Grapefruit Juice... opposite with codeine

[bcStoner420]

SWIM would just like everyone to know that the grapefruit juice trick is opposite when using codeine, it slows metabolism down so in this case less is converted to morphine, hence, it makes it suck ass. The only reason why he says this is because he has never seen this mentioned on the this forum before..

Reputation Comments on this post:

excellent point and a good notice of exceptions to grapefruit juice "rules"

[Jaded]

Thats pretty interesting, seeing as i always thought that grapefruit juice always potentiated the effects of codeine when taken with it. Where did you find this out?

[bcStoner420]

Just searched potentiating opiates, and it was on one of the sites. It makes good sense though when you think about it.

[Jaded]

Ah cool, thanks for that. I'll have a search in a moment and have a quick read...

[thatsall]

So what could increase the effects, anything?

[ningbar]

swim found two drugs that definitely potentiate codeine for him

1 Quinnine - easy enough to get (as a malaria prophylactic) - swims prescribbed it for muscle cramps

2 Cyclosporin - impossible to get (for transplant patients and those with autoimmune disorders) - swims one of the latter, its pretty horrible stuff tho you wouldnt want to take it unless you have to - its very liver toxic, swim gets LFTs every 2 weeks because of this (which for me has the advantage that it lets swim know hes not been taking too much acetaminophen)



swim finds if he takes his prescribed dose of both drugs an hour before he takes his hoarded prescribed codeine it greatly increases the effects

bad effects:

quinnine gives swim a bitter tasting dry mouth the next day, and if you take too much of it you will have a ringing sound in your ears for several days

cheers
Ningbar

Reputation Comments on this post:

Interesting anecdotal evidence about cyclosporin.

[ningbar]

forgot to mention that you are right about the grapefruit/codeine

its also a very bad idea to take grapefruit with cyclosporin (the doc warned me not to but i did anyway)

because it works on the P450/3A4 enzyme as well as the codeine important P450/CYP2D6 you end up absorbing far too much cyclosporin

killed the codeine buzz stone dead and made me violently ill the next day, i mean really fookin projectile vomiting sick

cheers
Ningbar

[thatsall]

Swim is perscribed lyrica, anti seizure med also perscribed for easing pain in patients that suffer from nerve pain. Swim was perscribed it off-label for anxiety relief. Swim feel like this increases the effects alot, but it is hard to tell because lyrica has a sort off drunken/GHB effect when taken at higher doses, so they might just be working together, but eaither way you look at it Swim would defintly say this is a very relaxing pharmacutical cocktail. Higly recomended.

[Forthesevenlakes]

SWIM experienced this the other day. somehow whatever it is in grapefruit juice ties up the p450 liver enzyme and prevents codeine from being converted (i think) into morphine, so pretty much it renders the codeine ineffective. luckily the same chemical in grapefruit juice can potentiate other opiates, so SWIM was lucky to have some hydrocodone on hand too.

[ojos_de_brujo]

Does this apply to grapefruit-aroma as well?
Swim has solluble tablets containing codeine and grapefruit-aroma (along with paracetamol, several types of salt, aspartame and sorbitol). Swim is not very happy about all the rubbish these tablets contain, but it will have to do. Only in small doses because of the paractamol of course. Extraction does not work because of the salts added to secure solution of the paracetamol.
Swim will have to speak harshly to her doctor for suscribing this scam of a product )

[Forthesevenlakes]

The grapefruit juice inhibition of liver enzymes is caused by furanocoumarin compounds, and not by the aromatic compounds in grapefruit, so SWIM does not think that the grapefruit-aroma would work. But, if anyone has tried this and has evidence to the contrary, please share!

[jonny thaiwongy]

anyone kno about orange juice? swim took 270mg DHC swallowed wit oj it didnt seem as intense as usual, and thats a high dose for swim!

[Paracelsus]

Orange juice doesn't inhibit CYP3A like grapefruit does, having no effect on the metabolism of dihydrocodeine.

[darkglobe]

This has all been discussed in the Codeine Potentiators thread, guys.

Grapefruit Juice theoretically has no positive net effect on Codeine metabolism. End of.

[snapper]

To potentiate codeine, one needs to upregulate cytochrome enzymes (ie-trigger the formation of more enzyme genetically due to demand). Two drugs that come to mind that do this over time are corticosteroids and phenobarbital (along with other barbituates, though pheno for sure). This would increase cytochomes and metabolize more codeine to morphine faster...

[Paracelsus]

If you think grapefruit juice inhibits CYP2D6, think again. Read this thread.

So codeine should actually be potentiated with grapefruit juice because less norcodeine is formed (CYP3A is inhibited).

The internet is full of statements that codeine’s effects are weakened by GFJ, because "it interferes with codeine to morphine conversion". Yet none of these statements has any factual basis since they all state that GFJ inhibits CYP2D6. Actually, at least two Bluelight members that I am aware of have reported definite potentiation of codeine with GFJ: frizzantik (13,000+ posts) and redeemer (2,000+ posts).

Same would also stand for dihydrocodeine (DHC).

It would be great if we had some experience reports about codeine or DHC with GFJ. SWIP might conduct such an experiment when he will have access to codeine/DHC again.

Snapper: While corticosteroids and barbiturates are known inducers of some P450 enzymes, they do not induce the enzyme relevant here (CYP2D6).

[Ethyl]

Allways taken for granted the statment that GFJ inhibits p450d26. I will say to Swie this stuff, and he will experiment.

[Ethyl]

Swie just took 150mg of CWE (including 5% loss) and he previously have drunk/eaten 2 grapefruits (ruby red), he eat the rind too, cause there wheres the goodies are..
He tells me he is experiencing a possible increase in effects (maybe it feels like 200/250mg), but there are other variables that may have influenced, including it's a new extract, and so potency may vary...; swie has lost some tolerance in the last days cause he weened himself.

In the next days Swie will experiment more, and exclude every other variable to see if it really works.. But it looks that it works!

Thanks Paracelsus for opening my eyes.. I should never taken for granted that GFJ inhibited 2d6. Never take things for granted, explore.. Thanks

[Zaprenz]

^ Inconsistent reports on Grapefruit juice interacting with codeine doesn't surprise SWIZ.

There are too many variables involved as well as codeine taken alone is still under debate exactly its main mode of action.

Mode(s) of action:

• Codeine
• Codeine-6-glucuronide
• morphine
• morphine-6-glucuronide
• ?others

Variables:

• Genetic variability in metabolism (inhibition of conversion to more active compounds, inhibition of breakdown of active compounds, variability in uptake etc)
• absorption & distribution - Inc Form of grapefruit (juice, fruit, extract), acidity, interactions with codeine preperation (tablet, solution, CWE)
• and many more

^Add to the above the placebo effects of anecdoctal reports means SWIM would guess there is no easy answer to whether or not grapefruit increases or decreases effect, duration, "high".

[Paracelsus]

Ethyl: glad that it seems to work. SWIE could try an identical amount of CWE in a week (a medical paper shows that inhibition of CYP3A is quasi-irreversible; CYP3A activity probably takes some 8 days to return to baseline). Just to see if it was placebo or not. Also, SWIP has noticed that (for him) red grapefruit potentiates tramadol but not DXM. White grapefruit potentiated DXM. SWIP hasn't tried white grapefruit with tramadol. Maybe white is more effective.

Zaprenz: Those compounds aren't modes of action. They're just codeine and some of its metabolites, of which morphine and morphine-6-glucuronide are active. That means that only CYP2D6 makes the codeine active. And grapefruit simply reduces the rate of N-demethylation of all these compounds (which to my knowledge are all inactive), probably also raising bioavailability in some other way.

[Zaprenz]

Well all four compounds do interact with the mu-opioid receptor, even straight forward codeine - its relative affinity is just so low that it may as well be ignored.

codeine-6-glucuronide...

Eighty per cent of codeine is conjugated with glucuronic acid to codeine-6-glucuronide. Only 5% of the dose is O-demethylated to morphine, which in turn is immediately glucuronidated at the 3- and 6-position and excreted renally. Based on the structural requirement of the opiate molecule for interaction with the mu-receptor to result in analgesia, codeine-6-glucuronide in analogy to morphine-6-glucuronide must be the active constituent of codeine. Poor metabolisers of codeine, those who lack the CYP450 2D6 isoenzyme for the O-demethylation to morphine, experience analgesia from codeine-6-glucuronide. Analgesia of codeine does not depend on the formation of morphine and the metaboliser phenotype.

http://www.ncbi.nlm.nih.gov/sites/en...indexed=google

^the above was published in 2000 and I think on another popular forum there was a discussion on this, can't remember the exact outcome.

Correct me if I'm wrong though, I just thought the old assumption that codeines main analgesic effects via demethylation to morphine is not the whole picture. I.e codeine-6-glucuronide could also contribute to mu-opioid agonism.

[monkeygone2heaven]

i would like this issue settled. you hear grapefruit good for codeine, bad for codeine... seems lots of people want to know.

swim would like to try testing it. an experiential test would be nice. take codeine same time of day, same foods ingested etc... and on another day, a week or so apart (with no codeine in between) do it with grapefruit juice.

swim doesn't think she'd get placebo as she's too aware and attentive to details but noone can ever rule it out so ideally we'd need to find a group of people to do this. that would be informative not just to see how variable the experience is but also to see if we get something beyond placebo (since we can't placebo control directly we can just assume it's 30-40% like it always is with any drug situation)

of course half people take grapefruit first, no grapefruit second day and vice versa for the other half.

anyway, there's an experiment that would help answer this question ) what can i say i always think in terms of experiments...

[Tortoise]

Hi guys, sorry to resurrect an old thread (it seems to bug some people for some reason) but Swim just wanted to tell you that after trying to potentiate codeine with grapefruit juice on two seperate occasions, he is not convinced that it works. In fact, he is quite convinced that it actually reduces the effect of codeine. Both times he tried drinking grapefruit juice an hour before taking a dosage of codeine that he usually gets a kick from and both times he barely felt anything at all. What a waste. He certainly won't be trying that again.

Swim now only ever uses a couple of antacid tablets 5 minutes before his codeine.

[Ale]

Originally Posted by ojos_de_brujo

Does this apply to grapefruit-aroma as well?
Swim has solluble tablets containing codeine and grapefruit-aroma (along with paracetamol, several types of salt, aspartame and sorbitol). Swim is not very happy about all the rubbish these tablets contain, but it will have to do. Only in small doses because of the paractamol of course. Extraction does not work because of the salts added to secure solution of the paracetamol.
Swim will have to speak harshly to her doctor for suscribing this scam of a product )

I don't see what's the matter with those tab's..which salt would it be that "secures" the solution of paracetamol? l really don't see how the salts present a problem.