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Why does opioid withdrawal produce flu-like symptoms?

Synaps3

Bluelighter
Joined
Sep 14, 2011
Messages
257
I am wondering this from a neuroscience perspective. Obviously, opioids produce pain killing and euphoric effects and in addition, they release histamine. So why does the withdrawal produce seemingly unrelated side effects? You would expect to have much increased sensitivity to pain and dysphoria, but that's about it. Instead, the predominant effects are flu-like symptoms and RLS (at least for most people). You would also think with all of the histamine release during use, that you would almost have the opposite withdrawal effects. I was hoping someone could explain why this is. I'm curious. Most other drugs seem much more clear cut. Like the absence of GABA drugs leads to anxiety and eventually seizures because the CNS is overexcited - that makes perfect sense, but opiates make no sense. It's like if god exists and was like, alright, we need some arbitrary punishment for abusing this stuff lol.
 
Afaik a major factor is a rebound surge in norepinephrine, also why clonidine is a good aid in withdrawal. I thought to remember a paper about choline being important too but I can't find it anymore, all I found in a quick search was inconclusive now. Yet anticholinergics appear to help too.

sci-hub's your friend said:

Personally I find the term 'flu-like' somewhat irritating because what really fucks me up about withdrawals in general is the mental uneasiness, anxiety, restlessness, hopelessness etc.. oh yeah, and the RLS which might be related to low dopamine (and high norepinephrine). Granted my experience of cold turkey is limited (thankfully) yet I don't find much similarities between w/d and the flu..
 
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