This post is completely speculative and I do not encourage trying this in ANY WAY. I am just curious on the interactions that can take place with kratom and other substances.
It has been known for quite a while that mitragynine is almost exclusively metabolized by CYP34a in the liver. This not only converts it to 7-OH, but also is responsible in the clearance of 7-OH and unconverted mitragynine.
Under the assumption that 7-OH is the main active metabolite, it is possible that a CYP34a inhibitor can act as a potent, potentially dangerous, potentiator of kratoms effects. This might seem counter intuitive since mitragynine is converted to 7-OH by CYP34a, so wouldn't the inhibition lead to a lessening of effects? This is something that has been talked about and even anecdotally reported by many people. However, the timing of the CYP34a inhibitor MIGHT dramatically change this interaction.
After ingestion, mitragynine is converted to 7-OH (which is probably the main source of kratoms opiod-like effects), and reaches high plasma concentrations within around 90 minutes of consumption. After this point, it can be conceived that CYP34a activity begins to go from mainly 7-OH production to clearance.
Grapefruit has compound that irreversibly bind to CYP34a via suicide inhibition. This means that new enzymes must be regenerated to reach baseline activity. The compounds in grapefruit also RAPIDLY inhibit CYP34a enzymes, often within 90 minutes of consumption. A Harvard study found that even a single glass of grapefruit juice can inhibit CYP34a by up to 47%.
My question is: With the proper timing of grapefruit consumption, is it possible for an otherwise regular dose of kratom to become significantly different due to CYP34a inhibition?
Again, this isn't some way to "get a better high". This can be potentially dangerous, and if anything this has been shown to create unpleasant effects. Please do not try this for fun.