Bupe Norbupe Theory

[DeathIndustrial88]

That is an interesting idea, although popular 8nhibitors are hard to find (RX only, usually) and cimetidine and White Grapefruit juice would inhibit 3A4, so more buprenorphine, less norbupe

(You can actually swallow buprenorphine with the aforementioned inhibitors and double or triple the BA%, though it is pointless when other routes work just fine)

Methadone, for those interested, 40mg with loads of inhibitors is better than 60mg without (amd especially 60mg compared to 80mmg)

So, the best inhibitor is *usually * a higher dose, the not always, unless you are doubling the dose

Back when I was into inhibitors I would take a fairly large dose of Methadone and Klonopin, and actually wake up high

A bit off topic, just a note on what inhibitors can do for certain drugs

I tried swallowing 4mg of bupe with about 400mg of cimitedine yesterday just to see what would happen (although I completely forgot that slowing bupe's metabolism comes into play here).

Felt effects, but not sure if I liked them or not. They did feel slightly different (almost dissociative) than the normal ROA I go with. Could have also been totally placebo. Took around 2hrs to notice something. Was also very tired and also took clonazepam, so hard to say if it truly did anything or not.

I'd love to find a way to make bupe more like a full agonist, other than just low doses, since you get tolerant to those too eventually anyway.

I take several meds a day and still have bad heroin & meth cravings. I see they are tinkering with dopamine receptor antagonists and such for "addiction". So rather than just making drugs legal and safe to purchase and use for educated adults, the big pharma complex would rather just block you from feeling well at all.

 

[ryax]

I hate to be the buzzkill, however Norbupe does not appreciably penetratre the central nervous system
.that is a FACT.

8mg buprenorphine sublingual or 1-2¿MG iv is the best dose

By the way for my peeps I am back, I lost my Dr though have a hookup now; am having to cut my dose in half though I will live (from 8mg clonazepam per day to 4mg)

And ftr, Valium is a rapid. Acting, short duration benzodiazepines... get over it people, Ativan last longer because it stays in the vascular compartment.

Sorry off topic I just get sick if that nonsense

i accidently posted the wrong link but you argued the entire thread for really no reason
heres a link to accumulation of buprenorphine and norbuprenorphine via different routes of ingestion i.e. sublingual + swallowing dose accidently

Opioid-induced constipation: rationale for the role of norbuprenorphine in buprenorphine-treated individuals

do you guys understand now?

 

[Lorne???]

i accidently posted the wrong link but you argued the entire thread for really no reason
heres a link to accumulation of buprenorphine and norbuprenorphine via different routes of ingestion i.e. sublingual + swallowing dose accidently

Opioid-induced constipation: rationale for the role of norbuprenorphine in buprenorphine-treated individuals

do you guys understand now?

Understand what? That demonstrates that you get more norbuprenorphine from tablets, probably because you swallow more, even though the BA% of strips is supposedly only slightly better (albeit more consistent)

Norbuprenorphine 8s not active at the CNS, unless MAYBE you got pure Norbuprenorphine and too a large dose

I am.not sure what the point of your link was, even if it was interesting

And I have not argued, I have stated facts: every scientific source says norbuprenorphine cannot penetratrte the CNS (at least not well enough) and as far as the benzo thing, I am the Benzodiazepine guru, and Ativan has longer lasting anticonvulsant effects than Valium, because it has a very poor lipid solubility, so like clonazepam, it exits the brain slower and is not distributed much out of the vascular compartment; clonazepam (Klonopin) has this same property except its T1/2 is the same as Valiums, so it is the longest lasting

There was a page with lipid solubility for the most common Benzodiazepines, however it seems to have disappeared

It also had binding affinity listed

I can tell you clonazepam had by far the highest binding affinity, over double that of Xanax, Valium had an exponentially lower binding affinity, yet the highest lipid solubility

Ativan(Lorazepam) was literally like 1% higher binding affinity than Klonopin, which had the lowest, and they are both the longest lasting besides uncommon ones like flurazepam(?)

Really wish I could fid that article...

Anyway, not arguing with anyone, I am chill

 

[G_Chem]

Dude you know I meant read the Ativan page to have it explain why Valium wears off faster, come on dude

https://www.google.com/url?sa=t&sou...0QFnoECAgQBQ&usg=AOvVaw32AL6BNgoruGigMHrQCzsc

[/URL]

This article says norbuprenorphine does not read readily cross the BBB; I had another one with great detail, though it is a PDF

Just Google it and every source will say Norbuprenorphine is not normally active at the CNS because it cannot Penetrate it

And ask the mods about me; ask Keif

I single handedly dispelled the rumors that oxycodone had high oral BA%, because SEVERAL studies place it at 50%, only a single study had the 87% figure, and it was 5 people in a study funded by the drug company

I also posted proof (with some help) that rectal.administration of * most * opioids results in a delayed onset, with an extended duration of action, especially with the Oxy- medication (oxycodone and oxymorphone) although there are exceptions like morphine and, heroin

(Not sure why morphine because it has poor solubility/ less than 100mg per ml and modest lipid solubility) although diamorphine is highly soluble, half a gram per ml for pure pharmaceutical grade heroin no 4 / diamorphine help, so that makes sense

Anyway I am rambling though I am not being lazy, I told everyone that horbupe is produced in highest quantities when swallowed, yet no on swallowed buprenorphine because it is a waste

Sometimes, if you are dealing with a vet who has been on this site a decade, you have to pull out pubned yourself if you disagree with such solid evidence

Not being rude just saying

There is simply NO WAY norbuprenorphine is activating Mu opioid receptors, every source mentions this, anyway, ask the mods, ask Keif, I have paid my dues

I hope this makes sense to everyone

(And anyone who takes Benzodiazepines should probably slow down and certainly check the Lorazepam page)

Peace -

Ummm once again what does the metabolism of lorazepam or diazepam have ANYTHING to do with buprenorphine and norbuprenorphine BBB permeability?… Even then extrapolations are just that.

Lol alright I’ll get right on asking around on your credentials. Your sig says your the expert so that must be true..

Great job with your 1 link, that doesn’t even work btw.

Dude I get it your egos big and you think you push weight around here. Facts push weight, of which you’ve shown absolutely zero after multiple times asking for such. On the contrary others have provided links which do work and prove their point.

-GC

 

[Lorne???]

Ummm once again what does the metabolism of lorazepam or diazepam have ANYTHING to do with buprenorphine and norbuprenorphine BBB permeability?… Even then extrapolations are just that.

Lol alright I’ll get right on asking around on your credentials. Your sig says your the expert so that must be true..

Great job with your 1 link, that doesn’t even work btw.

Dude I get it your egos big and you think you push weight around here. Facts push weight, of which you’ve shown absolutely zero after multiple times asking for such. On the contrary others have provided links which do work and prove their point.

-GC

... I have no ego, I am an ugly fucking loser who wasted a sharp mind

The link worked for me

Look, if you Google it, EVERY source says norbuprenorphine does not appreciably penetrate the CNS

Why should I post multiple links of a fact?

It Would? Be like posting even more limks.about oxycodone bioavailability: It is a fact that it's BA% is roughly 50%

If it pleases.you, when I gave time I shall post the links.from the front page of Google

What are you disputing? If you think norbuprenorphine is a great full agonist then swallow the bupe; you will be disappointed though

I am not sure why I rub you the wrong way , though you seem to be fighting a pure and simple fact

I was a mod, that does not make me perfect though I did help make the stickies, corrected misinformation and basically made the new Benzodiazepine thread

Not ego, I am a wreck, just a fact

I havebeenpolite, told you where to verify the facts, please do not be a snide smart-ass

Sincerely, Lorne
.

 

[Lorne???]

Seriously you are being an ass, stop.it, you are acting like an aids denials, amd I am.not much though I am the expert on Benzodiazepines

I pull.no weight around here anymore, except if I stay I shall once again be flooded with Benzodiazepine questions, which is not weight it is a responsibility

Seriously check yourself because you are coming off as a worm who cannot research anything for themselves and jabs at somebody who gives you facts and locations
.
Do not act like a little bitch

 

[Lorne???]

Buprenorphine: Biological Mechanisms, Applications and Perioperative Implications - Ambulatory Anesthesia Services | OBS Anesthesia Management Groups

Buprenorphine is an opioid drug that can be used to treat chronic pain or alleviate opioid addiction.1 Unlike other opioid drugs such as morphine and heroin, buprenorphine has a limit in its ability to produce a “high” or euphoric effect.1 Buprenorphine was discovered in 1966 as an alternative...

radiusanesthesia.com

Nice link that says norbuprenorphine does not cross the BBB, and thus has negligent effects, in fact Google quotes this review if you ask does norbuprenorphine cross the BBB

I will try to post more

Mods, feel free to merge this

 

[DeathIndustrial88]

Buprenorphine: Biological Mechanisms, Applications and Perioperative Implications - Ambulatory Anesthesia Services | OBS Anesthesia Management Groups

Buprenorphine is an opioid drug that can be used to treat chronic pain or alleviate opioid addiction.1 Unlike other opioid drugs such as morphine and heroin, buprenorphine has a limit in its ability to produce a “high” or euphoric effect.1 Buprenorphine was discovered in 1966 as an alternative...

radiusanesthesia.com

Nice link that says norbuprenorphine does not cross the BBB, and thus has negligent effects, in fact Google quotes this review if you ask does norbuprenorphine cross the BBB

I will try to post more

Mods, feel free to merge this

I believe you about the norbuprenorphine.

Only thing I can't understand is how does bupe cause respiratory depression at all then? If bupe doesn't cause respiratory depression, then how have there been OD's involving buprenorphine?
And from my own experience, when my tolerance was low and I use to chip with less than 1.5mg of SL buprenorphine, I absolutely experienced slower respiratory rate & the nods. If bupe doesn't cause respiratory depression & or the nods (which it really doesn't, once you go up higher and have a tolerance), than what does? Could peripherally acting norbuprenorphine affect respiratory rate?






Has anyone read this? Maybe I'm interpreting it wrong, but they're saying morphine & buprenorphine cause equivalent dopamine release? Actually buprenophine is higher. How is that possible? Would this not mean buprenorohine is more euphoric and reinforcing than morphine? Seems hard to believe.

Buprenorphine and morphine produce equivalent increases in extracellular single unit activity of dopamine neurons in the ventral tegmental area in vivo - PubMed

Buprenorphine is a synthetic opioid proposed as a potential treatment for drug abuse. Although buprenorphine is widely considered to be a partial agonist at opioid receptors, little is known of its electrophysiological effects in the central nervous system. Because buprenorphine has been...

pubmed.ncbi.nlm.nih.gov

"We report here that buprenorphine and morphine are equally effective in increasing the impulse flow of dopamine cells in the ventral tegmental area. Extracellular single unit activity was recorded from dopaminergic (DA) neurons in the ventral tegmental area (VTA) of chloral hydrate anesthetized rats. Standard physiological and anatomical criteria were used to identify DA neurons. Systemic injection of buprenorphine (5-200 micrograms/kg, i.v.) and morphine (1-10 mg/kg, i.v.) produced equal magnitudes of activation in a similar subset of DA neurons in the VTA (buprenorphine: 173%; morphine: 164 Unlike morphine, the activation by buprenorphine was not reversed by the opioid antagonist naloxone (50-100 micrograms/kg, i.v.), but this is consistent with the known pharmacodynamics of buprenorphine at opioid receptors. These studies demonstrate that acute administration of buprenorphine has morphine-like effects on the impulse activity of DA neurons"

But then there's also this..

Buprenorphine is a weak dopamine releaser relative to heroin, but its pretreatment attenuates heroin-evoked dopamine release in rats - PubMed

These findings support the notion that low-dose buprenorphine is a weak dopamine releaser relative to heroin and that buprenorphine pretreatment can block the dopamine-releasing effects of heroin. The finding that high-dose buprenorphine fails to increase dopamine release might explain its...

pubmed.ncbi.nlm.nih.gov

"Both buprenorphine and heroin produced changes in the frequency of transient dopamine release events, although the effect of buprenorphine was weak and only observed at a low dose"


Why only at a low dose? Does the ceiling effect or activation of other receptors come into play that blocks dopamine release when bupe is dosed too high?

 

[Lorne???]

Buprenorphine 8s so complicated

Because it has a ceiling effect, the dise response curve is all screwed up. If you have a lower tolerance and do a low dose, especially IV, it feels like a full agonist; as dose and tolerance increases you can start to tell it is a partial agonist. (Although IV or even IM still has pronounced effects) The fact it is a Kappa antagonist could also be coming into play here

And yes, PND effects could slow respiration based on what I have read

Your best bet with bupe is to keep your tolerance down and not take the 24mg pet day that is standard

I know someone who injects a LOT of buprenorphine, and even though they basically know less is more, they have, so far, refused to slow down

I hope they do

 

[Lorne???]

I believe you about the norbuprenorphine.

Only thing I can't understand is how does bupe cause respiratory depression at all then? If bupe doesn't cause respiratory depression, then how have there been OD's involving buprenorphine?
And from my own experience, when my tolerance was low and I use to chip with less than 1.5mg of SL buprenorphine, I absolutely experienced slower respiratory rate & the nods. If bupe doesn't cause respiratory depression & or the nods (which it really doesn't, once you go up higher and have a tolerance), than what does? Could peripherally acting norbuprenorphine affect respiratory rate?






Has anyone read this? Maybe I'm interpreting it wrong, but they're saying morphine & buprenorphine cause equivalent dopamine release? Actually buprenophine is higher. How is that possible? Would this not mean buprenorohine is more euphoric and reinforcing than morphine? Seems hard to believe.

Buprenorphine and morphine produce equivalent increases in extracellular single unit activity of dopamine neurons in the ventral tegmental area in vivo - PubMed

Buprenorphine is a synthetic opioid proposed as a potential treatment for drug abuse. Although buprenorphine is widely considered to be a partial agonist at opioid receptors, little is known of its electrophysiological effects in the central nervous system. Because buprenorphine has been...

pubmed.ncbi.nlm.nih.gov

"We report here that buprenorphine and morphine are equally effective in increasing the impulse flow of dopamine cells in the ventral tegmental area. Extracellular single unit activity was recorded from dopaminergic (DA) neurons in the ventral tegmental area (VTA) of chloral hydrate anesthetized rats. Standard physiological and anatomical criteria were used to identify DA neurons. Systemic injection of buprenorphine (5-200 micrograms/kg, i.v.) and morphine (1-10 mg/kg, i.v.) produced equal magnitudes of activation in a similar subset of DA neurons in the VTA (buprenorphine: 173%; morphine: 164 Unlike morphine, the activation by buprenorphine was not reversed by the opioid antagonist naloxone (50-100 micrograms/kg, i.v.), but this is consistent with the known pharmacodynamics of buprenorphine at opioid receptors. These studies demonstrate that acute administration of buprenorphine has morphine-like effects on the impulse activity of DA neurons"

But then there's also this..

Buprenorphine is a weak dopamine releaser relative to heroin, but its pretreatment attenuates heroin-evoked dopamine release in rats - PubMed

These findings support the notion that low-dose buprenorphine is a weak dopamine releaser relative to heroin and that buprenorphine pretreatment can block the dopamine-releasing effects of heroin. The finding that high-dose buprenorphine fails to increase dopamine release might explain its...

pubmed.ncbi.nlm.nih.gov

"Both buprenorphine and heroin produced changes in the frequency of transient dopamine release events, although the effect of buprenorphine was weak and only observed at a low dose"


Why only at a low dose? Does the ceiling effect or activation of other receptors come into play that blocks dopamine release when bupe is dosed too high?

Nice references, btw

 

[DeathIndustrial88]

This link says
"Current studies are focusing on norbuprenorphine, an N-dealkylated metabolite of buprenorphine. Norbuprenorphine is a likely contributor to the overall pharmacology of buprenorphine; in the mouse writhing test, norbuprenorphine provides antinociceptive efficacy similar to buprenorphine, with analgesic activity shown to be dose-dependent"

Europe PMC

Europe PMC is an archive of life sciences journal literature.

europepmc.org

I wonder what they mean by 'dose dependent' & what dose. Most likely, low doses. If norbupe were only peripherally active, wouldn't high dose bupe displace the norbupe still?

Shouldn't this mean there are various 'plateaus' to a bupe high/buzz? Kinda of like how DXM has different effects at different dosages.
You should feel different at different doses, depending on the ratios of bupe & it's metabolites in you.

I have noticed this myself, that doses under 2mg seem more heavy and sedating (not necessarily euphoric though), where doses around 2-4mg are mildly euphoric and stimulating & then the higher you go, the less pain relief it seems to have and eventually leads to dysphoria (in my experience). But this is with a tolerance to it. There have also been times where 16-24mg has also been sedating though, so I dunno.


It also shows that chronic use of buprenorphine/naloxone could lead to blocking dopamine leading to relapse potential (and probably depression in people who use bupe for it's antidepressant effect). But we also learned that bupe releases dopamine (albeit weakly). I couldn't quit understand in this article what exactly it was that was causing the block of dopamine, except that it was constant mu-blockading.

I'm just throwing this out there for those looking to learn more about bupe/norbupe.