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Grapefruit Juice as a Potentiator

frizzantik

frizzantik

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I posted this in OD as the Grapefruit Juice FAQ but i'd appreciate any comments from the ADD crowd as this isn't really my area of expertise
Grapefruit Juice FAQ

Grapefruit juice can act as a potentiator for the following prescription drugs sometimes used recreationally:
  • codeine
  • methadone
  • oxycodone (OxyContin, Percoset)
  • dextromethorphan (DXM)
  • alprazolam (Xanax)
  • clonazepam (Klonopin, Rivotril)
  • midazolam (Versed)
  • triazolam (Halcion)
Caution should be excercised if consuming grapefruit juice before or while taking these drugs. Though most people report mild potentiation (if any), if one is taking extremely large doses, any potentiation could be dangerous.

Method of Action
Grapefruit juice can inhibit the gastrointestinal activity of two enzymes known as cytochrome P450 CYP3A4 and CYP1A2, though the effect on CYP1A2 is minimal. This causes elevated plasma levels of some drugs, because they are able to pass into the bloodstream without being broken down by enzymes in the intestine. Due to variations in enzyme levels in the intestine from person to person, effects will vary.

The specific chemical responsible for this action is not known. There are a few suspects including various flavonoids and other phytochemicals called furanocoumarins. Concentrations of these compounds vary from one batch of juice to another. Higher concentrations are found in white juice compared to red, and the highest concentrations are found in the pulp of the fresh fruit. One glass (200 ml) of fresh juice was found to be equal in effect to two or three glasses of double strength reconstituted frozen juice. This suggests that store bought juice, which is often from concentrate, must be consumed in large quantites to for effects to be noticed. Consuption of 6-8 glasses of fresh juice may lead to inhibition of CYP3A4 in the liver. The potentiating effect of grapefuit juice may last 5 or mores hours after ingestion.

A Note on Codeine & Oxycodone
Codeine is metabolised by both CYP3A4 and CYP2D6. CYP3A4 metabolised codine into norcodine which isn't very active, while CYP2D6 metabolises codiene into morphine which is responsible for codiene's effect. When the CYP3A4 enzyme is inhibited by grapefruit juice, more codiene may be metabolised by CYP2D6. This is theoretical and is not supported by literature at this time.

Like codeine, oxycodone is metabolized by both CYP3A4 and CYP2D6, with the more potent metabolite, oxymorphone, produced by CYP2D6. When the CYP3A4 pathway is blocked, more oxycodone may be metabolised by CYP2D6.

Grapefruit Juice and Cimetidine (Tagamet)
Cimetidine acts on a different enzyme than grapefruit juice, specifically CYP2D6. CYP2D6 metabolises many opiates and opiods, but grapefruit juice has no effect on CYP2D6.

Sources:
http://www.postgradmed.com/issues/1999/11_99/cadieux.htm
http://www.powernetdesign.com/grapefruit/references/ref80abstract.html
http://www.mayo.edu/proceedings/2000/sep/7509r1.pdf
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&list_uids=10872589&dopt=Abstract
http://www.tthhivclinic.com/pdf/Recdrug2.pdf
 
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You might want to check out this abstract too. Put in something like "Although grapefruit juice is a well know inhibitors of CYP3A4/5 it also may have some action on CYP1A2, (I know you said that one), 2D6 and 2C9.
 
Bilzor, that abstract says "Inhibitor concentration required for half-maximal rate of inactivation (K(I)) values for bergamottin, DHB, GF-I-1, and GF-I-4 were calculated, respectively, as 40.00, 5. 56, 0.31, and 0.13 microM,"

i take that to mean bergamottin and DHB must have a lot higher concentrations to see inhibition, right? bergamottin was show to cause inhibition quite a few enzymes but only if it was in a very high concentration. i wonder how much of each of those 4 substances is in a glass of juice
 
40µM although not as potent as the others, still isn't like, weak. But yes, the most important thing is whether gastric and hepatic concentrations get up to those levels, which is a matter of the concent in the juice, absorption and metabolism... all of which are probably unknown.
 
How much grapefruit juice would you need to drink to optimise the effect of 300mg of codeine phosphate? Also should I drink it before I take the codeine? (and if so, how long before?)
Thanks,
Ashleigh
 
From the scientific studies I've read, you want to drink white grapefruit juice 30 minutes before taking the other drug. You'll want to drink at least 200mL, perhaps 500 to 750mL. One study I looked at used 600mL to represent "a lot of grapefruit juice" and 200mL to represent a standard cup of GFJ; they found that 600mL was much much more effective at potentiation than 200mL.

Ruby Red grapefruit juice is low in P450 competitive furanocoumarins and flavonoids compared to white grapefruit juice.
 
i just consumed 600ml/20oz of white grapefruit juice, tho i took 2mg alprazolam approx 20 minutes previous; the sedating effects are beginning to kick in once again and much harder this time! wow :D

i will definitely have to see how dosing after drinking the juice works as well and report back with results... if i'm able to type anything by then =D

this is great tho, that is, if it isn't too harsh on my liver, i can definitely extend my script further when needed

would dark chocolate/cacao nibs also work as a potentiator? i forget which enzymes it works on

peace
 
Gormur said:
i just consumed 600ml/20oz of white grapefruit juice, tho i took 2mg alprazolam approx 20 minutes previous; the sedating effects are beginning to kick in once again and much harder this time! wow :D
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Sedation is one thing, but I can't imagine that the anxiolytic effect of alprazolam will be augmented with CYP3A4 inhibition. By extension, the recreational/euphoric value of this type of potentiation is poor. It's not exactly the same as increasing your dose, and since alprazolam has an active metabolite, the synergism between drug and metabolite falls out of phase. Qualitatively speaking, it's hard to be calmly active when you're overly sedated.
 
I would have to disagree, it seems that in most people's trip reports they clearly experience potentiation of effects in addition to a longer duration. Also what is not recreation about either of these, sound like a plus to me.

Further most of the drugs we are talking about using GFJ with benefit from less metabolites and more of the parent compound in your blood stream. Oxy and Hydro are primary examples where only an inperceptable dose is converted into active metabolites stronger than the parent compound. For how little hydro/oxy-morphone that is yielded metabolically you are better off with higher concentrations of the parent compound.
 
theWorldWithin said:
I would have to disagree, it seems that in most people's trip reports they clearly experience potentiation of effects in addition to a longer duration. Also what is not recreation about either of these, sound like a plus to me.

Further most of the drugs we are talking about using GFJ with benefit from less metabolites and more of the parent compound in your blood stream. Oxy and Hydro are primary examples where only an inperceptable dose is converted into active metabolites stronger than the parent compound. For how little hydro/oxy-morphone that is yielded metabolically you are better off with higher concentrations of the parent compound.
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I've always found that GFJ doesn't let me function well while on alprazolam. That tends to kill the buzz for me. Last semester I coadministered the juice before an exam. Usually the xanax helps me concentrate by minimizing cognitive dissonance, but with the GFJ I couldn't even remember what the jacobeans were for spherical integration (rho squared sine phi where phi is the inclination from the positive z axis). I've always attributed this over-sedation to the role of the active metabolite being fucked with. If I'm wrong, then what's actually going on?

I just don't like the "flavor" of the buzz when I potentiate with GFJ. Same goes for hydrocodone. Strangely, the opposite is true for methadone. I even dissolve the Methadose wafers in grapefruit juice, and the high is significantly more intense. Maybe it has to do with the drug's duration of effect?

Thanks
 
Hard to say but I will state this: When I drink large amounts of GFJ I feel a definite alteration in perceptions and bodily functioning (specifically urinary problems). Perhaps this is just placebo in anticipation of the goodies I am about to consume but it seems quite defined to me. Something I do not experience in anticipation when there is no GFJ consumed.

So I certainly do not discount it altering the 'flavor' of the experience for you. I can say without a doubt there is more going on that a simply lengthened experience. However I can not explain the pharmacodynamics at play.
 
Now I think I'm correct on this, but the grapefruit will work as a potentioner regardless if you eat the oxycodone/snort it/ etc ... because this is working at the liver level at this point so it really wouldn't matter what route it enters the body.. correct?
 
how good is the Ruby Red Grapefruit juice form Publix? (the one that's 100% grapefruit juice and NOT made from concentrate)

would i be better switching to some brand of white grapefruit juice with pulp?\

oh and i'm using the potentiation effects for oxycodone
 
Just a thought with oxyxodone...

Those liver enzymes you are blocking???

Sure they metabolize oxycodone out of your body quicker, BUT

They also are responsible for metabolizing oxycodone into OXYMORPHONE

So when you do this you are missing out on part of what the enzymes break the drug into, which are other potent opiates.

The best potentiator to oxycodone is FAT. Yep FAT. Eat a ton of peanut butter.

http://www.purduepharma.com/PI/Prescription/Oxycontin.pdf

However, the peak plasma concentration of oxycodone increased by 25% when a OxyContin. 160 mg Tablet was administered with a high-fat meal
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So you can potentiate and still get all those yummy metabolites.

Let me tell you though - doing this will raise your tolerance quickly, be careful what you wish for!
 
So would eating a high-fat meal help if you are plugging? (I have to due to nausea with opiates).
I mean would you have to take it orally with a "ton of peanut butter", or would your serum lipids be increased and any ROA would be potentiated?
 
Korn3x said:
how good is the Ruby Red Grapefruit juice form Publix?
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It's OK for the price. I mean, there are better tasting Ruby Reds on the shelves, but with grapefruit juice who cares?

Winn-Dixie's is another story altogether. It tastes like straight ass.

Dole is also a good option. My personal favorite is Indian River, with Florida's Best running a close second.
 
seep said:
It's OK for the price. I mean, there are better tasting Ruby Reds on the shelves, but with grapefruit juice who cares?

Winn-Dixie's is another story altogether. It tastes like straight ass.

Dole is also a good option. My personal favorite is Indian River, with Florida's Best running a close second.
Click to expand...

ya i love indian river. i usually get their orange juice, but haven't had their gfj yet.
 
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