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Pharmacology - Why Tagamet (cimitidine) is NOT a good opiate potentiator.

Discussion in 'Opiates & Opioids' started by Herbal Healer 019, Oct 8, 2009.

  1. Herbal Healer 019

    Herbal Healer 019 Silver Member

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    There is a common misconception among opioid users in this forum, other forums, & on the street, and that is: a good potentiator for opiates or opioids is cimitidine (more commonly known as tagamet).

    The theory is that because cimitidine inhibits the CYP3A4 liver enzyme which is responsible for breaking down many opiates/oids into inactive metabolites (noroxycodone, norhydrocodone, etc..) that the opiate/opioid in question will have an increased effect & longer duration. While this is true to a certain extent, there is a vital peice of information regarding the pharmokinetics of cimitidine & it's enzyme inhibition that is widely overlooked by the opiaficionados out there.

    See not only does cimitidine inihibit the CYP3A4 enzyme it is also an inhibitor of a wide range of isozymes of the P450 enzyme system. In addition to the CYP3A4 enzyme, cimitidine (tagamet) also inhibits CYP1A2, CYP2C9, CYP2C19, CYP2E1, & most importantly the CYP2D6 liver enzyme.

    The opiates/opioids codeine, hydrocodone, & oxycodone are all CYP2D6 substrates meaning they all involve metabolism by the enzyme CYP2D6 on some level. Specifically codeine as many, if not all, of us well know metabolizes into morphine via CYP2D6, hydrocodone is metabolized into hydromorphone via CYP2D6, & oxycodone is metabolized into oxymorphone via CYP2D6.

    These metabolites I have just mentioned are all much stronger than codeine, oxycodone, & hydrocodone alone thus they are NOT good candidates for cimitidine (tagamet) potentiation unlike many benzodiazapines.

    Hope that helps:vibes:...Remember kids, eat your grapefruit:thumbsup:.
     
  2. nik12937

    nik12937 Silver Member

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    SWIM's heard this before, but SWIM's also heard that the amount of such substances that are converted into the stronger substances is small and therefore negligible. Plus, from SWIM's experience, after taking Tagamet and some hydros, the peak is stronger and the duration longer.
     
  3. Herbal Healer 019

    Herbal Healer 019 Silver Member

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    SWIM agrees that cimitidine IS in fact a potentiator to a degree but also an inhibiter of greater levels of euphoria that could be acheived with the combination of a CYP3A4 only inhibitor and a CYP2D6 inducer.

    Because Cimitidine is a potent CYP3A4 inhibitor it does potentiate opiates in that it increases the duration through inhibiting the enzyme responsible for eliminating the drug through inactive metabolites (CYP3A4) but because it has the potent ability to drastically reduce the amount of morphine created by codeine, hydromorphone created by hydrocodone, and oxymorphone created by oxycodone via CYP2D6 inhibition it isn't the most suitable potentiator for opiates.

    And actually the amounts of active and significantly more potent metabolites of codeine, hydrocodone, and oxymorphone are definately significant especially with codiene which is basically euphorically inactive without being converted into morphine via CYP2D6.

    Here are the percentages for the afformentioned CYP2D6 substrates.

    Hydrocodone- -Hydromorphone= a maximum yield of 25%

    Oxycodone- -Oxymorphone= average yield of 15%

    Codeine- -Morphine= average yield of 10%

    So with a CYP2D6 inducer thrown into the mix these conversions become significantly higher, conversly, a CYP2D6 inhibitor such as tagamet (cimitidine) would lower the yields of the more potent metabolites created via CYP2D6

    I hope that makes sense.
     
  4. visions710

    visions710 Newbie

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    Sorry about the necro-post, but I do have a question about this. Instead of taking the tagamet before (an hour or so before) taking the oxycodone for example, what about giving your liver some time to process the oxycodone into oxymorphone, thus preventing the enzyme from breaking down the oxymorphone your liver has already created from the oxycodone. Just a thought, any ideas? Thanks in advance.
     
  5. vervain

    vervain Titanium Member

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    Interesting info - citimidine & grapefruit are the two most-cited potentiators out there. To the commenter, what is the issue with grapefruit?

    I've never really closely examined my own subjective experiences after potentiating with these two substances. From casual & purely anecdotal memory I'd say they did somewhat improve both the high & the duration, but wouldn't unconditionally stand by those recollections. But certainly have never thought "man, that grapefruit and/or citimidine really messed up this high".

    So if these two are indeed considered not ideal, what are some recommended 'true' potentiators (i.e. directly increase opiate effects rather than magnify the experience thru effects of their own)?

    Edit: Ohhh, just now noticed all but the most recent post are 4 years old. Sorry to bring this back. However, if anyone these days does have info on the above, feel free to chime in...
     
  6. Snappydresser

    Snappydresser Silver Member

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    How about "Please don't discuss ratings in post."

    What are we? Automatons? Have we achieved victory over the orgasm?