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Buperenorphine potentiation with curry. Good food and a good buzz, a win win.

Honestly speaking, I'm not really sure any more whether it's norbuprenorphine that is more responsible for central mu opioid effects of buprenorphine. It's a P-glycoprotein substrate so its CNS penetration is strongly inhibited, it's actually largely responsible for peripheral side effects like slowed respiration which I definitely can often feel (it's quite pronounced especially if buprenorphine is combined with another drug that does that). Norbuprenorphine itself is also very weak as an analgesic compared to buprenorphine which is not necessarily a sign of low CNS concentration, but in my opinion it's doubtful that norbuprenorphine would have a low efficacy at mu receptors. Also, in PGP-deficient mice the analgesic effect of norbuprenorphine was more pronounced which suggests that PGP negatively affects CNS penetration (source).

As a side note, I used to drink a lot of grapefruit juice without thinking much how it would affect buprenorphine effects for me. When I realized that by blocking CYP3A4 I'm somehow lowering my norbuprenorphine levels, I stopped drinking the juice for a while. Honestly, I had much better effects when I was drinking it, especially in the duration of effects. I don't know to what extent it was related to CYP3A4 inhibition and higher bupe/norbupe ratio as I noticed that many things actually affect the absorption of buprenorphine sublingually and I often get very different effects from the same dose on various days. So my personal advice would rather be to inhibit CYP3A4 rather than activate it. Certainly a bit higher levels of buprenorphine won't cause much side effects as it's highly lipophilic and stays in the brain for a long time, on the other hand norbuprenorphine being a secondary amine is much more hydrophilic so it will migrate from the brain faster anyway causing side effects peripherally.
 
adder said:
Honestly speaking, I'm not really sure any more whether it's norbuprenorphine that is more responsible for central mu opioid effects of buprenorphine. It's a P-glycoprotein substrate so its CNS penetration is strongly inhibited, it's actually largely responsible for peripheral side effects like slowed respiration which I definitely can often feel (it's quite pronounced especially if buprenorphine is combined with another drug that does that). Norbuprenorphine itself is also very weak as an analgesic compared to buprenorphine which is not necessarily a sign of low CNS concentration, but in my opinion it's doubtful that norbuprenorphine would have a low efficacy at mu receptors. Also, in PGP-deficient mice the analgesic effect of norbuprenorphine was more pronounced which suggests that PGP negatively affects CNS penetration (source).
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Slowed respiration is mediated by central mu opioid receptors (most likely in the brain stem), not peripheral receptors in the lungs.
 
endotropic said:
Slowed respiration is mediated by central mu opioid receptors (most likely in the brain stem), not peripheral receptors in the lungs.
Click to expand...
Yeah, if the respiratory depression was due to norbupe then wouldn't buprenorphine produce a lot more respiratory depression? My understanding was always that there is a ceiling on the amount of respiratory depression produced by buprenorphine because it is a partial agonist, and its relative safety in overdose seems to support that.

Another question: if you could get more norbuprenorphine into the brain, wouldn't buprenorphine block most of the effect? (unless you were on a low dose)
 
It doesn't seem to have a lower affinity than buprenorphine according this article. I remember reading somewhere that normorphine doesn't have a lower affinity than morphine either.

Slowed respiration is mediated by central mu opioid receptors (most likely in the brain stem), not peripheral receptors in the lungs.
Click to expand...

What a stupid thing I wrote. Of course it is. :| When I read this, I suddenly remembered reading as a kid that medulla oblongata controls breathing...
 
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