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Opinions - Promethazine as opiate potentiator. At what point?

Discussion in 'Codeine' started by Smeg, May 29, 2010.

  1. Smeg

    Smeg Opiates & Opioids Staff Member

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    Red needs advice about the potential of promethazine to enhance the effects of codeine phosphate and tramadol. He was wondering at what point during the sequence of dosing of opiates/opioids should promethazine be consumed? Might it be before during or after?

    Red used codeine phosphate 90mg + tramadol 100mg In half hourly doses of 50mg. He weighs 140 pounds.
     
    Last edited: Aug 11, 2013
  2. Razorbladekiss

    Razorbladekiss Silver Member

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    I have used promethazine a few times with codeine. He always took a couple of prometh' pills just after the peak of the codeine high ... so any where between 1 hour and 2 hours after ingestion. If You took some after that it creates almost a 2nd high but a little different. Its nice to take prometh after the true codeine buzz has worn off and your ready to go to sleep (if You takes it at night).

    Swim advises that his mood changes on prometh and he fails to remeber what happened the night before. He has difficulty remembering things.

    If this worries swim, try taking diphenhydramine its very similar but I has no problem remebering the night before.
     
  3. [tanarilla.]

    [tanarilla.] Silver Member

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    My bunny thinks that diphenhydramine is more suitable to potentiate codeine, as it is a weaker anti-histamine, and will therefore cause less sedation. Unless of course, You goes for sedation.

    My bunny takes any potentiator approx. 20-30 mins before taking the codeine.
     
  4. Smeg

    Smeg Opiates & Opioids Staff Member

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    Red thanks yourazor and youtan for the advice. He tells me he goes for both recreational sedation and stimulation simultaneously. He told his carrier pigeon that it's possible to achieve both safely because of good DF counsel.
     
    Last edited: Aug 11, 2013
  5. midnightcast

    midnightcast Newbie

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    I have found:
    1) If taken 30min before codeine ingestion (to let them kick in both together) the high is experienced as one of sedation and the waves of codeine euphoria are diminished or blured out by the promethazine. Euphoria is not potentioated it is depotetntiated lol.
    2) If taken 30min after codeine, one can feel the codeien euphoria and by the time that start to fade, siwy finds themself on a more "darker" yet still in a little euphoric, sedated state.

    The rest just vary inbetween these two depending on the different time of ingestions of this product.

    SWIM out of all honesty found himself thinking about prometh and codeine rather than just the codeine, when he didnt have and phenergan and just had codeine. IT made him feel even more in his own safe world however in a sort of darker place, safe but dark lol. Like no one else could enter that dark space except himself. By euphoria SWIM means the waves that rush up and down when using codeine.
     
  6. Smeg

    Smeg Opiates & Opioids Staff Member

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    Red thanks youmidnight for option 2. A note left by his carrier pigeon endorses this method.
     
    Last edited: Aug 11, 2013
  7. Suboxer

    Suboxer Silver Member

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    Promethazine is not used, like cyclizine and diphenhydramine, to synergize with codeine, however horrible a term that may be when applied to anti-histamines, with anti-histamines.

    Promethazine, like glutethimide, is a true potentiator of codeine, as well as having what some view - spuriously (at least in the case of anti-histamines) - synergistic effects.

    Promethazine is a moderately strong CYP450 IIDVI enzyme inducer. CYP450 IIDVI is the enzyme that converts inactive codeine - methylmorphine, a prodrug for morphine - in to morphine by demethylation. In most people about 10% of the oral dose of codeine is converted in to morphine, so: 90mg codeine = 9mg morphine. Promethazine increases the amount of codeine converted to morphine in vivo by a factor of two, so the same 90mg of codeine is now equal to roughly 18mg of morphine, and, in addition, is made more sedative, less itchy (the itch is the best part of an opioid high besides the nod), and a slightly more effective painkiller (some anti-histaminics have what is called "analgesic sparing" properties, meaning, combined with an opioid, they increase the analgesia it provides synergistically) by the anti-histaminic and mild anti-psychotic effects of promethazine (promethazine is roughly 1/10 the potency of chlorpromazine [Thorazine, Largactil]).

    The drug, codeine, has no effects. It is converted to morphine by first-pass metabolism in the liver after it has been absorbed by CYPIIDVI. Taking the drug AFTER you've ingested the codeine does nothing but add an anti-histaminic effect on top of the codeine - it acts synergistically.

    If you take the promethazine one to two hours before you take the codeine, it is a true potentiator in addition to whatever "synergistic" effects it might have - it increases the maximum plasma concentration and area under the curve of morphine itself, increasing the actual height and duration of the opioid high - not just adding the effects of a sedative anti-histamine to it. So, for Christ's sake, take the promethazine BEFORE you take ANY of the codeine, and you'll get more of an opioid effect - if you take it after the codeine, YOU WONT! - you'll just have the effects of a sedating anti-histamine/anti-psychotic added to it.

    Now, the above information will get you more opioid bang for your buck - any one who says to take the promethazine after the codeine will not increase the opioid concentration in your blood one bit, but will just add promethazine "buzz" on top of it. Taking the promethazine with the first dose will work, albeit less well than taking it an hour before. For maximum effect, you should always take all your doses together (but be wary of risk of overdose) - all you're getting by taking one-half a dose every thirty minutes is about 55% of the high you would taking it all at once, and 200% the tolerance per "unit of high."

    Note: Promethazine effectively doubles the limit of codeine a person can metabolize, and thus benefits users of low to low-midrange tolerance as well. Normally 300mg of codeine can be metabolized in to only 30mg of morphine, and the liver enzymes are "saturated" in a sense - they can convert no more. This becomes 60mg while taking promethazine around one to two hours before use of the codeine.

    Note 2: Caution: I am unsure of the metabolism of tramadol, but tramadol itself is an extremely weak opioid, that, like codeine, must be demethylated, in the case of tramadol, in to o-desmethyltramadol (the "M1 metabolite" of tramadol) before it is active at the mu-opioid receptors (900x increased affinity compared to tramadol). Tramadol, before being metabolized, is merely a norepinephrine reuptake inhibitor and serotonin releasing agent. If the metabolism of tramadol to o-desmethyltramadol is also catalyzed by CYPIIDVI, you may be putting yourself at risk of opioid overdose by taking promethazine before the codeine and tramadol, because, in essence, you could be effectively doubling your active dosages.
     
  8. DSB100

    DSB100 Silver Member

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    my cat has just taken 25mg of phenergan, and is wondering whether taking her normal does of 300mg (ish) codeine would still be safe or best to take say 200mg first and see if she liked it ?
     
  9. DemonsSouls2010

    DemonsSouls2010 Newbie

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    The post above this is very intriguing. My friend's cat would also like to know what dosage of Phenergan to take, prior to injesting 240-300mg of Codeine? If the cat's Phenergans were 25mg each.

    Example: Take 2x Phenergan (25mg) 50mg, then 1-1.5hrs later take 240-300mg of Codeine.

    My friend's cat also took a Metabolism Supplement (Chormium Picolinate 400mcg) or (L-Carnitine 500mg) 1 hour prior to take 180mg of Codeine, and it seemed to prolong the cat's sedation. It did not increase the high, but lengthened the sedation. Could this be a viable solution, or was it a case of Tolerance-Bypass (as the cat has a medium-to-high tolerance).
     
  10. dripdiddydrip

    dripdiddydrip Silver Member

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    I agree with midnightcast, my pink elephant's experiences were substntially the samw, and I found no evidence on the internet that promethazine is an CYP450 inducer.

    Could it be possibly that even if it is an CYP450 inducer, the positive effects in terms of more morphine being created are less than the negative effects on the high by promethazine's antipsychotic propeties, the partial blocking of the brain's dopamine pathways?

    dripdiddydrip added 6 Minutes and 32 Seconds later...

    Also, codeine is metabolized by the enzyme CYP2D6, not CYP450, soo...
     
    Last edited: Jun 15, 2013
  11. Charopia

    Charopia Newbie

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    Actually codeine is metabolised by the cyp450 enzyme but more specifically the 2D6 substrate of cyp450, which the op pointed out using roman numerals, I also wonder if inducing the 2D6 removes the fabled ceiling effect?
     
  12. Disorder909

    Disorder909 Silver Member

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    I take 75mg Promethazine 1.5 hours before my prescribed dose defiantly in my case, increases the euphoria though sedate's the experience.
    For harm reduction I would say it means you could take 25% less of your normal dose.

    I take 3 Promethazine tablets then an hour later 1 4mg chlorphenamine maleate to stop itch then my dose 30 mins after that.