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.