consequences~~~Spring~~~

Hi Spring,

I need to edit this if it's being misunderstood.

I was typing directly from the book and it says bupe CAN be given orally, parenteral, or sublingual. Hmmmm.

(Gotta proofread what I write!)

Secondly, if one happened to OD on bupe (any drug can become toxic in the body if enough is ingested, injected, etc.), Naloxone is limited in it's ability to stop that OD because of bupe's strong affinity to MU. The parenthesis next to that was just me explaining that Naloxone, or Narcan, are used to stop an OD from other opiates.

I found this very interesting reading--thanks for bringing it to our attention (boy, you know you are really sick when you find stuff like this "interesting," but there you go...).

That brings up another question though--how hard IS it to OD on Bupe? As has been suggested, at a certain dose, Bupe may stop acting as an agonist and start acting as an ANTagonist. One of its annoying little quirks.

So, theoretically (let's hope it's only that), if one were to ingest still MORE Bupe, would its antagonist action bring you back, in effect, to where you started?
In other words, could you do so much that the antagonist effect would exactly match the agonist effect, meaning--what? You feel nothing at all?! So you come full circle back to normal!?
In which case, you could do still MORE (you know how we junkies are!), and you would start to get high again!! And more, and MORE until--!! You know what--the ANTagonist (the little bastard!) starts klcking in again, and you get caught up in its downdraft and go sailing right back to ground zero.
My god, it's an endless Buprenorphine cycle! Like one of those really bummer acid trips where the whole blasted Reality question comes on really intense and you suddenly "see" (in the Don Juan sense) for the first time with electrifying clarity that existence is nothing more than a great big cosmic whiz-bang, an endless concatenation of identical such 'mystic visions,' perpetrated on us by we never find out who and which goes on and on in countless endless, agonizing cycles and recycles of birth, life, death, rebirth, life, death, rebirth, life, death, rebirth and continues on and on for eon after measureless eon down to a sunless sea of madness and where's the stop button I want to get off... So on and so on.

So-o-o, the hapless addict could, would, and will presumably carry this nasty business on and on until he's wrung out the last bloody nickel from his bank account, having gone through whole kilograms of Buprenorphine while the its maker's stock climbs to all-time highs and the cooly ecstatic CEO is having fresh cases of Cuban cigars delivered to his yacht for the fundraiser which will help keep our favorite President in office another four years.

And all for what? A weenie little premature ejaculation of a "buzz" which you wouldn't wish even on that raunchy little 13-year-old niece of yours who sold you a large hunk of dandruff for crack.
Jesus, not to seem patronizing, but drug addicts are like, WAY ****ed up, you know what I mean? But wait a minute, maybe you don't, and it's my paranoia suddenly catching up to me! I'm thinking, "now when I click over this little software 'button,' will my message of hope and goodwill really go to those faithful few diligently trying to maintain discipline after connecting the chemical equivalent of a cattle prod to their opiate receptors a few thousand times too many, or does it get beamed directly to an antenna implant in John Ashcroft's brain and thirty seconds from now I'm gonna start hearing the wail of sirens, just like on that last STP trip, when I was sure THEY were coming for me???" ****, I don't know for sure anymore, but just to stay on the safe side, I want out of this script--must be a better way to live somewhere else.

See you all there? [?]
Tom

Whew!

That was some tangent there buddy!
I need to reread a few times before I absorb it...it's too early in the mornin'!

To answer the ODing on Bupe question: my understanding is that any chemical, if enough is ingested, can become toxic in the body. Whether or not you feel it (passes the blood brain barrier) is not relevant. Gotta protect that precious liver, as well as other organs. I have no idea how hard it is to OD on bupe, but I do believe it affects everyone very differently. So, I would guess that the potential overdose amount would vary as well.
Yes, at higher doses, depending on the individual, bupe does change it's function to antagonist. Odd drug. I'm sure 'they' will discover much more about it's action soon enough. Maybe something good, maybe something bad...we'll see.

Yep, Buprenorphine is one interesting drug.

It's strong affinity to the receptors make it such that it will bump off any full agonist opiate. It then will occupy that receptor for a LONG time blocking any opiate effect. The blockade effect may last 3-4 days depending on the dose.

Buprenorphine and ceiling.

Bupe has a low effect ceiling. After 2-6 mg SL the analgesic effects max out, then at 8mg the antagonist effect is the primary effect, making it impossible to feel any full agonist opiate effects. This blockade is VERY strong, and attempts to get "high" on opiates is futile. In larger doses Buprenorphine it's effects will eliminate what little analgesic effect it has and will do nothing except to extend the period of having to much bupe in your system.

Buprenorphine is almost impossible to OD from. The only cases are where people have taken high doses of benzo's with bupe.

RANT TO FOLLOW .. WARNING STRONG OPINIONATED TEXT TO FOLLOW

Now... Since the "man" is so paranoid you may get a buzz, regardless of how small, (unless it's booze and they get their tax money, or in your attempts to feel "normal" and you are taking antidepressants and giving $ to the legal drug cartel) They recommend maintenance doses of bupe high enough to make sure you are blocked.

They also feel low dose Buprenorphine maintenance will allow the addict to occasionally spike their bupe dose and get a SMALL buzz occasionally. At the higher doses you are tolerant and dependent, and above the analgesic dose level, so any attempt to spike your dose results in NOTHING. Sooooo at the expense of the patient in both $ (having to spend more on your bupe), higher dependence, longer and MORE difficult withdrawal, and side effects, the GOVERNMENT (and a lot of the medical community) is happier knowing you can't get a tiny "buzz". Oh, how thoughtful.

You would think they would call us patients since we are under medical supervision, but yet we are classified as quasi criminals even if we are dependent through no "fault" of our own, due to chronic pain management or other VALID medical reasons. We are addicts and junkies to them.

I am appalled at the lack of understanding by the medical community as to the extent of withdrawal Buprenorphine can cause. Maybe it's because they minimize the intensity of opiate w/d. They think it's just a bad flu that lasts a few days. So since w/d from H or Oxy is ONLY a bad flu w/d from long term Buprenorphine usage must be like a tiny cold and will be a non issue to them. I'll take the flu anyday instead of w/d.

If a non addict exhibited the protracted symptoms a person coming off a long term bupe usage did they would be PUMPING drugs into them. Why is it acceptable to treat them , but not understand and treat an addict suffering (and more so than most people getting antidepressants) for their pain?

WELL MY FRIENDS in the medical community, and the GOVERNMENT your lack of understanding screams IGNORANCE, and illustrates your underlying hatred + demonetization of people with this disease. In your lecherous greed for $ in a war against your own population, you are sucking the life blood from our economy, dividing the population, imprisoning sick people which results in a death sentence from AIDS and hep C obtained in YOUR prison system.

YOU should be held accountable for the inhumane atrocities against the people you incarcerate. But because you have demonized the addicts + recreational drug users you get away with it because they "deserve it". A 5 year sentence ends up being 5 years of torture and a death sentence because or your lack of compassion and inability to control what goes on in YOUR SYSTEM.

Now on to the BS of saying drug users are responsible for terrorism. Well listen pal, if you were not involved in this useless, vindictive "WAR ON DRUGS", accepted the fact they should be decriminalized or legal via prescription or other system, NONE of the effen $ would go into terrorism, so it's YOUR fault!

The drug cartels would disappear along with the associated violence. The crime rate would drop significantly, YOU WOULD LOOSE YOUR VIOLENT JOBS, the prisons would hole violent criminals not sick people, or recreational users (who by the way cause much less then 75% the problems than booze causes), their would be 100x (maybe 1000 x) more $ for treatment and recovery. To top it off the money would stay in the country, it would create legitimate non violent PRODUCTIVE jobs.

Ahhh, but since you want the $, love abusing people (because of your macho aggressive personality's) and the need for power, you will perpetuate a system that is failing miserably. At the expense of misery, suffering, torture, and murder, you get to bolster your pompous self righteous need to feel superior.


Who is societies REAL enemy here?

Oh why don't you continue your pristine life style, and go suck down a bottle of Jack Daniel's and go beat up your wife or a gay guy or an addict, or drive on the wrong side of the highway, or shoot down a plane full of nuns cuz you think they have drugs in the plane, bust some poor black kid for trying to make enough $ to eat, and the only way he can survive is selling drugs because YOUR system has caused all this BS.

Statistics tell the truth... Law Enforcement has the highest (or close to then highest) alcoholism rate.
Alcohol is directly responsible for over 75% of all violent crime.

So before you play the blame game go look in the mirror.

Humm, some resentment here.. A little pent up anger maybe, or is it frustration?

Way to stand up for what you think, Bup4! Glad not everyone's a chicken-sh** paranoic like me (bet that little antenna implanted in John Ashcroft's Mesozoic-era brain must really be tingling today, heh heh). What was that, a series of heavy knocks? Ohmigod, someone's at the door! It's not THEM, I hope, not already!? Sorry guys, I gotta go. (Wonder if I can fit in the broom closet?)
[8]

OH MY GOD!!!!

BUP!!!!!

BRAVO! BRAVO! BRAVO!!!!!!!

As you probably know, I am not even an addict. I'm just (according to the world, but NOT according to ME!) A MADWOMAN/FOOL who's spent almost two years now, just trying to understand my guy, who is fighting, fighting, fighting a heroin addiction.

I have been asking most of these SAME questions you've posed in your "rant", for a very long time!!! But everyone thinks I AM NUTS!!!! And I keep thinking "WHAT IS WRONG WITH THIS PICTURE??? Am I the only one who is thinking straight here?"

And mostly I am thinking "What the HELL is the medical and rehab industry DOING to all these people? And why doesn't anyone SEE any of this?"

There is NO ONE on this site, whom I have met, whom I don't think deserves more RESPECT, more DIGNITY, and more CARE from this damned world.

But all ANY of you get is LESS and LESS and LESS...

John, you have NO IDEA how I cry for all of you! You have NO IDEA how tremendously I admire all of your COURAGE! And you have NO IDEA how puny and helpless I feel to do a durned thing about anything.

If I am a person working on the periphery of the medical profession, and I am absolutely straight and sober, and I have 14 years of University education behind me, and NOBODY WILL LISTEN TO A WORD I SAY... and NO ONE WILL GIVE ME A STRAIGHT ANSWER to any question I pose on Kasey's behalf...

ACK! John, I guess all I am saying is I KNOW and FEEL your frustration, every single day, my friend!

And as sober/straight, boring, "Ms. Respectability" as I am, I THINK YOU ARE TOTALLY RIGHT!!!!

Absolute LOVE AND RESPECT to you, SIR!
GK

Just now read this.....Come on John, don't be shy. Speak up about what bothers you bro.

Seriously tho...you pretty much said it all....about all I can add is


A M E N

B R O T H E R !!!


Ohhh and Tom, loved your post...you paranoid-ly funny guy you!.

About the gov't:

When I was in college all of my papers had to do with drugs and the gov't or drugs and society in general.

Scary stuff!!

There is a book called: "Acid Dreams: LSD, the CIA, and the 60's Rebellion" by Martin A. Lee & Bruce Shlain. Well, that was an eye-opener. The events that took place are incredible and frightening. Good for instilling paranoia! This book examines how the CIA used LSD on unwitting participants right here in the good ol' US of A.

Also, another great one is called, "The Shadows of Power: The Council on Foreign Relations and the American Decline" by James Perloff. Now, this is not about drugs, is a dry read, but fascinating. Every item in the book is referenced in the Library of Congress. It will just blow your mind. When you learn who really runs this country things make a lot more sense. For many years, this book was VERY hard to find. Now, for some reason, it's on Amazon.com. You'll never look at the CFR the same way again (not that you've ever looked at them, I know I hadn't!).

Check them out on amazon.com. Please, if you read them, or have read them, let me know your opinions. Thanks!!

Research into Buprenorphine-Naloxone Combo Raise Questions of Safety, Ethics
by Dr. Andrew Byrne, General Practitioner (NSW, Australia)
*Buprenorphine and naloxone co-administration in opiate-dependent patients stabilized on sublingual buprenorphine. Harris DS,
Jones RT, Welm S, Upton RA, Lin E, Mendelson J. (2000), Drug and Alcohol Dependence 61:85-94.

This exhaustive and informative trial paper* on the co-administration of naloxone and buprenorphine tells us that a ten-minute IV infusion of the combination did not cause withdrawals in the subject patients, who were heroin addicts stabilised (sic) temporarily on buprenorphine maintenance 8 mg.

If I have understood correctly, this work has not supported the combination as being more or less “abusable” than simple buprenorphine on its own in such subjects. It has demonstrated that the naloxone is partially absorbed with 10% bioavailability and at least one objective physiological change (pupil size) in the subjects given it “blind” with their buprenorphine. The combination did, however, abolish cravings in the same way as the pure drug.

We know that if heroin addicts use buprenorphine (even without naloxone) they are likely to experience withdrawal symptoms on occasion and sometimes these will be very severe, due to the antagonist properties of the drug.

Regarding buprenorphine maintained patients, the authors state: “IV buprenorphine and naloxone produced subjective effects similar to those of SL [sublingual] buprenorphine and did not precipitate opiate withdrawal.”
It appears that some of the trial subjects may have had to return to street drug use after being released from this two-week trial. There are only limited chances of receiving agonist treatment in some areas and this is a major ethical dilemma for such research in America.

In my own practice in Sydney, I have prescribed buprenorphine (alone) for five heroin dependent patients, all of whom had failed at many previous treatments, including methadone. The results have been extremely positive and the patients are all most grateful for this innovation. They all stabilised (sic) on low doses and ceased other opioid use. It reminds me of the initial patients I had on methadone more than 15 years ago.

My own feeling is that the addition of naloxone is questionable and derives from motivations unrelated to ethical medical practice but as part of a law enforcement and “big-stick” approach.

There are unknown dangers of adding naloxone, so these must be balanced against KNOWN, and not just theoretical, benefits.

We do not know whether the combination is likely to solve “diversion” problems. The theory seems to assume patients are inherently dishonest, and this could add to the pre-existing stigma of addiction.
Also, the “punishment” strategy is known to generally be ineffective in this field.

Where buprenorphine is supervised like methadone (as in the new Australian proposals), such arguments are only academic since dispensed doses would be exceptional.

Good U.S. research also indicates that most diverted methadone is taken by addicts who would be assessed as appropriate for treatment, meaning that improving access and treatment quality could eliminate it, and it may even have a beneficial aspect if it encouraged some into treatment.

We should not support the use of new interventions unless they are proven to be both safe and effective. Would we put live yeast into penicillin capsules to dissuade people from injecting it?
I am not aware of any long-term research on naloxone... and naltrexone studies have not been without their problems. The jury is still out on this one, and the combination is still not proven safe to my mind, nor is it necessarily “effective”, not just for the immediate patient, but in the senses hoped for by its proponents.

Editor’s Note: As we have reported in past issues of Methadone Today, buprenorphine is an opiate agonist-antagonist (e.g.: it has both agonist and antagonist properties) that is already being used to treat opiate addiction in certain countries, such as France, and has been used for this purpose in the U.S. on a trial basis (FDA approval of the buprenorphine-naloxone combination for the treatment of opiate addiction is expected soon).

Unlike the current situation in Australia, buprenorphine will be prescribed/dispensed for unsupervised use in the U.S.; opiate addicts will be able to obtain treatment at a doctor’s office. The provider will not have to be accredited as is required of providers using methadone or LAAM to treat opiate addiction, under the current federal regulations.

Naloxone is an opiate antagonist, similar to naltrexone (used to reverse opiate overdoses, prescribed to former opiate addicts to block the effect of opiates should they relapse/use opiates, and administered in “rapid detox” procedures to precipitate withdrawal--see “Naltrexone Dangers” on page 2 of Methadone Today’s June 2001 issue).

Naloxone is being added to buprenorphine, supposedly, to deter individuals from injecting it in an effort to “get high”. Theoretically, if the combination were injected, the user would not feel any intoxication from it and, if opiate dependent, the naloxone may actually precipitate withdrawal.

For treatment of opiate addiction, buprenorphine is not swallowed but taken sublingually [held and absorbed under the tongue]. Proponents of the combination argue that naloxone will not induce withdrawal or decrease the effectiveness of the buprenorphine if the combination is taken sublingually.
As Dr. Byrne points out, this study appears to contradict the original premise behind the combination--when used IV, the naloxone did not appear to block the effects of the buprenorphine. This calls into question whether the addition of naloxone has any effect on the potential for abuse. Thus, it is shocking that such a drug is being added when it has not even been demonstrated that it is effective at reducing the probability of abuse.
It is not good enough that the drug is demonstrated to be safe (and many, like Dr. Byrne, are not even convinced of naloxone’s safety), but it must actually work as well.

Furthermore, Dr. Byrne is correct to question the entire purpose of adding naloxone. The term “effective” does not mean anything unless we know the purpose or goal (what is adding naloxone supposed to accomplish?).

We fail to see how adding naloxone to reduce diversion and abuse of the medication benefits patients. It is unethical to force patients to ingest a drug that is not medically necessary or helpful just to help make the job of law enforcement easier. If this is such a good idea, why not just prescribe opiate antagonists to every American simply to reduce the probability of opiate abuse? Thus, we are suspect of the addition of any drug that serves no medically justifiable purpose.

On the other hand, we must point out that policymakers might not permit buprenorphine to be prescribed at all for the treatment of opiate addiction if it were not combined with a drug like naloxone to supposedly reduce the risk of diversion and abuse. At the least, the U.S. Congress may not have allowed private physicians to prescribe buprenorphine (without being an accredited opiate treatment provider) in an unsupervised manner had naloxone not been added. Still, we are not convinced of its safety or if adding it is even ethical.

__________________

I love this place.

With the glass ceiling effect it is true: "LESS IS MORE". Great way to look at it. I say if you need 'em, take 'em! They're 10000000000 times better than injecting black tar heroin or crush oxycontin right? Exactly!

Oh, and Methadone is NO BETTER! Anyone who has problems with suboxone needs to ask themselves, whats the lesser of two evils? There ya go...

If it stops people from robbing convenience stores to feed their habit, I'm all for suboxone. It does serve a purpose, but it's too easy to get caught up in that, too.
At my meeting last night someone defined the difference of clean vs sober perfectly: clean is me not using, sober is me not robbing the 7-11 then coming back to the meeting and saying, "at least I didn't use". Big difference.

__________________
Listen: for this addict, the rooms of AA were the last thing I tried and the first thing that worked, but it only works if you work it.


Free since Thursday January 31, 2008.