Codeine-will it work? using SSRI

[nods]

Hi,

I' heard Codeine will/won't work while taking an SSRI? because of the CYP??? enzyme required to transform Codeine~Morphine becomes ineffective with SSRI use.

Any knowledgeable info?

Thanks

 

[brutus]

I've taken codeine probably around 10 times while taking an SSRI and still felt pretty high from the codeine. Of course this was after doing a CWE on 50ish pills. You should still feel the codeine, if not, perhaps you are just one of those who won't get high from codeine.

 

[Mr Blonde]

I used codeine quite a bit whilst on Zoloft, which is a CYP2D6 inhibitor and it still worked fine. I didn't even know about the interaction until about a month after I went off the Zoloft.

 

[nods]

Thanks MB, just wanted some feedback before i wasted my $$, yer CYP2D6 thats it, cool. Well if you didn't even know about the interaction while taking Zoloff, must still work.

Cheers

 

[Mr Blonde]

Keep in mind though I react strangely to codeine; I get a hell of a buzz out of it and I can go way above the ceiling dose, my tolerance right now is at about 900mg or so.

Though I'm tempted to believe that perhaps Zoloft is just a weak inhibitor, hence it's listed but doesn't have much of an actual effect on the enzymes. Let us know how it goes; what does of Zoloft are you on? I was on 50mg a day.

 

[nods]

Ok. Noone here in NZ takes Zoloft-never even seen it (it's not subsidised) Prozac 20mg, maybe stronger inhibitor? didn't really wanna go back on it, but things were going from bad to worse for some time and of all the drugs CLASSIFIED as ADs i'v tried it's the only one that works(when will Opi's return to this class?) my Psy has given me Rit@Dex-thou for ADHD of course .

 

[Mr Blonde]

Sorry for some reason I thought you were on Zoloft...

 

[sonic]

I used codeine quite a bit whilst on Zoloft, which is a CYP2D6 inhibitor and it still worked fine. I didn't even know about the interaction until about a month after I went off the Zoloft.

That's because it's CYP3A4 that turns codeine into morphine. Maybe zoloft is a potentiator if it only blocks CYP2D6. The OP can look up prozac in the Cytochrome P450 interactions PDF file found in the OD directory. I think white grapefruit juice has the potential to potentiate codeine and people who have stated otherwise are just confused about the specific enzymes and their role in metabolizing the pro-drug codeine. It'd seem that blocking CYP2D6 would force more of the drug to be broken down by other enzymes including CYP3A4 making slightly more morphine. It's just a theory some people have but it's logical.

 

[monstanoodle]

Citalopram is a strong CYP 2D6 Inhibitor.
When I tried Codeine when on Citalopram I got nothing. Wasted a large amount infact.

Other Inhibitors of CYP 2D6:

Bupropion
Celecoxib
Chloroquine
Chlorpheniramine
Cemetidine
Citalopram
Clomipramine
Cocaine
Desipramine
Diphenhydramine
Fluoxetine
Fluphenazine
Halofantrine
Haloperidol
Hydroxychloroquine
Inatinib
Levomepromazine
Methadone
Moclobemide
Norfluoxetine
Paroxtine
Perphenazine
Propafenone
Propoxyphene
Quinacrine
Quinidine
Ranitidine
Ritonavir
Sertraline
Terbinafine
Thioridazine

 

[Mr Blonde]

That's because it's CYP3A4 that turns codeine into morphine. Maybe zoloft is a potentiator if it only blocks CYP2D6. The OP can look up prozac in the Cytochrome P450 interactions PDF file found in the OD directory. I think white grapefruit juice has the potential to potentiate codeine and people who have stated otherwise are just confused about the specific enzymes and their role in metabolizing the pro-drug codeine. It'd seem that blocking CYP2D6 would force more of the drug to be broken down by other enzymes including CYP3A4 making slightly more morphine. It's just a theory some people have but it's logical.

It's CYP2D6 that turns codeine into morphine; CYP3A4 breaks it down into mostly inactive metabolites like nor-codeine, nor-morphine, etc...

See here for an article on someone who apparently metabolizes codeine into morphine quite well.

 

[rolls]

I've used codeine whilst on cypramil (Citalopram) and zoloft, I experienced zero difference in the high.

 

[djsim]

I'd tend to agree that anti-depressants dont effect codeine all that much. Keep in mind only ~10% of the codeine is being converted to morphine, so the CYP450 enzymes are nowhere near saturated from daily fluoxetine use. So yes, there is inhibition of that enzyme by the anti-depressant, but because only 10% of codeine is converted by this pathway, IMO/IME it's pretty safe to say it will work

 

[monstanoodle]

That 10% is what is converted to Morphine
There's other metabolites, a lot that don't have much affinity for mu receptors.

 

[Mr Blonde]

That 10% is what is converted to Morphine

That's what he (djsim) said.

There's other metabolites, a lot that don't have much affinity for mu receptors.

Yeah, but they sure can cause a nasty histamine reaction.

There are some studies out there showing one of the metabolites, codeine-6-glucorinide, may have some analgesic properties.

 

[Tchort]

As was said, several SSRI's/anti-Depressants are strong inhibitors of CYP2D6, and CYP2D6 is the enzyme responsible for converting on average 5-10% of the Codeine ingested into Morphine. Celexa, Prozac, Paxil & Wellbutrin are all anti-Depressants that could negatively impact the conversion of Codeine to Morphine. This isn't written in stone that if you are taking these anti-Depressants (or another strong inhibitor of CYP2D6) that it will block the euphoria of Codeine, or prevent the conversion to Morphine; just that it is a good possibility.

Strong inducers of CYP2D6 should be avoided as well. Glutethimide (Doriden) being the most famous example; a strong CYP2D6 inducer that when taken with Codeine ups the average percentage of Codeine to Morphine conversion from 5-10% to 30%. Taking a strong 2D6 inducer with Codeine could lead easily to an accidental fatal overdose in someone who is not tolerant or dependant.

 

[sonic]

It's CYP2D6 that turns codeine into morphine; CYP3A4 breaks it down into mostly inactive metabolites like nor-codeine, nor-morphine, etc...

See here for an article on someone who apparently metabolizes codeine into morphine quite well.

Right, I knew that. Sorry, and thanks for clearing things up. I just had a long day/night yesterday and got the 2 enzymes reversed. Grapefruit juice only inhibits CYP3A4 so it can force more of the codeine to be metabolized by CYP2D6. Also, alcohol is a moderate inducer of CYP2D6, so it can potentiate codeine. I'd recommend 1-2 drinks. Mixing downers can kill you of course. Be safe.

 

[serotonin-system]

Hi all,

Sorry to reserect an old thread but I'm looking for peoples actual EXPERIENCES in using codeine recreationally while on an SSRI (specifically citalopram). There has been a lot of talk of the theory behind why euphoria should be absent from codeine in someone taking an SSRI but I'm interested in peoples actual experiences with this.

I'm on 40 mg citalopram a day. Has anyone taken codeine while on this regieme? What where the effects and what dose of codeine did you take? Did any potentiators help? ie alcohol or grapefruit-juice?

Thanks a lot,

SS

 

[DJ25]

The antidepressants with the least inhibition of the CYP2D6 are Effexor and as Mr Blonde said Zoloft. Even though they use some of this enzyme it is rather weak. The strongest inhibitors are Prozac, Bupropion and Paroxetine. Mid range would be Esctialopram/citalopram and Fluvoxamine is metabolized by CYP3A4.

All these figures are not comprehensive of the whole breakdown just a rough guide to what I read last night as I'm going to the GP today to change to Sertraline as Im on DHC MR (modified release) to bridge until I start sub in a few weeks, GP doesn't do maintenance here so it's my local drug and alcohol service. But anyway I feel that Seroxat (Paroxetine) is killing the effects of the conversion to dihydromorphine (?) if that's what it get's metabolised to.

I also read that taking Bupropion with Prozac or Seroxat will inhibit CYP2D6 totally more or less. So where Pro drugs are concerned i.e. the codeine to morphine conversion it's a bad combo.

Most TCA's I think will inhibit CYP2D6 but I didn't really research there as I am not interseted in them for this situation.

I'll but up some references later if anyone's interested.

 

[opiyummm]

I used to be prescirbed Zoloft, the 50 mgs. For the short while I was on that I used codeine many times and didn't notice anything beyond the usual, for better or for worse.

 

[Mr Blonde]

DJ25: Do you have any links to sources for the classing of the effects of various anti-Ds on enzymes? Would be interested to see information on it.