Posted by Larry Hoover on March 4, 2005, at 10:32:19
In reply to Codeine produced the opposite effect!!!, posted by NARCOLEPTIC on March 3, 2005, at 16:36:22
> Took 15 mg of codeine for a dry cough post-flu. Never felt so alert and anxiety free in my life. No early-to-late afternoon sleepiness, mental fuzziness and limb weakness.
>
> How weird is that!??
>
> Although my name reads NARCOLEPTIC I have never been officially diagnosed as such.Here's the probable explanation for that effect.
Codeine is actually a pro-drug, with respect to its most commonly expected effects. A pro-drug is an inactive form of the drug, which becomes active upon being transformed by enzymes in the body, usually the liver's cytochrome (P450) enzymes.
Codeine is O-desmethylated to morphine by cytochrome 2D6. Typical rates of desmethylation are 4% per hour. Under ordinary circumstances, codeine is really analogous to slow-release morphine.
However, the 2D6 enzyme is quite a freak, genetically. Inter-individual variation in the activity of the 2D6 enzyme differs by 118-fold. Not per cent. Times. 118-fold variation is a rate differential of 11,800 per cent.
There are well over 100 different forms (genetically distinct alleles) of the 2D6 enzyme yet identified, and I have no doubt that if they continue to look, they will find more.
People who have the fastest rates of 2D6 activity are called extensive metabolizers. Codeine ingested by these individuals rapidly becomes morphine; psychoactive effects far exceed analgesic ones. They are high, plain and simple.
On the other end of the spectrum are poor metabolizers. Poor metabolizers get all of the unintended effects of codeine itself (constipation, dry mouth, sedation) without any of the high, or sometimes, even any analgesic effect.
Variability in 2D6 activity is very much a part of some people's poor response to SSRI meds. Knowing how you react to codeine is a pretty good indicator of 2D6 activity, and should be a factor influencing medication selection in other realms of treatment.
Lar
poster:Larry Hoover
thread:466068
URL: http://www.dr-bob.org/babble/20050304/msgs/466425.html