Grapefruit juice. Still high, oh my!

[Tortoise]

Howdy Peeps,

Johnnny McJohnson was very much a sceptic when it came to the potentiation of codeine with the use of grapefruit juice. He'd tried it twice with no success and believed it to be a bit of a myth.

Until this morning. At around 6am, J McJ took his usual dose of 340mg of codeine and discovered that it hit him much harder than usual. Then he remembered that he'd drank a tall glass of grapefruit juice the night before at around 8.30, not for any reason other than the fact that he truly enjoys a good glass of grapefruit juice. Coincidence? No way!

A little later on, at about 10am Johnny had another tall glass of GF juice and believe it or not, he can still feel the calm tranquility and cosiness of the codeine now at 3pm, a whole 9 hours after dosing!

He has done codeine, many, many times so he is not naive to its effects. Nor is a lack of tolerance likely to have caused this increase in subjective effects and duration as Johnny has well and truly overindulged this week. He was actually expecting the codeine to feel weaker, not stronger.

He concludes that grapefruit juice is definitely a good, effective potentiator of codeine and surmises that the grapefruit juice is best taken at least a few hours before the ingestion of codeine, rather than at the same time or just before.

Johnny McJohnson stands corrected on his prior view on the subject and is humbled by his discovery. He strongly urges others to try it but to reduce their dosage slightly. Oh, and although Ruby Red GF juice is easier on the tastebuds, it's actually the normal variety that is alleged to work best.

peace friends and play safe
A very hapy Tortoise

ps. group hug

[Ale]

Originally Posted by Tortoise

Howdy Peeps,

Johnnny McJohnson was very much a sceptic when it came to the potentiation of codeine with the use of grapefruit juice. He'd tried it twice with no success and believed it to be a bit of a myth.

Until this morning. At around 6am, J McJ took his usual dose of 340mg of codeine and discovered that it hit him much harder than usual. Then he remembered that he'd drank a tall glass of grapefruit juice the night before at around 8.30, not for any reason other than the fact that he truly enjoys a good glass of grapefruit juice. Coincidence? No way!

A little later on, at about 10am Johnny had another tall glass of GF juice and believe it or not, he can still feel the calm tranquility and cosiness of the codeine now at 3pm, a whole 9 hours after dosing!

He has done codeine, many, many times so he is not naive to its effects. Nor is a lack of tolerance likely to have caused this increase in subjective effects and duration as Johnny has well and truly overindulged this week. He was actually expecting the codeine to feel weaker, not stronger.

He concludes that grapefruit juice is definitely a good, effective potentiator of codeine and surmises that the grapefruit juice is best taken at least a few hours before the ingestion of codeine, rather than at the same time or just before.

Johnny McJohnson stands corrected on his prior view on the subject and is humbled by his discovery. He strongly urges others to try it but to reduce their dosage slightly. Oh, and although Ruby Red GF juice is easier on the tastebuds, it's actually the normal variety that is alleged to work best.

peace friends and play safe
A very hapy Tortoise

ps. group hug

That must be why most people seem to disagree about its effectiveness in boosting their Codeine high..because they drink it right at the same time..I doubt that they just prepare themselves for their experience a few hours earlier.This is quite a piece of advice.
Oh,by the way..do swiy know if it works even with pink grapafruit juice other than the plain yellow one?

[Tortoise]

Johnny has heard that the normal yellow variety is by far the most potent. Ruby red and pink grapfruit should work, just not as well. At least that's what he's heard but has never experimented.

[Niagara]

SWIM is wondering what colour of grapefruit juice Johhny McJohnson consumed? SWIM also wonders does Johhny believe that the colour had boost the experience?

SWIM also realises that this thread is semi old.

[Archenemy]

SWIM was wondering, will Hydrogenized Codeine (Hydrocodone) work that way with Grapefruit juice?

[Paracelsus]

Niagara: From Tortoise's second post, it seems most likely that he used yellow grapefruit. My pet vampire tells me that both kinds worked as a potentiator (he has experience with combining grapefruit juice with DXM and tramadol).

An increase in duration could be expected from many opiates when taken with grapefruit juice. Most likely all opiates & opioids based on morphine (heroin, codeine, dihydrocodeine, hydrocodone, oxycodone, oxymorphone, hydromorphone, etc.); tramadol and methadone are also potentiated by grapefruit. Tilidine is expected to be weakened by grapefruit juice.

[darkglobe]

Naringin is present in pretty much all GFJ.

SWIM used GFJ to potentiate an Opiate dosage recently, and 2 litres of GFJ, consumed over a few hours, definitely increased the effects.

The GFJ was purely pink GFJ. Not exactly scientific proof as such, but I think that pretty much sums it up.

[Tortoise]

Welcome back Darkglobe!! Were'n't you banned? We missed you.

[CocaColaCorp.]

Oy, can't believe no ones brought up our friend CYP2D6!! In laymens terms, this is the enzyme in our livers that metabolizes many drugs, notably codeine/morphine/hydrocodone/oxycodone/cocaine/fentanyl/diphenhydramine/dextromethorphan/cocaine/etc. There's quite a list! Anyways, grapefruit juice acts to inhibit this enzyme, thus slowing down the rate at which your body metabolizes the drug and further removes it from your body. The more concentrated the actual grapefruit is in the drink, the better it will work. Any grapefruit juice will work, but remember, certain "colors" are just mixed with other flavors, thus reducing potency of the actual grapefruit juice per drink. Also, Tortoise, is correct in that it takes several hours for this change in your liver to occur. Suggested to be taken the night prior as done above, or a minimum of 3 hours prior. My gold fish has informed my that while on a DXM voyage, he imbibed of this juice mid-trek, and after an hour reached a second seperate peak.

Thought this might be a little bit of help to all!

Reputation Comments on this post:

thanks for adding information

[Ethyl]

Originally Posted by CocaColaCorp.

Oy, can't believe no ones brought up our friend CYP2D6!! In laymens terms, this is the enzyme in our livers that metabolizes many drugs, notably codeine/morphine/hydrocodone/oxycodone/cocaine/fentanyl/diphenhydramine/dextromethorphan/cocaine/etc. There's quite a list! Anyways, grapefruit juice acts to inhibit this enzyme, thus slowing down the rate at which your body metabolizes the drug and further removes it from your body. The more concentrated the actual grapefruit is in the drink, the better it will work. Any grapefruit juice will work, but remember, certain "colors" are just mixed with other flavors, thus reducing potency of the actual grapefruit juice per drink. Also, Tortoise, is correct in that it takes several hours for this change in your liver to occur. Suggested to be taken the night prior as done above, or a minimum of 3 hours prior. My gold fish has informed my that while on a DXM voyage, he imbibed of this juice mid-trek, and after an hour reached a second seperate peak.

Thought this might be a little bit of help to all!

Just read around and you'll see a lot about your friend CYP2D6!!

[Paracelsus]

Grapefruit juice has no effect on CYP2D6. It inhibits CYP3A4. Use the search engine for more info.

[The_Doc_#_2]

"Tagamet should not be taken with codeine because it impairs the metabolism into morphine necessary for it to have any real effect. Grapefruit juice also has the same type of impact on liver enzymes. Tagamet and grapefruit juice will weaken codeine substantially."

Taken from: http://opioids.com/opiates/index.html
Maybe i'm missing something here.

Peace.

[Paracelsus]

Codeine is not active by itself. It undergoes two routes of metabolism: N-demethylation (major pathway) into the inactive norcodeine (by CYP3A4) and O-demethylation (minor pathway) into the (active) morphine (by CYP2D6). CYP2D6 inhibitors weaken codeine, because it's actually the morphine that produces opiate-like effects from codeine. CYP3A4 inhibitors potentiate codeine by inhibiting N-demethylation, thus making more available to O-demethylation into morphine.

If I recall correctly, cimetidine (Tagamet) inhibits both CYP2D6 and CYP3A4, along with some other enzymes from this family. Grapefruit juice inhibits CYP3A4, but has no effect on CYP2D6 (unlike many laypersons still think). As said before, use the search engine. I have posted a thread that explains this.

Reputation Comments on this post:

	Great info. Thanks so much for clarifying that issue.
	Poinently explained! GREAT

[CocaColaCorp.]

Originally Posted by Paracelsus

Grapefruit juice has no effect on CYP2D6. It inhibits CYP3A4. Use the search engine for more info.

Ah, I took a pot shot at it, I even had a full list in front of me... sad but meh.


Now any way to concentrate the active parts into a pill form?

Any research on what specifically causes this?

[Paracelsus]

Active constituents are bergamottin, dihydroxybergamottin. I heard the latter being used by bodybuilders because it potentiates steroids.

About the research: www.pubmed. com

[The_Doc_#_2]

Originally Posted by Paracelsus

Codeine is not active by itself. It undergoes two routes of metabolism: N-demethylation (major pathway) into the inactive norcodeine (by CYP3A4) and O-demethylation (minor pathway) into the (active) morphine (by CYP2D6). CYP2D6 inhibitors weaken codeine, because it's actually the morphine that produces opiate-like effects from codeine. CYP3A4 inhibitors potentiate codeine by inhibiting N-demethylation, thus making more available to O-demethylation into morphine.

If I recall correctly, cimetidine (Tagamet) inhibits both CYP2D6 and CYP3A4, along with some other enzymes from this family. Grapefruit juice inhibits CYP3A4, but has no effect on CYP2D6 (unlike many laypersons still think). As said before, use the search engine. I have posted a thread that explains this.

Thanks for clearing this layperson up

Peace.

[darkglobe]

Hey Doc- watch out for that opiods site you posted, it's full of old and outdated/inaccurate info. Just thought I'd give ya the heads up.

[robshaka]

I've read it stops codeine working.

[Paracelsus]

That is based on inaccurate information. Use the search engine for more information.

[samuraigecko]

Grapefruit juice enhances the effect of some commonly used medications by increasing their bioavailability via the selective down-regulation of a specific subfamily of the cytochrome P450 enzyme system in the small intestine.

Just thought that may help for a few. Grapefruit juice is not the only juice to do this but it is by far the most potent for this purpose.

Also one may want to take a look at THIS if they would like to know more.

Cheers.

[Ethyl]

take a look into pomegranate to, it inhbitis

Originally Posted by niner >>from other forum..

I'm taking pomegranate extract daily, so I looked further into the p450 inhibition issue. It turns out that many fruit juices are p450 inhibitors, chiefly CYP3A. (CYP = CYtochrome P450) Pomegranate juice is also a 2C9 inhibitor (PMID: 17132763). The juices are 3A inhibitors in the following order: grapefruit > black mulberry > wild grape > pomegranate > black raspberry. (PMID: 16415112) Starfruit is also inhibitory, although I don't know where it fits in this scheme. Lime juice was seen to be an apparent 3A4 inhibitor in some subjects. (PMID: 12811362) Even red wine is a mild 3A4 inhibitor, and can lead to clinically relevant inhibition in some people. (PMID: 11452240)

The fruit juices all appear to act via a mechanism-based process. This means that they are covalently alterning the p450 enzyme rather than just taking up space in the active site while they are present in high concentration. As such, the inhibition continues until the enzyme is recycled. After grapefruit juice consumption, it may take from 3 (PMID: 12891222) to 7 (PMID: 11061578) days for the metabolism of certain drugs to return to normal.

Several studies looked at fresh versus processed or heat treated juices, and saw no differences. This suggests that the inhibition is due to a reasonably robust small molecule, rather than a proteolytic activity.

The juices appear to affect only the enteric p450s. The hepatic p450s seem to be left alone, from my reading. Apparently some people have more p450 activity in the gut (and less in the liver?) than others, so the juices hit them harder.

Are these inhibitions clinically relevant? Yes, it appears that they are. "When simvastatin was taken with grapefruit juice, the mean peak serum concentration (Cmax) and the mean area under the serum concentration-time curve [AUC(0-infinity)] of simvastatin were increased 12.0-fold (P < .001) and 13.5-fold (P < .001), respectively, compared with control." (PMID: 11061578) "48-year-old man with possible underlying myopathy was successfully treated with ezetimibe 10 mg/day and rosuvastatin 5 mg every other day for 17 months. Three weeks before presentation, he began drinking pomegranate juice (200 ml twice weekly). He presented urgently with thigh pain and an elevated serum creatine kinase level (138,030 U/L, normal < 200 U/L). In conclusion, because both grapefruit and pomegranate juice are known to inhibit intestinal cytochrome P450 3A4, this report suggests that pomegranate juice may increase the risk of rhabdomyolysis during rosuvastatin treatment, despite the fact that rosuvastatin is not known to be metabolized by hepatic P450 3A4." (PMID: 16923466) This paper was published shortly before the paper that showed that pomegranate juice was a 2C9 inhibitor, and sure enough, rosuvastatin is metabolized by 2C9.

Pomegranate juice harmful? Like everything else that we are running experiments on ourselves with, it should be treated as a drug. In combination with statins, high dose pomegranate is indeed dangerous. Grapefruit juice is worse. If you are using these juices, you should make sure that any other drugs you take are safe in the presence of a 3A4 or 2C9 inhibitor.

From my own experience, pomegranate (at least in the dose of extract I use, approximately 660 cc/day juice equivalent) is not a super strong 3A4 inhibitor. One of my chronic medications is a 3A4 substrate, and I have used it with clarithromycin, an antibiotic (biaxin) that is a powerful 3A4 inhibitor. With biaxin, I strongly feel the overdose of the other med in a few days. I've been using pomegranate for about 2 weeks, and just the other night noticed a slight tinge of OD. So it's there, but not very strong. But that's me, and that's a medicine with a pretty good therapeutic index. I will keep taking pomegranate because it does great things, but will titrate my other meds as needed.

By the way, (as if this post were not long enough...) my doctor, a pretty smart guy, happily prescribed a 3A4 substrate and a potent 3A4 inhibitor to me at the same time, and my pharmacist cheerfully dispensed them. In theory, that never should have happened- so much for the theory. Whenever you get a prescription medication, ask the pharmacist for a package insert. (the one for the pros, not the Readers Digest version that they print out for consumers) It will usually discuss the metabolism of the drug in detail, and you can figure out for yourself if you might have a problem or not.

Thanks for the heads up on this, greece.

So, a mix of this juices would be even better: grapefruit > black mulberry > wild grape > pomegranate > black raspberry and possibly star fruit to (alltought not sure for codeine, but certainly good for other opiates.)

Reputation Comments on this post:

great information on fruits.

[Melalicious]

swim drunk 2lt of a yellow grapefruit juice, over probably 24hours just, and just over 3 hours ago swim had near normal dose of 170mg of codeine, and swim thinks she has noticed slight differences!! swim is still half and half on the grapefruit juice, but its been interesting reading what others have had to say! so swim things she will keep givin it a go

[Tortoise]

Swim is interested to know if anybody has tried potentiation with a whole grapefruit, as opposed to just the juice.

Swim plans to make this his next experiment.

[skits]

Swim would like to know SwiTortoise's results.
:]

[samuraigecko]

SWIMs father-in-law did, he was throwing up for a day . . lol.

Peace