A NEW Thought about Loperamide (not the same old debate)

[daddysgone]

Ok, I have no interest in getting into this debate regarding whether loperamide can or cannot act centrally, and thus create a typical opioid high.
However, I had a thought that seems like it would be a great idea for those of you that are attempting these insanely high doses in the hopes that you will achieve central affects.

My thought was if one could use an opioid ANTAGONIST which does NOT cross the blood brain barrier, this would be a godsend, for a number of reasons, for those of you experimenting with loperamide. There is a fairly recent drug called methylnaltrexone which is designed to do exactly what I described. It is an opioid antagonist which doesnt cross the BB. Thus, it would block loperamide (or any opioid) from binding to receptors in the gut, but because methylnaltrexone doesnt cross the BBB, it would theoretically, not effect loperamide's ability to bind to receptors in the brain.

So if one were to take something like methylnaltrexone along with loperamide, it would greatly help for a number of reasons.
First, it would essentially nullify the massive dosage of loperamide in your gut that would otherwise cause immense constipation.
Secondly, and Im only speculating here, if methylnaltrexone is blocking loperamide from binding in the gut, it would seem to me that there would then be much more available loperamide in the bloodstream, which would faciliate higher concentrations reaching the receptors in the brain.
My reasoning is that because loperamide has such a high affinity for receptors in the gut, when a dose is taken, nearly all of it binds to gut receptors and thus very little is left free to bind to central receptors in the brain. If something like methylnaltrexone was used concurrently with loperamide, it would block loperamide from binding in the gut, and thus much more of it would be free to bind in the brain.

Again...this is all just theoretical. At the very least however, I have to imagine that something like methylnaltrexone would GREATLY help with the constipation which would likely result from these massive doses of loperamide.

Any thoughts on this?-DG

 

[Desdenova]

I suppose it's possible, but it would depend on exactly how the mechanism of the blood brain barrier works.

If it can only keep out a certain amount of chemical, and anything over that amount would get past, or if it's more like a wall, and the question isn't about "overwhelming its defenses", but physically getting past a barrier

And the methylnaltrexone is a good idea in terms of nullifying the massive constipation you would get. But last I heard, the only formulation was available was injectable vials. And since it's pretty new, it would likely be expensive/hard to find

 

[swilow]

BBB doesn't work by leeping out X amount of a molecule, but it works by keeping X amount of a certain shaped molecule out.

 

[daddysgone]

BBB doesn't work by leeping out X amount of a molecule, but it works by keeping X amount of a certain shaped molecule out.

well......sort of

I know what you are saying, and in theory that is correct. But im fairly certain that it has been demonstrated that when taken in massive doses, some molecules that ordinarily would not get past the BBB, will in small amounts.

 

[djsim]

The only reason loperamide has such a high affinity for peripheral receptors is because it is all relative. It simply can't reach central opiate receptors

 

[beta1]

Any Loperamide thread more than 1 paragraph = tl;dr

 

[daddysgone]

Any Loperamide thread more than 1 paragraph = tl;dr

sorry, i dont understand your abbreviations. tl;dr?? care to explain

 

[Lustmord]

Just inject it into your brain.

 

[drug struggler]

off topic here I'm sorry... however, I took loperamide, around 14mg's yesterday (not the disgusting doses we've read about when people try to abuse it) when I ran out of suboxone. As well as keeping diarrhea at bay, I am adamant that it reversed my cold chills and sweats. Simply put, before I took the loperamide I had sweats and cold chills, afterwards they were gone. Now, how could this be if the sub blocks the action of any opiates? I know that loperamide doesn't cross the BBB. So what happened? I am extremely sensitive to opiate wd's and know my body pretty well after 10yrs of opiate addiction so I'm almost 100% this was not a placebo. Did the loperamide absorbed thru my gut relieve the opiate wd's? I was sick of the debate of loperamide myself and didn't think I'd contribute to the posts/misleading/confusion, but I was just too uncomfortable and wanted to try something. I'd have to try it again to be more certain (I have subs again) but yesterday's experience was positive for loperamide.

 

[daddysgone]

off topic here I'm sorry... however, I took loperamide, around 14mg's yesterday (not the disgusting doses we've read about when people try to abuse it) when I ran out of suboxone. As well as keeping diarrhea at bay, I am adamant that it reversed my cold chills and sweats. Simply put, before I took the loperamide I had sweats and cold chills, afterwards they were gone. Now, how could this be if the sub blocks the action of any opiates? I know that loperamide doesn't cross the BBB. So what happened? I am extremely sensitive to opiate wd's and know my body pretty well after 10yrs of opiate addiction so I'm almost 100% this was not a placebo. Did the loperamide absorbed thru my gut relieve the opiate wd's? I was sick of the debate of loperamide myself and didn't think I'd contribute to the posts/misleading/confusion, but I was just too uncomfortable and wanted to try something. I'd have to try it again to be more certain (I have subs again) but yesterday's experience was positive for loperamide.

My GUESS (just a guess), is that a small amount of loperamide did get thru the BBB and gave you central effects (thus relieving some of your withdrawal symptoms). I know Im going to get flamed by those on here that are completely convinced that loperamide is completely incapable of crossing the BBB and therefore your relief was only due to placebo effect.
Im a bit more open minded on this subject. I will readily admit Ive not experimented with loperamide so I cannot speak from experience. However, I also think my lack of experience is irrelevant because it would only represent one person's experience, making it meaningless.

My open-mindedness stems from all of the reports from people like you, who are clearly opiate dependant, and experience significant relief from withdrawal (not just cessation of diarrhea), upon taking large doses of loperamide. There are just too many anecdotal reports out there from people just like you, for me to dismiss loperamide and attribute all the profound cessation of withdrawal, to placebo alone.
Anyone who is opiate-dependant, knows how powerful opiate withdrawal is. I find it nearly impossible to imagine that there are so many people out there who have simply "duped" their bodies into believing that they have ingested an opioid that is acting centrally, and that this placebo effect accounts for the relief of their withdrawal. It seems far more likely to me to accept that after all, loperamide IS an opioid, and perhaps in large doses, an unknown quantity is capable of passing through the BBB more readily then was previously thought. Just my thoughts-DG

 

[beta1]

off topic here I'm sorry... however, I took loperamide, around 14mg's yesterday (not the disgusting doses we've read about when people try to abuse it) when I ran out of suboxone. As well as keeping diarrhea at bay, I am adamant that it reversed my cold chills and sweats. Simply put, before I took the loperamide I had sweats and cold chills, afterwards they were gone. Now, how could this be if the sub blocks the action of any opiates? I know that loperamide doesn't cross the BBB. So what happened? I am extremely sensitive to opiate wd's and know my body pretty well after 10yrs of opiate addiction so I'm almost 100% this was not a placebo. Did the loperamide absorbed thru my gut relieve the opiate wd's? I was sick of the debate of loperamide myself and didn't think I'd contribute to the posts/misleading/confusion, but I was just too uncomfortable and wanted to try something. I'd have to try it again to be more certain (I have subs again) but yesterday's experience was positive for loperamide.

It wasn't placebo, loperamide is great for w/ds.

 

[drug struggler]

^ thanks for the affirmation, but any idea how this is possible? Again, the sub was still blocking my receptors (it was only 1.5 days since my last 2mg's of sub)

I'm simply assuming the lope got thru my gut and was able to curb wd's... I could be way off base. But even if some got thru the BBB, it wouldn't be able to get thru the bupe. Hell, I'm not complaining, just curious

 

[QuasiStoned]

^^^
I dunno drug struggler, that is weird because should block other opiates. Whatever the case, loperamide can be a lifesaver during withdrawal. This is the usual debate over loperamide though, many people believe that it does not cross the BBB in any significant amount to get people high or relieve withdrawals.

Firsthand experience from a lot of people suggests otherwise, but then those who disagree often write it off as placebo.

It seems that with loperamide, it goes one of three ways. Some people experience nothing from loperamide except relief from the explosive shits. Some people experience significant reduction in withdrawals, and some people claim to experience a high (often times in ridiculous dosages, say 100mg or so).

Just FYI, my personal experience has been that loperamide can reduce or almost completely reverse my withdrawal symptoms in dosages around 20mg. They will not get me high though, not even if I push the dosage up.

 

[dopiate]

^ thanks for the affirmation, but any idea how this is possible? Again, the sub was still blocking my receptors (it was only 1.5 days since my last 2mg's of sub)

I'm simply assuming the lope got thru my gut and was able to curb wd's... I could be way off base. But even if some got thru the BBB, it wouldn't be able to get thru the bupe. Hell, I'm not complaining, just curious

The simple fact that you were experiencing withdrawal symptoms is explanation enough why an opiate would relieve them.

Buprenorphine does not create a force field around your receptors, it simply fills them and doesn't budge til it wears off.

Your w/d symptoms indicate that you didn't have the appropriate amount of bupe that you're used to.

36 hours is enough time to remove a significant amount of bupe from your receptors.

So an opiate that makes it to the receptors will occupy those receptors.

 

[sixpartseven]

^ thanks for the affirmation, but any idea how this is possible? Again, the sub was still blocking my receptors (it was only 1.5 days since my last 2mg's of sub)

I'm simply assuming the lope got thru my gut and was able to curb wd's... I could be way off base. But even if some got thru the BBB, it wouldn't be able to get thru the bupe. Hell, I'm not complaining, just curious

Loperamide MAY have a higher affinity for the receptors than Suboxone does? I don't think there is any literature explaining the difference in affinity for these two substances. Just because Buprenorphine has a higher affinity than other opiates does NOT mean it has THE HIGHEST affinity of ALL opiates. I know Loperamide does have a very high affinity for Mu receptors, so it's possible it's stronger than Buprenorphines.

Also, there's a chance your last dose of Suboxone had worn off by the time you took it? There's quite a few possibilities.

Loperamide is not COMPLETELY blocked by the BBB. And it's not really the "blocking" that you have to contend with. P-glycoproten pumps push it back out once it does cross, but it does not push ALL of it back out, so some does get to the CNS, thus, mitigation of withdrawal symptoms.

That's why the people who get "high" from Loperamide take 200mg, because at that dose, enough can cross over to get them "high." (I say high in quotes because it's not a traditional opiate high, and it doesn't work for everyone)

When you took your dose of Loperamide, you took enough so that the amount you needed to relieve the withdrawal symptoms got through to the CNS. It does work. It worked for me. It's how I quit Suboxone. I switched to moderate-dose Loperamide and tapered down. I stated at about 48mg and dropped down to 2mg over 2 months, then just stopped taking it and was fine.

It definitely works for withdrawal, but getting high from it is reckless and there is no guarantee you will get high from it, which is why it's pointless to take those massive doses. As long as your tolerance to other opiates isn't ridiculously high, 60mg is the most anyone should have to start with when trying to ease off their opiate of choice. Sometimes that much isn't even required, so as always, start small and work your way up till you find your dose, then taper down over a period of time.

If your tolerance is so high that 60mg isn't enough, I suggest tapering down a little bit with whatever opiate it is you use, THEN switch when no-more than 60mg of Loperamide will help you.

 

[drug struggler]

The simple fact that you were experiencing withdrawal symptoms is explanation enough why an opiate would relieve them.......
So an opiate that makes it to the receptors will occupy those receptors.

Yeah I understand this, makes perfect sense, thanks... But it's freakin' loperamide! You know, when you think of someone able to handle 160mg a shot to taking 14mg loperamide and noticing it eliminates mild wd it's really amazing. I guess I'm more astonished because when I first got off of suboxone after over a year of maintenance (my dr didn't have me taper correctly and I didn't know about BL) I came off of 2 mg's sub cold turkey and (after that length of time) was in wd's considerably, I took about 20 mg of oxycodone and still had wd's... I should think 20mg oxy would curb wd better than 14mg loperamide. But this time around it was only 1 week on sub that the lope helped wd so perhaps that's why? Who knows... thanks everyone

EDIT... sixpartseven post appeared while I was typing this... "Loperamide MAY have a higher affinity for the receptors than Suboxone does? I don't think there is any literature explaining the difference in affinity for these two substances. Just because Buprenorphine has a higher affinity than other opiates does NOT mean it has THE HIGHEST affinity of ALL opiates. I know Loperamide does have a very high affinity for Mu receptors, so it's possible it's stronger than Buprenorphines.

Also, there's a chance your last dose of Suboxone had worn off by the time you took it? There's quite a few possibilities.

Loperamide is not COMPLETELY blocked by the BBB. And it's not really the "blocking" that you have to contend with. P-glycoproten pumps push it back out once it does cross, but it does not push ALL of it back out, so some does get to the CNS, thus, mitigation of withdrawal symptoms."

Thank you! This is exactly what I was looking for... I'll be tapering my sub to a very, very low level this week, then I will switch to loperamide and taper that accordingly.

 

[Lost and Confused]

How is this not the same old debate?

Regardless of the MOA, the debate once again comes to whether or not it can cross the BBB.

 

[sixpartseven]

^ Always does, because people never do their research. They just read the first thing they see and stick with that.

 

[Lustmord]

Alright, new question.. Can Loperamide cross the BBB?

 

[ArtVandalay]

Jesus, will this loperamide debate ever end? It seems like every few months a new lope thread pops up.