I think that people are getting confused because they are thinking of different things when they talk of "potentiation". Really, there are three separate things that we are confusing with each other, name; Potentiation: Increased Bioavailablity; lastly, Inhibition of Metabolism/Drug Accumulation.
Potentiation occurs when two drugs work synergistically (or additively) with each other, acting in unique ways to increase the total effect, resulting in a higher effect than what you would get if you added the result of using each seperately. I never really thought of combing other drugs with opiates as potentiation, rather, the opiate should just always be there, and then I mixed in various drugs as I got my hands on them, etc. I guess one good (great) potentiator is benzodiazepines. I know this field as I used to collect and sample them like delicacies when I used to be a pharmacist. I was always partial to chlordiazepoxide (note - methadone with benzo's can be very dangerious - benzo's are usually invovled in most methadone overdoses, and usually have caused respiratory depression.)
Marijuana is very good, as is DXM, ketamine. Some people use stimulants , cocaine/crack, meth, or hallucinogens such as psilocybin. I guess the question you need to answer first is what is about opiates you want to potentiate.
NO SIMPLE ANSWERS Drugs which in inhibit the metabolism of opiates (such as cimetidine, many SSRI's, some antifungals, etc - are generally inhibitors of cytochrome P450 isoenzymes in the liver (and there are as many types of these as you can count)). The list of these interactions is large and can be complicated and I won't go into it here as it is available in many other sources/references.
One class of drugs commonly encountered is SSRI's class of antidepressants. Several of these drugs inhibit various and sundry different P450 enzymes - different SSRI's inhibit different enzymes, and different enzymes are responsible for the metabolism of different opiates. Consult such a table for specific details. I know that for methadone, each of fluvoxamine, fluoxetine, and sertraline can inhibit the metabolism of methadone by inhibition of various P450 isoenzymes. When the metabolism of drugs is inhibited in the liver (and/or the gut, drug levels can increase in two ways. Increased availability, and decreased elimination
Increased Bioavailability - Drugs taken orally that are usually metabolized extensively by first past metabolism in the liver (or gut) during absorption, can have sudden, possible large, increases in bioavailability if the enzyme responsible for its metobolism is inhibited. When grapefruit juice is drunk before (about an hour) taking a dose of methadone, the amount of methadone absorbed can increase between 5 to 15, sometimes even up to 30%. This is the equivalent of taking an additional 5 to 15% methadone. This is not really potentiation, more like addition. Of course, the ultimate ways to increase bioavailability is to change the route - to IV if possible, to a lesser degree but still highly effective is the newly popular method of insuffulation (snorting). Growing up, I never would have dreamed I would one day prefer to snort my tablets.
Decreased Elimination Opiates metabolized in the liver (all of them (that I can think of)) can also have their metobolism inhibited (we are no longer talking about first pass metobolism) by drugs which directly inhibit some of the enzymes that metabolize (and inactivate) our precious dose. SSRI's love to do this for us, as well as cimetidine, and 3.5 trillion other drugs (however, a great many of these interactions have no clinical relevance and are barely perceivable, if at all, other than for a placebo effect). Again, various drugs affect various opiates, but their are patterns to the madness (but they are a secret). This inhibition does not result in a higher dose absorbed (all though it could do that in addition), nor dose it alter the peak levels achieved following a single dose opiate (their are exceptions to every opiate rule). However, enzyme inhibition can result in prolonged activity (yeah for more nodding off), usually to a moderate extent. Most of these interactions are not clinically relevant, but some combinations can have dramatic effects (personal experience as cited below) generally as the result of drug accumulation.
Methadone is notorious for this, as its usually half life is between 12 and 36 (to 48 to 60 or more hours, it varies a little bit). Because of this, there is always still a lot of drug remaining from the previous dose (typically half the previous dose when methadone is dosed daily)when it is time for the next dose. Slowing the metabolism of methadone can result in a gradual but pronounced increase in drug levels, reaching it's peak in 5 half-lives (i.e. 2.5 to 7 to even more DAYS). For me, it was fluvoxamine and methadone (a mistake I allowed my doctor to make twice). Fluvoxamine inhibits cytochrome 2D6 in the liver, one of the main enzymes that deactivate methadone. This resulted in a longer half life, resulting in more drug left over when the next dose is due, resulting in slowly climbing blood levels, followed by a 1 month stupor where I wandered the winter landscape of northern BC walking an hour through storms everyday for one hour to get my daily dose of sunshine. This eventually led to me in the the psych ward for 2 weeks over Christmas (I don't remember most of it. This was all due to drug induced delirium via methadone (I was only 31 years old (and it was Christmas))),
(of course, remember, 5 half lives to peak levels, 5 half lives to eliminate 98% of the opiates from your body (you may need to know that if you have a drug test coming up).
