Abstract
The ongoing opioid crisis, centered in the United States, demands new insights into the complex and largely unknown mechanisms of opioid tolerance and addiction. Opioids, ranging from the natural opiates such as morphine to synthetic alternatives such as fentanyl, are widely used in the clinic as analgesics for acute and chronic pain. However, long-term administration of opioids may result in tolerance development and thus increase the risk of overdose and death. Broad availability of both prescription and illegal opioids has fueled substance use disorders.
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