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Opioids Caffeine = increases the metabolism of codeine into morphine?

ChemicallyEnhanced

ChemicallyEnhanced

Bluelighter
Joined
Apr 29, 2018
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Since caffeine inhibits CYP2D6, surely this means that - if taken before or with codeine - it would increase the amount of codeine that is converted into morphine?

Can anyone confirm if this is true or if I'm sciencing wrong?
 
From what I understand caffeine is added to many formulations to speed it to your brain faster. Things like Excedrin, Fioricet, and others. The caffeine doesn't increase the amount of codeine.....30 milligrams is 30 milligrams....but it does hit you faster. I was surprised at the amount of drugs that have caffeine but it makes sense. If we are in pain, the quicker it can hit, the better. But as far as increasing the chemical ( be it codeine or aspirin or butalbital ) the amount of that will not increase.
 
"Some medications are CYP2D6 inhibitors and reduce or even completely block the conversion of codeine to morphine. The best-known of these are two of the selective serotonin reuptake inhibitors, paroxetine (Paxil) and fluoxetine (Prozac) as well as the antihistamine diphenhydramine (Benadryl) and the antidepressant bupropion (Wellbutrin, also known as Zyban). Other drugs, such as rifampicin and dexamethasone, induce CYP450 isozymes and thus increase the conversion rate.

CYP2D6 converts codeine into morphine, which then undergoes glucuronidation. Life-threatening intoxication, including respiratory depression requiring intubation, can develop over a matter of days in patients who have multiple functional alleles of CYP2D6, resulting in ultrarapid metabolism of opioids such as codeine into morphine.[38][39][40]"

wikipedia
Ratched, I think the logic is that if you have several metabolic routes of which some lead to inactive compounds and some active compounds, you get more bang if you block the routes leading to inactive compounds
 
Pissed_and_messed said:
"Some medications are CYP2D6 inhibitors and reduce or even completely block the conversion of codeine to morphine. The best-known of these are two of the selective serotonin reuptake inhibitors, paroxetine (Paxil) and fluoxetine (Prozac) as well as the antihistamine diphenhydramine (Benadryl) and the antidepressant bupropion (Wellbutrin, also known as Zyban). Other drugs, such as rifampicin and dexamethasone, induce CYP450 isozymes and thus increase the conversion rate.

CYP2D6 converts codeine into morphine, which then undergoes glucuronidation. Life-threatening intoxication, including respiratory depression requiring intubation, can develop over a matter of days in patients who have multiple functional alleles of CYP2D6, resulting in ultrarapid metabolism of opioids such as codeine into morphine.[38][39][40]"

wikipedia
Ratched, I think the logic is that if you have several metabolic routes of which some lead to inactive compounds and some active compounds, you get more bang if you block the routes leading to inactive compounds
Click to expand...

I also take a high dose SSRI, so would that increase the amount of codeine converted into morphine?

I know nicotine does, as they've been actual studies proving it. I think on average it increased it by 55%
 
ChemicallyEnhanced said:
Are you sure?
Click to expand...
Yeah, we already discussed this in a thread some months back

Codeine has 2 metabolization routes

95% of it gets metabolized by 3a4 into norcodeine, which is inactive. This is the path highly preferred by the liver.

5% gets metabolized by 2a6 into morphine

By inhibiting 3a4 it forces more of the codeine to be metabolized by 2a6, thus generating more morphine
 
Snafu in the Void said:
Yeah, we already discussed this in a thread some months back

Codeine has 2 metabolization routes

95% of it gets metabolized by 3a4 into norcodeine, which is inactive. This is the path highly preferred by the liver.

5% gets metabolized by 2a6 into morphine

By inhibiting 3a4 it forces more of the codeine to be metabolized by 2a6, thus generating more morphine
Click to expand...

How do you inhibit 3a4 then?
 
Many antidepressants inhibit Cyp2d6 as well so they will do the opposite, causing less morphine to be generated. Same for tramadol, when I was on venlafaxine I could take 500mg of it (not recommended anyways to take tram on S/NRIs) without feeling a thing. Yeah, what you want is a 3A4 inhibitor or a 2D6 inducer but I don't think the latter exists (?).

I don't think caffeine does anything really to the metabolism of codeine. It might increase the pain killing effects but by little, like those pills which contain a NSAID and caffeine.
 
plumbus-nine said:
Many antidepressants inhibit Cyp2d6 as well so they will do the opposite, causing less morphine to be generated. Same for tramadol, when I was on venlafaxine I could take 500mg of it (not recommended anyways to take tram on S/NRIs) without feeling a thing. Yeah, what you want is a 3A4 inhibitor or a 2D6 inducer but I don't think the latter exists (?).

I don't think caffeine does anything really to the metabolism of codeine. It might increase the pain killing effects but by little, like those pills which contain a NSAID and caffeine.
Click to expand...

Sounds accurate. I take 250mg Sertraline (plus 75mg Trazodone...for sleep, and not an SSRI, but still an anti-depressant?). I'm prescribe the codeine 30's (no acetaminophen), and can take 6 or 8 and feel NOTHING. Even if I take like 6 or 8 every 4 hours, I barely get any pain relief. In contrast, a 20mg morphine (chewed for rapid onset) actually helps my pain quite a bit. I don't get any buzz or anything from it (none at all), but it takes my pain from where I feel like screaming to being bad, but in a way that I can tolerate and function.
 
I'm calling my doctors tomorrow because my quality of life is utter shit right now. I wanna explain all of this to them and ask if they won't increase my opiates, can they at least give me the equivalent dose of my codeine, but just in morphine (because of this 2a6/3a4 stuff)....but I'm sure ya'll know that doctors tend to HATE IT when you sound like you know what you're talking about. Especially if they don't know this enzyme stuff and I have to explain it to them - even if I'm tactful and not patronizing or know-it-all sounding - they're gonna hate that I know more than them (on this one very small area).

Anyone know (roughly) what kinda % efficacy increase I'll get if I have say, a large glass of white grapefruit juice, half an hour before my codeine.
 
goodjunkie said:
Yea but it also inhibits cyp2d6 🙁
Click to expand...
I haven't looked this up with gf juice, but isn't CYP2D6 the enzyme responsible for demethylation (specifically methoxy (codeine) to hydroxy (morphine)) ?

If so you won't want to take grapefruit with your codeine. It will inhibit the conversion of codeine into morphine.
 
From my experience nothing increases opiates. I read somewhere that trying to potentiate at most would increase the blood levels up to 4%. Caffeine speeds up your metabolism so the drug would probably hit you faster.
 
ChemicallyEnhanced said:
What would that do?
Click to expand...

Opioids - Caffeine = increases the metabolism of codeine into morphine?

Since caffeine inhibits CYP2D6, surely this means that - if taken before or with codeine - it would increase the amount of codeine that is converted into morphine? Can anyone confirm if this is true or if I'm sciencing wrong?
bluelight.org bluelight.org

According to this article gf juice is a potent inhibitor of CYP2D6 which is responsible for the demethylation of codeine into morphine AFAIK.
Grapefruit is a potent enzyme inhibitor

If you inhibit this enzyme then none or very little of the orally consumed codeine will be metabolized into morphine. Equals bad.

What you want is a coenzyme or catalyst that will increase demethylation (so that more morphine is generated) not something that will hinder the enzyme's ability to demethylate.
 
simstim said:

Opioids - Caffeine = increases the metabolism of codeine into morphine?

Since caffeine inhibits CYP2D6, surely this means that - if taken before or with codeine - it would increase the amount of codeine that is converted into morphine? Can anyone confirm if this is true or if I'm sciencing wrong?
bluelight.org bluelight.org

According to this article gf juice is a potent inhibitor of CYP2D6 which is responsible for the demethylation of codeine into morphine AFAIK.
Grapefruit is a potent enzyme inhibitor

If you inhibit this enzyme then none or very little of the orally consumed codeine will be metabolized into morphine. Equals bad.

What you want is a coenzyme or catalyst that will increase demethylation (so that more morphine is generated) not something that will hinder the enzyme's ability to demethylate.
Click to expand...

Thanks, this is really helpful.
Do you know what WILL increase demethylation?
 
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