> 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.
A controversial and hypothetical drug which might help addicts would be a companion drug that somehow prevented the development of tolerance. I know nothing about the brain so that's probably laughably impossible, but if it existed it could cheapen the cost of a habit and lead to fewer ODs because they would have no need to chase their tolerance to feel the same effects. It would certainly have other side effects because someone could essentially just remain high 24/7 (in the extreme case).
Yeah, because it is the high they are after, but not working in the brain would make opioids completely useless for depression and anxiety (for which it really does wonders).
My want is for relieving pain in the body without making me feel high, I actually assumed you want it in the body not brain, as the brain effects are the feel-good effects, but really not sure or familiar with how they work.
I have went through most NSAIDs, they do not compare to opiates at all, and when I mean all, I am referring to prescription-only NSAIDs, too. There was a time when I mixed diclofenac, naproxen, and ibuprofen, too, none of them helped (separately and mixed). Kratom, however, did.
If I were to have fever, I would not take opiates though, I do not think they reduce inflammation or fever.
There are prescription-grade NSAIDs that make Advil look like candy, but they're admittedly still not as heavy-hitting as bona fide painkillers. Great for inflammatory pain though.
Not just your GI, but they increase your risk of cardiovascular issues as well, among many others, whereas opiates do not cause any of those horrible side-effects. Dose matters, it does matter with NSAIDs, too, if I pop 10 acetaminophen, you can rest assured I will have liver cirrhosis.
Would you mind elaborating on what you've used / your experiences? I'm curious (without wanting to encourage further use) how definite it is that they don't make you high as opposed to that you need higher (no pun intended) doses to get high than other people. Are they effective at relieving physical pain for you?
It wouldn't surprise me if either were true - it's definitely the case that different people need different opiate doses to get the same effects (even for their first dose, not considering developed tolerance), I've known people for whom OTC (over the counter, no prescription needed) cocodamol - 8mg codeine + 500mg paracetamol, x1-2 per dose - contained enough codeine for them to feel a bit high, meanwhile other people like me need prescription strength (30-60mg) codeine to feel any benefits at all, and don't feel remotely high from it.
I also had a friend once who literally couldn't get high from weed, it has no effect on him - at least up to the amount tested, which was him smoking & vaping several grams of a strong strain of cannabis that got the rest of the room extremely high with much less of it. He tried on various other occasions, included edibles from a coffeeshop in Amsterdam, never any effects.
I have tried oxycodone (40 mg, went way above 80 mg too) and it did not make me high at all, people talk about a state of bliss and whatnot but I have never experienced it.
Most substances do not affect me the way they affect others; I have depression & anxiety and I have tried almost all antidepressants (along with mood stabilizers) to no effect.
I suspect it may have to do with my brain lesions (I have MS), but I am not quite sure.
That said, opiates do help with my physical symptoms, and only them, unfortunately.
> people like me need prescription strength (30-60mg) codeine to feel any benefits at all, and don't feel remotely high from it.
It is interesting though. Oxycodone is way stronger than codeine, and 80 mg is considered a very high dose yet it does not make me high, with or without tolerance.
My sister has defective P450 and your experience is the same as hers with opiates and other drugs, e.g. they are entirely ineffective when taken orally.
