Buprenorphines effects at higher and lower doses

[Tylercwxzy]

I always thought, as I'm sure others do that the higher dose of bupe causes more antagonist effect than the lower doses do. But I was looking around on the web after plugging an entire sub instead of my usual half (So 4mgs instead of 2 due to bio.) and getting a warm glow and found this:
Abstract
Buprenorphine is a mixed opioid agonist/antagonist analgesic. This study was designed to determine the role of opioid receptor subtypes, especially κ3, in buprenorphine-induced analgesia in mice. Buprenorphine, when injected systemically, revealed a potent analgesic effect by tailflick assay, with a biphasic dose–response curve, which was reversed by naloxone. The presence of analgesic cross-tolerance between buprenorphine and naloxone benzoylhydrazone (NalBzoH) and morphine indicated a role for κ3 and μ receptor subtype in buprenorphine analgesia. Additional studies with selective opioid antagonists indicated κ1 mechanisms of action. We did not detect any involvement of the δ receptor subtype. Low doses of buprenorphine antagonized morphine analgesia, while high doses of buprenorphine coadministered with morphine elicited increasing analgesia in a dose-dependent manner. These findings suggest that buprenorphine elicits analgesia through an interaction with κ3 receptors and to a lesser extent with κ1 as well as its activity as partial μ receptor agonist.

So are they saying the higher doses actually increased the morphines ability at killing pain, not really saying it increased euphoria but from the sounds of it, you would think the bupe would take over and just kick all them morphine out of your system. But co-administering both? Strange news to me. I was wondering if anyone else has more information about buprenorphines affects at high doses and if its more of an antagonist or agonist compared to low doses such as between 0.3mg-2mg ?

OH! by the way, happy thanksgiving everyone.

[blackman]

I don't know anything about the scientific part of suboxone,
but from personal experience and talking with friends it seems that
there isn't much more of an opiate feeling above say 12-16mgs or so?

What I mean is that if you take 12mg the "high" won't be much different than if you took 32mg.
But this is really just from personal experience.
I don't really know why it works that way.

[Thanat0s]

something due the 'partial agonist/antagonist' profile\

makes it seem to block itself
above 8mg sublingual IME

higher dose give more side effect
and less opi glo

'blows'
if you have a moremoremore personality.


edit:
hrm
if the morph and bupe act on diff specific receptor differently a synergy could be present, no?

my pharmokeenetucks sux anymore.

[Tylercwxzy]

Well I believe its because of the mixed agonist/antagonist properties that limit it, which is why I would think the bigger the dose the more likely it is to block morphine's analgesia effects on the body. But according to the experiment it increased it, with a high dose and decreased it with a lower one. You are right though, the higher you go doesn't truly mean you get higher because of the limits of mixed opiates compared to pure agonist like morphine which have no ceiling effect. I just find opiates effects interesting in general and how they work on the human body. I'm just trying to figure out if there is evidence of what everyone says that lower doses of buprenorphine have more agonist properties than larger doses which supposedly have more antagonist effects.

[blackman]

Yeah thanat0s, it is more like 8mg.

Yep Tyler, i also think the effects of opiates on the body are really interesting, yet occasionally annoying at the same time.

I always wish I could get blasted on 24mg of suboxone. What a waste though.

[30_Units]

Something I'm wondering about is what their definition of high and low dose buprenorphine happens to be.

Would there be a pdf or graph associated with this data? It could be helpful.

Neat though. Bupe's a weird drug.

[Tylercwxzy]

I'd like to know to, but the rest of the site is "pay-to-view" only, they only show a paragraph of information about the experiment. http://www.sciencedirect.com/science...ad8de5f06cc532

Interesting indeed, i'm curious because other mixed agonists like pentazocine and stadol seem to increase effects as the dose is increased up until the ceiling effect, but effect the Kappa receptors more than the Mu. Bupe seems to mainly effect mu receptors more which are responsible for pain relief/euphoria, as with the kappa is responsible for some breathing effects and dysphoria but they seem to be more euphoric than bupe from other accounts. Idk for sure, just trying to figure it out.