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https://www.readbyqxmd.com/read/28409564/predictors-of-naltrexone-response-in-a-randomized-trial-reward-related-brain-activation-oprm1-genotype-and-smoking-status
#1
Joseph P Schacht, Patrick K Randall, Patricia K Latham, Konstantin E Voronin, Sarah W Book, Hugh Myrick, Raymond F Anton
Naltrexone reduces drinking among individuals with alcohol use disorders (AUDs), but is not effective for everyone. Variability in its effects on reward-related brain activation, genetic variation, and/or cigarette smoking may account for this mixed response profile. This randomized clinical trial tested naltrexone's effects on drinking and alcohol cue-elicited brain activation, evaluated whether OPRM1 A118G genotype or smoking moderated these effects, and explored whether medication effects on cue-elicited activation predicted subsequent drinking...
April 14, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28398354/global-genetic-variation-of-select-opiate-metabolism-genes-in-self-reported-healthy-individuals
#2
F R Wendt, G Pathak, A Sajantila, R Chakraborty, B Budowle
CYP2D6 is a key pharmacogene encoding an enzyme impacting poor, intermediate, extensive and ultrarapid phase I metabolism of many marketed drugs. The pharmacogenetics of opiate drug metabolism is particularly interesting due to the relatively high incidence of addiction and overdose. Recently, trans-acting opiate metabolism and analgesic response enzymes (UGT2B7, ABCB1, OPRM1 and COMT) have been incorporated into pharmacogenetic studies to generate more comprehensive metabolic profiles of patients. With use of massively parallel sequencing, it is possible to identify additional polymorphisms that fine tune, or redefine, previous pharmacogenetic findings, which typically rely on targeted approaches...
April 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28379874/effects-of-single-nucleotide-polymorphisms-on-surgical-and-post-surgical-opioid-requirements-a-systematic-review-and-meta-analysis
#3
Siu-Wai Choi, David M H Lam, Stanley S C Wong, Haydn H C Shiu, Amy X M Wang, Chi-Wai Cheung
OBJECTIVES: There is great heterogeneity in the way individuals respond to medications. Inherited differences, such as Single Nucleotide Polymorphisms (SNP), can influence the efficacy and toxicity of drugs. This meta-analysis aims to collate data from studies investigating the effect of SNPs on post-operative and/or intra-operative opioid requirements. METHODS: This meta-analysis was conducted following PRISMA guidelines. Eligibility criteria for studies in this meta-analysis were reporting amount of post-operative and/or intra-operative opioid used as the primary outcome and genotyping patients for SNPs in one of the following genes; OPRM1, CYP2D6, CYP3A4, CYP3A5, COMT, UGT2B7 or ABCB1...
April 4, 2017: Clinical Journal of Pain
https://www.readbyqxmd.com/read/28376280/independent-and-interactive-effects-of-oprm1-and-dat1-polymorphisms-on-alcohol-consumption-and-subjective-responses-in-social-drinkers
#4
Elise M Weerts, Gary S Wand, Brion Maher, Xiaoqiang Xu, Mary Ann Stephens, Xiaoju Yang, Mary E McCaul
BACKGROUND: The current study examined independent and interactive effects of polymorphisms of the mu opioid receptor gene (OPRM1, A118G) and variable number tandem repeats of the dopamine transporter gene (DAT1, SLC6A3) on alcohol consumption and subjective responses to alcohol in 127 young, healthy, social drinkers. METHODS: Participants completed an in-person assessment, which included self-reported alcohol drinking patterns and blood sampling for DNA, and in a second visit, a cumulative alcohol dosing procedure with subjective ratings across multiple time points and breath alcohol concentrations (0...
April 4, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28349993/cannabinoid-receptor-type-1-and-mu-opioid-receptor-polymorphisms-are-associated-with-cyclic-vomiting-syndrome
#5
Andrzej Wasilewski, Urszula Lewandowska, Paula Mosinska, Cezary Watala, Martin Storr, Jakub Fichna, Thangam Venkatesan
OBJECTIVES: Cyclic vomiting syndrome (CVS) is a disorder defined by recurrent, unexplained episodes of severe nausea and vomiting. Our aim was to investigate whether CVS and pathophysiological mechanisms underlying this condition are associated with selected variations in genes encoding the components of the endogenous cannabinoid and opioid systems. METHODS: This case-control study included 65 patients with CVS-16 male and 49 female, and 1,092 healthy controls-525 male and 567 female from the 1000 Genomes Project...
March 28, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28346387/oprm1-c-118a-g-polymorphism-and-duration-of-morphine-treatment-associated-with-morphine-doses-and-quality-of-life-in-palliative-cancer-pain-settings
#6
Aline Hajj, Lucine Halepian, Nada El Osta, Georges Chahine, Joseph Kattan, Lydia Rabbaa Khabbaz
Despite increased attention on assessment and management, pain remains the most persistent symptom in patients with cancer, in particular in end-of-life settings, with detrimental impact on their quality-of-life (QOL). We conducted this study to evaluate the added value of determining some genetic and non-genetic factors to optimize cancer pain treatment. Eighty-nine patients were included in the study for the evaluation of palliative cancer pain management. The regression analysis showed that age, OPRM1 single nucleotide polymorphism (SNP), as well as the duration of morphine treatment were significantly associated with morphine doses at 24 h (given by infusion pump; p = 0...
March 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28343361/genetic-dissociation-of-morphine-analgesia-from-hyperalgesia-in-mice
#7
Gina F Marrone, Valerie Le Rouzic, Andras Varadi, Jin Xu, Anjali M Rajadhyaksha, Susruta Majumdar, Ying-Xian Pan, Gavril W Pasternak
RATIONALE: Morphine is the prototypic mu opioid, producing its analgesic actions through traditional 7 transmembrane domain (7TM) G-protein-coupled receptors generated by the mu opioid receptor gene (Oprm1). However, the Oprm1 gene undergoes extensive alternative splicing to yield three structurally distinct sets of splice variants. In addition to the full-length 7TM receptors, it produces a set of truncated variants comprised of only 6 transmembrane domains (6TM). OBJECTIVES: This study explored the relative contributions of 7TM and 6TM variants in a range of morphine actions...
March 25, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28339912/pharmacogenomics-and-patient-treatment-parameters-to-opioid-treatment-in-chronic-pain-a-focus-on-morphine-oxycodone-tramadol-and-fentanyl
#8
Renae A Lloyd, Elizabeth Hotham, Catherine Hall, Marie Williams, Vijayaprakash Suppiah
Objective. : Opioids are one of the most commonly prescribed medicines for chronic pain. However, their use for chronic pain has been controversial. The objective of this literature review was to identify the role of genetic polymorphisms on patient treatment parameters (opioid dose requirements, response, and adverse effects) for opioids used in malignant and nonmalignant chronic pain. The opioids that this review focuses on are codeine, morphine, oxycodone, tramadol, and fentanyl...
February 24, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28320034/variations-in-infant-cyp2b6-genotype-associated-with-the-need-for-pharmacological-treatment-for-neonatal-abstinence-syndrome-in-infants-of-methadone-maintained-opioid-dependent-mothers
#9
Helen Mactier, Poppy McLaughlin, Cheryl Gillis, Michael David Osselton
Background Neonatal abstinence syndrome (NAS) in infants of methadone-maintained opioid-dependent (MMOD) mothers cannot be predicted in individual cases. We investigated whether variation in infant genotype is associated with severity of NAS. Methods This is a pilot observational cohort study of 21 MMOD mothers and their newborns. Infant buccal swabs were obtained soon after delivery, together with a maternal blood sample for the determination of maternal plasma methadone concentration. Genomic variation in five opioid-related genes (ABCB1, COMT, CYP2B6, CYP2D6, and OPRM1) was ascertained from infant buccal swabs and related to need for pharmacological treatment of NAS...
March 20, 2017: American Journal of Perinatology
https://www.readbyqxmd.com/read/28319053/alternatively-spliced-mu-opioid-receptor-c-termini-impact-the-diverse-actions-of-morphine
#10
Jin Xu, Zhigang Lu, Ankita Narayan, Valerie P Le Rouzic, Mingming Xu, Amanda Hunkele, Taylor G Brown, William F Hoefer, Grace C Rossi, Richard C Rice, Arlene Martínez-Rivera, Anjali M Rajadhyaksha, Luca Cartegni, Daniel L Bassoni, Gavril W Pasternak, Ying-Xian Pan
Extensive 3' alternative splicing of the mu opioid receptor gene OPRM1 creates multiple C-terminal splice variants. However, their behavioral relevance remains unknown. The present study generated 3 mutant mouse models with truncated C termini in 2 different mouse strains, C57BL/6J (B6) and 129/SvEv (129). One mouse truncated all C termini downstream of Oprm1 exon 3 (mE3M mice), while the other two selectively truncated C-terminal tails encoded by either exon 4 (mE4M mice) or exon 7 (mE7M mice). Studies of these mice revealed divergent roles for the C termini in morphine-induced behaviors, highlighting the importance of C-terminal variants in complex morphine actions...
April 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28282362/gene-to-gene-interactions-regulate-endogenous-pain-modulation-in-fibromyalgia-patients-and-healthy-controls-antagonistic-effects-between-opioid-and-serotonin-related-genes
#11
Jeanette Tour, Monika Löfgren, Kaisa Mannerkorpi, Björn Gerdle, Anette Larsson, Annie Palstam, Indre Bileviciute-Ljungar, Jan Bjersing, Martin Ingvar, Malin Ernberg, Martin Schalling, Eva Kosek
Chronic pain is associated with dysfunctional endogenous pain modulation, involving both central opioid and serotonergic (5-HT) signaling. Fibromyalgia (FM) is a chronic pain syndrome, characterized by widespread musculoskeletal pain and reduced exercise-induced hypoalgesia (EIH). In this study, we assessed the effects of three functional genetic polymorphisms on EIH in 130 patients with FM and 132 healthy controls (HC). Subjects were genotyped regarding the mu-opioid receptor (OPRM1) gene (rs1799971), the serotonin transporter (5-HTT) gene (5-HTTLPR/rs25531) and the serotonin-1a receptor (5-HT1a) gene (rs6296)...
March 7, 2017: Pain
https://www.readbyqxmd.com/read/28273335/a-cis-eqtl-in-oprm1-is-associated-with-subjective-response-to-alcohol-and-alcohol-use
#12
Jacqueline M Otto, Ian R Gizer, Joseph D Deak, Kimberly A Fleming, Bruce D Bartholow
BACKGROUND: A functional polymorphism within the μ-opioid receptor (OPRM1) gene, rs1799971 (A118G), previously has been associated with measures of alcohol use and sensitivity to its effects, but findings have been inconclusive. A recent study suggested that a second nearby variant within OPRM1, rs3778150, is robustly associated with heroin dependence and fully explained a smaller observed association with rs1799971. Given evidence that the rs3778150-C allele is associated with decreased OPRM1 expression levels in the human brain, the current study sought to test the hypothesis that rs3778150 represents a causal variant within OPRM1 that increases risk for a variety of alcohol use phenotypes...
May 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28267064/nerve-injury-induced-epigenetic-silencing-of-opioid-receptors-controlled-by-dnmt3a-in-primary-afferent-neurons
#13
Linlin Sun, Jian-Yuan Zhao, Xiyao Gu, Lingli Liang, Shaogen Wu, Kai Mo, Jian Feng, Weixiang Guo, Jun Zhang, Alex Bekker, Xinyu Zhao, Eric J Nestler, Yuan-Xiang Tao
Opioids are the gold standard for pharmacological treatment of neuropathic pain, but their analgesic effects are unsatisfactory in part due to nerve injury-induced downregulation of opioid receptors in dorsal root ganglia (DRG) neurons. How nerve injury drives such downregulation remains elusive. DNA methyltransferase (DNMT)-triggered DNA methylation represses gene expression. We show here that blocking the nerve injury-induced increase in DRG DNMT3a (a de novo DNMT) rescued the expression of Oprm1 and Oprk1 mRNAs and their respective encoding mu-opioid receptor (MOR) and kappa-opioid receptor (KOR) proteins in the injured DRG...
March 4, 2017: Pain
https://www.readbyqxmd.com/read/28194850/cannabidiol-reduces-ethanol-consumption-motivation-and-relapse-in-mice
#14
Adrián Viudez-Martínez, María S García-Gutiérrez, Carmen María Navarrón, María Isabel Morales-Calero, Francisco Navarrete, Ana Isabel Torres-Suárez, Jorge Manzanares
This study evaluated the effects of cannabidiol (CBD) on ethanol reinforcement, motivation and relapse in C57BL/6 J mice. The effects of CBD (60 mg/kg, i.p.) on blood ethanol concentration, hypothermia and handling-induced convulsions associated to acute ethanol administration were evaluated. The two-bottle choice paradigm was performed to assess the effects of CBD (30, 60 and 120 mg/kg/day, i.p.) on ethanol intake and preference. In addition, an oral ethanol self-administration experiment was carried out to evaluate the effects of CBD [a single s...
February 13, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28188737/genetic-variation-in-the-behavioral-effects-of-buprenorphine-in-female-mice-derived-from-a-murine-model-of-the-oprm1-a118g-polymorphism
#15
Caroline A Browne, Rebecca L Erickson, Julie A Blendy, Irwin Lucki
Pharmacogenetic studies have identified the non-synonymous single nucleotide polymorphism (A118G) in the human mu opioid receptor (MOR) gene (OPRM1) as a critical genetic variant capable of altering the efficacy of opioid therapeutics. To date few studies have explored the potential impact of the OPRM1 A118G polymorphism on the pharmacological effects of buprenorphine (BPN), a potent MOR partial agonist and kappa opioid receptor antagonist, which is approved by the FDA for the treatment of opioid addiction and chronic pain...
May 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28185645/mu-opioid-receptors-in-gamma-aminobutyric-acidergic-forebrain-neurons-moderate-motivation-for-heroin-and-palatable-food
#16
Pauline Charbogne, Olivier Gardon, Elena Martín-García, Helen L Keyworth, Aya Matsui, Anna E Mechling, Thomas Bienert, Taufiq Nasseef, Anne Robé, Luc Moquin, Emmanuel Darcq, Sami Ben Hamida, Patricia Robledo, Audrey Matifas, Katia Befort, Claire Gavériaux-Ruff, Laura-Adela Harsan, Dominik von Elverfeldt, Jurgen Hennig, Alain Gratton, Ian Kitchen, Alexis Bailey, Veronica A Alvarez, Rafael Maldonado, Brigitte L Kieffer
BACKGROUND: Mu opioid receptors (MORs) are central to pain control, drug reward, and addictive behaviors, but underlying circuit mechanisms have been poorly explored by genetic approaches. Here we investigate the contribution of MORs expressed in gamma-aminobutyric acidergic forebrain neurons to major biological effects of opiates, and also challenge the canonical disinhibition model of opiate reward. METHODS: We used Dlx5/6-mediated recombination to create conditional Oprm1 mice in gamma-aminobutyric acidergic forebrain neurons...
May 1, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28121474/elevated-levels-of-dna-methylation-at-the-oprm1-promoter-region-in-men-with-opioid-use-disorder
#17
Ghasem Ebrahimi, Gholamreza Asadikaram, Hamed Akbari, Mohammad Hadi Nematollahi, Moslem Abolhassani, Gholamabbas Shahabinejad, Leyla Khodadadnejad, Mohammad Hashemi
BACKGROUND: The mu-opioid receptor, encoded by mu-opioid receptor gene (OPRM1), has an important role in the development of addiction to opioids. Its aberrant reduction on the cell membrane is responsible, at least in part, for tolerance and physical dependence. OBJECTIVES: The present study was designed to identify the relationship between opium consumption and epigenetic mechanisms involved in opium addiction. METHODS: Genomic DNA was extracted from the peripheral blood of 66 men with opium use disorder and 57 healthy men as a control group...
January 25, 2017: American Journal of Drug and Alcohol Abuse
https://www.readbyqxmd.com/read/28115739/genome-wide-association-study-of-therapeutic-opioid-dosing-identifies-a-novel-locus-upstream-of-oprm1
#18
A H Smith, K P Jensen, J Li, Y Nunez, L A Farrer, H Hakonarson, S D Cook-Sather, H R Kranzler, J Gelernter
Opioids are very effective analgesics, but they are also highly addictive. Methadone is used to treat opioid dependence (OD), acting as a selective agonist at the μ-opioid receptor encoded by the gene OPRM1. Determining the optimal methadone maintenance dose is time consuming; currently, no biomarkers are available to guide treatment. In methadone-treated OD subjects drawn from a case and control sample, we conducted a genome-wide association study of usual daily methadone dose. In African-American (AA) OD subjects (n=383), we identified a genome-wide significant association between therapeutic methadone dose (mean=68...
March 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28097908/common-and-specific-genes-and-peripheral-biomarkers-in-children-and-adults-with-attention-deficit-hyperactivity-disorder
#19
Cristian Bonvicini, Stephen V Faraone, Catia Scassellati
OBJECTIVES: Elucidating the biological mechanisms involved in Attention-deficit/hyperactivity disorder (ADHD) has been challenging. Relatively unexplored is the fact that these mechanisms can differ with age. METHODS: We present an overview on the major differences between children and adults with ADHD, describing several studies from genomics to metabolomics performed in ADHD children and in adults. A systematic search (up until February, 2016) was conducted. RESULTS: From a PRISMA flow-chart, a total of eligibility 350 studies from genomics and metabolomics were found for cADHD and 91 for aADHD...
January 18, 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28092646/ex-vivo-nonviral-gene-delivery-of-%C3%AE-opioid-receptor-to-attenuate-cancer-induced-pain
#20
Seiichi Yamano, Chi T Viet, Dongmin Dang, Jisen Dai, Shigeru Hanatani, Tadahiro Takayama, Hironori Kasai, Kentaro Imamura, Ron Campbell, Yi Ye, John C Dolan, William Myung Kwon, Stefan D Schneider, Brian L Schmidt
Virus-mediated gene delivery shows promise for the treatment of chronic pain. However, viral vectors have cytotoxicity. To avoid toxicities and limitations of virus-mediated gene delivery, we developed a novel nonviral hybrid vector: HIV-1 Tat peptide sequence modified with histidine and cysteine residues combined with a cationic lipid. The vector has high transfection efficiency with little cytotoxicity in cancer cell lines including HSC-3 (human tongue squamous cell carcinoma) and exhibits differential expression in HSC-3 (∼45-fold) relative to HGF-1 (human gingival fibroblasts) cells...
February 2017: Pain
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