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This human laboratory paradigm examined whether the AA versus AG\/GG genotypes determined opioid response profiles. Individuals with limited opioid exposure (N\u2009=\u2009100) completed a five\u2010day within\u2010subject, double\u2010blind, placebo\u2010controlled, residential study. Participants were admitted (Day 1), received 4\u00a0mg hydromorphone (Day 2) and 0\u00a0mg, 2\u00a0mg and 8\u00a0mg hydromorphone in randomized order (Days 3\u20135) and completed self\u2010reported visual analog scale (VAS) ratings and Likert scales, observed VAS, and physiological responses at baseline and for 6.5\u00a0h post\u2010dose. Outcomes were analysed as peak\/nadir effects over time as a function of genotype (available for N\u2009=\u200996 individuals; AG\/GG\u2009=\u200913.5%, AA\u2009=\u200986.4%). Participants with AG\/GG rated low and moderate doses of hydromorphone as significantly more positive (e.g., Good Effects VAS, coasting, drive, friendly, talkative, stimulation) with fewer negative effects (e.g., itchy skin, nausea, sleepiness), and were also observed as being more talkative and energetic relative to persons with AA. Persons with AG\/GG were less physiologically reactive as determined by diastolic blood pressure and heart rate, but had more changes in core temperature compared with those with AA. Persons with AA also demonstrated more prototypic agonist effects across doses; persons with AG\/GG showed limited response to 2\u2009mg and 4\u2009mg. Data suggest persons with AG\/GG genotype experienced more pleasant and fewer unpleasant responses to hydromorphone relative to persons with AA. Future studies should replicate these laboratory findings in clinical populations to support a precision medicine approach to opioid prescribing.<\/jats:p>","DOI":"10.1111\/adb.13355","type":"journal-article","created":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T12:05:00Z","timestamp":1702987500000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Polymorphisms in the A118G SNP of the OPRM1 gene produce different experiences of opioids: A human laboratory phenotype\u2013genotype assessment"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3746-3108","authenticated-orcid":false,"given":"Kelly E.","family":"Dunn","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew 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S.","family":"Maher","sequence":"additional","affiliation":[{"name":"Department of Mental Health Johns Hopkins University School of Public Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill A.","family":"Rabinowitz","sequence":"additional","affiliation":[{"name":"Department of Mental Health Johns Hopkins University School of Public Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric C.","family":"Strain","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Antoine","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine  Baltimore Maryland 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