Jeepers creepers. The same questions keep coming up time and time again. Maybe I will start to work on a brief document regarding the enzymatic metabolism of various opiates (i.e. which cytochrome is primarily responsible) and a table of p450 inhibitors broken down by subtype of isozyme activity.
Generally, for any enzyme inhibitor, taking it before you dose is a good idea, and, depending on the half life of your enzyme inhibitor and the half life of your opiate, redosing is a good idea. I am on methadone, and recently started to take Cat's Claw with it. I have been finding that it does indeed seem to increase the half life, allowing more drug to accumulate OVER TIME, as well as allowing the methadone to act for a longer period of time. I have said it 5 zillion times before, but I will say it again, p450 enzyme inhibitors are not actually "potentiators" of opiate effect, but rather, the are inhibitors of opiate metabolism. Again, different opiates are metabolized by different subsets of P450 enzymes, and different chemicals inhibit the activity of different subsets of enzymes. You have to match up the metabolic route of a particular opiate with the correct enzyme inhibitor. This does not "potentiate" the effect of the opiate, it merely keeps it from being metabolized as quickly, therefore prolonging the duration of effect. With opiates that are subject to a high first pass metabolic effect, enzyme inhibition can have a large effect on just how much opiate makes it into your blood stream, and hence into your brain. Also, if you take the same opiate chronically, and take the correct enzyme inhibitor chronically, there is the possibility of a much larger accumulation of opiate in your system - again, this is not an immediate effect but one that slowly sets in. Remember, for ANY drug taken chronically, a dose change (which some inhibitors basically cause by increasing the amount of drug that enters circulation), it takes 5 half lives to reach 98 percent of the new steady state serum level. As well, enzyme inhibitors basically result in an increase in the half life of other drugs metabolized primarily by the inhibited enzyme, thus, if you don't change the schedule of your drug consumption, each subsequent dose will add the same amount of drug to the blood levels, but your blood levels will not have dropped by as much from your last dose as compared to if you have not taken an enzyme inhibitor. I think this is pretty much basic pharmacokinetics.
When you are talking about a true potentiator, you are referring to an additive or synergistic effect between two different drugs, generally, two drugs that work by different mechanisms. This is no longer pharmacokinetics, now you have entered the realm of pharmacodynamics.
As far as benzo's go, alprazolam and clonazepam are two benzo's most favorited by methadone maintenance patients in some cities. Different people will react slightly different to different benzo's, it really is a matter of personal preference. There are some subtle receptor binding differences between some benzo's, but for the most part that is strictly academic. Trial and error is the best way to find out which benzo you prefer the most. For me, I love chlordiazepoxide, the very first benzo to hit the North American (and maybe the worlds) market. I also love diazepam because of it's rapid onset of activity. However, it has a very long half life, which is not always a good thing. Alprazolam seems to have the best of both worlds. I would not suggest banging benzo's as they are notoriously water insoluble, but snorting them works great, and I love the taste (which is mostly the taste of the sugar filler in the tabs.
Other substances mentioned by others in these posts could also work well, although I have little experience with them other than with alcohol, THC, DXM, and some psychedelics. So experiment away. Just remember that you are gambling with your life - anybody can develop a devastating addiction on opiates, one that you would be lucky to survive let alone ever be "cured", at least that is my experience, and what I have seen happen to countless others.
