Opioids The Ultimate Opiate Potentiation Thread

[ro0ga]

In terms of potentiating oxycodone and codeine specifically with an antihistamine, diphenhydramine is not the best choice. The reason for this is because diphenhydramine inhibits CYP2D6; CYP2D6 is the enzyme which is responsible for metabolizing both codeine and oxycodone to their two more potent metabolites (morphine and oxymorphone, respectively). Thus, diphenhydramine will inhibit this conversion, causing the opiates to be converted to their less potent metabolites. This isn't 100%, so by taking diphenhydramine, you're not completely eliminating the two more potent pathways, but you are decreasing them.

People will still say that diphenhydramine makes oxycodone and codeine more "noddy" or more intense, and that is true as well. But it's not because of a metabolic pathway, it's the drowsy-ing effect of diphenhydramine being synergistic with the drowsy-ing (noddy) effect of the opiates. Diphenhydramine definitely acts more as a potentiator than a "de-potentiator", but there is that slight enzyme inhibition which is a minor drawback.

So, diphenhydramine DECREASES potent metabolite production, but INCREASES some of the euphoric properties due to it's own mechanism of action. What to do? Doxylamine is a better alternative. Doxylamine will give the user a better "nod" and increase the euphoria, and doxylamine will not alter any of the CYP enzymes. Even better, DOXYLAMINE + Grapefruit Juice. Doxylamine for it's euphoric properties being additive with the opiate, and Grapefruit Juice to inhibit CYP3A4, thus allowing more free oxycodone and codeine to be a substrate for CYP2D6 (aka more morphine and more oxymorphone).


Here is a quick overview of it:

2D6
Oxycodone -------> Oxymorphone (GOOD!)

3A4
Oxycodone -------> Noroxycodone (NOT AS GOOD!)

>>Diphenhydramine inhibits 2D6, so you end up with more Noroxycodone.
>>Grapefruit Juice inhibits 3A4, so you end up with more Oxymorphone.
>>Doxylamine is about equal to diphenhydramine in terms of its drowsy-ing, euphoric effect, while having NO effect on enzymes.


Don't get me wrong...diphenhydramine will probably produce a more intense high if you were to take it with oxycodone or codeine, it's just not the best choice if you're really looking to potentiate the drugs to their fullest extent.

 

[happyneedles]

Potentiating Dilaudid/Hydromorphone

(I am having a problem with the search option, so if this has already been addressed, please link me to another thread, and I apologize )

I just had IMs of both Dilaudid and promethazine, and I was wondering what would be the best way to potentate it. I have diphenhydramine 25 mg tablets, the 50mg gels, and klonopin.

I am asking because I am in severe pain, and it is not going away at the moment.

 

[xxkcxx]

Hi, you can find all that info here:


The Ultimate Opiate Potentiation Thread

 

[happyneedles]

Thanks! I'm having a ridiculously hard time finding what's best with hydromorphone specifically, which is a result of distraction from my pain, but hopefully I can figure it out. I'm still just trying to find with one of the potentaters I have would be more sufficient.

 

[Jabberwocky]

thank m'darlin kc.

ill merge anyway

 

[rainbowdemon]

I have 30 mg MS-Contin, but no regular strength Benedryl. I do, however, have the 50 mg Walmart-brand diphenhydramine liquigels (like Unisom). Since most of the responses on here are about taking it in tablet form, would a 50 mg liquigel be too strong to take with the MS?

Diphenhydramine is the only active ingredient in Benadryl. So, any generic sleep aid is the same thing. Just a whole lot cheaper.

 

[happyneedles]

Diphenhydramine is the only active ingredient in Benadryl. So, any generic sleep aid is the same thing. Just a whole lot cheaper.

I have no recollection of even posting that, haha. Terrible. I knew that, but thanks for responding to my stupid question.

As for the Dilaudid question, I was just asking which one (diphenhydramine or Klonopin) would be a better combination with the Dilaudid. That's why I listed what I had on hand... even if the diphen gel caps and the diphen tablets were redundant. Sorry about that confusion.

 

[xxkcxx]

I would say take 50mg of diphen, and then like 30 minutes later take the MS Contin.

 

[fm1983]

This thread is too much mumbo jumbo and not enough solid info. The first post should show all the potential potentation tools and a run down of each one (What to use, how much to take, how long before, etc).

It's hard to sort through 30+ pages and find solid answers on what works and what doesn't work. Maybe there is a way we can organize this thread.

 

[Unknown]

^^^
If you want to make an organized version, go ahead!

 

[evolutionofthemind]

One enzyme metabolizes opioid prodrugs into their active metabolites (oxycodone -> oxymorphone; hydrocodone -> hydromorphone; codeine -> morphine). As we all know, oxycodone itself is not active at the opioid receptors; the goal is to have the body metabolize it to , both of which are potent opioid agonists. So inhibiting this enzyme would be a bad thing if you're after opioid potentiation, since less of your drug would be metabolized to its active compounds. I believe this enzyme is CYP2D6, but I actually have no idea and am no chemist, so I'm probably wrong.

Some opioids don't require this metabolization. For example, both oxymorphone and hydromorphone can be given in their pure forms -- hydromorphone's brand name is Dilaudid. Morphine is active without any metabolization. Etc.

Another enzyme in the liver (CYP34A? 3A4? Fuck, who knows) is responsible for This is the enzyme to inhibit, and is why things like grapefruit juice, tagamet, some stomach acid medications, etc. work -- they inhibit this enzyme.

This method of potentiation does not increase peak plasma levels of the active opioid in the blood, so it won't make the high any more intense. However, it increases the duration of a given plasma level, so you stay higher for longer.

As another poster mentioned, opioids (and other psychoactive compounds) generally dislike acidic environments, so go easy on the grapefruit juice if you're eating your opioids. Might be better to eat tagamet (cimetadine) instead.

Ok so what I take out of this is that grapefruit juice, or anything else that inhibits whatever enzyme the liver produces to hinder a drug's breakdown would be BAD for oxycodone as oxycodone needs to be metabolized into noroxycodone and oxymorphone. But then you go on to say that (say grapefruit juice) breaks down opiates into their inactivemetabolites. Are you saying to use grapefruit juice with oxycodone or stay away?

Color me confused..

 

[Free_Man**]

Stop the press *** stop the press***

ok guys im here to quell the doubts about quinine / tonic water with codeine

taken before it does not work

it dampenes the buzz - a lot

it must be an inhibitor

it does not work




that is all

 

[catbird]

grapefruit juice does not work with opiates! that rumor got started becuase it potentiates the phuc out of xanax and other benzos. There is absolutely no evidence that grapefruit juice does anything good for opiate, though. if there is, please post! the only evidence i've seen on this thread is anecdotal - we're talking about some serious placebo effect.

 

[evolutionofthemind]

Ok I have a sort of off the wall question. I have always done a bit of medium aerobic exercise a few mins after chewing up my oxycdone pills. My base theory is that as aerobic exercise gets blood flow moving and releases a lot of different chemicals from the brain, blood flow moves faster through the body, to and from the brain, etc. that it would offer a bit of a potentiating effect.. thoughts?

 

[evolutionofthemind]

Anyone.....? Anyone........? Bueller..........? Bueller..........................?

 

[socio]

grapefruit juice does not work with opiates! ... There is absolutely no evidence... if there is, please post!

Sorry to say, but you're mistaken. If you search you'll find that grapefruit juice (or tagamet) potentiates many drugs that are metabolized by the CYP3a4 liver enzyme into less- or non-psychoactive metabolites. There is plenty of evidence... This particular example is a little bit indirect, but, just quickly googling "morphine CYP3a4" I find:

Identification of CYP3A4 and CYP2C8 as the major cytochrome P450 s responsible for morphine N-demethylation in human liver microsomes.
Projean D, Morin PE, Tu TM, Ducharme J.
Xenobiotica. 2003 Aug;33 ( 8 ) :841-54.
Conclusion: More than 90% of morphine N-demethylation could be accounted for via the action of both CYP3A4 and CYP2C8. 4. The in vitro findings suggest that hepatic CYP3A4, and to a lesser extent CYP2C8, play an important role in the metabolism of morphine into normorphine.

In this example, normorphine is not psychoactive, so when CYP3A4 makes this happen, you feel less high. Inhibiting CYP3A4 with tagamet or gf juice will make you feel more high [EDIT: I.E. higher at any given moment, or rather, feel high longer, depending on how you look at it]. The metabolites are different for other opiates, but the same principle applies (for most, except ones like codeine which needs to be metabolized into morphine; for those, inducers like st. john's wort might work, idk?).

 

[Self-Aware]

Tonight I'll be dosing 200-300 mg codeine, CWE orally.

I'll be using promethazine to potentiate the effects, (user) suggested I take an equal dose of promethazine considering my tolerance to opiates is reasonably high.

Seriously? 200-300 mg of promethazine?


I keep hearing different things, it's shitting me off lol, what will potentiate the opiate better; taking the promethazine 30 mins BEFORE dosing the codeine or 30 mins AFTER dosing?

 

[NeighborhoodThreat]

uhhh

I think 200 to 300mg of prometh would just put you to sleep. When it comes to antihistamines and opiates, don't overdo the antihistamines...doesn't just apply to promethazine, but to all the first-generation sedating antihistamines (diphenhydramine, doxylamine, etc)

 

[Self-Aware]

Cheers mate. I ended up just doing 100mg of prometh about a half hour prior to dosing (codeine) 200-300mg

Got sedation? lol

 

[evolutionofthemind]

When it comes to antihistamines and opiates, don't overdo the antihistamines...doesn't just apply to promethazine, but to all the first-generation sedating antihistamines (diphenhydramine, doxylamine, etc)

What does that mean exactly.. I usually take a few benadryls with my opiates. Usually 1 or 2 with oxycodone, methadone or morphine and about 2-4 with PPD. Does this sound like about the right dosage?