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Forcing Loperamide through the BBB

jasoncrest

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There's a thread by TheTripDoctor on Loperamide in Other Drugs, it seems that he found the way to enjoy Loperamide....

In the thread, it has been said that the way to feel an effect from Loperamide is to take a very large amount of it (just like GABA doesn't cross the BBB, but is taken in 1 to 5 grams doses, so a part of it goes through the BBB)

I would like to read an advanced drug discussion on this subject.

#Is it true that if you take a very large amount of a substance that doesn't cross the BBB, some of it will cross the BBB.

#If this is true, is it possible to know how many mgs Loperamide will cross the BBB if you eat 10 grams of Loperamide?

(If there's no answer to this question, do we know how many mgs GABA cross the BBB when someone eat 10 grams of GABA powder?)

Any input, info?
 

robatussin

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would the consipation rate be worth it? 10 grams is at least 5000 times the recommended dose
 

Smyth

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Steve actually said 50mg did the job but that u have to take some other weird antihistamine pill to potentiate the loperamide. But u cant just go into a pharmacy store or u end up paying too much money since loperamide is not distributed in units that can maintain this dose.
 

raybeez

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Smyth said:
Steve actually said 50mg did the job but that u have to take some other weird antihistamine pill to potentiate the loperamide. But u cant just go into a pharmacy store or u end up paying too much money since loperamide is not distributed in units that can maintain this dose.

^^^

My understanding of his post was that loperamide was active if:

1. Large doses were taken (ie 50mg)
2. Smaller doses were taken with tagamet, which increased the bioavailability/AUC of the drug by inhibiting its metabolism.
 

mitogen

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robatussin said:
would the consipation rate be worth it? 10 grams is at least 5000 times the recommended dose
good fucking point. there is no god damn WAY that I would want to take an overdose of this stuff. I already have bad enough constipation and haemarrioids as it is. I wonder what would actually happen to your GI tract if you took that much. Seems we have a guinea pig... Perhaps we could ask him to give an experience report...;)

We were actually talking about this a while ago if you look in the archives. Maybe 6 months ago? I think it turned out that loperamide does actually cross but is pumped out straight away by P-glycoprotein. Better check that... We decided that a combination of the correct CYP450 inhibitor and a P-glycoprotein inhibitor should allow the loperamide to stay in the brain long enough to have an effect. We discussed various PGP inhibitors and basically came to the conclusion that yes this was feasible, but a.) PGP is there to protect the brain, and is probably something that is not really worth screwing around with, and b.) PGP inhibitors are not that common/accessible, and are usually lab-grade [2 problems with this are accessibility, and the fact that only very small amounts would be used in labs to treat cell cultures etc. so one probably wouldn't be able to obtain enough from a lab to actually dose with]
 
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jasoncrest

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I was just curious. (very curious in fact).

I wouldn't take large doses of Loperamide, it would be too expansive, and I think the side-effects aren't worth it...
(and I'm on Methadone by the way, and can get Morphine for a cheap price)

But I'm still curious....
What doses of Loperamide would be equivalent to 300mg Codeine?

(or: when a substance is unable to cross the BBB, how many do you have to take to make some of it cross the BBB?)
 

bingey

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^
yeah i always use it for potentiation cause its the cheapest thing around in holland however in france its fricking expensive (1 euro here)

i took like 40 mg doses with say codeine and it really helps it along

however in those kind of doses it can be very bad for you and damage the intestines i found out the bad way although i never had a doctor check it out.


and it doesnt work that way jcrest , maybe 30 mg of loperamide equals 20-40 mg of codeine in the head but like 400-500 in the body without the histamine release.

however its very good for potentiating when taken a bit before the other opiate the loperamide will fill up the opiate receptors in your body so more of the good opiate will go to your brain.

however i think with your prices it aint wort it

i like it because is potentiation without interference like with a benzo or an antihistamine
 

splenda

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jasoncrest said:
I was just curious. (very curious in fact).

I wouldn't take large doses of Loperamide, it would be too expansive, and I think the side-effects aren't worth it...
(and I'm on Methadone by the way, and can get Morphine for a cheap price)

But I'm still curious....
What doses of Loperamide would be equivalent to 300mg Codeine?

(or: when a substance is unable to cross the BBB, how many do you have to take to make some of it cross the BBB?)
That really is unchartered ground, what you're asking.

We don't have conclusive evidence yet as to the (exact) amount of loperamide it takes to cross the BBB, or if everything is just a very good placebo effect.

8( 8(
 

bingey

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^
its not placebo

loperamide should not be used on people under 12 years old

and drowsiness is listed as a side effect on the generic loperamide leaflet over here (netherlands)

its terribly horribly weak since it hardly crosses the blood barrier
 

Abraxus

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I just read a post today in the alt.drugs.hard newsgroup by a poster named Purple Pimp 2121. He claims to have ingested 200mg of loperamide and that he got high from it. There have been a few posts there about it from this poster, and he seems quite convinced that taking high doses produces a definate opiate effect. I haven't tried it, and probably won't. Definately a less than scientific experiment, but it's something. He also states that the constipation from such a dose is not as bad as with a high dose of any other opiate and that an OTC laxative cures it.
 

jasoncrest

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If there's an Opioid related to Fentanyl, OTC in almost every country, that can give opiate-like effects at the 200mg dose (which is not a dose for an Opioid, you need more than 200mg of many opiate like Morphine, Meperidine/Pethidine, Codeine, Meptazinol to feel a strong effect orally), this should be tried by someone...

I really would like to try it (even if 200mg Loperamide would be more expansive than 14 tablets of 100mg Morphine capsules), if I was not on Methadone.

It seems to be foolish or dumb, but this is only because Loperamide has been commercialized in 2mg doses for decades...
If Loperamide was commercialized as 800mg capsules for strong chronic pain, the idea of getting high on it wouldn't be so surprising...


(it would have MANY side-effects, there would be a big overdose risk, but this is already the case with many Opioids commercialized, isn't it?)
 

bingey

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related to fent but if it crossed the blood barrier like fent 2 mg would kill most people now wouldnt it.

i could try it but i already know it would be crap an opiate virgin might get a nod going on from as little or much as 100.

also you should look into snorting it , i think it would definetly help with getting it to your brain (this isnt very scientific but eck if someone is gonna do some experimenting)

if you guys raise the funds ill go find an willing opiate virgin
 

Abraxus

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BingeBoy said:
related to fent but if it crossed the blood barrier like fent 2 mg would kill most people now wouldnt it.

i could try it but i already know it would be crap an opiate virgin might get a nod going on from as little or much as 100.

also you should look into snorting it , i think it would definetly help with getting it to your brain (this isnt very scientific but eck if someone is gonna do some experimenting)

if you guys raise the funds ill go find an willing opiate virgin
Excellent...We shall sacrifice said opiate virgin at midnight June 6, 2006. The opiate gods will be pleased, no?
 

DrEIMiller

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I wzas searching thtrough google groups today as well and there was talk of using quercetin (a flavnoid) to get more loperimide to cross the BBB. And there was study done at Temple where quinidine was used to increase the amount of loperimide crossing the BBB.

The quercetin is OTC at health food stores. This was purely hypothetical, I think someone said it could possible work but no amounts and methods of admin were specified.

The quinidine (a sterepisome of quinine) had definite opiate response - pupil constriction, etc. I believe it was 600 mg of quinidine and 16 mg of loperamide.

I see if I can find the info and repost it here.
 

DrEIMiller

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This post references both quercetin and quinidine

Steve Dyer wrote (several months ago):


> It turns out, however, that this behavior of loperamide is
> the result of the activity of a specialized ATP-activated "G protein"
> whose job it is to pump out such nasty stuff back across the blood
brain
> barrier as fast as it arrives. If you overwhelm the G protein by
keeping
> it busy with something else, loperamide once again becomes a
traditional
> mu opioid drug. Mice that lack this G protein which have been
administred
> loperamide behave like they've been given overdoses of morphine and
then
> they die. The only allusion I've seen to human beings has been a
recent
> abstract which reported that people taking 16mg of loperamide (8 2mg
caps)
> along with 600mg quinidine (a stereoisomer of quinine used as an
> antiarrythmic drug) exhibited uncharacteristic "respiratory
depression"; no
> comments on the degree of respiratory depression (a characteristic of
> mu-opiate activity), nor how it make them feel.

> I'm no expert on this subject, but there are probably whole families
of
> specialized G proteins which act as "pumps" against certain toxins
> (such mechanisms have been implicated in the development of resistance
> to certain toxic cancer chemotherapeutic agents such as cisplatin.)
> At the very least, this would suggest some caution using loperamide in
> people taking quinidine. 600mg of quinidine is hardly a harmless drug
> itself to produce an unquantified and itself potentially dangerous
high
> from an otherwise licit OTC product. But it makes you wonder what
else
> would be a suitable substrate for this G protein.



If there's any substrate suitable for turning loperamide
(e.g. Imodium brand) into a drug of abuse, I think
I know what it is.

There are several membrane proteins (MDR1, MRP1-6)
which have been identified (or tenatively identified) as
drug efflux pumps responsible for multidrug resistance
in cancer chemotherapy. They have in common the
ATPase binding cassette (ABC) [1].


Quercetin, a flavonoid, is known to inhibit these pumps
by inhibiting the ATPase activity [2, 3]. Quercetin is
easily absorbed in large quantity from the gut [4] and
well-tolerated by the IV route [5]. Quercetin is widely
available in oral dosage forms from so-called "health
food" stores, and in pure form over the Internet.


Therefore, I predict loperamide with quercetin is the
magic combination which would have opioid activity
in the central nervous system.


1. Kool et al, "MRP3, an organic anion transporter
able to transport anti-cancer drugs", PROC NAT
ACAD SCI, v 96, p 6914-6919.


2. Conseil et al, "Flavonoids: A class of modulators
with bifunctional interactions at vicinal ATP- and
steroid-binding sites on mouse P-glycoprotein",
PROC NAT ACAD SCI, v 95, p 9831-9836.


3. Shapiro and Ling, "Effect of Quercetin on
Hoechst 33342 Transport by Purified and
Reconstituted P-Glycoprotein, BIOCHEM
PHARMACOL, v 53, p 587-596.


4. Wiseman, "The bioavailability of non-nutrient
plant factors: dietary flavonoids and phyto-
oestrogens", PROC NUTR SOC, v 58,
p 139-146.


5. Ferry et al, "Phase I Clinical Trial of the
Flavonoid Quercetin: Pharmacokinetics and
Evidence for _in_Vivo_ Tyrosine Kinase
Inhibition", CLIN CANCER RES, v 2,
p 659-668.


http://groups.google.com/group/sci.med.pharmacy/browse_thread/thread/e8d603f255af18fa/546746858d2fc5bd?q=loperamide+quinidine&rnum=1#546746858d2fc5bd
 

BilZ0r

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^ Steve Dyer is a bit confused. It's not a G-protein, they are multidrug transporters, like P-glycoprotein.

Unfortunately, I don't really think I believe that there was a study where animals died from loperamide mediated opioid overdose after inhibition of multidrug transporters as cited above. Inhibition of these transporters in animals by knockout of the gene, or with quinidine, causes about a 10x increase in uptake of the drug [1]. Still, in humans quinidine has some effects on loperamide [2].
 

mitogen

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BingeBoy said:
^
yeah i always use it for potentiation cause its the cheapest thing around in holland however in france its fricking expensive (1 euro here)

i took like 40 mg doses with say codeine and it really helps it along

however in those kind of doses it can be very bad for you and damage the intestines i found out the bad way although i never had a doctor check it out.


and it doesnt work that way jcrest , maybe 30 mg of loperamide equals 20-40 mg of codeine in the head but like 400-500 in the body without the histamine release.

however its very good for potentiating when taken a bit before the other opiate the loperamide will fill up the opiate receptors in your body so more of the good opiate will go to your brain.

however i think with your prices it aint wort it

i like it because is potentiation without interference like with a benzo or an antihistamine
I understand the mechanism by which you propose that loperamide potentiates other opioids - same reason they add carbidopa to L-dopa: the carbidopa doesn't get into the brain so it works nicely for competing with l-dopa at somatic enzymes.

On a scale from 1-10 (where 1 is nothing and 10 is, say, a doubling of efficacy) how would you rate the effectiveness of a.) a therapeutic dose, b.) twice the therapeutic dose and c.) a massive dose like you have been talking about - say 40mg?

To be honest, considering the price of loperamide in the form of immodium (perhaps a prescription could be cheaper,) its probably easier and more constructive to simply go find some more commonly used opioids.
However, if anyone does happen to find a supply of quinidine, I'd love to hear the results. As I mentioned, we've discussed this before, and nobody really tried doing anything. That quinidine study does look interesting, for sure.
 
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bingey

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^mitogen
forget the therapeutic doses

however from 15-40 mg onwards it will have a noticeable effect like 1-3 i think on your scale ( a normal benzo dose will be 10 cause it makes me halve my opie dose )


im not good with the numbers but lets say its one of those things that makes a dose of codeine under 300 mg worthwhile e , greatly adds to the itch and actually gives me opiate pupils instead of very slighly contracted pupils in this setting it also makes me itch. 300 mg of codeine on itself wont maybe the first day i havent been using opiates for a few months now.


however what i would like to state again and a reason why i like it (i dislike antihistamines for instance and will only add them to the mix if absolutely necessary even though those have a shared pathway or something) is that it doesnt taint the opie feel and seems to add to euphoria rather than sedation.

ps this bit is from the cold water world potentiator page (http://adhpage.tripod.com/potentiators.htm) :

26. Loperamide (Immodium): This drug is related to meperidine/pethidine (Demerol) but does not cross the blood-brain barrier in sufficient quantities to cause euphoria. However, the consumption of doses of 150-300% of the therapeutic dose when mixed with high doses of codeine or meprobamate have been reported to produce a weak Darvon-like buzz aside from the effects of the other drugs.
 
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