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!!

[honourableone]

Very interesting post regarding the grapefruit juice, and likes the theory a lot, but SWIM has no experience there.

SWIM does, however, like tea a lot . SWIM doesn't think the theanine in green tea has any pharmacological effects on caffeine, just that the effects make those of caffeine feel reduced. Green tea actually has caffeine in it, and higher quality teas usually have more, although higher quality teas paradoxically feel more calming. This is because higher quality teas also have more theanine - this is called the "theanine effect". SWIM doubts the effectiveness of this on such large amounts of caffeine ingestion however - it is most useful at the end of a long day with lots of caffeine intake throughout. If SWIY wants to try using tea again, quality is very important (try specialist shops or health shops rather than supermarkets, although "clipper" isn't a bad make), and SWIM reccomends white tea as it has more theanine than any other type of tea (and is SWIMS favourite in general). Loose leaf tea will also have more theanine, as teabags are made with lower quality "tea dust".

On a side note, SWIM once made 6 cups of white tea, left to cool, and then drank all of them one after the other. This was an attempt to experience a larger dose of theanine, and the experience was nice (SWIM thinks such amounts of theanine would be perfect for people who meditate (as would just a single cup for that matter - the ancient buddhists knew their stuff)), but the method of ingestion isn't reccomended due to the acute water intoxication it produced (SWIM feels very stupid for not thinking of that).

[RoboCodeine7610]

On a side note, SWIM once made 6 cups of white tea, left to cool, and then drank all of them one after the other. This was an attempt to experience a larger dose of theanine, and the experience was nice (SWIM thinks such amounts of theanine would be perfect for people who meditate (as would just a single cup for that matter - the ancient buddhists knew their stuff)), but the method of ingestion isn't reccomended due to the acute water intoxication it produced (SWIM feels very stupid for not thinking of that).

Not if you boil it down to half or less of the volume.But did you actually suffer from water intoxication?

[honourableone]

Yes, SWIM did a little bit. But he has Gilbert's Syndrome and believes this makes him unnaturally thirsty (he is in better control of it now), and has experienced it before. Drinking too much water is VERY unpleasant.

Boiling down to half of the volume is interesting idea that SWIM should have thought of (if it wouldn't damage the theanine), although SWIM knows using boiling water on green and white teas (80 degrees celcius is recommended for white) can make them very bitter, so boiling them to such an extent wouldn't taste very nice. But still, it is something SWIM may try in the future if he ever gets the urge.