Mixing partial mu opioid receptor agonists with full mu opioid agonists?

[TheJuner]

Sorry if this is a silly question but could one combine a partial mu opioid receptor agonist like pentazocine or buprenorphine with a full mu opioid receptor agonist like morphine or oxycodone and expect the two substances to synergize? Or will the mixed agonist/MOR agonist-antagonist block the effects of the full agonist.

 

[Psycho_Logic]

Hi. Never did it so this is pure speculation. But my opinion is if:

1) The dose of buprenorphine is on the lower side (>0.5mg).
2) The person has moderate to high tolerance and not enough full agonist.

I can see it being usefull. But how will low dose buprenorphine interact with oxycodone regarding "synergy" (will the combo be more pleasant) I don't know. Too many unknown variables. If one is experienced opioid user it would be wise to half the full agonist dose. Something like take 0,25-0,5 mg of buprenorphine first and after 1 hour take half of the usual oxycodone dose. Assess when oxycodone kicks in fully and up by 25% of usual oxycodone dose. Stop hoing higher.

IMPORTANT: If one is not already dependent on oxycodone I would advise against mixing opioids. Taking mentioned doses of buprenorphine will not protect you from opioid OD. If you will play with fire no matter what - use harm reduction aproach. Opioids are amongst least forgiving drugs if the dose is not precisely adjusted.

 

[TheJuner]

Hi. Never did it so this is pure speculation. But my opinion is if:

1) The dose of buprenorphine is on the lower side (>0.5mg).
2) The person has moderate to high tolerance and not enough full agonist.

I can see it being usefull. But how will low dose buprenorphine interact with oxycodone regarding "synergy" (will the combo be more pleasant) I don't know. Too many unknown variables. If one is experienced opioid user it would be wise to half the full agonist dose. Something like take 0,25-0,5 mg of buprenorphine first and after 1 hour take half of the usual oxycodone dose. Assess when oxycodone kicks in fully and up by 25% of usual oxycodone dose. Stop hoing higher.

IMPORTANT: If one is not already dependent on oxycodone I would advise against mixing opioids. Taking mentioned doses of buprenorphine will not protect you from opioid OD. If you will play with fire no matter what - use harm reduction aproach. Opioids are amongst least forgiving drugs if the dose is not precisely adjusted.

Thank you for your response, though I should add that I wasn't asking this question because I want to use a partial opioid agonist to potentiate the effects of a full opioid agonist. And by synergy I am not just referring to whether the combination will intensify the euphoric effects of the full opioid agonist, but also synergy when it comes to analgesia (for example someone wearing a buprenorphine patch then taking instant release oxycodone if they find themselves in excruciating pain or vice-versa). And yeah I agree with you that buprenorphine will not protect you from overdosing, the fact that it acts as a partial agonist doesn't mean it can be used as a sort of preemptive antagonist that will eliminate the risk of overdose.

 

[Psycho_Logic]

Well taking oxycodone on top of 2mg of buprenorphine will help with the pain. But some where after the 8mg buprenorphine mu receptors are almost all occupied. In that case fentanyl patches/tablets (prescribed by the doctor so one knows the dose) is a better choice do to fent high μ-opioid receptor affinity. Other opiods that could work are hydromorphone and oxyomorphone as thrir affinity to μ-opioid receptor is much higher than oxycodones. Amount of oxycodone (and a bit of oxymorphone as metabolite) one would have to take for oxycodone to squeeze in amd occupie μ-opioid receptor would be too high for it to be worth it if the dose of buprenorphine is in the blockage territory. Take all this with a truckload of salt cause I am no doctor or scientist and am giving sn opinion.

 

[Coffeeshroom]

From personal experience I can add that for me when I was on bupre and got to a low dose of 500mcg I could use H a few hours later and it worked. I also did the same with MsCotin but waited about roughly 12 hrs before dosing and also once it hit me hard and could feel it.

But with all that said I don't think there was any synergy effect. Just the feeling of the drug I took.

Also have to add I had to take more then my normal dose if I wasn't on maintenance dose of bupre. I also did this when I even had up 2mg in my system but never higher. But mostly it was at low dosages of sub 1mg (700-500mcg)

This is all from my own personal experience and knowing my body and limits

 

[negrogesic]

Mixing partial mu opioid receptor agonist like pentazocine or buprenorphine with a full mu opioid receptor agonist such as morphine or oxycodone will not result in additional or synergistic effects

Its more common of a scenario when someone is on say bupe and decides to to take a sufficient amount of say fentanyl to break through the grip that bupe has on the MOR. But together they are not synergistic or additive

 

[Señor Moreno]

No, they don't synergize; the parctial agonist just negates the full agonist effects, but you definitly can avoid a pwd to happen. I know it cause when we were very young we had hose Buprex 0,2mg, that we used for h wds.
It worths saying that buprenorphine was a relatively new drug and Internet didn't exist, information was next to none and we were too stupid to care, anyway
One day I was doing my h shot and I decided that I might just drop one Buprex in, just for the hell of it and thinking that it would potentiate the h like we knew that benzos did. So I did it and slamed that weird mix. All what happened was exactly nothing. It didn't get me high, like that h alone would; I was not in withdrawal so I didn't feel it fixing me either and I didn't enter any precipitated wd. Nothing at all happened. Turned out that 0,2 mg weren't enough to precipitate wd, but it's superior afinity was indeed enough to get hold of the receptors and didn't allow me to feel shit from that h, good h from those years.
It goes without saying that I was a kid and had no clue about wtf I was doing

 

[TheUltimateFixx]

No, they don't synergize; the parctial agonist just negates the full agonist effects, but you definitly can avoid a pwd to happen. I know it cause when we were very young we had hose Buprex 0,2mg, that we used for h wds.
It worths saying that buprenorphine was a relatively new drug and Internet didn't exist, information was next to none and we were too stupid to care, anyway
One day I was doing my h shot and I decided that I might just drop one Buprex in, just for the hell of it and thinking that it would potentiate the h like we knew that benzos did. So I did it and slamed that weird mix. All what happened was exactly nothing. It didn't get me high, like that h alone would; I was not in withdrawal so I didn't feel it fixing me either and I didn't enter any precipitated wd. Nothing at all happened. Turned out that 0,2 mg weren't enough to precipitate wd, but it's superior afinity was indeed enough to get hold of the receptors and didn't allow me to feel shit from that h, good h from those years.
It goes without saying that I was a kid and had no clue about wtf I was doing

ohh what a waste man Xd

 

[Pickledlemons]

Does it really matter if its partial or full? (when it comes to synergy) Isn't it more about binding affinity and potency? If they're fighting for limited receptors I mean, that not going to help you. I would honestly just stick to one opioid at a time, if you must add to it somehow, take a small benzo dose (and I mean small) or perhaps phenibut, maybe gabapentin?

Some people like to drink on opioids but thats never really done it for me. Plus alcohol is a notoriously bad mix for pretty much everything.

 

[daturetard]

Does it really matter if its partial or full? (when it comes to synergy) Isn't it more about binding affinity and potency? If they're fighting for limited receptors I mean, that not going to help you.

Yes, it does matter. The partial agonists will cap out at a lower amount of receptor activation. https://external-content.duckduckgo.com/iu/?u=https://www.biologyonline.com/wp-content/uploads/2019/10/Types-of-agonists-vs.-receptor-response-diagram.png&f=1&nofb=1&ipt=bdc638564008089818a29898a8b7752a50709922507c360322c63cab86bb7e2a&ipo=images Roughly half, most of the time, and I'm almost certain partial agonists can also function as antagonists.

I would honestly just stick to one opioid at a time.

Agreed.

E: also, no, like most above said, the bupe will cancel out the full agonist.

 

[krkkhed]

I took ~0.2mg buprenorphine (IV) this morning when I woke up (4 hours ago at this point), and just now shot some heroin, and I feel like the two are working together in a way. Maybe because of the tiny dose of bupe, but I got a rush from the H. And now I feel like I normally do on heroin, it was a weak shot though so not super strong.
I think it might synergize or small bupe dose might help boost a full agonist but reading around it seems this doesn't make any sense biologically/pharmacologically. Maybe it's just me, maybe it's placebo but it would be a pretty strong one at that, and I did have constricted pupils after the H shot that I didn't have before (buprenorphine doesn't really constrict my pupils that much, plus I had looked at them earlier and they were normal size) so that might indicate some actual effects? I don't know.

 

[daturetard]

I took ~0.2mg buprenorphine (IV) this morning when I woke up (4 hours ago at this point), and just now shot some heroin, and I feel like the two are working together in a way. Maybe because of the tiny dose of bupe, but I got a rush from the H. And now I feel like I normally do on heroin, it was a weak shot though so not super strong.
I think it might synergize or small bupe dose might help boost a full agonist but reading around it seems this doesn't make any sense biologically/pharmacologically. Maybe it's just me, maybe it's placebo but it would be a pretty strong one at that, and I did have constricted pupils after the H shot that I didn't have before (buprenorphine doesn't really constrict my pupils that much, plus I had looked at them earlier and they were normal size) so that might indicate some actual effects? I don't know.

Unrelated, but is there any significance to your name and profile picture other than reading as "crackhead"? Because if not you might want to change it to one K on the end there, just me personally tho.

 

[someguyontheinternet]

Yes, it does matter. The partial agonists will cap out at a lower amount of receptor activation. https://external-content.duckduckgo.com/iu/?u=https://www.biologyonline.com/wp-content/uploads/2019/10/Types-of-agonists-vs.-receptor-response-diagram.png&f=1&nofb=1&ipt=bdc638564008089818a29898a8b7752a50709922507c360322c63cab86bb7e2a&ipo=images Roughly half, most of the time, and I'm almost certain partial agonists can also function as antagonists.

Agreed.

E: also, no, like most above said, the bupe will cancel out the full agonist.

Just to expand on these ideas a bit:

Partial agonists can act as antagonists when they have a higher affinity than the endogenous ligand, in this case that would be one of the opioid neuropeptides.

Buperenorphine has a really high affinity so it kicks out other molecules from the binding slot but doesn't activate the receptor as much as full agonists. If you were to mix a lower affinity partial agonist the full agonist would win out

When it comes to g-protein biased agonists things are a little different. The current leading hypothesis has to do with the mu opioid receptor taking on slightly different conformations depending on what intracellular components are interacting with the receptor. This changes the shape of the binding site which means that some compounds will bind g-protein receptors but not beta-arrestin receptors because the binding site is different. If you mix a biased agonist with an unbiased agonist it could theoretically be possible to get more mu receptor activation due to the difference in binding sites

Not all mu receptors will have just beta-arrestin or just g-proteins bound, some may interact with both and some may also dimerize with other surface proteins which also impact binding site conformation leading to several slightly different receptor populations which different compounds will have different affinities for

 

[krkkhed]

Unrelated, but is there any significance to your name and profile picture other than reading as "crackhead"? Because if not you might want to change it to one K on the end there, just me personally tho.

I used to smoke crack occasionally when I was 13-14 and was a member of a lot of online drug communities, one in particular, which already had a user named Crackhead so I just used Ks instead. And here I just dropped the letter A for whatever reason. Not gonna change the name, I've used it for 7 years so I've taken a liking to it even though it's a bit stupid.