Possible Grapefruit Juice Potential for Greater Tramadol Experience

Discussion in 'Tramadol' started by DrMuffy, Apr 18, 2007.

  1. DrMuffy

    DrMuffy Silver Member

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    Grapefruit Juice Potential for Greater Tramadol Experience​
    SWIdr recently did a little research on the effects of grapefruit juice on tramadol. It seems that a tramadol experience (potentiated by grapefruit juice) can be much more stronger based on some people's (including himself) experiences. So SWIdr decided to see if there was anything relating grapefruit juice (directly and or indirectly) to the tramadol experience. He is not very educated when it comes to the termonology of pharmacology and such, so he apologizes if he uses terms incorectly and or contradicts himself. SWIdr very much welcomes: Corrections, additional information, and replies to his findings.

    The following exerpt is talking about codeine and tramadol:
    “Both agents are prodrugs; that is, the parent compound is essentially devoid of analgesic activity but the active demethylated metabolites—morphine in the case of codeine and O-demethyl tramadol in the case of tramadol—are responsible for the analgesic activity.”
    source- http://jada.ada.org/cgi/content/full/135/3/298

    "(+/-)-Tramadol is a synthetic analogue of codeine. It is a central analgesic with a low affinity for opioid receptors. Its selectivity for mu receptors has recently been demonstrated, and the M1 metabolite of tramadol, produced by liver O-demethylation, shows a higher affinity for opioid receptors than the parent drug. The rate of production of this M1 derivative (O-demethyl tramadol), is influenced by a polymorphic isoenzyme of the debrisoquine-type, cytochrome P450 2D6 (CYP2D6)."
    source- http://opioids.com/tramadol/index.html

    -SWIdr’s Notes: Grapefruit Juice has been known to interfere with the metabolism of codeine and a lot of other drug’s. Grapefruit juice works mainly on the P450 cytochromes and can tie up the liver. It seems that some people do not metabolize tramadol it into its M1 active O-demethyl metabolite, which produces greater effects than other metabolites of tramadol. So grapefruit juice may help with the o-demethylation of tramadol, which would explain the greater effects for users of tramadol who potentate it with grapefruit juice.

    “With prodrugs like codeine and tramadol, people who metabolize them poorly exhibit little analgesic activity with the intake of these drugs because they do not form the necessary active metabolites, while people who metabolize them extensively readily form the active metabolites and exhibit significant analgesia.”
    source- http://jada.ada.org/cgi/content/full/135/3/298

    -SWIdr’s Note: This is why some can feel the (recreational) effects of tramadol, while some do not, since their livers metabolize poorly and cannot create O-demethyl tramadol, which is its M1 metabolite.

    SWIdr's Conclusion- Grapefruit juice does seem to help with tramadol experiences one way or another. According to the information SWIdr found: grapefruit juice plays an important potentiating factor by helping with the metabolism. Besides helping the experience last longer and such, it seems to help with the o-demethylation of tramadol, which creates a stronger experience. Again SWIdr welcomes: Corrections, additional information, and replies to his findings and or sources.
     

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    1. 5/5,
      Beautifully expressed information despite the "disclaimer" at th start.
      Jul 2, 2012
    2. 5/5,
      Good post, interesting ideas on this oddball molecule
      Oct 3, 2011
    3. 4/5,
      Good, informative post
      Aug 15, 2009
    4. 5/5,
      A little late, but very good post!
      Oct 7, 2007
    5. 4/5,
      Good intelligent research. Great member.
      Apr 19, 2007
  2. RTR

    RTR Newbie

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    Swin knows this isn't grapefruit juice, but Smin had 300mg of Tramadol around 10:30am and was really nice. At 5:00pm, the buzz was gone and Swim still had some pain relief. Swim Decided to drink some Arizona Raspberry Iced Tea and in a couple minutes a buzz started to kick in and lasted for about 40 minutes. I would like it if swiys would also try this tea with their Tramadol.
     
  3. DrMuffy

    DrMuffy Silver Member

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    SWIdr will most definatly try to test out this experiment You talks about. Meanwhile he has been testing out tramadol doses with and without grapfruit juice. Without the juice, its definatly not as fun, but who knows, could be placebo....
     
  4. Swimster

    Swimster Palladium Member

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    I had positive effects too. With Grapefruit-Juice. He though it was just a myth at first. But it seems to take the pre-end of the ride and turn it back into a Buzz-"Prefix", if you know what swim means. It was strange to belive at first for he.
     
  5. DrMuffy

    DrMuffy Silver Member

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    SWIdr tried tramadol without grapefruit juice tonight, and did NOT experience effects at the normal grapfruitjuice potentiated dose (which was 150-300mgs). He had to use 800mgs of tramadol to obtain the same opiate effects, exept there was much more Serotonin and Norepinephrine activity, which stimulated SWIdr way more than usual, which was undesirable (sp?). This experiment also compliments SWIdr's findings, but of course it could have been placebo (but he highly doubts it).
     
  6. Bajeda

    Bajeda Super Moderator Platinum Member & Advisor

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    Thats a rather high dose of Tramadol, and much more risky. If swiy's tolerance is so high that he needs to use that level dose he sould consider cutting back and/or abstaining for a while.

    Some files in the archive may be of interest to swiy, particularly the one documenting recreational use of Tramadol.
     
  7. DrMuffy

    DrMuffy Silver Member

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    Thanks you so much SWIbejeda!!:) Theses articles were very helpful, not to mention interesing. Yes, 800 mgs of Tramadol is a very high dose, but SWIdr is trying to ween himself of of it, (and he usually takes smaller doses anyways).
     
  8. Swimster

    Swimster Palladium Member

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    No joke!! Swim heard 400mg's was a 24H max, And this was the max he ever took! Seisures and other risks are real possible, even at doses as low as 200mg's!

    So SwiDr. should be carefull!! Altough, You has done things worse than this, like taking Tram with caffeine!(MAOI,risk of SerotoninSyndrome,Ouch!) So don't feel bad. SwiDr. should of checked out doses, first tho.(perhaps erowid).

    Anyway, perhaps Placebo, tho. I heard other substances, that this rumor associated with, was a false myth.
     
  9. DrMuffy

    DrMuffy Silver Member

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    ^^^^^^^^^
    Now that would be bad, yikes!! SWIdr is pretty sure his tolerace and the effects of the grapefruit juice/tramadol are not placebo (since he has been experimenting for over 10 days now with the substance).


    Yes SWIdr uses lesser doses most of the time (when using grapfruit juice), also SWIdr forgot to mention he took 1 mg of clonazepam with the second dose of tramadol to help avoid seizures (if in fact it does help). SWIdr regret this stupidly high dose, which could have ended up much worse, and will try to avoid other large doses in the future!
     
  10. Bajeda

    Bajeda Super Moderator Platinum Member & Advisor

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    You should be extra cautious with such actions as taking other substances with the Tramadol, even if it helps in some regards! Tramadol is known to be much more dangerous when taken with other CNS depressants, as you saw with the files in the archive!

    Take care now, You doesn't want to have any problems weaning himself off Tramadol use!
     
  11. DrMuffy

    DrMuffy Silver Member

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    Very true!! SWIdr realized how messed up he could have been since most of those tramadol ODs involve benzos, yikes:eek: !!! Well SWIdr is going to keep doing with the lower doses of tramadol with grapefruit juice, until he slowely weens off the substance.

    Warning: Doing these experiments/recreational abuse all these days in a row has created quite a tolerance and even an addiction to the substance, so if anyone elso decides to try this combo, BE CAREFUL!!!
     
  12. Bajeda

    Bajeda Super Moderator Platinum Member & Advisor

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    Be sure to stay healthy and try to keep active so You doesn't keep the weaning process in mind too much.

    Some Kava or Valerian or some other nice calming and euphoric ethno could possibly be helpful as You gets down to much lower doses.
     
  13. Paracelsus

    Paracelsus Platinum Member & Advisor

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    As far as I know, the enzymes responsible for O-demethylation of substances like codeine, DXM and tramadol is CYP2D6. From most circumstantial evidence it seems that grapefruit inhibits this enzyme, making the O-demethylation slower. That potentiates DXM, makes codeine weaker and should make tramadol weaker (in theory). Since grapefruit does without doubt potentiate tramadol, other mechanisms are probably responsible for the potentiation. (Please correct me if I'm wrong somewhere).

    my tramadol+grapefruit experiment from last night:

    SWIM drank grapefruit juice from two grapefruits over the course of an hour.

    After finishing the grapefruit juice, SWIM consumes 200mg Tramadol HCl (in liquid form).

    First effects were felt about 60 minutes after consumption and consisted of warmness, some itching and some sedation.

    After another hour, the experience gets more and more intoxicating and sedating. ~ 30 minutes later, SWIM decides to take a nap.

    I didn't really fall asleep, but didn't stay awake either. He just lay on his bed with eyes closed, and he thinks he dreamt a little (he can't remeber what). It was strange, I was semi-conscious, not being able to decide of he was just thinking about something or dreaming about it.

    After some 45 minutes, SWIM forced himself to get out of the bed and stay awake. The itching got quite uncomfortable, but it was no big deal.

    After 30 minutes, the tiredness overwhelmed SWIM and he decided to go to bed. The tramadol was still acting quite powerful, so SWIM put himself into a lateral position (to prevent choking on vomit - better safe than sorry/dead) and slowly faded into that familiar dreamlike state. The bad thing was that I was getting tired, but not able to fall asleep.

    I spent half the night in that dreamy state, but he was getting bored of it and trying to get some sleep, but it wouldn't come until about 4-5 AM (GMT+2.00). And I had to wake up at 06.30.

    Mild pain relief was still noticeable 15 hours after consumption.

    Maybe I will try a herbal downer to help him sleep next time. If there's gonna be a next time.
     
    1. 5/5,
      A detailed painstaking and enlightening report. Thanks for this.
      Jul 2, 2012
  14. DrMuffy

    DrMuffy Silver Member

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    ^^^^^^^^^
    Yeah SWIdr kinda got confused with th whole O-demethylation part, but knew that grapefruit (usually speeds thing up, so he just kinda conclued that it worked on hat liver process also. This experience was a good exemple of either a placebo effect (doubt it) or a real emaple of grapefruit juice potentiating Tramadol (somehow)......Say, in't DXM a (distant) member of the opiate family, so maybe it could be some molecular structers had th same OH group or something else....(SWIdr doesn't know his termonolgy of pharmacology and mplecules, so please excise him for mis9information).
     
  15. Swimster

    Swimster Palladium Member

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    This is Extremely common! I believe that the end part(which lasts like 8hrs or so depending on dose), is the comedown part, in which, at first seems pleasant(unusually), but gets exsausting after say around 5 hours! Anyway, it can seem hallucigenic, or something similar, when trying to sleep, and almost impossible. <i>Note:by "Hallucigenic", I am not comparing to any real hallucinations, but rather a sort of ironic weirdness.
     
  16. DrMuffy

    DrMuffy Silver Member

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    ^^^^^
    Yes many people experience these side effects of Tramadol, but other's dont. (According to erowid): the onset is about 15 minutes, it "coming up" part can differ from person to person, but it usully last anywher from 15 minutes to an hour, the plateau can last from 2-8 hours, and the comedown is about 5 hours.
    SWIdr doesn't have the effect mentioned above, but of course he does also take Soma and Xanax with his Tramadol sometimes, so those could explein it. Also the half life of tramadol is about 8 hours or so, so when it leaves your system, so do most of the good/bad parts, which would leave one in a semi-depressed state (it acts on the Serotonin and Norepinephrine receptors too), but the effects of the Serotonin and Norepinephrine may still keep one slightly stimulated.
     
  17. delphinen

    delphinen Mercury Member

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    Tramadol binds to opiate receptors in 15 to 30 minutes after ingestion. After 2 to 3 hours, it gets metabolized to the lovely O-demethyl, which binds too far more to opiate receptors than Tramadol, and its also too much stronger.
     
  18. Nicaine

    Nicaine Titanium Member

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    I think a carefully planned dosing regimen could be far more effective than grapefruit juice, although the two methods could of course be combined. He actually started experimenting with this yesterday, but cut it short when his kratom arrived. It did seem to be working very well for the short time he tried it.

    (1) Take 50mg of Tramadol.
    (2) Take another 50mg 1 1/2 hours later.
    (3) Take another 50mg 2 hours later, and continue taking 50mg ever 2 hours until the desired effect is reached. One should not exceed the daily 400mg limit.

    This is based on the fact that the parent drug has a half life of ~5 hours, and the active metabolite 9+ hours. IMO the worst method would be to take a large loading dose... the best would be to dose small/often and allow the active metabolite to build up in the bloodstream, while giving the parent drug time to clear.
     
  19. Psych0naut

    Psych0naut Platinum Member

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    I think what You is describing is what is called the nod. A state where one is half asleep and drifting through weird dreams, but still half awake as well. This happens with all opiates and opioids in high doses, I have experienced this with tramadol and opioids as well.
     
  20. Paracelsus

    Paracelsus Platinum Member & Advisor

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