• 🇳🇿 🇲🇲 🇯🇵 🇨🇳 🇦🇺 🇦🇶 🇮🇳
    Australian & Asian
    Drug Discussion

    Welcome Guest!
    Posting Rules Bluelight Rules
  • AADD Moderators: andyturbo

Codeine and CWE Megathread - The long awaited!

Status
Not open for further replies.
filter paper thanks to my university's chemistry lab manages to give a pretty good end result of CWE. doesn't soak up a bunch of the liquid used as well, meaning there isn't any need to wring out the filter at the end. pretty much 99%+ of whatever is soluble in the cold water ends up in the cup for consumption ;)
 
Managed to buy a box of mydol from one of the local chems today. 40 x 15/500s. Easy as shit too, gotta love those blase weekend pharmacists!
 
Hi everyone, havent posted in a while, new job super busy yada yada

Anyway, quick question I was hoping to pick you guys' brains a bit. Been doing CWEs for 5 years +, average twice a week dose, tolerance very high, each dose 800mg+.

Until recently that is. Been off everything for about a month or more. Let's say 6 weeks. Question is, I want to dose but I like my life so I don't want to overdose. How much do you think my tolerance has dropped off? What do you think would be a good dose to sort of "test" my way back in?
 
Well fuck you aint gonna OD and kill yourself. Even with 1g of codeine.

If you were running 800mg before Id say go 500-600mg. Thats what I'd do anyway. Maybe even 400mg as an experiment to see what a break of 6 weeks does to tolerance. You can always do more next time.

...................

A separate question for Mr Blonde... dude what did you say was the reason Mydol is allowed to be sold again? Thought you said it was something do with codeine phosphate versus codeine or something, but the Mydol box lists it as codeine phosphate just like everything else.

Just curious.
 
I read somewhere that the liver can't convert more than 400 mg of codeine to the 10% equivalent of morphine at one time.

So taking any more than that is pontless, I'm trying to find the link for you before you ask.

cheers
 
Claims about the supposed "ceiling effect" of codeine doses seemed to rest on the assumption that high doses of codeine saturated CYP2D6, which prevented further conversion of codeine to morphine, which is simply incorrect since we now know that codeine-6-glucuronide (C6G) is the main metabolite responsible for codeine's analgesia
 
Last edited:
webbykevin said:
I read somewhere that the liver can't convert more than 400 mg of codeine to the 10% equivalent of morphine at one time.

So taking any more than that is pontless, I'm trying to find the link for you before you ask.

cheers
Click to expand...

No it definitely isnt pointless.
 
88brenno said:
Claims about the supposed "ceiling effect" of codeine doses seemed to rest on the assumption that high doses of codeine saturated CYP2D6, which prevented further conversion of codeine to morphine, which is simply incorrect since we now know that codeine-6-glucuronide (C6G) is the main metabolite responsible for codeine's analgesia
Click to expand...

No, we do not know that C6G is the metabolite that is majorly responsible. There have been one or two small studies in rats/mice and that is it, not enough to completely change the understanding of how codeine works. You would be discounting morphine's effects to say that C6G is the 'major' metabolite.
 
Institute for Anaesthesiology, Academic Hospital St Radboud, Nijmegen, The Netherlands.


Abstract

Eighty per cent of codeine is conjugated with glucuronic acid to codeine-6-glucuronide. Only 5% of the dose is O-demethylated to morphine, which in turn is immediately glucuronidated at the 3- and 6-position and excreted renally. Based on the structural requirement of the opiate molecule for interaction with the mu-receptor to result in analgesia, codeine-6-glucuronide in analogy to morphine-6-glucuronide must be the active constituent of codeine. Poor metabolisers of codeine, those who lack the CYP450 2D6 isoenzyme for the O-demethylation to morphine, experience analgesia from codeine-6-glucuronide. Analgesia of codeine does not depend on the formation of morphine and the metaboliser phenotype.


PMID: 11092114 [PubMed - indexed for MEDLINE]
Click to expand...
http://www.ncbi.nlm.nih.gov/pubmed/11092114
 
^ That's a pretty big claim for them to be making, and I still would not be believing it based just on the conclusions those researches came to. One problem is the fact that the whole point of adding glucuronic acid to a molecule is to make it easier to excrete. Usually the resulting compound has a greater water solubility; this has the potential to alter the compounds ability to cross the BBB; in rats they have demonstrated that C6G forms a stable molecule that has similar affinity, though lesser potency, for opioid receptors compared to codeine but this has not been demonstrated in humans as far as I am aware.
 
Pharmacokinetics and metabolism of codeine in humans

Abstract
Codeine (30 mg phosphate) was metabolized by eight human volunteers to the following six metabolites: codeine-6-glucuronide 81·0 ± 9·3 per cent, norcodeine 2·16 ± 1·44 per cent, morphine 0·56 ± 0·39 per cent, morphine-3-glucuronide 2·10 ± 1·24 per cent, morphine-6-glucuronide 0·80 ± 0·63 per cent, and normorphine 2·44 ± 2·42 per cent. Two out of eight volunteers were unable to O-dealkylate codeine into morphine and lack therefore the cytochrome P450 IID6 isoenzyme. The half-life of codeine was 1·47 ± 0·32 h, that of codeine-6-glucuronide 2·75 ± 0·79 h, and that of morphine-3-glucuronide 1·71 ± 0·51 h. The systemic clearance of codeine was 2280 ± 840 ml min−1, the renal clearance of codeine was 93·8 ± 29·8 ml min−1, and that of codeine-6-glucuronide was 122 ± 39·2 ml min−1. The plasma AUC of codeine-6-glucuronide is approximately 10 times higher than that of codeine. Protein binding of codeine and codeine-6-glucuronide in vivo was 56·1 ± 2·5 per cent and 34·0 ± 3·6 per cent, respectively. The in vitro protein binding of norcodeine was 23·5 ± 2·9 per cent; of morphine, 46·5 ± 2·4 per cent; of normorphine, 23·5 ± 3·5 per cent; of morphine-3-glucuronide, 27·0 · 0·8 per cent; and of morphine-6-glucuronide, 36·7 ± 3·8 per cent.
Click to expand...
 
webbykevin said:
I read somewhere that the liver can't convert more than 400 mg of codeine to the 10% equivalent of morphine at one time.

So taking any more than that is pontless, I'm trying to find the link for you before you ask.

cheers
Click to expand...

The effects will def be stronger if u use more pills because a lot gets lost in the process of the CWE. Not sure how much but u def loose a little bit. 700-800mg is twice as strong than 400mg. Whoever said its useless to dose more than 400mg has never experienced the effects of Codeine. Dont believe everything thats on the internet.
 
Codeine (30 mg phosphate) was metabolized by eight human volunteers to the following six metabolites: codeine-6-glucuronide 81·0 ± 9·3 per cent, norcodeine 2·16 ± 1·44 per cent, morphine 0·56 ± 0·39 per cent, morphine-3-glucuronide 2·10 ± 1·24 per cent, morphine-6-glucuronide 0·80 ± 0·63 per cent, and normorphine 2·44 ± 2·42 per cent. Two out of eight volunteers were unable to O-dealkylate codeine into morphine and lack therefore the cytochrome P450 IID6 isoenzyme. The half-life of codeine was 1·47 ± 0·32 h, that of codeine-6-glucuronide 2·75 ± 0·79 h, and that of morphine-3-glucuronide 1·71 ± 0·51 h. The systemic clearance of codeine was 2280 ± 840 ml min−1, the renal clearance of codeine was 93·8 ± 29·8 ml min−1, and that of codeine-6-glucuronide was 122 ± 39·2 ml min−1. The plasma AUC of codeine-6-glucuronide is approximately 10 times higher than that of codeine. Protein binding of codeine and codeine-6-glucuronide in vivo was 56·1 ± 2·5 per cent and 34·0 ± 3·6 per cent, respectively. The in vitro protein binding of norcodeine was 23·5 ± 2·9 per cent; of morphine, 46·5 ± 2·4 per cent; of normorphine, 23·5 ± 3·5 per cent; of morphine-3-glucuronide, 27·0 · 0·8 per cent; and of morphine-6-glucuronide, 36·7 ± 3·8 per cent.
Click to expand...

Well at least that study involves humans, but apart from noting that two of the participants were unable to metabolize codeine to morphine it does not talk about analgesia or other effects. So unless there is something else in the full text there is no proof there. The AUC simply tells us that a greater quantity was metabolized into morphine, and we also see from the quote that plasma protein binding of C6G was less then seen with both codeine and morphine; although it is unbound drug that exhibits a pharmacological effect, the unbound drug is also immediately subject to the processes of metabolism and excretion.

When there is a study showing that C6G administered to human volunteers has analgesic and other pharmacological properties, which perhaps might be antagonized by naltrexone, then I will believe it. It's not as if I have a vested interest in it being either way, just that I want to see the proper evidence that it has these effects in humans.
 
Okay but how come it says:

codeine-6-glucuronide 81·0 ± 9·3 per cent , morphine 0·56 ± 0·39 per cent

Thats the part that made me think c-6-g had more to do with it.
 
^ Those numbers are from the part where it is talking about the quantities of metabolites produced. If C6G were active, that would simply show that it is far less potent then morphine is. How much of a metabolite is produced depends on a lot of things, such as an enzyme's affinity for the substrate, the enzyme's efficiency, other drugs inhibiting or inducing enzymes, etc... and even if a large amount of a metabolite is produced, it does not show that it is having the desired effect. After all, the body is producing these metabolites in an effort to make excretion easier, it just so happens that the demethylation route produces morphine and that this has an pharmacological effect on humans.

To show that C6G has effects on humans, it would need to be prepared in pure form and administered to human volunteers to assess pharmacological action. Perhaps it could also be radio labelled and we could see if it crosses in to the brain in a significant quantity.
 
Codeines conversion to morphine isn't the sole reason for its analgesia.

It also metabolises into codeine-6-glucuronide which is why the ceiling dose of codeine doesn't mean the ceiling in terms of effects profile.
 
How the shit did I not see all those replies about the metabolisation before I posted mine :|.

Blondey, AFAIK the most recent studies done seem to support the idea that C6G is as responsible for codeines analgesia as morphine is. I'll see if I can dig up those studies.
 
^ I'd like to see those studies if you can find them. As I said before, all I have seen is studies on rodents and mice which can give very different results sometimes compared to what you would see in humans. Really there need to be studies looking JUST at C6G, not at C6G as a metabolic product of codeine among other products before it can be conclusively said to be active as people claim it to be. There may be other reasons for the 'ceiling effect' not occurring as was once believed, for example a misunderstanding of the enzymes involved.

Have you ever considered studying Pharmacology M_B you seem to know your shit
Click to expand...

It would be interesting, that's for sure. Maybe they'd give me a lab and let me do some really interesting research of my own. :)
 
I'm feeling like the luckiest person ever!! I have been living in Australia for three years now and have been self-medicating with OTC codeine to counter-act damage done to my nervous system due to contact with pesticides. Admittedly a newbie in most cases, I am truly grateful to find this CWE technique posted. With my tolerance escalating, the damage I am doing with the added paracetamol is becoming paramount. Good bye liver damage (paracetamol, anyway).
 
Status
Not open for further replies.
Top