Combinations - Codeine potentiators and caffeine inhibitors

[RoboCodeine7610]

Hello,

In swim's country,there aren't tylenol #1 or similar co-codamol tablets avaliable.Instead they have brands like Solpadeine and Fevadol Plus which contain 30mg of Caffeine per pill instead of 15mg.This bothers swim because it get's him really anxious and gives him muscle twitches all over.

But not long ago he heard about green tea inhibiting caffeine and thought he'd give it a try.He also heard about grapefruit juice potentiating the codeine and wanted to try it out too so he did and here's a letter he sent me:

1st test: Green tea

I put ~1 Liter of water in a metal pot and added 6 bags of green tea (Lipton).Boiled it down to about 1/2 Liter and drank the disgusting liquid (the whole 1/2L).

+1:00 Did a CWE on 24 Solpadeine Tablets of (500mg/30mg/8mg) and drank on an almost empty stomach.

+1:15 I start to feel the codeine kicking in, still can't feel the caffeine.

+1:30 Can definitely feel the caffeine, and although I'm not sure if the tea inhibited it, I can tell you there wasn't a noticeable difference.

Conclusion:If green tea does inhibit the effects of caffeine it does not do so with acute ingestion of a large amount.It might, however do so if consumed chronically for prolonged periods of time, as you suggested.

2nd test: Grapefruit Juice

I squeezed about 14-18 grapefruits into ~2 Liters of juice and drank it all over a period of about 2 hours.The times below start from when I finished all the juice.

+1:30 Did a CWE on 24 Solpadeine Tablets (500mg/30mg/8mg) and drank all the liquid(100ml) at once.

+1:45 I start to feel the codeine kicking in but a lot slower than usual.There's no itching.

+2:15 I feel the codeine much more strongly now but it's not the same .It has been potentiated for sure, but not in the way you would expect. There's a lot more euphoria but it is somehow "cleaner".It is more pleasurable than plain codeine for sure, but it comes on slowly, therefore lacking the "rush".

+3:30 I can still feel it but most of the euphoria is gone.I'm really surprised it lasted this long since it normally lasts 2-2 1/2 hours and then it's gone.It was more enjoyable than normal and I think it is definitely worth the trouble.

Conclution: Grapefruit juice DOES potentiate codeine for sure, and I think I have an explanation for the change in effects.

The conversion of codeine to morphine occurs in the liver and is catalysed by the cytochrome P450 enzyme CYP2D6. CYP3A4 produces norcodeine and UGT2B7 conjugates codeine, norcodeine and morphine to the corresponding 3- and 6- glucuronides.

So basically the Codeine - Morphine convertion is catalysed by CYP2D6 while the Codeine - Norcodeine, UGT2B7, codeine-6-glucuronide etc...Is catalysed by the CYP3A4enzyme.

Now grapefruit juice inhibits the CYP3A4 which, in theory should leave more unmetabolized codeine to be metabolized by CYP2D6 into morphine, therefore potentiating the codeine.

Now, as I said in my trip report, the trip came on slowly and was "cleaner" so here's my theory.I think most of codeine's immediate effects come from codeine-6-glucuronide and not morphine, and by inhibiting CYP3A4 you're inhibiting codeine-6-glucuronide production, therefore leaving you with mostly a morphine high.

So yeah, grapefruit juice will potentiate and prolong the effects of codeine but at the same time it'll inhibit a lot of the "rush" which might be why everybody seems to be in disagreement about weather it potentiates or inhibits codeine.


swim would appreciate any input, weather from a pharmacological point of view or just an experience.


HAPPY NEW YEAR!!