I'm not sure about the specifics with piperazine, but generally when there is competitive enzyme inhibition the effect is acute: concentrations of the drug become unusually high as the body cannot eliminate it at the normal rate. If a lower dose is taken then in theory the effects should be normal. Enzyme inhibition should definitely not have a direct effect on the comedown or aftereffects, but these may be changed as a result of unusually high peak concentrations.
There is definitely competitive enzyme inhibition between piperazine and MDMA. Thats what all the reports suggest at least.
Based on the experiences we hear about on ED many people have awful comedowns and after effects from the piperazine MDMA combo. I would be very sure the enzymes are a big factor in this. Clearly all the research is animal based and nothing is for certain but it certainly seems that way.
I think you might be playing down the enzyme theory a bit. Not sure if this is correct.
I am also certain one of the reasons why MDMA gets dangerous at high dose is because of Enzyme inhibition it effectively inhibits itself being broken down.
Unfortunately we don't truly understand the comedown of pure MDMA, so adding pipes adds confusion, but my bets would be on a pharmacological effect as opposed to some strange metabolite floating around as a reult of interactions between the two drugs and their enzymes.
There are many med reports out there that all seem to point at inhibition of the P450 enzymes being the route of the cause.
I have personally been very badly effected by a mixture of BZP and MDMA I was awake for three days after the event. I felt very very intoxicated. Lack of break down would certainly make sense for this type of symptom and also the dreadful aftermath.
I would certainly never say it is irrelevant, but because enyzymes are generally not saturated it's certainly not a priority. Unless we're talking about non-competitive inhibitors (like grapefruit), in which case the interactions can be dangerous.
Im not so sure about lack of priority. Anything that inhibits your enzymes particularly the P450 enzymes that break down other drugs is a big issue in my eyes.
I relate it to my own condition. I have been completely wiped out by this drug > drug interaction so when ever I hear mention of an OP thinking about mixing piperazines, RCs etc with MDMA I always walk on the side of caution suggesting low dose etc.
At the end of it all do any of us really know why two drugs interact in a certain way? Probably not but enzyme inhibition is a good reason not to mix stuff with MDMA thats all im saying.
My advice for MDMA and diazepam would be to bear in mind that the opposite effects of each drug will probably make it feel like you have taken less than you actually have. Unless you want to dull the roll or are treating symptoms of overdose, I would avoid the combination.
I would agree that mixing a benzo with MDMA would likely be a dull roll.
What effect swapping a benzene ring to a thiophene ring does in terms of effect I have no idea. but briefly looking over the wiki article I did notice this statement:
Many lethal etizolam overdoses were due to drug interactions.
On this basis I would still stand by my words to the OP and proceed with serious caution if choosing to mix this thienodiazepine with MDMA.
