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Paradoxical Reactions and Inverse Agonists

Posted by Quintal on August 17, 2007, at 18:10:45

I've noticed for a while now that as I've built up tolerance to codeine, after each dose it actually seems to be *causing* pain. It reminds me of those ill-defined aches and pains, like currents running through the body, that one gets on high doses of GHB. Also, there is a mild pain in my back and shoulders. Last night I felt ill after taking my usual dose, so much so that I feared I'd accidentally taken an overdose. A great heaviness descended upon me, accompanied by a wave of sickness, leaving me feeling weak and faint. I'm starting to wonder if I have a bleeding ulcer which the ibuprofen has re-opened now my stomach acid is back on?

Anyway, today I felt much better when I got up so I didn't want to take any codeine in case it made me ill again. I've been fine all day without it - no pain or withdrawal symptoms at all. Yesterday I felt ill all day with it - pain despite taking a larger dose than the day before and a horrible malaise, which is the opposite of the usual effect it has on me. The day before, I ran out of codeine and I felt ill all day without it, withdrawal symptoms and awful aches and pains. So what's going on? I think Larry Hoover once had a similar experience with an opiate, so I'd be interested to hear what happened there.

I'm also thinking about the article I posted a week or so ago on benzodiazepine withdrawal, where the receptors can become locked into the inverse agonist configuration and thereby cause the opposite effect of the drug. I haven't examined that theory carefully, and it may just apply to people suffering lingering withdrawal symptoms after the drug has been discontinued, and therefore be irrelevant to this, but I wonder if there is a technical explanation for this phenomenon? Maybe the best thing to do is taper off to regain tolerance?

I'm thinking of substituting it with Parnate and Xanax for a month or so. I have some Parnate left over from my prescription last October and it's mildly dopaminergic so might take up the slack in my dopamine system. One batch goes off at the end of this month so I need to get it used up anyway and now would be a good time. I also need to stay away from the ibuprofen (in Nurofen Plus) as it cant be good for my poor stomach any more. I actually felt something wobbling around in there today, a fleshy mass of some sort. Not nice, but I'm not going back to the doctor unless it flares up again.

Q


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poster:Quintal thread:776820
URL: http://www.dr-bob.org/babble/20070815/msgs/776820.html