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Opioids Codeine

katamaranas

katamaranas

Greenlighter
Joined
Feb 2, 2015
Messages
18
Hi folks.
Could you please elighten me why codeine phosphate doesnt do much even 1000mg and dehydrocodeine does, even if its only 200mg.I heard something that it could be something with my liver enzymes or smth.
 
The principal pathways for metabolism of codeine occur in the liver, although some metabolism occurs in the intestine and brain [Articles:18187562, 8875123]. Approximately 50-70% of codeine is converted to codeine-6-glucuronide by UGT2B7 [Article:9010622]. Codeine-6-glucuronide has a similar affinity to codeine for the mu opioid receptor, coded for by the OPRM1 gene. Approximately 10-15% of codeine is N-demethylated to norcodeine by CYP3A4. Norcodeine also has a similar affinity to codeine for the mu opioid receptor [Article:8818573]. Between 0-15% of codeine is O-demethylated to morphine, the most active metabolite, which has 200 fold greater affinity for the mu opioid receptor compared to codeine. This metabolic reaction is performed by CYP2D6 [Articles:2049245, 1867957, 18781855].
Click to expand...

from Codeine and Morphine Pathway, Pharmacokinetics

basically some people don't do a good job at metabolizing codeine thus do not experience much from the opiate.

according to that article, 0-15% of the codeine dose is O-demethylated to morphine which is the main active metabolite.
 
Codeine is a pro-drug and needs to be metabolized into morphine and other metabolites, CYP2D6 being responsible for metabolizing codeine into morphine, but due to a mutation people can be poor metabolizers, meaning that not much/no codeine is converted to morphine, so they don't feel much/anything from it
And there's a ceiling effect, meaning that after a certain amount of codeine (I think something around 600mg) the enzymes are saturated, meaning there effects won't increase anymore, but duration of action can be longer
 
You can potentiate but unless you've got a prescription on the national health that sounds like a waste of money when taking a gram of the stuff. Also dihydrocodeine is about twice as strong so 200mg of DHC might be equivalent to 20-30mg of oxycodone, so you're not taking a low dosage of DHC when comparing the two (unless you've got a tolerance, of course). You could always try plugging, potentiation like promethazine, phenylalanine, or grapefruit juice, etc., etc.
Honestly though, dihydrocodeine and codeine are BOTH metabolised by CYP2D6, so if one is working and the other isn't I really can't tell you why. Not much research has been done into the digestion and conversion of dihydrocodeine (not as much as codeine, morphine, oxy or OM anyway) because 1) It's neither an essential medicine according to the WHO, or a substitute for one; and 2) It's too weak as an analgesic for America to care about prescribing it, so possible major metabolites (as in C6G for codeine) may not have been discovered, but the metabolisation of DHC to morphine is done by the same enzyme as codeine.

I'm sorry I can't be of too much help but I just wanted to say that you're probably NOT CYP2D6 deficient, especially if drugs like DXM work for you, as DXM is metabolised by 2D6 as well
 
isaaccain said:
p sure taking after the effects have started will help potentiate the morphine, right?
Click to expand...

Depends if it's metabolized via first pass (i.e. by the cytochrome P450 family) or if,because the codeine is metabolized in the liver, it just undergoes phase II metabolism (i.e. glucuronidation) because iirc gfj won't inhibit glucuronidation
 
Take your tolerance into account as well of you have one. Codeine becomes pretty ineffective for those who use more potent Opioids over long term.
 
I have very high tolerance to any opiats naturally ,I use it once a week or even once a month,I never go more then two days in a row,not sure why,but it was always like that.What is strange to me that, for example tramadol or dihydrocodeine works like opiat needs to work,but when it comes to codeine phosphate I do not feel much of it,I mean even if I tripple the dose.
 
I agree with klienerkiffer inhibition of enzyme p450 cyp2d6 is not effective and most if not all inducers of this enzyme have been to my knowledge phased out due to either inefficacy, toxicity, or fatal interactions. And even in a perfect world where you could pull them out of thin air carry toxicity and major side effects and a very narrow theraputic range.
 
Codeine does not need to be turned to morphine to be active, its glucuronide metabolite is also active as an opioid.

I think dihydrocodeine is metabolized more than codeine is, either that or it actually binds to mu-opioid receptor with enough affinity to matter.

And taking grapefruit juice and codeine is pretty counterpoductive: morphine is not metabolized by cyp2d6 the same way codeine would be.
 
sucks for you man, my issue is actually the oppostie; i get a nice euphoric buzz from codeine but literally nothing from DHC. so weird.
 
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