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Although chronic opioid use is commonly accompanied by deficits in social functioning, little is known about the impact of chronic NMPOU on social cognitive functions. Social neuroscience models suggest that empathy activates similar or even equivalent neural structures as those underpinning the first\u2010hand experience in that emotional state (e.g., pain). Therefore, we measured subjective and psychophysiological responses during an empathy\u2010for\u2010pain task in 23 individuals with NMPOU, objectively confirmed by hair and urine testing, and compared them with 29 opioid\u2010na\u00efve healthy controls. NMPOU individuals showed lower other\u2010related and self\u2010related unpleasantness ratings when seeing others in pain than controls. No differences between the control and NMPOU group were found in skin conductance responses and heart rate variability (HRV) assessed by root mean square of successive differences (RMSSD) in response to the task. However, RMSSD\u2010HRV was strongly negatively correlated with self\u2010related unpleasantness and craving in the NMPOU group. A subsequent mediation analysis showed a total effect of RMSSD\u2010HRV on self\u2010related unpleasantness with no mediation of craving. This indicates that stronger emotion regulation indexed by high RMSSD\u2010HRV might have downregulating effects on sharing others\u2019 pain in NMPOU individuals but not in healthy controls, which was further accompanied by decreased ratings of<jats:italic>personal distress<\/jats:italic>and<jats:italic>empathetic concern<\/jats:italic>. These results contribute to a better understanding of social functioning in chronic opioid users, suggesting adequate emotion regulation and empathy trainings as therapeutic targets for future interventions of opioid use disorders and long\u2010term pain treatment with opioids.<\/jats:p>","DOI":"10.1111\/psyp.13776","type":"journal-article","created":{"date-parts":[[2021,2,13]],"date-time":"2021-02-13T23:50:14Z","timestamp":1613260214000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Chronic non\u2010medical prescription opioid use and empathy for pain: Does pain make the difference?"],"prefix":"10.1111","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9823-5171","authenticated-orcid":false,"given":"Sara L.","family":"Kroll","sequence":"first","affiliation":[{"name":"Experimental and Clinical Pharmacopsychology Department of Psychiatry, Psychotherapy, and Psychosomatics Psychiatric Hospital 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