> I wanted sort of the opposite of this for opioids - work in the body, not the brain
That's already how some anti-diarrheals work like loperamide. And some anticonstipation drugs like oral naloxone and methylnaltrexone that work as peripheral or locally-acting antagonists
Yes but loperamide doesn't alleviate pain, which maybe just that opioids only alleviate pain if they do reach the brain, but I did see trials for non-bbb crossing ones that were for pain so not sure what's going on there.
It's possible that the analgesic and euphoric effects of opioids are one and the same. In other words, it's centrally dampening the experience of pain, both physical and mental. One is experienced as analgesia and the other as pleasure, but both may share the same mechanism, making one impossible without the other.
That's already how some anti-diarrheals work like loperamide. And some anticonstipation drugs like oral naloxone and methylnaltrexone that work as peripheral or locally-acting antagonists