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Codeine Metabolism (Any thoughts)

A

aj1976

Bluelighter
Joined
Aug 27, 2007
Messages
51
Hi,
Any thoughts/observations on the study below?


Codeine analgesia is due to codeine-6-glucuronide, not morphine.
Vree TB, van Dongen RT, Koopman-Kimenai PM.

Institute for Anaesthesiology, Academic Hospital St Radboud, Nijmegen, The Netherlands.

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]
 
Perhaps, but do remember that analgesia does not equal euphoria. Also remember that codeine itself has some activity before it gets metabolized.
 
Why doesn't glucuronidation prevent morphine from crossing the BBB, given the extreme polarity of the metabolite?
 
maybe a little bit off topic but why/how codeine (phosphate) when IVed gives an amazing rush&euphoria like heroine? where i live IV codeine is very common and people love it, i know junkies quit h and start doing IV codeine. it can even make you nod as hell but also some find IV codeine is a nasty thing to do because of the extreme blushing/redness on chest/face area, extreme racing heart, extreme fever like side effects but still i believe its one of the most euphoric rushes one can get

i wonder this cuz i know codeine (methyl morphine) should be demethylated to morphine in the body. any ideas?
 
^ Wow, I have a hard time believing that first paragraph. Not necessarily calling you a liar, but what the fuck?

Anyway, its been said a million times, and this is ADD thus the posters should be above average intelligence, but if you care about your health/safety do not shoot codeine!
 
^^ i stop IVing that shit years ago (i didnt say i IV codeine nowadays also), what i say is there are many people here still doing it and if it must be demethylated in the body first how can it give intense rush such as potent opioids? pls make this clear before someone start talking about IVing codeine phosphate causes pulmonary edema etc.
 
elektra said:
maybe a little bit off topic but why/how codeine (phosphate) when IVed gives an amazing rush&euphoria like heroine? where i live IV codeine is very common and people love it, i know junkies quit h and start doing IV codeine. it can even make you nod as hell but also some find IV codeine is a nasty thing to do because of the extreme blushing/redness on chest/face area, extreme racing heart, extreme fever like side effects but still i believe its one of the most euphoric rushes one can get
Click to expand...

I thought IV Codeine was extremely dangerous; and i also thought that it was not really enjoyable.
Can you tell us more about this practice elektra?
(how many milligrams people usually shoot?)

elektra said:
i wonder this cuz i know codeine (methyl morphine) should be demethylated to morphine in the body. any ideas?
Click to expand...

elektra said:
if it must be demethylated in the body first how can it give intense rush such as potent opioids?
Click to expand...

I think that no matter how you take it (IV, IM, SC, intranasal, smoked, oral), Codeine still goes to the liver to be metabolized to Morphine.
 
^^ your answers waiting you in your inbox :)
sorry guys i first saw the jason's pm and reply it. if jason wants to share the info ask him :)
 
^ Perhaps, but again - it is simpler really, codeine DOES have an affinity for opioid receptors as-is!

The thing with IVing codeine is that it would induce a "rush" of histamine that can cause severe reactions like pulmonary oedema. I would not be surprised if IVing codeine can cause some people to go into anaphylaxis.

Perhaps IVing it with an antihistamine would help? I don't know. And elektra, thats just lazy! You could simply cut/paste what you sent to jason.
 
redeemer said:
Or the brain perhaps...

Unique Brain Enzyme Converts Codeine To Morphine

This could be why elektra and others report effects that are more instantaneous than one would expect if the codeine had to go through the liver first...
Click to expand...

now thats something interesting we got here i think

Jamshyd said:
^ Perhaps, but again - it is simpler really, codeine DOES have an affinity for opioid receptors as-is!

The thing with IVing codeine is that it would induce a "rush" of histamine that can cause severe reactions like pulmonary oedema. I would not be surprised if IVing codeine can cause some people to go into anaphylaxis.

Perhaps IVing it with an antihistamine would help? I don't know. And elektra, thats just lazy! You could simply cut/paste what you sent to jason.
Click to expand...

sorry but i dont keep PMs both inbox or sent PMs, delete them after receive/send thats why its up to jason:)
 
Jamshyd said:
^ Perhaps, but again - it is simpler really, codeine DOES have an affinity for opioid receptors as-is!
Click to expand...
True, it does have affinity for the µ receptor, but it is 300 times less than that of morphine (1), so it would take quite a dose of intravenous codeine to achieve the same activation of that receptor as a recreational shot of morphine. Assuming, of course, that equally sized doses of codeine and morphine produce equal concentrations of the drug at the receptor site, and that a double dose of codeine causes the concentration to be twice as much at the receptor site. I really don't know if such a proportionality exists.

Then again it could be activity at some receptor or a multitude of receptors we have no idea existed. I'm certainly not concluding anything yet.

Consider that if the demethylation of codeine in the brain is what causes at least some of the effects of IV codeine, only about 10% of the codeine in a 50 mg dose would have to be converted in order for it to produce effects. And the decreased polarity of the methyl-ether group at the 3-position as opposed to morphine's hydroxy group could allow for faster BBB penetration adding to the rush. Providing the difference in polarity is great enough of course; I don't know if it is.

(1)

Jamshyd said:
The thing with IVing codeine is that it would induce a "rush" of histamine that can cause severe reactions like pulmonary oedema. I would not be surprised if IVing codeine can cause some people to go into anaphylaxis.
Click to expand...
It is dangerous indeed, and I'm definitely not recommending anyone do it, I'm just trying to elucidate the actions behind the effects. I thought of adding a warning to my previous post but I figured if anyone is going to inject codeine after reading the other warnings in this thread, me repeating the advice probably won't make a difference.

For anyone thinking about doing it I suggest a Google search of "intravenous codeine". Here are some results from the first page:

Hypoxaemia and hypotension after intravenous codeine phosphate
Profound hypotension following intravenous codeine phosphate
Seizures with Intravenous Codeine Phosphate

:\
 
redeemer said:
Hypoxaemia and hypotension after intravenous codeine phosphate
Profound hypotension following intravenous codeine phosphate
Seizures with Intravenous Codeine Phosphate

:\
Click to expand...
Eegads... seizures, hypoxia + profound hypotension = "death" 8o.
 
The topic of IV Codeine deserves a thread for it only I think, and in ADD.
I just opened it, "IV Codeine", in ADD.
 
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