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Re: Opiates = the Devil Amphetamines = Angels?

Posted by Larry Hoover on November 5, 2002, at 10:27:06

In reply to Opiates = the Devil Amphetamines = Angels?, posted by Jerrympls on November 5, 2002, at 0:10:05

> 1) What's the difference between taking Vicodin (schedule III) for depression vs. amphetamine (schedule II) for depression?
>
> 2) What's the difference between taking Vicodin for depression vs. Prozac? With Prozac you have to take it every day and if you go off of it you have to go slowly because of the severe withdrawl.
> Anyone out there have an opinion? Insight?
>
> Thanks
>
The answer to your questions is exceedingly complex. I'm not going to suggest that I've mastered the complexity, but I think I understand enough about the pharmacology to say that I don't think there's a person alive who understands the whole thing. Anyway.....

Your body has an emergency system that handles pain. Pain, of course, is your body telling you that you're injured. But sometimes, experiencing pain is contrary to survival. Like being able to run on a broken leg.....if it gets you away from the lion... Many people in traumatic situations feel no pain....until later.

Long ago, we figured out how to activate that system artificially, using opiates. And, like the arrogant people we really are, we labelled the receptors for these exogenous (from outside) substances opiate receptors (as if Mother Nature had anticipated the opium poppy). Those receptors really are meant to bind with a variety of hormones like endorphins and enkephalins (and probably many other substances we've yet to stumble across).

We're only just beginning to realize the variety and extent of the various classes of opiate receptors, and how they affect other aspects of our mind/body interactions aside from pain, per se.

Pain is the sort of experience that can be assessed quite readily. Western medical science has primarily focussed on the analgesic aspects of opiates. We can rank the various opiates on a scale of analgesia. Analgesia occurs because the opiates bind to, and activate, particular opiate receptors involved in what is called nociception (pain sensing). The analgesic opiates bind to these receptors much more tightly than they do other classes of opiate receptors which we associate with euphoria and other mood-altering effects. In essence, the pain receptors get theirs first, and only after those receptors are saturated does an appreciable amount bind to the other ones. One of the ways to measure analgesic opiate dosages is to assess the "buzz factor". If you're getting too much of a buzz, your pain receptors are saturated. Of course, people not experiencing pain saturate their pain receptors quite easily, and a buzz is the only appreciable result.

Even what I've said so far is simplistic, so bear with me. We've discovered a vast number of ways to modify the base alkaloids found in opium. Each different compound has a different binding profile than any of the others. That is to say, each will have a different affinity for each of the numerous types and classes of opioid receptors. Heroin is a great pain-killer, but we know it binds other receptors too.

The ideal antidepressant opiate will not bind to pain-killing opiate receptors. It will not bind to receptors in the gut (leading to constipation). Blah blah blah. And it will not cause up-regulation of receptor synthesis. That's the big problem with opiates. When receptors saturate, the body makes more of them, to return sensitivity to the system. Your body quickly accomodates to the exogenous opiate, and you have to continually increase the dose to get the same effect.

Like I said at the beginning, the opioid system of receptors seems to be fine-tuned for emergency activation. Swift up-regulation of receptor synthesis seems to support that position. Chronic activation of the system seems to be mediated by other factors, and that's a whole 'nother essay.

Do any opiates work primarily as antidepressants? Well, the jury's still out on that one. The "war on drugs" political movement is certainly supressing research in this field. Recent abuses of sustained-release oxycodone don't work in our favour, either.

There are three semi-synthetic opiates which do seem to have promise as antidepressants, but it's likely that newer versions will be more specific in mode of action (if it ever comes to pass that the research is funded). Those three are dextromethorphan, tramadol, and buprenorphine.

There may be others, but even though these seem to have mood-elevating effects, it does seem that the effect is transitory. We haven't figured out why, or what to do about it.

 

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poster:Larry Hoover thread:126471
URL: http://www.dr-bob.org/babble/20021101/msgs/126509.html