Grapefruit Juice FAQ|
Grapefruit juice can act as a potentiator for the following prescription drugs sometimes used recreationally:
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.
- oxycodone (OxyContin, Percoset)
- dextromethorphan (DXM)
- alprazolam (Xanax)
- clonazepam (Klonopin, Rivotril)
- midazolam (Versed)
- triazolam (Halcion)
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.