The State of Hydrocodone Potentiation in 2015 (a.k.a. Up-to-Date Knowledge)

[StillHere]

For clarification: The purpose of this thread is that, currently, there are no viable hydrocodone potentiation solutions available in the knowledge-pool of the internet.

So I have seen just about as much knowledge as one could grasp with a sweep of the web on hydrocodone potentiation, applied a lot of it in my own use experimentally, etc. It seems there is no new knowledge out on specific potentiation on hydrocodone (the effects in general of hydrocodone, as in potentiation of the medication itself and not of additive effects). Does anyone have any knowledge to offer? Here's a run-down of what could possibly be mentioned:

Grapefruit juice - slows metabolism of hydrocodone enzymatically, gives you less of a peak to your euphoria in exchange for increasing duration of action, slows come-up and come-down

Tagamet/Quinine - proven to decrease efficacy of hydrocodone, albeit with some of the same prolongation effect of GFJ

Benadryl/antihistamines - antihistamines that do not enzymatically inhibit hydrocodone are only shown to add to sedative effects, not to the effects of hydrocodone itself; diphenhydramine (benadryl) and other antihistamines that inhibit enzyme pathways of which hydrocodone is a substrate (2D6 in this case) are shown to decrease the efficacy of hydrocodone, of course with some additive sedation potentiation however

Dextromethorphan - not a potentiator of hydrocodone but theorized to prevent tolerance

NSAIDs i.e. Ibuprofen, Naproxen - potentiate to a small-degree local analgesic actions of hydrocodone in areas of pain, but not actually hydrocodone itself

Antacids - potentiate hydrocodone by theoretically decreasing the amount of hydrocodone destroyed by basifying the stomach. I somewhat believe in this as I have sometimes seen marked improvement of effects with concurrent antacid administration (and sometimes not).

So those are just a few things that come to mind that are commonly mentioned. As you can see, none of them truly potentiate hydrocodone, it is either additive effects or slowing of hydrocodone's metabolism, thereby decreasing peak efficacy. The wild-card is antacids.

Potentiation as medically defined (Source: http://www.indiana.edu/~engs/rbook/drug.html) - "Potentiation occurs when two drugs are taken together and one of them intensifies the action of the other. This could be expressed by a +b= B. As an example, Phenergan(R), an antihistamine, when given with a painkilling narcotic such as Demerol(R) intensifies its effect, there by cutting down on the amount of the narcotic needed."

(Note: In the above example of Phenergan and Demerol, Demerol does not need the 2D6 pathway so promethazine's inhibition of that pathway is fine. Not the case with hydrocodone.)

So as you can see, up to as much as I know and the internet has supplied, the choice for maximum efficacy of hydrocodone is simply taking hydrocodone by itself, and possibly with DXM beforehand if the NDMA tolerance build-up theory is true. As well, I believe to an extent in the theory of antacids helping as I feel that I have reaped some benefit from that in increasing bioavailability of hydrocodone after oral administration.

Do we have any new knowledge? Is there something I am missing that isn't some ambiguous research chemical? What is the state of knowledge on hydrocodone potentiation in 2015?

 

[falsifiedhypothesi]

You probably won't find much more than you already know. For the most part the only people interested in potentiation are those who use recreationally and most of us aren't biochemists who are working to pioneer new techniques. I'm not meaning to deter anybody but that's just my take on your predicament.

 

[cuivre]

Yeah, I agree entirely with falsified. You might find something you didn't already know in the Opiate Potentiaton Megathread, but otherwise you seem to pretty much know what to do in terms of that.

You did leave out quinine, though, which is found in tonic water. Similar effects to WGFJ and cimetidine, but still worthwhile.

Personally, I disagree that White GF juice or cimetidine give you a lower peak--quite the opposite-- and I drink a huge glass of WGFJ and tonic water daily. If you have been avoiding these for this reason, you should try them. Certainly not everyone will have the same experience as the next person, but there's a reason WGFJ + cimetidine +/- tonic water and antacids (for oral use) is basically the gold-standard for opioid potentiation among recreational users. Of course it depends on what you're looking for, but if you're looking to get more out of the same dose of hydrocodone, then certainly "the choice for maximum efficacy" is not merely taking it by itself and maybe with antacids. This may be "cleanest" feeling and maybe that's what you want, but it is surely not the most efficient.

Beyond this, any drug that also inhibits the CYP3A4 will work about the same way as grapefruit juice but could be more effective in its action, although WGFJ is highly effective at achieving the same result. For example, I believe verapamil hydrochloride is also a CYP3A4 inhibitor.

 

[Jktm]

CYP3A4 inhibition also leads to larger amounts of the metabolite hydromorphone. When one path is clogged it tries to get out the others.