Enzyme Problem with Codeine?

[OverteHorizonRadar]

My whole family has a CYP2D6 enzyme dysfunction, and I know because they have gotten tests done. I haven't. I get high off of Oxycodone and percocets, but i never get high of Tylenol 3. Even before a surgery, the doctor gave me a shot of pure codeine, and I ended up not having the surgery that day( cancer comes before cysts). I didn't feel anything all day. So am I fucked for not metabolizing codeine? thanks!

 

[THC2LSD]

Damn, the real "White man's burden," being unable to use codeine. A horrible joke about a condition most common in Caucasians. Oh well, at least you now have a legit excuse to be given morphine or hydromorphone instead:D.

Some have speculated that codeine's main metabolite codeine-6-glucuronide has some effect, perhaps a major part of the effects. Other believe that codeine is basically useless for poor metabolizers and the morphine gives the effects.

Codeine's a weak painkiller, especially for something like cancer. It has a favorable side effect profile up to 60mg, then it's not as good as others. He should've given you just about anything else but codeine or tramadol. Like oxycodone, morphine, hydromorphone and even hydrocodone. There are other options out there. But who knows, maybe this doc is a asshole who'd give an old lady dying of cancer ibuprofen.

 

[cook]

Yeah, it is not that uncommon that codeine doesn't work at all and your family history is probably the best indicator. Don't worry, you haven't lost anything because there are far more efficient and more recreational pain killers available anyway.

 

[Swimmingdancer]

Did you feel pain relief? For many people codeine is not a very euphoric drug. Poor metabolization of codeine into morphine is quite common - an estimated 1 in 10 people - so if you felt little effects from usual to high doses, and you do not have an opioid tolerance, then it's very possible you could have abnormally low CYP2D6 activity. If your whole family has CYP2D6 dysfunction, that I would assume it is very likely that you do too. No way to tell for certain without testing, but from the info you've provided it sounds like you're either a poor CYPD26 metabolizer and/or your expectations for codeine are too high. Only around 0%-20% of codeine is converted to morphine, and around 50-70% of codeine is converted by a different enzyme to codeine-6-glucuronide, it's other main active metabolite which is now believed to be responsible for a portion of codeine's analgesia, so if someone was a low CYP2D6 activity they should apparently still be able to get some analgesic effect from codeine. It is theorized by some that the morphine might be more responsible for any euphoria though.

What I don't understand is why codeine is injected. Wouldn't that decrease its effects? I assume you mean intramuscular injection, since intravenous injection is not done as it is very dangerous.

If codeine doesn't work for you, then just tell doctors that in the future.

 

[THC2LSD]

What I don't understand is why codeine is injected. Wouldn't that decrease its effects?

Believe it or not, no. Codeine is twice as strong SC/IM and kicks in much faster. That's why hypodermic codeine pills are sometimes used.

 

[Swimmingdancer]

Believe it or not, no. Codeine is twice as strong SC/IM and kicks in much faster. That's why hypodermic codeine pills are sometimes used.

I believe you, that just seems so weird to me. If codeine is a pro-drug, how can it kick in faster and be stronger when IM'd? Codeine itself must be active, so you would be getting far less morphine and codeine-6-glucuronide, and slower metabolization to those metabolites, but the effects would be mainly from the codeine itself?

 

[dais]

Some have speculated that codeine's main metabolite codeine-6-glucuronide has some effect, perhaps a major part of the effects. Other believe that codeine is basically useless for poor metabolizers and the morphine gives the effects.

codeine-6-glucuronide is thought to be mainly responsible for the euphoria created. the morphine is responsible for analgesia.

Codeine's a weak painkiller, especially for something like cancer. It has a favorable side effect profile up to 60mg, then it's not as good as others. He should've given you just about anything else but codeine or tramadol. Like oxycodone, morphine, hydromorphone and even hydrocodone. There are other options out there. But who knows, maybe this doc is a asshole who'd give an old lady dying of cancer ibuprofen.

i disgaree it's a weak painkiller, well, for those who are extensive metabolisers or who have no problems with metabolsing it. i'm in the boat where it's extremely useful (at the 60-90mg dose) for coming off rather high benders on morphine in particular - other opioids as well in my case.

doctors have a responsibility of care and starting out on codeine is perfectly acceptable for starting with, especially in today's world where the heavier narcotics are being clamped down on.

 

[THC2LSD]

I believe you, that just seems so weird to me. If codeine is a pro-drug, how can it kick in faster and be stronger when IM'd? Codeine itself must be active, so you would be getting far less morphine and codeine-6-glucuronide, and slower metabolization to those metabolites, but the effects would be mainly from the codeine itself?

Codeine's bioavailability is about 50-60%. AFAIK almost all of that is codeine-6-glucuronide. Codeine-6-glucuronide is about 60% as strong an analgesic as codeine in rats, not sure about humans. Some have theorized that codeine-6-glucuronide gives a decent amount, perhaps most of the analgesic effects. Others have found that poor metabolizers and those on drugs that block CYP2D6 get more side effects and much less analgesia.

It could be that more codeine is available for conversion to morphine. The enzymes are found in the blood and other organs, not just the liver and GI tracts. Also sometimes changing the ROA can have dramatically different effects. Morphine is stronger than heroin intrathecally, as well as very long acting, like 12 hours. Methadone is twice as strong IV as PO. With methadone IV gives higher brain concentrations whereas PO gives higher liver/GI concentrations.SC/IM methadone are rather unpredictable. Methamphetamine is much stronger IV/smoked than PO, even though it has excellent bioavailability. Also a "button"(bootleg mandrax, methaqualone) has good PO bioavailability, but one 200-400mg pill can give up to 16, knock you on your ass, "OMG I'm high" hits. With IV methaqualone a hypnotic dose, 300mg, give surgical anesthesia for 15 minutes. 20mg of PCP IV with produce general anesthesia, but a similar dose snorted, PO, and slowly smoked with get you really high but somewhat conscious; it too has good PO bioavailability.

Also the codeine itself is active. Not very strong but does something. Someone said in Turkey it's common to IV OTC codeine tablets. They said it has a very strong but really dirty rush. I do not recommend IV due to toxicity. Hopheads(opium smokers) actually prefer opium with a high codeine content over one with a higher morphine content. Then you have lean blunts. I've had opiate users swear up and down that lean blunts do produce an opiate effect. Not strong but noticeable. I tried it but the blunt was poorly rolled and ripped apart. It did seem to do something but didn't try enough to tell. At the very least it makes the blunt burn slower.

codeine-6-glucuronide is thought to be mainly responsible for the euphoria created. the morphine is responsible for analgesia.

I've never heard or read that. I've read some stuff that says it might have analgesic effects but nothing on euphoria. I'd be very surprised if it was more euphoric than morphine itself. Do you have something that says that?

i disgaree it's a weak painkiller, well, for those who are extensive metabolisers or who have no problems with metabolsing it.

It's weak but it's on the second step of the WHO's pain management ladder, after NSAIDs have failed. I agree that it's a good pain reliever, especially compared to tramadol(seizures) and darvon(heart problems). But it's side effect/effectiveness profile is good up to 60mg IR, after that it has worse side effects. For something like cancer they may need something stronger, because they may have a short time left in this world. They should be as pain-free as possible. Although codeine is a good starter drug and is often adequate.

doctors have a responsibility of care and starting out on codeine is perfectly acceptable for starting with, especially in today's world where the heavier narcotics are being clamped down on.

This is true, codeine should be tried first. But if it doesn't work something else should be used. However in the US hydrocodone's generally preferred. It's good too.

It's really sad how in most of the world most people will die in pain due to lopsided drug treaties favoring western nations and pharma, backwards views on pain(often from religion), and laws limiting production and distribution of opiates. Most die getting only ibuprofen or Ultram at the very best. It's not due to cost, legit morphine's cheap as fuck. It's due to the "War On Drugs"(TM).

 

[dais]

I've never heard or read that. I've read some stuff that says it might have analgesic effects but nothing on euphoria. I'd be very surprised if it was more euphoric than morphine itself. Do you have something that says that?

sorry, my mistake, it is thought to be the main metabolite which produces analgesia.

it was late at night and i got things mixed around, thanks for fixing that up!

i get great analgesia and euphoria from codeine - think i may be an extensive metaboliser.

It's weak but it's on the second step of the WHO's pain management ladder, after NSAIDs have failed. I agree that it's a good pain reliever, especially compared to tramadol(seizures) and darvon(heart problems).

thank fuck that shit has finally been taken off the market.

 

[Swimmingdancer]

Codeine's bioavailability is about 50-60%. AFAIK almost all of that is codeine-6-glucuronide. Codeine-6-glucuronide is about 60% as strong an analgesic as codeine in rats, not sure about humans. ... It could be that more codeine is available for conversion to morphine.

Those ideas make sense.

Some have theorized that codeine-6-glucuronide gives a decent amount, perhaps most of the analgesic effects. Others have found that poor metabolizers and those on drugs that block CYP2D6 get more side effects and much less analgesia.

Yeah, I've never understood this because if it is true that codeine-6-glucuronide is responsible for most of the analgesia, then why should poor CYP2D6 metabolization make such a noticeable difference? I get almost no effects from codeine other than a lot of unpleasant side effects.

Methadone is twice as strong IV as PO. With methadone IV gives higher brain concentrations whereas PO gives higher liver/GI concentrations.SC/IM methadone are rather unpredictable. Methamphetamine is much stronger IV/smoked than PO, even though it has excellent bioavailability.

Really?? That's very interesting. I've never dared IV methadone because doctors are always saying it already has a 90% BA orally and IVing gives you way more risks with no noticeable increase in effect. They also like to say there are awful side effects from IVing methadone, but I wonder if they either are just assuming liquid methadone (with sweeteners/flavourings etc), which would obviously probably be a terrible idea to IV, or if they are just trying to scare people away from injecting any form of methadone?

It's true that bioavailability does not equal effects.

 

[dais]

I've never dared IV methadone because doctors are always saying it already has a 90% BA orally and IVing gives you way more risks with no noticeable increase in effect.

there's a reason why you shouldn't IV methadone. it wreaks havoc on your veins, completely destroying them. every formula, whether it be orally dispensed or tablet form, they have additive to deter IV use which are further detrimental to your veins and circulatory system.

watering down the liquid forms only dilutes the solution further, does nothing to ease the damage being done.

coming from a subjective point of view there was no difference in IV and oral methadone. perhaps a quicker onset with IV.

 

[Swimmingdancer]

Sorry for derailing the thread. The only unsafe ingredient in mine is microcrystalline cellulose. Couldn't that be removed with a micron filter or CWE or something? Just curious, not actually planning on doing it. Also curious why THC2LSD said methadone was 2x as strong IV.

 

[dais]

while microcrystalline cellulose is insoluble in water it's the particle size that makes the difference, which can pass through even a .22 micron filter. which would leave the user with a build up of it's fibers within their circulatory system, etc.

twice as strong, no, definitely not. quicker onset of action, yes.

 

[Swimmingdancer]

while microcrystalline cellulose is insoluble in water it's the particle size that makes the difference, which can pass through even a .22 micron filter. which would leave the user with a build up of it's fibers within their circulatory system, etc.

twice as strong, no, definitely not. quicker onset of action, yes.

If it's something you would never do, how to you know that all it provides is a quicker onset? I mean, that's what I've always heard too, but I am curious why THC2LSD said the effects were stronger.

Unless I am misunderstanding, doesn't that link you provided say that the size of microcrystalline cellulose particles range from about 6 microns to around 500 microns? If that is the case, it would not pass through a 0.22 micron filter. And I have read elsewhere that the average size of mc particles found in pills is around 90 microns.

Apologies to the OP for this thread going onto a different topic.

 

[dais]

sorry, again, i misread that article a little. i should concentrate a little better when making statement. in my opinion i don't think th average user is using a micron, so the MC will likely pass through their filter (cotton, etc) - i should double check my stats there. there's a thread floating around with stats comparing the different choices of filters. i'm not on my usual computer with bookmarks.

it's something i have done, i have injected methadone. it's not worth it's weight in salt.