From: (Jakub Buzdygan) Subject: codeine FAQ - update 2 Date: 1996/04/30 newsgroups: alt.drugs,rec.drugs.misc,alt.drugs.hard [...] [Pharmacology and Drug Interactions In order to take full advantage of codeine, it is helpful to be familiar with some relevant pharmacology: *CYP2D6 The body converts codeine into morphine (~10%) by using the so called P450 cytochrome pathway, especially cytochrome 2d6 (cyp2d6). Unfortunately, cyp2d6 is missing in about 7% of the white population, and its manifestation is quite variable in the rest. Individuals who inherited a cyp2d6 deficiency will get many of the adverse effects associated with codeine but little euphoria. If codeine just doesn't work for you, this may be why. Some drugs also interfere with cyp2d6. Prime among these are the SSRIs, with the exception of Zoloft (if I remember correctly). The most potent inhibitor is paroxetine (paxil), followed by fluoxetine (prozac). If you are taking an SSRI, you will probably experience a markedly decreased euphoria when using codeine. I have done codeine while taking paxil server times, and the high was variable: ok once or twice, nonexistent at other times. In addition I got weird side effects for several days (buzzing in the head/etc). If you're on an SSRI it might be a good idea to skip the dose for a few days (if you can handle this without relapsing into depression, or if you don't care). Most SSRIs have half lifes of only a day or so; the exception is prozac with a 1/2 life of 7 days. Finally, codeine itself is a cyp2d6 inhibitor. This means that taking the whole dose as quickly as possible will probably give you the biggest high. To test this theory I split a 350mg dose into 3 parts taken about 45 minutes apart. This lead to more side effects and a poor high. On the other hand, this might have been due to paxil which I was on at the time. If you've tried this yourself, let me know what happened. *GLUTHETHIMIDE A combination of codeine and gluthethimide (a sleeping agent) has been used in some places as a heroin substitute. Gluthethimide is an enzyme-inducer, and it allows the body to convert more than 10% of codeine into morphine. Note that this combination increases the addiction potential of codeine. *CAFFEINE The faq mentions that most of the caffeine in the origical product will end up in the filtered solution. The pharmacological results of this combination are not clear. One study found that caffeine reduced the incidence of acetominophen related liver disorders in mice; another study found that it increased hepatotoxicity in mice. Who knows what it does in humans. Since caffeine is a stimulant and morphine a depressant, its presence will also probably spoil the high a little. Unfortunately, I haven't found an easy way to get rid of the stuff. If you have any ideas, mail me.] ==================================================================== From: (Samson) Subject: Re: Phenergan really doesn't boost your narcotics buzz Date: 1996/07/23 newsgroups: alt.drugs.hard Jeffrey A. Smith wrote: > The drug Phenergan (promethazine) is an anti-nausea drug, related to the > antipsychotic drugs like Thorazine. the reality of it is that > these type of drugs work by blocking the dopamine and the histamine > receptors in parts of the brain. Promethazine is an H1-receptor blocking agent with many indications. But, although it is a phenothiazine derivative, its structure differs from other phenothiazines in such a way as to make meaningless any pharmacological comparison. (Something about a branched side chain and no ring substitution, but I don't know much about dat chem stuff...) The DA-blocking potency of promethazine is 1/10th that of chlorpromazine, which is a fairly low potency DA-blocker itself, which means that at humanly tolerable doses (say, under a gram), its D2 blocking action is of no consequence.