{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe mu‐opioid receptor gene (OPRM1) encodes a receptor that is pivotal in mediating reward, reinforcement, and addictive behaviors. Functional polymorphisms—most notably the A118G variant that alters beta‐endorphin binding affinity—have been implicated in susceptibility to alcohol and drug dependence, as well as in differential responses to opioid antagonists. Clinical studies have shown that carriers of such variants display altered cue reactivity and automatic approach biases toward alcohol‐related stimuli, thereby influencing treatment outcomes in conditions such as alcohol dependence and heroin addiction."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, OPRM1 variation influences receptor expression, mRNA processing, and intracellular signal transduction. Experimental studies reveal that allele‐specific differences—reflected in variations in mRNA yield, translational efficiency, and receptor protein levels—alter downstream processes such as cAMP accumulation and G protein activation. These molecular differences contribute to the observed interindividual variability in opioid pharmacokinetics, analgesic efficacy (including outcomes in postoperative and cancer pain settings), and overall opioid responsiveness."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "31"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOPRM1 also plays a critical role in the modulation of pain and affective processing. Neuroimaging investigations have demonstrated that endogenous opioid release within regions such as the anterior cingulate, insula, and periaqueductal gray is associated with reductions in both physical pain and the distress of social rejection. This dual involvement in sensory and affective dimensions of pain elucidates the receptor’s contribution not only to conventional analgesia and placebo effects but also to the regulation of social pain and emotional resilience."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "32", "end_ref": "37"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its established roles in addiction and pain regulation, aberrant OPRM1 signaling has broader clinical implications. Studies indicate that dysregulated mu‐opioid receptor activity may modulate growth factor receptor pathways and promote epithelial–mesenchymal transition in certain cancers, while alterations in receptor availability have been linked to hedonic eating and obesity. Thus, the functional status of OPRM1 is emerging as a critical factor in diverse pathophysiological processes ranging from tumorigenesis to metabolic dysregulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "38", "end_ref": "42"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "C Y Szeto, N L Tang, D T Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between mu opioid receptor gene polymorphisms and Chinese heroin addicts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuroreport (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/00001756-200105080-00011"}], "href": "https://doi.org/10.1097/00001756-200105080-00011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11338173"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11338173"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "David W Oslin, Wade Berrettini, Henry R Kranzler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A functional polymorphism of the mu-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropsychopharmacology (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.npp.1300219"}], "href": "https://doi.org/10.1038/sj.npp.1300219"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12813472"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12813472"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "P Klepstad, T T Rakvåg, S Kaasa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The 118 A > G polymorphism in the human mu-opioid receptor gene may increase morphine requirements in patients with pain caused by malignant disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Anaesthesiol Scand (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1399-6576.2004.00517.x"}], "href": "https://doi.org/10.1111/j.1399-6576.2004.00517.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15504181"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15504181"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Gavin Bart, Mary Jeanne Kreek, Jurg Ott, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased attributable risk related to a functional mu-opioid receptor gene polymorphism in association with alcohol dependence in central Sweden."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropsychopharmacology (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.npp.1300598"}], "href": "https://doi.org/10.1038/sj.npp.1300598"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15525999"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15525999"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lara A Ray, Kent E Hutchison "}, {"type": "b", "children": [{"type": "t", "text": "A polymorphism of the mu-opioid receptor gene (OPRM1) and sensitivity to the effects of alcohol in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Alcohol Clin Exp Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/01.alc.0000148114.34000.b9"}], "href": "https://doi.org/10.1097/01.alc.0000148114.34000.b9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15608594"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15608594"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Huiping Zhang, Xingguang Luo, Henry R Kranzler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between two mu-opioid receptor gene (OPRM1) haplotype blocks and drug or alcohol dependence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddl024"}], "href": "https://doi.org/10.1093/hmg/ddl024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16476706"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16476706"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Esther van den Wildenberg, Reinout W Wiers, Joelle Dessers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A functional polymorphism of the mu-opioid receptor gene (OPRM1) influences cue-induced craving for alcohol in male heavy drinkers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Alcohol Clin Exp Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1530-0277.2006.00258.x"}], "href": "https://doi.org/10.1111/j.1530-0277.2006.00258.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17207095"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17207095"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Joel Gelernter, Ralitza Gueorguieva, Henry R Kranzler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Opioid receptor gene (OPRM1, OPRK1, and OPRD1) variants and response to naltrexone treatment for alcohol dependence: results from the VA Cooperative Study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Alcohol Clin Exp Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1530-0277.2007.00339.x"}], "href": "https://doi.org/10.1111/j.1530-0277.2007.00339.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17374034"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17374034"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Raymond F Anton, Gabor Oroszi, Stephanie O'Malley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Gen Psychiatry (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/archpsyc.65.2.135"}], "href": "https://doi.org/10.1001/archpsyc.65.2.135"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18250251"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18250251"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "O Levran, D Londono, K O'Hara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic susceptibility to heroin addiction: a candidate gene association study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Brain Behav (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1601-183X.2008.00410.x"}], "href": "https://doi.org/10.1111/j.1601-183X.2008.00410.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18518925"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18518925"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Francesca M Filbey, Lara Ray, Andrew Smolen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential neural response to alcohol priming and alcohol taste cues is associated with DRD4 VNTR and OPRM1 genotypes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Alcohol Clin Exp Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1530-0277.2008.00692.x"}], "href": "https://doi.org/10.1111/j.1530-0277.2008.00692.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18540916"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18540916"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "R W Wiers, M Rinck, M Dictus, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Relatively strong automatic appetitive action-tendencies in male carriers of the OPRM1 G-allele."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Brain Behav (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1601-183X.2008.00454.x"}], "href": "https://doi.org/10.1111/j.1601-183X.2008.00454.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19016889"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19016889"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Yuchen Liu, Dameng Li, Zhengya Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeted exosome-mediated delivery of opioid receptor Mu siRNA for the treatment of morphine relapse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep17543"}], "href": "https://doi.org/10.1038/srep17543"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26633001"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26633001"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "M R Hoehe, K Köpke, B Wendel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sequence variability and candidate gene analysis in complex disease: association of mu opioid receptor gene variation with substance dependence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2000)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/9.19.2895"}], "href": "https://doi.org/10.1093/hmg/9.19.2895"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11092766"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11092766"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Gary S Wand, Mary McCaul, Xioaju Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The mu-opioid receptor gene polymorphism (A118G) alters HPA axis activation induced by opioid receptor blockade."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropsychopharmacology (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S0893-133X(01)00294-9"}], "href": "https://doi.org/10.1016/S0893-133X(01"}, {"type": "t", "text": "00294-9) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11751037"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11751037"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Jörn Lötsch, Michael Zimmermann, Jutta Darimont, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Does the A118G polymorphism at the mu-opioid receptor gene protect against morphine-6-glucuronide toxicity?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anesthesiology (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/00000542-200210000-00011"}], "href": "https://doi.org/10.1097/00000542-200210000-00011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12357145"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12357145"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Carlos A Hernandez-Avila, Gary Wand, Xingguang Luo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between the cortisol response to opioid blockade and the Asn40Asp polymorphism at the mu-opioid receptor locus (OPRM1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.10054"}], "href": "https://doi.org/10.1002/ajmg.b.10054"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12627468"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12627468"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Ene-Choo Tan, Chay-Hoon Tan, Umavathy Karupathivan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mu opioid receptor gene polymorphisms and heroin dependence in Asian populations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuroreport (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/00001756-200303240-00008"}], "href": "https://doi.org/10.1097/00001756-200303240-00008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12657887"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12657887"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Ying Zhang, Danxin Wang, Andrew D Johnson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Allelic expression imbalance of human mu opioid receptor (OPRM1) caused by variant A118G."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M504942200"}], "href": "https://doi.org/10.1074/jbc.M504942200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16046395"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16046395"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Albert Arias, Richard Feinn, Henry R Kranzler "}, {"type": "b", "children": [{"type": "t", "text": "Association of an Asn40Asp (A118G) polymorphism in the mu-opioid receptor gene with substance dependence: a meta-analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Alcohol Depend (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.drugalcdep.2005.11.024"}], "href": "https://doi.org/10.1016/j.drugalcdep.2005.11.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16387451"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16387451"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Laurent Coulbault, Marc Beaussier, Céline Verstuyft, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Environmental and genetic factors associated with morphine response in the postoperative period."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Pharmacol Ther (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.clpt.2006.01.007"}], "href": "https://doi.org/10.1016/j.clpt.2006.01.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16580900"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16580900"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Wen-Ying Chou, Cheng-Haung Wang, Ping-Hsin Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human opioid receptor A118G polymorphism affects intravenous patient-controlled analgesia morphine consumption after total abdominal hysterectomy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anesthesiology (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/00000542-200608000-00016"}], "href": "https://doi.org/10.1097/00000542-200608000-00016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16871067"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16871067"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "W-Y Chou, L-C Yang, H-F Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of mu-opioid receptor gene polymorphism (A118G) with variations in morphine consumption for analgesia after total knee arthroplasty."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Anaesthesiol Scand (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1399-6576.2006.01058.x"}], "href": "https://doi.org/10.1111/j.1399-6576.2006.01058.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16879459"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16879459"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Cielito C Reyes-Gibby, Sanjay Shete, Trude Rakvåg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain: OPRM1 and COMT gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pain (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.pain.2006.10.023"}], "href": "https://doi.org/10.1016/j.pain.2006.10.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17156920"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17156920"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Thomas Kroslak, K Steven Laforge, Robert J Gianotti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The single nucleotide polymorphism A118G alters functional properties of the human mu opioid receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1471-4159.2007.04738.x"}], "href": "https://doi.org/10.1111/j.1471-4159.2007.04738.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17877633"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17877633"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "D Campa, A Gioia, A Tomei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of ABCB1/MDR1 and OPRM1 gene polymorphisms with morphine pain relief."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Pharmacol Ther (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.clpt.6100385"}], "href": "https://doi.org/10.1038/sj.clpt.6100385"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17898703"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17898703"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "David A Nielsen, Vadim Yuferov, Sara Hamon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased OPRM1 DNA methylation in lymphocytes of methadone-maintained former heroin addicts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropsychopharmacology (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/npp.2008.108"}], "href": "https://doi.org/10.1038/npp.2008.108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18650805"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18650805"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Masakazu Hayashida, Makoto Nagashima, Yasuo Satoh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analgesic requirements after major abdominal surgery are associated with OPRM1 gene polymorphism genotype and haplotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharmacogenomics (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2217/14622416.9.11.1605"}], "href": "https://doi.org/10.2217/14622416.9.11.1605"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19018716"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19018716"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Svetlana A Shabalina, Dmitri V Zaykin, Pavel Gris, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expansion of the human mu-opioid receptor gene architecture: novel functional variants."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddn439"}], "href": "https://doi.org/10.1093/hmg/ddn439"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19103668"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19103668"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Carmen Walter, Jörn Lötsch "}, {"type": "b", "children": [{"type": "t", "text": "Meta-analysis of the relevance of the OPRM1 118A>G genetic variant for pain treatment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pain (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.pain.2009.07.013"}], "href": "https://doi.org/10.1016/j.pain.2009.07.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19683391"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19683391"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Frances E Lennon, Tamara Mirzapoiazova, Bolot Mambetsariev, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Mu opioid receptor promotes opioid and growth factor-induced proliferation, migration and Epithelial Mesenchymal Transition (EMT) in human lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0091577"}], "href": "https://doi.org/10.1371/journal.pone.0091577"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24662916"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24662916"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Roger B Fillingim, Lee Kaplan, Roland Staud, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The A118G single nucleotide polymorphism of the mu-opioid receptor gene (OPRM1) is associated with pressure pain sensitivity in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pain (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jpain.2004.11.008"}], "href": "https://doi.org/10.1016/j.jpain.2004.11.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15772909"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15772909"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Tor D Wager, David J Scott, Jon-Kar Zubieta "}, {"type": "b", "children": [{"type": "t", "text": "Placebo effects on human mu-opioid activity during pain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0702413104"}], "href": "https://doi.org/10.1073/pnas.0702413104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17578917"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17578917"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Richard E Harris, Daniel J Clauw, David J Scott, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased central mu-opioid receptor availability in fibromyalgia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.2849-07.2007"}], "href": "https://doi.org/10.1523/JNEUROSCI.2849-07.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17855614"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17855614"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Richard E Harris, Jon-Kar Zubieta, David J Scott, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on mu-opioid receptors (MORs)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuroimage (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuroimage.2009.05.083"}], "href": "https://doi.org/10.1016/j.neuroimage.2009.05.083"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19501658"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19501658"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Baldwin M Way, Shelley E Taylor, Naomi I Eisenberger "}, {"type": "b", "children": [{"type": "t", "text": "Variation in the mu-opioid receptor gene (OPRM1) is associated with dispositional and neural sensitivity to social rejection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0812612106"}], "href": "https://doi.org/10.1073/pnas.0812612106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19706472"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19706472"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "D T Hsu, B J Sanford, K K Meyers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Response of the μ-opioid system to social rejection and acceptance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/mp.2013.96"}], "href": "https://doi.org/10.1038/mp.2013.96"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23958960"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23958960"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Caroline A Davis, Robert D Levitan, Caroline Reid, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dopamine for \"wanting\" and opioids for \"liking\": a comparison of obese adults with and without binge eating."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Obesity (Silver Spring) (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/oby.2009.52"}], "href": "https://doi.org/10.1038/oby.2009.52"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19282821"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19282821"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Biji Mathew, Frances E Lennon, Jessica Siegler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The novel role of the mu opioid receptor in lung cancer progression: a laboratory investigation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anesth Analg (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1213/ANE.0b013e31820568af"}], "href": "https://doi.org/10.1213/ANE.0b013e31820568af"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21156980"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21156980"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Donna A Volpe, Grainne A McMahon Tobin, R Daniel Mellon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Uniform assessment and ranking of opioid μ receptor binding constants for selected opioid drugs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Regul Toxicol Pharmacol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yrtph.2010.12.007"}], "href": "https://doi.org/10.1016/j.yrtph.2010.12.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21215785"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21215785"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Frances E Lennon, Tamara Mirzapoiazova, Bolot Mambetsariev, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of the μ-opioid receptor in human non-small cell lung cancer promotes Akt and mTOR activation, tumor growth, and metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anesthesiology (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/ALN.0b013e31824babe2"}], "href": "https://doi.org/10.1097/ALN.0b013e31824babe2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22343475"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22343475"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Henry K Karlsson, Lauri Tuominen, Jetro J Tuulari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Obesity is associated with decreased μ-opioid but unaltered dopamine D2 receptor availability in the brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.4744-14.2015"}], "href": "https://doi.org/10.1523/JNEUROSCI.4744-14.2015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25740524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25740524"}]}]}]}