• Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

  • N&PD Moderators: Skorpio

Advanced Q's about Codeine

jasoncrest

jasoncrest

Bluelighter
Joined
Sep 15, 2003
Messages
3,952
Location
France
I have a few questions concerning Codeine.
Many of these questions are linked, and one clear reply could answer 3 of them at once...

Some of them are about Codeine metabolism. Codeine is metabolized by glucuronidation to Codeine-6-glucuronide, and by demethylation to Morphine, via CYP2D6 enzymes.

# Codeine is metabolized to Morphine by CYP2D6 enzymes. So inducing this enzyme should potentiate Codeine.
But I've read that CYP2D6 enzymes number comes from genes, and cannot be raised...
But there are, according to some websites, CYP2D6 inducers, such as Rifampin or Dexamethasone...
So what's true?

#
It can be speculated that in case of inhibition of glucuronidation, the amount of codeine available for other pathways especially O-demethylation to morphine is increased, resulting in higher morphine serum levels and therefore higher analgesic efficacy.
Click to expand...
There are many references saying that Diclofenac, a Codeine glucuronidation inhibitor, is a Codeine potentiator; so can really more Codeine be "pushed" to demethylation when glucuronidation is inhibited?

# Concerning the 2 questions above, I read somewhere that Dexamethasone was a CYP2D6 inducer; and read somewhere else that it (and other Glucocorticoids) potentiate Codeine by inhibiting glucuronidation, like Diclofenac.
So I bought Beclomethasone, which is very close to Dexamethasone, and I swear that it potentiated Codeine in an amazingly strong way.
So, are Glucocorticoids real Codeine potentiators?
Do they potentiate Codeine by glucuronidation inhibition or by inducing CYP2D6?

# This question was asked recently in Basic Drug Discussion, but I think it has to be asked here to find its answer:
Exposed to light or high temperature codeine breaks down. My question is what it breaks down to. Is it 3-desoxymorphine? Or maybe some changes in the furan ring? Is any of the products active?
Click to expand...

# This question was asked by me in Other Drugs, where it didn't find its answer, I REALLY would like to know the answer...
My question is simple:
-intravenous Codeine is unplesant and dangerous
-intramuscular Codeine is highly effective and safe,
so:
-is smoked Codeine freebase like IV Codeine (dangerous) or like IM Codeine (effective, safe)?
-is snorted Codeine like IV Codeine (dangerous) or like IM Codeine (effective, safe)?
Click to expand...

Thanks in advance to the one who can answer these 5 questions (or at least a few of them...)
 
If you're going to use a glucocorticoid such as dexamethasone, you may as well just IV the codeine anyway, since the major contraindication was a negative histaminergic response? Dexamethasone and rifampin are kind of dangerous drugs to be pursuing for use in enhancing an opiate high anyway, the first because it can induce depression (TPH-2 inhibitor) and mess up the immune system, and the second because of hepatotoxicity.

According to this paper, rifampin actually possibly reduces the activity of codeine anyway, depending on the user's phenotype..

Codeine O-demethylation to produce morphine can be significantly induced by rifampin, but this induction is phenotypically determined. However, because (relative to base-line values) rifampin enhanced codeine N-demethylation more than codeine O-demethylation, morphine plasma concentrations were reducedand hence codeine's pharmacodynamic effects were attenuatedin EMs of debrisoquin.
Click to expand...

When I was younger (and more stupid), I snorted a bunch of codeine while terribly drunk, and I still lived to tell about it...

Edit: I'm not totally sure about the IVing since it's not instrinsically active and maybe still dangerous from a pulmonary edema standpoint?
 
Last edited:
I´ll rephrase one of the question:
What makes IV use of Codeine dangerous, but IM safe?
And concerning pharmacokinetics, is the intranasal route closer to the IV route or the IM route?
Same question for smoking, is it closer to shooting IV or IM? (concerning Codeine)

nuke said:
According to this paper, rifampin actually possibly reduces the activity of codeine anyway, depending on the user's phenotype..
Click to expand...

Anyway it would be stupid to take Rifampin just as a potentiator...
I think it reduces Codeine activity because it induces CYP2D6 (so more Codeine converted to Morphine) but also induces CYP3A4 a lot (so the Morphine is broken down and eliminated much quicker.....)
 
There are many references saying that Diclofenac, a Codeine glucuronidation inhibitor, is a Codeine potentiator; so can really more Codeine be "pushed" to demethylation when glucuronidation is inhibited?


This sounds interesting, do you have any links to the references? Has anyone experienced this first-hand.
 
What makes IV use of Codeine dangerous, but IM safe?
And concerning pharmacokinetics, is the intranasal route closer to the IV route or the IM route?
Same question for smoking, is it closer to shooting IV or IM? (concerning Codeine)
Click to expand...

IM is safe (well, safer) than IV because peak plasma levels are reached within 15 minutes and plateau for about an hour (the abcess created by IM injection slowly seeps into the arterial-venous system, whereas IV is rapid).

Intranasal codeine is probably closer to IM, and probably isn't terribly unsafe (rectal usage of codeine has been evaluated and is as safe as IM). It might be wise to space intranasal doses over 30m-1h, though.

I would not recommend smoking because of the amount of codeine required for effect, and because plasma levels will peak very quickly with this method, similar to IV.
 
nuke said:
IM is safe (well, safer) than IV because peak plasma levels are reached within 15 minutes and plateau for about an hour (the abcess created by IM injection slowly seeps into the arterial-venous system, whereas IV is rapid).

Intranasal codeine is probably closer to IM, and probably isn't terribly unsafe (rectal usage of codeine has been evaluated and is as safe as IM). It might be wise to space intranasal doses over 30m-1h, though.

I would not recommend smoking because of the amount of codeine required for effect, and because plasma levels will peak very quickly with this method, similar to IV.
Click to expand...

Thank you, this is exactly the reply I was hoping for.

MONSTA!! said:
This sounds interesting, do you have any links to the references? Has anyone experienced this first-hand.
Click to expand...

I looked through google for Diclofenac-Codeine potentiation, and in fact I found as much papers saying that Diclofenac doesn´t inhibit Codeine´s glucuronidation than papers saying the opposiate...

One paper said that in vitro studies show that Diclofenac inhibit Codeine´s glucuronidation, but in vivo studies show the opposite.

And anyway, even if Diclofenac would inhibit Codeine´s glucuronidation, it is not even sure that more Codeine would be thus available for other pathways, such as demethylation to Morphine....

Zodiaccupuncture said:
or u coud get some real drugs.
Click to expand...

I get all the real drugs I want eventhough I am mostly into Buprenorphine.
I don´t think I will be one day able to get high on Codeine again, but it still interests me enough to open threads about it.....
 
codeine goes to hydrocodone in 1 move very easily. I would persue that method if you have any quantity to go at...
 
gannesh said:
tramadol is a very effective potentiating agent, if that is what your looking for
Click to expand...

Doesn't tramadol use the same cytochrome to O-demethylate (the M1 metabolite providing most of the punch)? If so, then surely they would simply compete. I guess I don't understand how that would potentiate anything.

Like I said, best use for codeine is making hydrocodone. Oh, similarly, DHC is best used to make DHM or hydromorphone...
 
Why make hydrocodone when one can make oxycodone with about as much effort (sure, higher dose req. , but more euphoric)? Or, hydromorphone if you have ze way of removing that pesky methoxy. Or/then one could turn that ketone into a =CH2, boosting activity significantly =) .

Um yeah I believe that Tramadol does indeed use the same, so yeah they'd compete for demethylation, not an ideal situation.
 
MattPsy said:
Why make hydrocodone when one can make oxycodone with about as much effort (sure, higher dose req. , but more euphoric)? Or, hydromorphone if you have ze way of removing that pesky methoxy. Or/then one could turn that ketone into a =CH2, boosting activity significantly =) .

Um yeah I believe that Tramadol does indeed use the same, so yeah they'd compete for demethylation, not an ideal situation.
Click to expand...

Well, oxycodone is a bitch to make from codeine. Hydrocodone is very simple. I totally agree that then swapping the =O with a =CH2 is THE way to go, having said which, the conditions for making this change are somewhat more complex than initially making the =O in the first place. If your into doing that, then removing the N-CH3 and swapping it for a -CH2-CH2-Aromatic grouping would increase the potency an awful lot as well. You can knock off the N-CH3 in several ways, but the polonovski reaction looks like the most reliable.

Glad to have someone to confirm my suspicions about tramadol. Of course, chemistry only gives part of the story. I've never noticed tramadol boosting codeine, but maybe it DOES for some people, subjectivly at least.

H-)
 
Is it just me or did IV'ing codeine suddenly rear its unprepossessing face in the conversation? Iv'ing codeine will cause pulmonary edema so its not recommended. I think IM is alot safer (at least i've not heard anything wrong with it) but I generally thought that administering it as a suppository or orally was the most efficient means since it has to be metabolised hepatically.
 
You must log in or register to reply here.
Top