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Opioids The Ultimate Opiate Potentiation Thread

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^Thats why i wish some of those mofos would post here, i agree with you 100%.

Callin all moderators....
 
Where is negrogesic and naturalone when we want to put together an all-encompassing guide...
 
200mg of hydroxyzine will potentiate opiates pretty well but a major side effect is dry mouth and extreme drowsiness (so much so you cant really enjoy the nod)
Grapefruit Juice is good but fresh Grapefruit is much better
Benadryl and doloxymine succinate are about equal, doloxymine is a tad stronger
Im receiving 120mg of Klonopin soon and my mother most likely has some darvocet that I can ask her about so Ill let you all know how the opium potentiation with that works out
 
Weebl8bob said:
200mg of hydroxyzine will potentiate opiates pretty well but a major side effect is dry mouth and extreme drowsiness (so much so you cant really enjoy the nod)

200mg Hydroxyzine is too much.
50mg (100mg max) is a good dose.

Weebl8bob said:
Benadryl and doloxymine succinate are about equal, doloxymine is a tad stronger

I think you mean Doxylamine, then Benadryl is stronger than Doxylamine, but I think Doxylamine is better, because it has less anticholinergic effects for the same sedation.
(it's the sedative effect of antihistamines that potentiate opiates, not the anticholinergic effect, right? I'm not sure..)
 
This post will restate some info found in other posts in this thread that is especially true, and then it will list three methods of potentiation that I have not seen in this thread, at least explained in any useful detail.

There are four types of opioid potentiators to my knowledge. Note that other sedatives, like benzos, antihistamines, alcohol, THC, etc., aren't really potentiators; their depressant effects combine synergistically with the depressant effects of the opioids and result in a more intense experience than either drug taken alone. This is not potentiation. Which isn't to say people don't enjoy it or that I'm judging it, but potentiation involves physiologically/chemically affecting the way a given substance is metabolized/absorbed/used in/by the body to increase its effects and/or duration.

1) CYP-enzyme inhibitors. There are a collection of enzymes primarily in the liver each beginning with the designation CYP. At least two are involved in the metabolization of opioids, but in two entirely different ways.

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 noroxycodone and oxymorphone, 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 breaking down active opioids into their inactive metabolites. 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.

2) NMDA antagonization. The relationship between NMDA antagonization and opioid potentiation is not known (at least to my knowledge, like I said I'm no chemist or pharmacist or MD, so I probably know fuck all), but a number of studies have been run. Their results are somewhat contentious.

The vast majority of the studies' conclusions support the notion that NMDA antagonists, when administered with a therapeutic opioid dose, potentiate the effects of the opioid; that is, the effects are increased (a lower dose with an NMDA antagonist will yield the same therapeutic effects as a higher dose without).

Where the studies differ, however, is on whether NMDA antagonists result in the prevention of tolerance formation, and also the attenuation (reduction) in tolerance. Some studies showed evidence of tolerance blockage and/or attenuation; others showed evidence to the contrary. Either way, it is intriguing.

NMDA antagonists include Dextromethorphan (DXM), the active ingredient in most OTC cough suppressants; Ketamine, and PCP. The studies I've read that used DXM employed some absurd dose like 4-5mg/kg. The required dose for Ketamine would obviously be much less.

If you're a reasonably smart person and you have a low/baseline opioid tolerance, and you want to become a guinea pig, experiment with this methodology and post your results. My tolerance is too large to really analyze small changes and/or the blockage of any further tolerance formation, so I can't really try it. The one thing I'll say is to be careful with OTC DXM preparations -- make sure the ONLY active ingredient is DXM; a lot will contain guanfisine (that is spelled wrong, but it's an expectorant and you shouldn't take very much of it), acetaminophen (tylenol), pseudoephedrine, etc. None of these things are very good for you in the amounts you would have to consume to get a dose of DXM high enough to work in this context, and in fact, they could kill you. If you want to be a guinea pig, be a careful and smart one, or a dead one.

3) CCK inhibitors. This is my favorite type of potentiator because of ... forgive the pun, but all of the potential. CCK is a peptide released in the brain/spinal column when opioid receptors are agonized (activated). It tends to build up in chronic users. Some reasonably smart person thought that it might be related to tolerance in some way, so studies were manifested that dosed people with CCK inhibitors along with their opioid dosages to see if anything good happened.

Boy howdy.

CCK inhibitors are not only shown to potentiate the therapeutic effects of the opioids (up to a 50% reduction in morphine dose was noted in one study with the same analgesia), but they are also shown to prevent the formation of tolerance and also to attenuate any existing tolerance over a period of time. I'll say it again. CCK inhibitors may attenuate existing opioid tolerance over a period of time.

The reason this is so exciting (and also kind of sad) is because one CCK inhibitor, Proglumide (brand name Milid; used to be used to treat stomach ulcers which also have a relationship to CCK; has been surpassed by more effective stomach ulcer meds that are not CCK inhibitors), is incredibly cheap to manufacture, is not a controlled substance, and is readily available. Providing a cheap, safe means to reduce opioid tolerance would solve part of "the drug problem" as well as relieving the suffering of countless chronic pain sufferers maxed out on opioids due to fear of respiratory arrest. Yet it appears there is little to no active research going on in this arena.

Proglumide can be purchased overseas. The effective dose is 200mg daily. However, Proglumide is in itself tolerance-forming, so the recommended regimen would be a week-on, week-off Proglumide schedule. Doses lose effectiveness above 200mg, so taking more will do less.

Proglumide is expensive when bought from an online pharmacy -- someone as keen and resourceful as I should be able to procure a large quantity (it's very cheap) from a domestic chemical supplier (it's not a controlled substance), but I have yet to acquire the means to do so. I can speak from experience however that Proglumide works very well in this capacity. If anyone has any stories about this or any other CCK inhibitors, please post.

4) Ultra-low dose opioid antagonist. This is probably the most interesting potentiator of the bunch, involving the administration of an "ultra-low" (micrograms) dose of an opioid antagonist (naloxone, naltrexone; the stuff you get spiked with if you have an opioid OD that displaces all of the opioids from your receptors and throws you into miserably acute withdrawal in 7-8 seconds) along with a therapeutic dose of opioid.

Like #3, this approach has been shown to increase the action of opioids, requiring lower doses, and has been shown to block and reduce the formation of tolerance. Unlike #3, this approach has been patented by a pharma company and the resulting drug is in phase III or IV clinical trials, combining a low dose of antagonist with a therapeutic opioid, reducing potential for addiction, dose requirements, and all that other good stuff.

Unlike #3, this approach is a bit difficult for the DIY guinea pig. Accurately measuring the appropriate dose of naloxone/naltrexone, particularly if yours comes in pill form (ReVia or Suboxone, for example), is quite difficult. Even if you have ampoules of naloxone, an accurate measurement could be quite difficult.

The theory behind it is that opioid antagonists have slightly more affinity for the delta receptor (there are four opioid receptors; mu is the one of interest, responsible for analgesia and euphoria) than the mu receptor. A very low dose will bind entirely to the delta receptors, blocking action there while the opioid binds to the rest of the receptors. The delta receptor has been associated in the past with the formation of tolerance, so since it is not being agonized, tolerance cannot begin to form, and the same dose remains effective for much longer.

Another approach related to this one is to manufacture an opioid with mixed agonist/antagonist activity (agonistic at one receptor, antagonistic at another). One example is Tramadol (Ultram) which does some wacky shit at different receptors; I forget the details. However, another more interesting example is Buprenorphine, a potent delta antagonist, but only a mu partial-agonist. You'll note that buprenorphine does not result in tolerance, most likely due to its delta antagonization.

So that's all I have to say about that. Be safe.
 
Oooh Pick me!!!
Okay So Ive taken tramadol with opium and can note that I get a MUCH better nod than I normally would from such a dose
 
jasoncrest said:
Is Proglumide the only CCK inhibitor available?

Surely not, but it's the only one of which I am aware, and its properties (non-controlled substance, cheap, domestically manufactured) make it a favorable one with which to experiment.
 
okay my mum got her darvon (HCl YES! Water soluble) and ill tell you all how it goes once my tolerance goes down :)
 
To answer someone's question from before...

yes, opioids can be stacked upon one another to create a greater effect. For an intense nod: at about t + 1 hr after taking 60 mg of methadone i will dose 10-20 mg of fentanyl so that both are peaking at the same time. When doing this, i end up using about a 1/3 of what i normally need to take to get me by.

Also, i've used very high doses of cimetidine with methadone, oxycodone, and fentanyl. It works VERY well with fentanyl, decent with oxycodone, and alright with methadone. But i have had to gradually increase my dose to insane amounts with cimetidine--the liver enzymes learn to cope with the stress being put on them and therefore the liver increases their production. IME at least..
 
first you need to take 200+ mg's of morhine to get that fuzzy feeling then after about an hour snort about 80-160 mg's of Old Charlie then when u start scratchin ur nose u smoke some fucking chronic-indonesia you know that shits gonna make u seizya---thats how we do shit down south at least
 
So diacetyl: upon reading your very informative post, it seems like trying anything via the NMDA route would prove to be quite insufficient. Am I right? Afterall, the point is to be higher on opiates, not to be blasted in another dimension by a dissasotiative.

jasoncrest said:
Is Proglumide the only CCK inhibitor available?
That's exactly what I was thinking...then I read the post below. So now I gotta aquire a boat load of this somehow. Why can't it just be OTC dammit! I'm going to have to at least try this out with my methadone. I wouldn't need to use it all the time, so I wouldn't have to worry about tolerance to it. If there is a possibility that methadone will be potentiated by up to 50%...well shit, I'm game! :\
 
Interaction

First, it should be noted that even within a similar class of drugs, most of the members are metabolised in different ways. I posted about this yesterday i think, i listed the specific enzymes for each drug.

And, like others have said, theres a difference between additive CNS depression, and potentiation of a single drug.

It should be noted that most of the phenathrene (natural) opiates are in fact active themselves, yes they are metabolized to other chemicals/active drugs, but the amount is what matters.

Hydrocodone gets metabolized extensively, but how much gets turned into hydromorphone? nearly none. From the Journal of Pharmacology and experamental theraputics Vol. 281, Issue 1, 103-108, 1997 "Hepatic conversion of hydrocodone to hydromorphone is of almost no consequence in determining the effects of hydrocodone"

Oxycodone is in fact active by itself, its a very strong Mu and Kappa receptor ligand, with comparable binding efficiency to other opiates in the same class. From Drug metabolism and Disposition DMD 32:447-454, 2004 "Leow and Smith (1994) reported that noroxycodone exhibited modest analgesic potency after i.c.v. administration in the rat." Also "Inhibition of CYP2D6 by quinidine did not attenuate the opioid-induced side effects of oxycodone in human volunteers". In addition, "Plasma oxymorphone concentrations were below the limit of the assay." Also from Current Medical Research and Opinion 20(6):911-918, 2004 "Although oxycodone is itself metabolically converted to oxymorphone, it has been suggested that this conversion is not important for its analgesic activity.[

This means that despite the fun metabolites, most opiates are themselves responsible for their activity, and you are better off preventing their metabolism. Most of those metabolites get further altered and then removed from the body before they have any chance to get to a place that would take them to the brain (the liver wont help them there)

I suggest we either delete all the posts after the first one, and combine the right info into it, or forget it entirely. Long threads help people even less than searching through clinical studies and research papers :)
 
Thought I would throw in my 2 cents as far as potentaition I have personally experienced:

Phenergan and diphenhydramine - Defenite potentation. Seems to increase the sedation effects of opiates.

Benzo's - My least favorite narc potentation. In small doeses, benzo's increase the sedation effects of narcs. In moderate to high doeses, it seems to kill the narc effects, and you can only feel the benzos

Grapefruit juice - Overrated. I cant tell the diference

DXM, Ketamine - New one for me. I will try this asap and report back ;)
 
DexterMeth said:
Again though, anything about methadone POTENTIATION?

Fluvoxamine, this is a SSRI that inhibits almost all CYP enzymes (just like Cimetidine/Tagamet).
I think every other potentiators have been quoted in this thread....
 
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