Thursday, August 18, 2016

Receptor Sensitivity Homeostasis

And for that matter, I’ve met a few people who never seem to develop tolerance for benzodiazepine sleeping pills. You see this same pattern for opiates used as painkillers. I spent so many years confused about whether people develop tolerance to these or not, and my final conclusion is that some people do and some people don’t and if you try to find a coherent universal pattern here you will go insane.
Essay writers all need physics and programming.

If the user repeatedly clicks the 'OK' button, some programs will crash and some don't and if you try to find a coherent universal pattern here you will go insane.
It's called a 'bug,' and someone suitably knowledgeable about the program and the language it's written in can find and fix the bug. The issue with benzos is the program is executed in proteins and the language it's written in is GATTACA.
I spent so many years confused about whether programs crash or not.
Yet it never occurred to him that 'programs' isn't a natural kind at this level of detail. Programs vary in their bugginess and thus their responses to input. Programs also vary in function and implementation, so the exact same input may produce, variably, good output, buggy output, and correct output that is identical to the buggy output due to the 'bug' being correct behaviour for that program, and 'fixing' it would break six other things.

I don’t know who first discovered that low-dose naltrexone could help potentiate the effect of opiates
This is one of the first things I would have thought of, because I know receptor sensitivity is homeostatically regulated. (I think I confirmed this from one of Sapolsky's behavioral biology lectures.) There's a target range of stimulation, and the body attempts to meet it. It can use impulses/behaviour, self-medication, hormone regulation, and if those don't work, it tunes receptor sensitivity. You can see this happen very quickly with taste and smell. However, since it's a range, it's possible to get stuck at the extrema. There's hysteresis.

Addiction is often the result of the target range itself getting deformed, so no reasonable amount of natural stimulation can hit it, even with maximally aggressive tuning. Alternatively, the tuning process can itself be buggy.

Naturally pain receptors are highly resistant to this effect, much the way sharks don't get cancer. It became well-tuned and stayed that way, and is now selected for being conservative.

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