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  #1  
Old 18-10-2010, 03:58
synonymous synonymous is offline
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Naloxone not absorbed myth

Swim knows the often repeated company line about naloxone not being absorbed sub-lingual and beleaved it was true until he tried both Subutex and Suboxone. Swim has tried both many times now and it is utterly clear to him that naloxone does get absorbed.

Subutex gives swim nice warm relaxed feeling and back pain goes away completely.Swim feels good all day.

Suboxone gives swim dizzy nauseous feeling and then he feels achy and sore after a couple of hours. With Suboxone the warm relaxed feeling never really comes but just moments or hints of nice feeling come and go.

Maybe Swim is just sensitive... Maybe not. How many swimmers have the same experiences?

Swim knows Australian ambulance service use naloxone nasal spray for heroin over dose. Why would naloxone aborb through nasal mucus membrane but not oral mucus membrane?
Naloxone is lipophilic enough to cross blood brain barrier and the mucus membrane in mouth is a phospholipid...

It doesn't add up.
I have a link for a study showing 50% of patients switched from Subutex to Suboxone had adverse side effects after switch.
But I can't post a link...
google this title if you are curious:
A retrospective evaluation of patients switched from buprenorphine (subutex) to the buprenorphine/naloxone combination (suboxone)

Post Quality Evaluations:
interesting start of a thread
Excellent idea for a thread,with potential 'evidence' from a reliable source.Well done!!
  #2  
Old 18-10-2010, 11:57
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AW: Naloxone not absorbed myth

The first is "your" Study:

Quote:
Abstract

BACKGROUND: In Finland, buprenorphine (Subutex) is the most abused opioid. In order to curb this problem, many treatment centres transferred ("forced transfer") their buprenorphine patients to the buprenorphine plus naloxone (Suboxone) combination product in late 2003.

METHODS: Data from a retrospective study involving five different treatment centers, examining the effects of switching patients to Suboxone, were gathered from 64 opioid-dependent patients who had undergone the medication transfer.

RESULTS: Most patients (90.6%) switched to Suboxone at the same dose of buprenorphine that they had been receiving as Subutex (average 22 mg). The majority of these patients (71.9%) were maintained at the same dose of Suboxone throughout the 4-week study period. During the first 4 weeks, 50% of the patients reported adverse events and at the four month time point, 26.6% reported adverse events. However, due to adverse events one patient only discontinued treatment with Suboxone during the 4-week study period, and five during the four month follow-up period. Of the 26 patients in the follow-up period, Suboxone was misused intravenously once each by 4 patients and twice by 1 patient. These 5 patients all reported that injecting Suboxone was like injecting "nothing" with any euphoria, or that it was a bad experience.

CONCLUSION: We conclude that when patients are transferred from high doses (> 22 mg) of buprenorphine to the combination product, dose adjustments may be necessary especially in the later phase of the treatment. We recommend that a transfer from Subutex to Suboxone should be carefully discussed and planned in advance with the patients and after the transfer adverse events should be regularly monitored. With regard of buprenorphine IV abuse, the combination product seems to have a less abuse potential than buprenorphine alone.

Source:
http://www.ncbi.nlm.nih.gov/pubmed/18559110

Versus



Quote:
Abstract

Abuse and misuse of pharmacological therapies represent major challenges in the healthcare system, particularly in patients receiving long-acting opioid drugs for the treatment of heroin or opioid addiction. The partial mu-opioid receptor agonist buprenorphine is used to treat opioid dependence, but diversion and misuse may occur.

The sublingual combination formulation of buprenorphine and the opioid receptor antagonist naloxone (buprenorphine/naxolone) is associated with a reduced abuse potential, and has been shown to have promising efficacy for the treatment of opioid dependence. This observational study assessed the safety and efficacy of sublingual buprenorphine/naloxone combination therapy in patients with opioid dependence after therapeutic switch from buprenorphine monotherapy. A total of 94 patients being treated with buprenorphine monotherapy (average dose 8 mg/day; mean duration of therapy 840 days) were switched to buprenorphine/naloxone combination therapy. Patients were asked to rate their level of satisfaction with buprenorphine/naloxone combination treatment with respect to the management of withdrawal symptoms, and urinary toxicology tests were carried out before and 14 days after switching to combination therapy. Within 3 months, 75/94 patients (80%) previously treated with buprenorphine monotherapy had switched to sublingual buprenorphine/naloxone combination treatment (average dose buprenorphine 8 mg).

Among patients receiving combination treatment for >3 months, 83% were receiving medication either weekly or fortnightly, based on the results of toxicological testing. A reduction in positive urinary toxicology tests was observed in patients within two weeks after being switched to combination treatment (before switch: 28, 9 and 2 positive tests for heroin, cocaine and heroin + cocaine, respectively vs 11, 3 and 1 after switch) and a total of 64 patients of the 75 who switched to combination therapy (85%) were satisfied with the management of withdrawal symptoms during buprenorphine/naloxone treatment.

Few adverse events were reported and no patients dropped out of treatment. This study shows that switching from buprenorphine monotherapy to sublingual buprenorphine/naloxone combination therapy is effective and well tolerated, and associated with good control of withdrawal symptoms in the majority of patients. In addition, combination therapy reduced illicit drug use (based on negative urinary toxicology texts) and allowed the time between clinic visits to be increased.
Source: http://www.ncbi.nlm.nih.gov/pubmed/20450243

They changed from average 22mg. a Day, so they get ca. 6mg, of Naloxone, that is by far to high


Imo. it must be logical that the Naloxone had a influence.
Ie. the Problem of Constipation is much lower in the Suboxone-Group,
my idea is that Naloxone contribute that!

Post Quality Evaluations:
Added two excellent studies to further the debate (inc.one of behalf of a new member).Thanks

Last edited by Spucky; 18-10-2010 at 12:05.
  #3  
Old 18-10-2010, 17:28
kailey_elise Gold member kailey_elise is offline
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Re: AW: Naloxone not absorbed myth

Quote:
Originally Posted by Spucky View Post
They changed from average 22mg. a Day, so they get ca. 6mg, of Naloxone, that is by far too high

Imo. it must be logical that the Naloxone had a influence.
Ie. the Problem of Constipation is much lower in the Suboxone-Group,
my idea is that Naloxone contribute that!
This is true...I had completely forgotten about the Naloxone factor in Suboxone, in a way.

I wonder if people who continue to crave while on high dose Suboxone treatment (3 & 4 tablets a day, ie., 24mg/6mg & 32/8mg) aren't, in fact, screwing themselves over with the excessive Naloxone.

And that probably is a big part of why people, once stabilised on Suboxone (meaning, they've been on it a few weeks & all the other opioids are out of their systems), seem to find 4mg/1mg and less most effective/"euphoric".

Very interesting.

~Kailey
  #4  
Old 19-10-2010, 10:17
Spucky Spucky is offline
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AW: Naloxone not absorbed myth

@ Kailey-Chan,

afaik. this high dosage of Subutex/ Suboxone above 8mg. a Day will be not metabolized,
to give a Patients more than 8mg. a day is a waste of Money!

Buprenorphine is not made for everyone, some People need stronger Opioids!
(like Methadone or Diamorphine)

In the last weeks there is a Witch-hunt going on, suddenly Methadone is the bad one,
i am a little bit scared that soon "they" (the military-industrial and Pharmaceutical Complex) will allow only Buprenorphine-Products!
  #5  
Old 29-11-2010, 07:27
Eden Eden is offline
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Re: AW: Naloxone not absorbed myth

Quote:
Originally Posted by kailey_elise View Post
This is true...I had completely forgotten about the Naloxone factor in Suboxone, in a way.

I wonder if people who continue to crave while on high dose Suboxone treatment (3 & 4 tablets a day, ie., 24mg/6mg & 32/8mg) aren't, in fact, screwing themselves over with the excessive Naloxone.

And that probably is a big part of why people, once stabilised on Suboxone (meaning, they've been on it a few weeks & all the other opioids are out of their systems), seem to find 4mg/1mg and less most effective/"euphoric".

Very interesting.

~Kailey

WOW! what you surmise with regard to the "less is more" concept just blew my socks off!After all these years I dont know why it didnt occur to me that it was only the folks I have known taking Suboxone and NOT Subutex who have made the claim that less is more. WOW...thanks for the post...I have lots to think about for awhile.
  #6  
Old 29-11-2010, 16:42
kailey_elise Gold member kailey_elise is offline
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Re: Naloxone not absorbed myth

No problem, Eden!

More food for thought - the Suboxone group might additionally find "less is more" because the small doses of Naloxone that do get absorbed act as "Ultra Low Dose Naltrexone" in a way, making the lower doses of buprenorphine more effective than when in the Subutex formulation.

So, for Suboxone at least, taking less is more euphoric because less Naloxone is absorbed, with the potential addition of the opioid working more efficiently BECAUSE of the small amount of Naloxone absorbed!

Now, this is all theory; I have no studies to back this up. But it makes sense in many ways, and I think there could be something to it!

~Kailey
  #7  
Old 30-11-2010, 16:33
dyingtomorrow dyingtomorrow is offline
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Re: Naloxone not absorbed myth

SWIM has some anecdotal evidence he could add.

SWIM has been on and off Suboxone dozens of times. He could attest to what Spucky said, because he noticed that dropping from 16mgs+ down to 8mgs+ felt like no difference at all. He also found that he could drop his dose every 2-3 days by 2mgs and experience almost no noticable effects. Getting down to 1-2mgs the difference became a little more noticiable, but slowly tapering off from there was still not a problem at all. He'd usually go down to .5mgs or less as part of his quick taper.

However, when he was on Subutex (switching on and off a few times) he noticed a big difference. It was far more difficult to taper off, and the effects of each dose drop were a lot more noticiable.

SWIM has read medical documentation for Suboxone which indicates that even orally, or to a greater extent nasally, a small amount of Naloxone is still absorbed. SWIM has a theory that this small amount of Naloxone is partially what makes the tapering process so easy with Suboxone. That while most of the receptors are filled with Buprenorphine, a small amount are bound with Naloxone. Other studies have shown that taking low doses of Naloxone at night can induce the body to start producing more endorphins and elevate mood, and this could perhaps explain why it seems like one's tolerance is lowering with Suboxone, and why lower doses can have the same effectiveness after a couple day plateau dose. Alternately, it could just be the Buprenorphine itself, since it has such low receptor activity that the body might feel that it is still lacking in "proper endorphins." Or perhaps both.

SWIM can also say that, normally he would snort his Suboxone doses as he was tapering down, which, along with the greater bioavailability, would very likely result in a greater amount of Naloxone being absorbed. He noticed a difference in tapering difficulty when he tried using it orally instead of nasally, orally being more difficult, perhaps because he was absorbing less Naloxone.

Just some theories that have come to SWIM's mind, explaining some of the effects he has experienced between Suboxone and Subutex.
  #8  
Old 30-11-2010, 21:53
Eden Eden is offline
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Re: Naloxone not absorbed myth

Quote:
Originally Posted by dyingtomorrow View Post

...However, when he was on Subutex (switching on and off a few times) he noticed a big difference. It was far more difficult to taper off, and the effects of each dose drop were a lot more noticiable...
This is amazing! Can SWIM estimate how many times this comparison has been done? A donkey I know would be highly interested in this information because he(the donkey) has experimented with low-dose Naltrexone etc.
  #9  
Old 01-12-2010, 00:12
Naked Lunch Naked Lunch is offline
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Re: Naloxone not absorbed myth

Even if it is absorbed its irrelevant as Naloxone does not reverse Buprenorphine like it does Heroin.
Straight from a med School handbook BTW.

How this works in real life, well, who knows...

I've been taking Subutex and Suboxone legally* (*Hence, the reason why I use "I" )for years and have no problems with it.(I do 3 days on Subutex and 4 on Suboxone and I feel the same everyday.
  #10  
Old 01-12-2010, 09:29
Spucky Spucky is offline
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AW: Re: Naloxone not absorbed myth

Quote:
Originally Posted by Naked Lunch View Post
Even if it is absorbed its irrelevant as Naloxone does not reverse Buprenorphine like it does Heroin.
Straight from a med School handbook BTW.
Afaik. this is not 100% true,
Naloxone drives Buprenorphin away from the Receptor
but only for a short Time (ca. 20min)

In a Overdosage a constant Monitoring is needed
and a 3-5 Times continual injection of Naloxone to reach the safe Haven!
  #11  
Old 01-12-2010, 11:17
catseye Gold member catseye is offline
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Re: Naloxone not absorbed myth

Quote:
The respiratory depressant effects of buprenorphine are not fully reversed by naloxone. Doxapram has been used in milder cases of buprenorphine overdose as a respiratory depressant (1-4mg/min) although severe cases may require IPPV.
From Cambridge University Opiates Poisoning guide.
IPPV means intermittent positive pressure ventilation (eg mechanical ventilation).

As Spucky says, the major problem with using naloxone to counter-act opiates with a long half-life is Naloxones inherently short duration action - so in cases like this close monitoring and re-administration may be needed for 48-72 hrs.

As naloxone is so short acting and is not easily absorbed orally at low doses, it will have little to no effect if the Suboxone is taken as directed - if it's crushed and injected, well that's another story! John Hopkins University is currently looking at buprenorphine's dose response curve (ie the 'less is more' idea) but haven't released their findings yet. In animal studies, bupe response has a bell shaped distribution curve with very high doses (ie well over the 32mg 'ceiling dose' for humans) producing less results than mid-range doses.

In response to the OPs original question, my guess is that the reason intra-nasal naloxone is more readily absorbed is for two reasons:
1) the method of administration is (or should be!) via atomizer which is absorbent-enhancing. Fine particle atomization maximizes nasal bioavailability compared to sprays or drops.
2) the fact that the nasal mucosal membrane is in close contact with the blood stream (via the nasal mucosal vasculature). It is also directly in contact with the brain through the olfactory mucosal membrane nose-brain pathway (the area of smell at the top of the nasal cavity). Since the olfactory mucosa is in direct contact with the brain, medication can absorb directly from the olfactory mucosa into the brain CSF and actually skip the blood stream/blood brain barrier.

Its also worth mentioning that the concentration of the nasal administration route - 1mg/1ml - is highly concentrated vs. the small sublingual amounts available in suboxone.
  #12  
Old 01-12-2010, 19:05
Eden Eden is offline
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Re: Naloxone not absorbed myth

Quote:
Originally Posted by Naked Lunch View Post
Even if it is absorbed its irrelevant as Naloxone does not reverse Buprenorphine like it does Heroin.
Straight from a med School handbook BTW.

Ok lets break this down: Part One: "...Naloxone does not reverse Buprenorphine like it does Heroin.." Taken in context this is correct. However,does it eventually and when done properly under medical supervision"reverse Buprenorpine? YES.

The following excerpt is taken from The Journal of The American Society of Anesthesiologists**: (Note:quoted in it's entirety as I believe it is pertinent to the thread.):

"...Background: The objective of this investigation was to examine the ability of the opioid antagonist naloxone to reverse respiratory depression produced by the μ-opioid analgesic, buprenorphine, in healthy volunteers. The studies were designed in light of the claims that buprenorphine is relatively resistant to the effects of naloxone.
Methods: In a first attempt, the effect of an intravenous bolus dose of 0.8 mg naloxone was assessed on 0.2 mg buprenorphine–induced respiratory depression. Next, the effect of increasing naloxone doses (0.5–7 mg, given over 30 min) on 0.2 mg buprenorphine–induced respiratory depression was tested. Subsequently, continuous naloxone infusions were applied to reverse respiratory depression from 0.2 and 0.4 mg buprenorphine. All doses are per 70 kg. Respiration was measured against a background of constant increased end-tidal carbon dioxide concentration.
Results: An intravenous naloxone dose of 0.8 mg had no effect on respiratory depression from buprenorphine. Increasing doses of naloxone given over 30 min produced full reversal of buprenorphine effect in the dose range of 2–4 mg naloxone. Further increasing the naloxone dose (doses of 5 mg or greater) caused a decline in reversal activity. Naloxone bolus doses of 2–3 mg, followed by a continuous infusion of 4 mg/h, caused full reversal within 40–60 min of both 0.2 and 0.4 mg buprenorphine–induced respiratory depression.

Conclusions: Reversal of buprenorphine effect is possible but depends on the buprenorphine dose and the correct naloxone dose window. Because respiratory depression from buprenorphine may outlast the effects of naloxone boluses or short infusions, a continuous infusion of naloxone may be required to maintain reversal of respiratory depression..."

Eden added 10 Minutes and 8 Seconds later...

Part Two: Btw Naked Lunch-this is not in any way to pick on you.This is purely in the interest of accuracy and keeping the thread on track.


Quote:
Originally Posted by Naked Lunch View Post
...Even if it is absorbed its irrelevant as Naloxone does not reverse Buprenorphine like it does heroin...
The original comment about Suboxone vs. Subutex made by "dyingtomorrow" is absolutely relevant because the comparison is drawn between partial agonists(Subutex and Suboxone) and really has nothing to do with heroin(full agonist).Again, just trying to keep this discussion on track and accurate


**Van Dorp E. et al. (2006) Naloxone reversal of buprenorphine- induced respiratory depression. Anesthesiology 105 (1): 51-57

Post Quality Evaluations:
for using a nd named a real source!

Last edited by Eden; 01-12-2010 at 19:11. Reason: Added source
  #13  
Old 02-12-2010, 00:30
Naked Lunch Naked Lunch is offline
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Re: Naloxone not absorbed myth

Nice to know.

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