Opioid agonists are very complex in their actions and withdrawal is only complicated by the myriad of chemical changes. The biggest one that seems to produce discomfort is norepinephrine (NE). NE is a natural stimulant and the levels of NE are depressed with opioids, so withdrawal leads to a reversal of this depression or suppression causing the cells to release massive amounts, thus resulting in muscle cramps, increased pulse, hot/cold flashes, and chills.
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