norbuprenorphine

[rashandreflex]

there is another thread on this from 2004, but it doesn't answer my questions.

from what i understand, norbuprenorphine is a more potent mu and kappa opioid receptor agonist than bupe is. however, it doesn't cross the BBB as well as bupe does. someone who knows about the pharmacology of the substance, please correct me if i'm wrong.

i am assuming that buprenorphine become norbuprenorphine in the gut due to exposure to stomach acid (again, please correct me if i'm wrong.)

if that assumption is correct, would it be possible to crush a buprenorphine tablet up, let it sit in lemon juice or ascorbic acid for a couple hours and then either evaporate the acid and snort the remainder or just plug the resulting solution?

would this lead to a better high?

(yes, i have plugged substances dissolved in acid before, and it doesn't hurt too bad....works like a charm with those damn adderall xr beads)

 

[phr]

Buprenorphine gets metabolized into norbuprenorphine in your liver, by 3A4.

What you're proposing wouldn't work.

Here's a little bit about which receptors they bind to:

In the present study, we have shown that norBUP has a distinctly different pharmacological profile from BUP although both have high affinities for µ-, delta -, and kappa - opioid receptors and low affinities for the ORL1 receptor. NorBUP is a full agonist at the delta -receptor, whereas BUP is an antagonist. Both are partial agonists at µ- and kappa -receptors, with norBUP having higher efficacy than BUP. NorBUP and BUP are less efficacious at the kappa -receptor relative to the µ-receptor. To the best of our knowledge, this represents the first characterization of pharmacological activities of norBUP at cloned µ-, delta -, and kappa - opioid receptors and the ORL1 receptor.

You could read the full study here.


Edit: If you are interested in experimenting with norbuprenorphine, you could try inducing 3A4. Personally, I wouldn't bother. As far as the BBB crossing speed, that mostly comes into play when you're IV'ing substances and are looking for a rush.

 

[AlphaOdure]

from what i understand, norbuprenorphine is a more potent mu and kappa opioid receptor agonist than bupe is. however, it doesn't cross the BBB as well as bupe does. someone who knows about the pharmacology of the substance, please correct me if i'm wrong.

This means that norbuprenorphine will produce extreme physical side effects relative to theraputic levels of the drug--agonist activity will be a lot more present in the lungs and gut than in the brain; causing overdose by respiratory depression in the recreational dose range.

i am assuming that buprenorphine become norbuprenorphine in the gut due to exposure to stomach acid (again, please correct me if i'm wrong.)

Buprenorphine isn't taken orally; due to extreme first pass metabolism that renders the drug pharmacologically inactive in the brain. Norbuprenorphine is a major dealkylated metabolite of Buprenorphine and is metabolized in the liver, not the stomach--b/c the most frequent MOA are IV, IM, and sublingual.

if that assumption is correct, would it be possible to crush a buprenorphine tablet up, let it sit in lemon juice or ascorbic acid for a couple hours and then either evaporate the acid and snort the remainder or just plug the resulting solution?

You could do this; but the resulting powder wouldn't be norbuprenorphine. Acids are notoriously unfriendly to Buprenorphine.

 

[AlphaOdure]

Blaaaaah, you beat me to in phrozen!

sheesh, you typed that response of up fast. Your post wasn't there when i was typing my "Quick Reply"--i should've known you'd beat me to the punch. heh heh...

 

[rashandreflex]

how stupid of me....the liver slipped my mind.

does anyone have any experience with norbuprenorphine as to whether it's actually more euphoric?

also, AO could you refresh me as to 34A blockers?

 

[phr]

I don't think anyone, outside of a small select few who were apart of studies, has tried pure norbuprenorphine.

If you want to try to metabolize more bupe into norbupe, you want a 3A4 inducer.

Learn it, live it.

 

[AlphaOdure]

Theortically, maybe small amounts of Nalmefene would help in partially antagonizing some physical side effects. I know antagonists are generally ineffective and/or less effective in reversing buprenorphine, but norbuprenorphine is a different story.. its not as competitive as bupe itself. Nalmefene may be preferable to using naloxone since nalmefene is considerably less potent, has a harder time crossing the BBB, and is a non specific opioid antagonist.

Just an idea...

 

[AlphaOdure]

Moderate CYP3A4 inducers-

aminoglutethimide, dexamethasone, glucocorticoids, glutethimide, griseofulvin, nafcillin.

Stronger CYP3A4 inhibitors-

aprepitant, carbamazepine, efavirenz, ethosuximide, garlic supplements, modafinil, nevirapine, oxcarbazepine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine, and possibly even St. John's Wort.

------------------------------

Hmmm, i'd be interested to hear if anyone experiments w/ this and see's any added recreational value to buprenorphine as a result... garlic supplements are easy enough to get ahold of; and so are a number of those other chemicals. I know for a fact cimetidine worked effectively at inhibiting the metabolization of methadone; it would draw out the duration of its effects for me. But i've never really experimented w/ inducers.

 

[phr]

After doing a little bit of research, AO is right. Norbupe may be deadly at recreational doses.

High dose buprenorphine is used as substitution treatment in heroin addiction. However, deaths have been reported in addicts using buprenorphine. The role of norbuprenorphine, an N-dealkyl metabolite of buprenorphine, was hypothesized to explain these fatal cases. We determined the median intravenous lethal dose (LD[50]) of norbuprenorphine in male Sprague-Dawley rats. The effects of a single intravenous dose of 3 or 9 mg/kg norbuprenorphine alone on arterial blood gases were studied. Finally, the effect of pre- and post-administrations of buprenorphine on norbuprenorphine-induced changes on arterial blood gases were analyzed. Norbuprenorphine's LD[50] was 10 mg kg[-1]. Norbuprenorphine 3 mg kg[-1] produces the rapid onset of sustained respiratory depression, as demonstrated at 20 min by a maximal significant increase in PaCO[2](8.4 ± 0.9 versus 5.7 0.1 kPa), decrease in arterial pH (7.25 ± 0.06 versus 7.44 ± 0.01), and hypoxia (8.3 ± 0.6 versus 11.1 ± 0.2 kPa). Buprenorphine not only protected against the effects of 3 mg kg[-1] norbuprenorphine in a dose-dependent manner but also reversed the effects when given afterward. Binding experiments suggest a role for mu- and to a lesser extent for delta-opioid receptors in buprenorphine protective effect against norbuprenorphine-induced respiratory depression. In conclusion, our data clearly show that norbuprenorphine alone causes important deleterious effects on ventilation in rats. However, buprenorphine protective effect calls into question the role for norbuprenorphine in respiratory toxicity associated with buprenorphine use.

Source.

 

[phr]

Hmmm, i'd be interested to hear if anyone experiments w/ this and see's any added recreational value to buprenorphine as a result... garlic supplements are easy enough to get ahold of; and so are a number of those other chemicals. I know for a fact cimetidine worked effectively at inhibiting the metabolization of methadone; it would draw out the duration of its effects for me. But i've never really experimented w/ inducers.

Well, after reading what I just quoted above, I wouldn't mess with trying to induce 3A4 to get more norbupe. Hell, I might even try inhibiting it.


In the big suboxone/buprenorphine thread, someone asked if anyone has any experience with potentiating bupe. No one responded, but it seems like "classical" potentiation, inhibiting 3A4, may work.

 

[AlphaOdure]

^ ^ ^
This is probably why there have been deaths associated w/ buprenorphine mixed w/ certain depressants (since some downers are potent C3A4 inducers). Buprenorphine on its own is relatively safe. Even at ungodly high doses respiratory depression is negligible relative to traditional opioids. So if you do decide to experiment w/ inducers, be careful as fuck.. and get back to us.

 

[AlphaOdure]

but it seems like "classical" potentiation, inhibiting 3A4, may work.

You really think so? I think this would really just draw out the duration a bit longer instead of making the effects more intense. For example, I used huge amounts of cimetidine w/ methadone for this purpose, and it was decently effective--but it definitely didn't serve any logical purpose other than saving me a bit more money since i was buying it from illicit sources. And it definitely didn't increase the high, it only increased the duration of effects.

Therefore, since this isn't really an issue w/ Rx'd buprenorphine; i would think inhibitors wouldn't really be of value.. seeing as though most of us don't get any recreational or euphoric effect out of it as it is (at least i don't). I mean, sure, it could make you feel more "normal" for longer, but usually one feels "normal" as it is as soon as they are stablized on a particular dose of bupe that suites them.

But I suppose if one's tolerance is low enough so that they enjoy buprenorphine recreationally; they could also perhaps use inhibitors as an aid in extending the duration of its peak effects.

 

[phr]

It seems like inhibiting 3A4 does potentiate buprenorphine.

A small in-vitro study in liver microsomes [5] demonstrated an increase in buprenorphine levels probably caused by the inhibition of buprenorphine metabolism by ritonavir at CYP3A4. Atazanavir also appeared to inhibit the metabolism of compounds at CYP3A4 [6]. In pharmacokinetic studies, atazanavir has not been demonstrated to increase the levels of methadone or result in symptoms of opiate excess [7]. In clinical trials, however, atazanavir increased saquinavir levels, thus requiring reduced dosing of saquinavir when combined [8]. A recent pharmacokinetic study [9] demonstrated that both atazanavir and ritonavir independently boosted saquinavir drug levels, possibly through independent mechanisms. Atazanavir is also an inhibitor and inducer of p-glycoprotein [10] and an inhibitor of uridine diphosphate-glucuronosyl transferase 1A1 [11]. Importantly, uridine diphosphate-glucuronosyl transferase 1A1 is involved in the phase II metabolism of buprenorphine [12], and its inhibition by atazanavir may further increase drug levels. Therefore, in these three cases, it is possible that atazanavir or ritonavir inhibited the major phase I metabolic pathway (CYP3A4), or that atazanavir inhibited the major phase II pathway for buprenorphine, resulting in increased levels and clinical symptoms of opiate excess. Until further data are available, specifically from well-conducted pharmacokinetic drug interaction studies of buprenorphine with ritonavir, atazanavir or both, the use of buprenorphine in combination with ritonavir and atazanavir should be undertaken cautiously. Induction with buprenorphine should begin at reduced dosing, and dose escalation should occur at a slower than usual pace to allow providers to assess for opiate excess and to allow patients to become accustomed to the effects of buprenorphine.

Source

 

[phr]

You really think so? I think this would really just draw out the duration a bit longer instead of making the effects more intense. For example, I used huge amounts of cimetidine w/ methadone for this purpose, and it was decently effective--but it definitely didn't serve any logical purpose other than saving me a bit more money since i was buying it from illicit sources. And it definitely didn't increase the high, it only increased the duration of effects.

Edit: 3A4 inhibition can affect strength(and therefore plasma levels) as well as duration.

Therefore, since this isn't really an issue w/ Rx'd buprenorphine; i would think inhibitors wouldn't really be of value.. seeing as though most of us don't get any recreational or euphoric effect out of it as it is (at least i don't). I mean, sure, it could make you feel more "normal" for longer, but usually one feels "normal" as it is as soon as they are stablized on a particular dose of bupe that suites them.

But I suppose if one's tolerance is low enough so that they enjoy buprenorphine recreationally; they could also perhaps use inhibitors as an aid in extending the duration of its peak effects.

You're right. Potentiating would really be of use only to recreational bupe users.


//I don't find bupe recreational either. And I never really got into potentiating. My potentiation = bigger shot

 

[AlphaOdure]

^ ^ ^
Thanks for the resources phrozen.. the pharmodynamics of buprenorphine are surprisingly complex..

 

[phr]

the pharmodynamics of buprenorphine are surprisingly complex..

And some may say a waste of time if you don't find bupe recreational... :D


Whatever. We've derailed rash's thread enough...

 

[AlphaOdure]

And some may say a waste of time if you don't find bupe recreational...

Well, personally, bupe has saved my life. Yea it sometimes sucks not catching a buzz once in a while.. but it sure beats living that miserable life of active addiction!

We've derailed rash's thread enough...

Agreed </end derailment>

 

[Coley24]

Get this!

I shot 4mg of subutex up the other day, 15 hours after my last methadone dose of 80mg. I got so sick that i had to get rushed to the ER. It wou;dnt been that bad if i was in my right mind and was under control! I was in such a panic i nearly fainted. I was vomiting uncontrollable and sweating along with absolute panic!! I could have punched a wall and wouldnt have felt it. On the way to the ER i stuck my head out the window and counldnt even feel the wind.

What the hell happen? Was that a panic attack along with the side affects? It wore off after 1 hour and i was totally fine the next night except that i was thinking about it.

I actually believed that i was going to die!! what happened??

 

[jasoncrest]

I shot 4mg of subutex up the other day, 15 hours after my last methadone dose of 80mg. I got so sick that i had to get rushed to the ER. It wou;dnt been that bad if i was in my right mind and was under control! I was in such a panic i nearly fainted. I was vomiting uncontrollable and sweating along with absolute panic!! I could have punched a wall and wouldnt have felt it. On the way to the ER i stuck my head out the window and counldnt even feel the wind.

What the hell happen? Was that a panic attack along with the side affects? It wore off after 1 hour and i was totally fine the next night except that i was thinking about it.

I actually believed that i was going to die!! what happened??

Precipitated withdrawal.
If you're addicted to Opioids and take Buprenorphine too soon, it throws you into hardcore withdrawal.
For Methadone, you should wait 72 hours after your last dose before taking Buprenorphine.

 

[Coley24]

No this wasnt withdrawal! Ive been an oxycontin addict for 3 years now and have been in withdrawal, i have also beenin withdrawal from taking my sub to early and this wasnt withdrawal