Opioids Codeine and Grapefruit juice confusion?

[Forever Changes]

I have used the search engine on this topic but keep reading conflicitng information/opinions on this matter.

I know Codeine is a prodrug and requires enzymes in the liver to metabolise it properly. So my question is basically, does drinking grapefruit juice with Codeine enhance or inhibit the effects of the drug if you are a poor metaboliser of it (which I think I am) ?

 

[4meSM]

Being a poor codeine metabolizer means you're deficient in CYP2D6 which converts codeine to morphine. Grapefruit juice inhibits CYP3A4 which is basically one of the main metabolic pathways for codeine (norcodeine is inactive). Therefore, drinking the juice should increase the effects (at least a bit) by making the codeine in your system more available to whatever CYP2D6 you have.
But I wouldn't expect a huge difference...

 

[Forever Changes]

Being a poor codeine metabolizer means you're deficient in CYP2D6 which converts codeine to morphine. Grapefruit juice inhibits CYP3A4 which is basically one of the main metabolic pathways for codeine (norcodeine is inactive). Therefore, drinking the juice should increase the effects (at least a bit) by making the codeine in your system more available to whatever CYP2D6 you have.
But I wouldn't expect a huge difference...

Thanks for clarifying. Do you think Grapefruit juice might also enhance the effects of other opiates like Tramadol, Dihydrocodeine, Tapentadol or even Kratom?

 

[4meSM]

Thanks for clarifying. Do you think Grapefruit juice might also enhance the effects of other opiates like Tramadol, Dihydrocodeine, Tapentadol or even Kratom?

Inhibiting CYP3A4 should enhance the opioid effects of tramadol and dihydrocodeine (the latter is active on its own though), at least in theory.
For kratom I'm not sure and there's not enough research either, it's also more complex pharmacologically speaking.

 

[TheUltimateFixx]

For kratom I'm not sure and there's not enough research either, it's also more complex pharmacologically speaking.

As per second-hand anecdote at least it seems to. Some time ago I remember telling Wizard to put some lemon juice in his kratom and he said it really increased the high.

 

[Snafu in the Void]

As per second-hand anecdote at least it seems to. Some time ago I remember telling Wizard to put some lemon juice in his kratom and he said it really increased the high.

It just makes it hit faster

 

[4meSM]

Well, CYP3A actually converts mitragynine into some of its active metabolites, so one would think that grapefruit juice would decrease its opioid effects. However the full picture could be more complex, I believe there's some kind of interaction/synergy between mitragynine and its active metabolites.
Is someone willing to try it? I would but I don't usually drink grapefruit juice.

https://pubs.acs.org/doi/10.1021/acs.jmedchem.1c01111

 

[MsDiz]

Just to add, don't drink grapefruit juice if you're taking blood pressure medication or statins.

 

[4meSM]

As per second-hand anecdote at least it seems to. Some time ago I remember telling Wizard to put some lemon juice in his kratom and he said it really increased the high.

I think that's just because lemon juice or any acidic substance increases the solubility of mitragynine (protonation of the nitrogen atom) and thus makes it hit faster and stronger as Snafu said.

Edit: that being said, stomach acid is pretty strong so I'm not sure whether taking the kratom and the lemon juice separately makes any difference at all...
I don't remember if lemon juice contains enzymes that help degrade plant matter, but that could be another factor.

 

[brokedownpalace10]

What's grapefruit juice do for Morphine? So, how would it affect poppy seed wash?