Kratom Any other non-responders here?

[plumbus-nine]

I know Kratom respectively its primary alkaloid mitragynine is just a partial agonist and that one shouldn't expect a herbal oxy but I keep reading that people get even nods from pretty low kratom dosages and also horrific, opioid like withdrawals from slightly higher dosages while all I ever get and got is some relaxation, it's enough for me to continue use of Kratom but only because I currently don't have access to better drugs. It has a nice similarity with caffeine (but isn't stimulating on its own for me) and this all independent of the strain, color or vendor. Tried a bunch of them, both different colors, different origins and vendors and always the same result. A 20x extract was a bit more opiatey when snorted but only for the very first time. Kratom also exhibits a pronounced ceiling for me, like 2.5g are threshold, 5g a bit more, but if I take more than 5-10g I get no increase in effects whatsoever. I know of a friend who has similar but even weaker response but most reports I read here are much stronger.

Anybody having a clue why this might be - possibly related to metabolism, maybe some people metabolize mitragynine -> 7-OH mitragynine more efficiently than others? Any potentiators which might work around this? I'd love to have more powerful effects from this drug, as it's among the very few which I can easily source here. Black seed oil maybe? Or ultra low dose naltrexone (might be difficult to get tho because Rx only due to the structural similarity with opiates, sigh the local drug politics here drive me nuts).

 

[negrogesic]

Could be a metabolic issue, specifically CYP3A4 (which converts mitragynine to the much more active 7-hydroxymitragynine).

I found out first hand how important the effect of the CYP3A4 enzyme was to kratom's effect when I quite unexpectedly went into precipitated kratom withdrawal after taking the COVID medication paxlovid (which contains the very powerful CYP3A4 inhibitor ritonavir).

I was dependent on kratom at the time, around 40-50 grams/day, and an hour after taking my first dose of paxlovid i started feeling tense, cold, watery eyes, yawning nonstop, and I realize oh shit, this paxlovid stuff has ritonavir in it, and it's precipitating kratom withdrawal.

Sure enough, i did some searches and found people on reddit reporting the same shit. One guy even wound up in the hospital due to the withdrawal because he didn't put 2+2 together and didn't realize his issue was opioid withdrawal (I guess he thought it was a new phase in COVID symptoms or something). He kept on taking his kratom but it wasn't doing shit.

I wound up driving to a headshop and got a bunch of OPMS liquid extract and drank it with the logic that if I took enough total mitragynine it would stop the withdrawal even if it didn’t convert to any 7-hydroxymitragynine because mitragynine itself has some affinity for the MOR in its own right so enough should do something. It worked, and I stopped taking the paxlovid (I didn't even need it, i was just taking it as prophylactic against potential "long-covid" because im a bit of a hypochondriac)

In any event, that is how important CYP3A4 is to the effect of kratom.