{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T23:58:28Z","timestamp":1767830308678,"version":"3.49.0"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T00:00:00Z","timestamp":1607904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1060992"],"award-info":[{"award-number":["1060992"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1043633"],"award-info":[{"award-number":["1043633"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1101974"],"award-info":[{"award-number":["1101974"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Sleep Research"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Questionnaire\u2010based studies have suggested genetic differences in sleep symptoms in chronic opioid users. The present study aims to investigate if there is a genetic effect on sleep architecture and quantitative electroencephalogram (EEG) in response to acute morphine. Under a randomized, double\u2010blind, placebo\u2010controlled, crossover design, 68 men with obstructive sleep apnea undertook two overnight polysomnographic studies conducted at least 1\u00a0week apart. Each night they received either 40\u00a0mg of controlled\u2010release morphine or placebo. Sleep architecture and quantitative EEG were compared between conditions. Blood was sampled before sleep and on the next morning for genotyping and pharmacokinetic analyses. We analysed three candidate genes (<jats:italic>OPRM1<\/jats:italic> [rs1799971, 118 A\u00a0&gt;\u00a0G], <jats:italic>ABCB1<\/jats:italic>[rs1045642, 3435 C\u00a0&gt;\u00a0T] and <jats:italic>HTR3B<\/jats:italic> [rs7103572 C\u00a0&gt;\u00a0T]). We found that morphine decreased slow wave sleep and rapid eye movement sleep and increased stage 2 sleep. Those effects were less in subjects with <jats:italic>HTR3B<\/jats:italic> CT\/TT than in those with CC genotype. Similarly, sleep onset latency was shortened in the <jats:italic>ABCB1<\/jats:italic> CC subgroup compared with the CT\/TT subgroup. Total sleep time was significantly increased in <jats:italic>ABCB1<\/jats:italic> CC but not in CT\/TT subjects. Sleep apnea and plasma morphine and metabolite concentration were not confounding factors for these genetic differences in sleep. With morphine, patients had significantly more active\/unstable EEG (lower delta\/alpha ratio) during sleep. No genetic effects on quantitative EEG were detected. In summary, we identified two genes (<jats:italic>HTR3B<\/jats:italic> and <jats:italic>ABCB1<\/jats:italic>) with significant variation in the sleep architecture response to morphine. Morphine caused a more active\/unstable EEG during sleep. Our findings may have relevance for a personalized medicine approach to targeted morphine therapy.<\/jats:p>","DOI":"10.1111\/jsr.13249","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T15:49:08Z","timestamp":1608047348000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The effect of acute morphine on sleep in male patients suffering from sleep apnea: Is there a genetic effect? An RCT Study"],"prefix":"10.1111","volume":"30","author":[{"given":"Luke","family":"Rowsell","sequence":"first","affiliation":[{"name":"Centre for Integrated Research and Understanding of Sleep (CIRUS) Woolcock Institute of Medical Research Sydney Medical School the University of Sydney Sydney Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin Guang\u2010Ao","family":"Wu","sequence":"additional","affiliation":[{"name":"Centre for Integrated Research and Understanding of Sleep (CIRUS) Woolcock Institute of Medical Research Sydney Medical School the University of Sydney Sydney Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brendon J.","family":"Yee","sequence":"additional","affiliation":[{"name":"Centre for Integrated Research and Understanding of Sleep (CIRUS) Woolcock Institute of Medical Research Sydney Medical School the University of Sydney Sydney Australia"},{"name":"Department of Respiratory and Sleep Medicine Royal Prince Alfred Hospital (work performed) Sydney Local Health District Camperdown Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith K.H.","family":"Wong","sequence":"additional","affiliation":[{"name":"Centre for Integrated Research and Understanding of Sleep (CIRUS) Woolcock Institute of Medical Research Sydney Medical School the University of Sydney Sydney Australia"},{"name":"Department of Respiratory and Sleep Medicine Royal Prince Alfred Hospital (work performed) Sydney Local Health District Camperdown Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheila","family":"Sivam","sequence":"additional","affiliation":[{"name":"Centre for Integrated Research and Understanding of Sleep (CIRUS) Woolcock Institute of Medical Research Sydney Medical School the University of Sydney Sydney Australia"},{"name":"Department of Respiratory and Sleep Medicine Royal Prince Alfred Hospital (work performed) Sydney Local Health District Camperdown Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew A.","family":"Somogyi","sequence":"additional","affiliation":[{"name":"Discipline of Pharmacology Adelaide Medical School University of Adelaide Adelaide Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald R.","family":"Grunstein","sequence":"additional","affiliation":[{"name":"Centre for Integrated Research and Understanding of Sleep (CIRUS) Woolcock Institute of Medical Research Sydney Medical School the University of Sydney Sydney Australia"},{"name":"Department of Respiratory and Sleep Medicine Royal Prince Alfred Hospital (work performed) Sydney Local Health District Camperdown Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3975-6214","authenticated-orcid":false,"given":"David","family":"Wang","sequence":"additional","affiliation":[{"name":"Centre for Integrated Research and Understanding of Sleep (CIRUS) Woolcock Institute of Medical Research Sydney Medical School the University of Sydney Sydney Australia"},{"name":"Department of Respiratory and Sleep Medicine Royal Prince Alfred Hospital (work performed) Sydney Local Health District Camperdown Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,12,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/PGPM.S29272"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.2172"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100385"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/pme.12226"},{"issue":"3","key":"e_1_2_10_6_1","first-page":"1165","article-title":"Pharmacogenetic determination of the effects of codeine and prediction of drug interactions","volume":"278","author":"Caraco Y.","year":"1996","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2014.59"},{"issue":"5","key":"e_1_2_10_8_1","first-page":"e006818","article-title":"Can variability in the effect of opioids on refractory breathlessness be explained by genetic factors?","volume":"5","author":"Currow D. 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