Pharmacology - Grapefruit Juice and Benzodiazepines

Discussion in 'Benzodiazepines' started by azrael2600, Oct 16, 2006.

  1. azrael2600

    azrael2600 Silver Member

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    swim receved a new script for xanax and picked it up at the prescription at a local pharmacy. what suprised I was the patient education paper that usually comes along with prescriptions. I was particularly interested in the part on how to use the medicine. Swim will quote the paper:
    Eating grapefruit or drinking grapefruit juice while you are taking this medicine may increase the amount of this medicine in your blood, which may increase your risk for serious side effects.
    I was wondering what this was all about? how does grapefruit juice increase the amount of xanax in your blood?
    could anybody clarify what this is about?
     
    Last edited: Oct 16, 2006
  2. allyourbase

    allyourbase Palladium Member

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    Re: xanax and grapegruit juice?

    grapefruit juice is a cytochrome inhibitor; theyre afraid You might get high. and that could lead to dancing.
     
    Last edited by a moderator: Dec 11, 2008
  3. Forthesevenlakes

    Forthesevenlakes Platinum Member

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    Re: xanax and grapegruit juice?

    to my understanding, grapefruit juice would slow the metabolism of xanax, thus increasing the amount of xanax in the bloodstream, and the amount available to the brain.

    This grapefruit juice phenomena works with many other drugs, too, SWIM's found it effective with potentiating DXM and opiates.

    like ayb says...this combination could lead to dancing, so use caution and put on swiy's dancin' shoes.
     
  4. azrael2600

    azrael2600 Silver Member

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    Re: xanax and grapegruit juice?

    swim tried an experiment this morning before taking swim's morning dose of xanax. swim drank an 8oz. glass of grapefruit juice on an empty stomach 30 min prior to taken swims morning dose. I did notice a slight difference, in that I felt slightly more buzzed, than if I took swim's normal dose without without the grape fruit juice.
     
  5. Wyborowa

    Wyborowa Silver Member

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    The Combined Grapefruit Juice and Benzodiazepines Thread

    Not i know that grapfruit potentiates xanax's effect, would it also work well with klonopin?

    Siwm takes .5mg 4x's a day. If I started drinkin grapefruit juice, would it increase the effects? Doesn't it have to be ocean spray only? thanks!
     
  6. Riconoen {UGC}

    Riconoen {UGC} Newbie

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    Re: Klonopin and grapfruit

    I think it would since they are closely related. but I don't know.
     
  7. Jatelka

    Jatelka Psychedelic Shepherdess Platinum Member & Advisor

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    Re: Klonopin and grapefruit

    Clonazepam (like alprazolam) is metabolised by the cytochrome P450 system of liver enzymes. Grapefruit juice is an inhibitor of these enzymes. Fewer enzymes = more clonazepam around.

    Bear in mind that inhibiting P450 may well increase you's risk of od: Proceed with caution.

    SWIJ doesn't think the brand of juice will have much effect ;)
     
  8. Blur

    Blur Newbie

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    Re: Klonopin and grapefruit juice

    This trick only works with triazolobenzodiazepines (Xanax, Halcion) and Cimetidine inhibits the P450 enzyme subtypes that metabolize these drugs much more strongly than grapefruit juice. You get an increase in the AUC (area under the curve), Cmax, and drug clearance is also decreased. Try about 600 mg of generic tagamet about an hour before a xanax dose. Serzone is an even more potent inhibitor. Basically you can half your dose by predosing with cimetidine (w/ xanax or halcion).
     
  9. calmascanbe

    calmascanbe Newbie

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    Re: Klonopin and grapefruit juice

    SWIM might be a little confused by the difference of oppinions about grapefruit juice doubling the potentcy of clonazepam. Would another SWIM be willing to clarify if it works or not with clonazepam? Thanks
    Any experience is very welcome.
     
  10. Jatelka

    Jatelka Psychedelic Shepherdess Platinum Member & Advisor

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    Re: Klonopin and grapefruit juice

    From rxlixt:

    "Although clinical studies have not been performed, based on the involvement of the cytochrome P-450 3A family in clonazepam metabolism, inhibitors of this enzyme system, should be used cautiously in patients receiving clonazepam."

    SWIJ has no direct experience to report however.
     
  11. calmascanbe

    calmascanbe Newbie

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    Re: Klonopin and grapefruit juice

    Thanks for the reply Jatelka. SWIM personally has never tried the combination , but SWIM might in the near future.If I do I will update the results.
     
  12. DrMuffy

    DrMuffy Silver Member

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    Re: Klonopin and grapefruit juice

    SWIdr has tried potentiating many benzos using different brands of grapefruit juice. This trick works on all the benzos SWIdr has tried it on (alprazolam, clonazepam, lorazepam, and diazepam). You might want to be careful though, because different people metabolized their stomach contents different and one could OD or get basically the same results by using this trick.
     
  13. smithdogg1

    smithdogg1 Guest

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    Re: Klonopin and grapefruit juice

    How much grapefruit juice does one have to drink in order to get noticeable effects? And should it be done 30 mins or so before taking the pill?
     
  14. DrMuffy

    DrMuffy Silver Member

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    Re: Klonopin and grapefruit juice

    Well like SWIdr said, it depends on one's metabolisim to deduce the amount of grapefruit juice one would have to drink. SWIdr is roughly 200lbs and has a moderate (more on the slower side) metabolism and can drink up to 32 fl oz of pure grapefruit juice (most of the time less) to acheive the potentiate his benzos enough. Of course You would (ballpark guess) probably have to drink around 8-16 fl oz, but decide for yourself. And yes, it works much better if You drinks the juice from an hour to thirty minutes before he plans on ingesting the benzos.
     
  15. Jatelka

    Jatelka Psychedelic Shepherdess Platinum Member & Advisor

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    There’s been quite a lot of conflicting information about whether or not various benzos are potentiated by grapefruit juice or not: So here for you’s viewing pleasure is what SWIJ has been able to dig up.

    Grapefruit juice inhibits Cytochrome P450 (CY3PA specifically), which is found both in the liver and the wall of the small intestine. These enzymes metabolise benzodiazepines. The theory is, is that if the enzymes are inhibited then there will be greater bioavailability of the drug (for example, requiring lower doses to get the same effect). However it’s not quite so simple. This effect only comes into play if the parent drug is subject to extensive first pass metabolism. Drugs with high oral bioavailability (because of low first pass metabolism) are not affected by enzyme inhibition significantly.

    Obviously grapefruit juice does not have an effect if benzodiazepines are taken parenterally (IV or IM), because first pass metabolism is eliminated.

    SWIJ has seen it stated in various places on the net that it is only ruby grapefruit that has effect: Not so. Most of the studies were done with normal white grapefruit.

    So, here we go.

    Benzos definitely potentiated by grapefruit juice:

    Triazolam (Halcion), Diazepam (Valium) and Midazolam (Versed)

    Benzos definitely NOT potentiated by grapefruit juice:

    Alprazolam (Xanax)

    Benzos theoretically potentiated by grapefruit juice, but effects probably not clinically significant (because of high oral bioavailability):

    Clonazepam (Klonopin), Lorazepam (Ativan), Chlordiazepoxide, Flurazepam (Dalmane), Temazepam (Restoril)

    NB: No studies have been done on these benzos specifically

    Another factor that comes into play is the duration of intake of grapefruit juice. Triazolam particularly has been studied. Studies have shown that although a single glass of juice increases plasma concentrations and half-life, repeated glasses of juice over three days has an even greater effect. This effect lasts for about 3 days after discontinuation of grapefruit juice.

    Some other tit bits gleaned: Grapefruit juice is not the only juice to inhibit CY3PA. Others having an effect are: black mulberry > wild grape > pomegranate > black raspberry. All however have less of an effect than grapefruit. Star Fruit also appears to be a potent enzyme inhibitor. Pomegranate juice also inhibits CY3PA

    On a side note: Other downers affected by grapefruit juice are: Buspirone (strongly clinically significant), Zaleplon (moderate significance), and Zolpidem (unlikely to be clinically significant).

    See here for some papers from our wonderful archive:

    Triazolam and Grapefruit Juice
    Repeated Consumption af Grapefruit Juice and Triazolam and Alprazolam
    Repeated consumption of Grapefruit Juice and Alprazolam
    Inhibition of CY3PA by Grapefruit Juice
    Interaction between Grapefruit Juice and Diazepam
    Interaction between Grapefruit Juice and Midazolam
     
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  16. Alicia

    Alicia Gold Member

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    Swia herself noticed a potentiation in effects with clonazepam when she was using them. she had read it increased the effect and got curious so tried it with a smaller amount then normal she had drunk the gf juice a hour before hand on an empty stomach before swia had 2 mg. She does not condone this but had noticed an increase in effects comparing to what would of been a small dose. DO not combine this mix with alcohol specially spirits, if u do the end result is not pretty..;)
     
  17. DrMuffy

    DrMuffy Silver Member

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  18. csharpprogrammer

    csharpprogrammer Titanium Member

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    Does drinking grapefruit juice only work when taking benzos by mouth, or does it potentiate an IV dose too?
     
  19. DrMuffy

    DrMuffy Silver Member

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    The answer is no. Grapefruit juice works by inhibiting liver enzymes, which can help potentiate a number of drugs. But when one IV's a drug, the first-pass metabolism in the liver is skipped, so grapefuit juice wouldn't help.
     
  20. Sickpup

    Sickpup Newbie

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    Re: Klonopin and grapefruit juice

    Just take and do all the things the warnings say not to,and You will be styling,J/k.I tested this with xanax and grapefruit juice,and would say got a 30% boost in effectiveness.Tagement tip sounds good.I wouldn't mess around potentiating k-pin,they have a rediculus long half life as it is,I am a benzoid ,and I cant take that build up after 2-3 months.If someone added to that build up,You would probably lose basic motor control within a week.