Pharmacology - Opioid Tolerance: Reversing Receptor Sensitivity

[fiveleggedrat]

So Swim's been hitting the books lately, and studying lots of medical papers that he'll get to uploading later. He is trying to find a way to reduce the permanent tolerance he has gained, even after taking breaks for months from opioids. He no longer gets ANY euphoria from opioids, and tramadol just completely stopped working.

This all focuses strongly on the Mu receptor. Not interested in playing with K or Delta or any other receptors, since euphoria is tied mostly to the Mu receptor.

So Swim has 3 theories so far:

1) 50mg naltrexone daily regiment (While sober, obviously!) for 1-2 weeks. This in theory would sensitize receptors. Most papers I read say that people often OD when coming off an antagonist, although that could be just from lack of physical tolerance. Swim is very certain of this theory and that blasting the brain the naltrexone for a while would make it sensitive again to endorphins, and therefore, opioids. Cheap to test.

Edit: This idea centers on the use of an antagonist in general. Naltrexone seems like the best choice so far. Also, the 50mg dose is speculation based on what Swim has read.

2) iNOS inducible inhibition. (inducible nitric oxide synthase inhibition). Not even going to attempt to explain this, it's complicated. I'll go in-depth into all 3 of these options later, explaing why I think they would work. More or less, sounds to prevent regulation of the mu receptor. This one sounds good on paper, but would be very expensive to test.

3) Using NMDA antagonists to temporarily or perm. reduce tolerance. Learned about this one studying receptors and neurotransmitters. Cheap to test common ones like DXM and n2o but Swim wants to test this with MK-801. Too bad it's rare and expensive.

Anyone have any opinions/thoughts?

Reputation Comments on this post:

	good thread
	great research
	you really got something goin, hopefully we'll find it.
	Knowledgable, informative post
	Interesting thread.