Abstract
Prior to the mid-20th century, the acute euphoric effects of opioid drugs and their ability to alleviate depression were primary reasons for physician prescriptions of opioid drugs. This practice was abandoned and discouraged once it was recognized that tolerance, withdrawal, and dependence lead to iatrogenic addiction and opioid use disorder. Nevertheless, the field has far from discarded the connection of the opioid systems with depression [recently reviewed by Jelen et al. (1)], including evidence that nonmedical opioid use may precipitate new-onset depressive episodes (2).
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