Opioids Cross-tolerance and redosing and promethazine

[fishmael]

Hey ya'll.
I was curious, are oxycodone/hydrocodone/codeine create cross tolerances? like if i do hydrocodone 2 days in a row, and want to take oxy on day 3, will it be less effective? Likewise, if a hydrocodone dose i took 4 hours ago is wearing off, can i take some oxy to get high again? and if so, will it be less effective?
Does promethazine do anything to relieve opioid itchiness? Does it potentiate the effects of opioids? I forget why they bottle it with codeine in that syrup.
thank you!

 

[ErgicMergic]

Yes, any mu-opioid agonists create cross tolerances with eachother. It is always best to rotate opioids once in a while to mix it up a bit, and doing so might help prevent cross tolerance, but only slightly so.

If you smoke weed, and let's just say you prefer indica strains, I can use this analogy: you get stoned whether you smoke Skywalker, Popeye, Granddaddy Purple, Master Kush, or Bubba Kush, but they all have a very slightly different profile of active cannabinoids, in different ratios basically, so using a new strain every time you blaze is a nice way to keep your tolerance from gaining to one strain in particular, but it won't prevent overall tolerance to THC and CBD by doing so.

As for the codeine/promethazine, they add prometh since it is a CYP2D6 inducer meaning it makes thatt liver enzyme more active, which is desirable in the case of codeine since codeine needs adequate copies of CYP2D6 to be converted in to significant amounts of morphine. Other CYP2D6 inducers include ethanol, but drinking that with codeine is dangerous in excess, and I find even two beers or more to dirty up the euphoria and clean high of opiates.

 

[fishmael]

Yes, any mu-opioid agonists create cross tolerances with eachother. It is always best to rotate opioids once in a while to mix it up a bit, and doing so might help prevent cross tolerance, but only slightly so.

If you smoke weed, and let's just say you prefer indica strains, I can use this analogy: you get stoned whether you smoke Skywalker, Popeye, Granddaddy Purple, Master Kush, or Bubba Kush, but they all have a very slightly different profile of active cannabinoids, in different ratios basically, so using a new strain every time you blaze is a nice way to keep your tolerance from gaining to one strain in particular, but it won't prevent overall tolerance to THC and CBD by doing so.

As for the codeine/promethazine, they add prometh since it is a CYP2D6 inducer meaning it makes thatt liver enzyme more active, which is desirable in the case of codeine since codeine needs adequate copies of CYP2D6 to be converted in to significant amounts of morphine. Other CYP2D6 inducers include ethanol, but drinking that with codeine is dangerous in excess, and I find even two beers or more to dirty up the euphoria and clean high of opiates.

does that mean promethazine boosts hydro/oxy, too? I'm not sure if they use the same liver enzymes. also is there a chart to somehow see which opioids target which agonists in the brain?
also, i tried googling, but it didn't help. is promethazine sold OTC in the USA?

 

[sekio]

Promethazine is not OTC in the US, but diphenhydramine (Benadryl) is - and that will work fine.
I was under the impression that most of the time combining an antihistamine and an opioid is simple synergy. That is, any increase in blood levels you get from the antihistamine blocking or inducing metabolism is insignificant, when you factor in how sedated the antihistamine alone would make you.

The general consensus is that antihistamines boost all opioids through their subjective effects. Only some of the potentiation comes from enzyme inhibition/induction.
For the *codone drugs (especially codeine), increasing/inducing CYP2D6 activity will increase blood levels of the corresponding morphone drugs (or morphine from codeine).
For all the other drugs, blocking metabolism at CYP3A4 will stop the "main" metabolic breakdown route, and keep more drug in your blood longer.

See also:
http://www.bluelight.ru/vb/threads/184919-Opioids-as-prodrugs-Basic-review

Tl;dr
Block 3A4; induce 2d6, especially for codeine.
Don't worry about it too much if you can't find the right potentiatiors; just stick with diphenhydramine and cannabis then.