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What's behind the "less is more" effect of Buprenorphine?

jasoncrest

jasoncrest

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With Buprenorphine, a lot of people say that "less is more".
It means that taking less gives a better effect.
I wonder what causes this?

I think I read somewhere (it was on bluelight or an the opiophile message board I think) that this was because Bupe at a low dosage (0,2 to 1mg) is a full mu agonist, while at higher doses, it's a partial mu agonist...

But I can't find any info on this...
Does anyone have a theory on this subject? Is it true that "less is more"?
 
Only thing I can think of is that bup has a low affinity antagonist activity, but I doubt it.

From looking at GTP turnover experiments thers is no sign of that

opioidInducedG-proteinActivation.gif


OpioidReceptorAgonistGProteinAcitivity.gif
.


I suppose the other possibility is that one of buprenorphins metabolites, is an antagonist, which actually gets to clinically important concentrations; but the evidence is that bups main metabolite is an agonist [1]... so I don't know.
 
For me, 'less is more' means that bupe is a strong med that can hold me from opiate sickness on 2mg's or 10mg's. I get the same effects from the 2mg's as I would the 10mg's so for me less is more, in that sense.

I think I read somewhere (it was on bluelight or an the opiophile message board I think) that this was because Bupe at a low dosage (0,2 to 1mg) is a full mu agonist, while at higher doses, it's a partial mu agonist...
Click to expand...

I recall reading something similar to that also, although I thought it was an article. Oh well I am on house arrest for the next 4 months so maybe Ill find the time to find it. :\
 
For me, 'less is more' means that bupe is a strong med that can hold me from opiate sickness on 2mg's or 10mg's. I get the same effects from the 2mg's as I would the 10mg's so for me less is more, in that sense.
Click to expand...
If low doses saturated the receptor, then it's possible that there would be no differenece between 2 and 10mg... I suppose it's possible you then get spill over onto other opioid receptors, which reduces the fun of the experience...
 
I think those graphs seem to indicate that "less is the same as more", which is what people seem to be saying. The effect doesn't really change much once a certain level of agonist concentration is reached (eg - mMOR-CHO cells, bupe concentration between 10 and 100 nM, net stimulated binding stays around 40 fmol/mg). In other words - the ceiling effect which gives bupe such a great safety profile. But why such a non-linear dose response curve? (compared with, say, morphine)
 
The effect of "not really changing" isn't "less is more" it's "more is the same".

Non-linear? You mean that little dip in the second set of graphs? It's probably just a mistake.
 
ayjay said:
I think those graphs seem to indicate that "less is the same as more", which is what people seem to be saying. The effect doesn't really change much once a certain level of agonist concentration is reached
Click to expand...

I agree with that. I don't think that "less is more", but "less is the same than more".
(unless you're addicted to high doses, then with 2mg you won't be fine, you need your 24mg to be fine)
 
Then that makes perfect sense, if you're dosed to reach saturation, then less would be the same as more... and you couldn't do that with normal opiates, as saturating doses would kill you.
 
I read somewhere that high doses of BUP hit the OLR1 receptor (Opiate Like Receptor, from my bad memory) that oppose the Mu- receptor.

But low doses of BUP do not.
 
The drug company rep told us that its only a partial antagonist at lower doses as well so that people on doses below 16 ml could use on top with dose dependant effect.

I would guess its getting enough to cover your cluck (remembering to take it so that you don't precepitate withdrawel) and remove the temptation to dabble while minimising the dose. (which is important in terms of brain chemistry adaptation LTP & LTD)
 
Dr. Beat said:
I read somewhere that high doses of BUP hit the OLR1 receptor (Opiate Like Receptor, from my bad memory) that oppose the Mu- receptor.

But low doses of BUP do not.
Click to expand...

That's really interesting, you got any source? link?
 
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