{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T08:20:56Z","timestamp":1779178856991,"version":"3.51.4"},"reference-count":74,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:00:00Z","timestamp":1632960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Ghrelin may influence several alcohol\u2010related behaviors in animals and humans by modulating central and\/or peripheral biological pathways. The aim of this exploratory analysis was to investigate associations between ghrelin administration and the human circulating metabolome during alcohol exposure in nontreatment seeking, heavy drinking individuals with alcohol use disorder (AUD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used serum samples from a randomized, crossover, double\u2010blind, placebo\u2010controlled human laboratory study with intravenous (IV) ghrelin or placebo infusion in two experiments. During each session, participants received a loading dose (3\u00a0<jats:italic>\u00b5<\/jats:italic>g\/kg) followed by continuous infusion (16.9\u00a0ng\/kg\/min) of acyl ghrelin or placebo. The first experiment included an IV alcohol self\u2010administration (IV\u2010ASA) session and the second experiment included an IV alcohol clamp (IV\u2010AC) session, both with the counterbalanced infusion of ghrelin or placebo. Serum metabolite profiles were analyzed from repeated blood samples collected during each session.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In both experiments, ghrelin infusion was associated with an altered serum metabolite profile, including significantly increased levels of cortisol (IV\u2010ASA <jats:italic>q<\/jats:italic>\u2010value\u00a0=\u00a00.0003 and IV\u2010AC <jats:italic>q<\/jats:italic>\u00a0&lt;\u00a00.0001), corticosterone (IV\u2010ASA <jats:italic>q<\/jats:italic>\u00a0=\u00a00.0202 and IV\u2010AC <jats:italic>q<\/jats:italic>\u00a0&lt;\u00a00.0001), and glycochenodeoxycholic acid (IV\u2010ASA <jats:italic>q<\/jats:italic>\u00a0=\u00a00.0375 and IV\u2010AC <jats:italic>q<\/jats:italic>\u00a0=\u00a00.0013). In the IV\u2010ASA experiment, ghrelin infusion increased levels of cortisone (<jats:italic>q<\/jats:italic>\u00a0=\u00a00.0352) and fatty acids 18:1 (<jats:italic>q<\/jats:italic>\u00a0=\u00a00.0406) and 18:3 (<jats:italic>q<\/jats:italic>\u00a0=\u00a00.0320). Moreover, in the IV\u2010AC experiment, ghrelin infusion significantly increased levels of glycocholic acid (<jats:italic>q<\/jats:italic>\u00a0&lt;\u00a00.0001) and phenylalanine (<jats:italic>q<\/jats:italic>\u00a0=\u00a00.0458).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>IV ghrelin infusion, combined with IV alcohol administration, was associated with increases in the circulating metabolite levels of corticosteroids and glycine\u2010conjugated bile acids, among other changes. Further research is needed to understand the role that metabolomic changes play in the complex interaction between ghrelin and alcohol.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14719","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T08:37:55Z","timestamp":1632991075000},"page":"2207-2216","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effect of intravenous ghrelin administration, combined with alcohol, on circulating metabolome in heavy drinking individuals with alcohol use disorder"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0825-4956","authenticated-orcid":false,"given":"Olli","family":"K\u00e4rkk\u00e4inen","sequence":"first","affiliation":[{"name":"School of Pharmacy University of Eastern Finland Kuopio Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0902-4212","authenticated-orcid":false,"given":"Mehdi","family":"Farokhnia","sequence":"additional","affiliation":[{"name":"Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section Translational Addiction Medicine Branch National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research Baltimore and Bethesda Maryland USA"},{"name":"Department of Mental Health Johns Hopkins Bloomberg School of Public Health Johns Hopkins University Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton","family":"Kl\u00e5vus","sequence":"additional","affiliation":[{"name":"Institute of Public Health and Clinical Nutrition University of Eastern Finland Kuopio Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seppo","family":"Auriola","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Eastern Finland Kuopio Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marko","family":"Lehtonen","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Eastern Finland Kuopio Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara L.","family":"Deschaine","sequence":"additional","affiliation":[{"name":"Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section Translational Addiction Medicine Branch National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research Baltimore and Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daria","family":"Piacentino","sequence":"additional","affiliation":[{"name":"Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section Translational Addiction Medicine Branch National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research Baltimore and Bethesda Maryland USA"},{"name":"Center on Compulsive Behaviors National Institutes of Health Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly M.","family":"Abshire","sequence":"additional","affiliation":[{"name":"Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section Translational Addiction Medicine Branch National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research Baltimore and Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelley N.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Translational Analytical Core National Institute on Drug Abuse Intramural Research Program Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7284-8754","authenticated-orcid":false,"given":"Lorenzo","family":"Leggio","sequence":"additional","affiliation":[{"name":"Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section Translational Addiction Medicine Branch National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research Baltimore and Bethesda Maryland USA"},{"name":"Center on Compulsive Behaviors National Institutes of Health Bethesda Maryland USA"},{"name":"Translational Analytical Core National Institute on Drug Abuse Intramural Research Program Baltimore Maryland USA"},{"name":"Medication Development Program National Institute on Drug Abuse Intramural Research Program National Institutes of Health Baltimore Maryland USA"},{"name":"Center for Alcohol and Addiction Studies Department of Behavioral and Social Sciences Brown University Providence Rhode Island USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,9,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29867"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2006.00238.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ALC.0000087581.13912.64"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000054680"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-018-0099-1"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00115.2004"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v067.i01"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12665"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.01.037"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2008.06.022"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-018-1367-3"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.06.012"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874467208666150817111419"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M017368"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/stresses1010003"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyab004"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2019.02.008"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.226"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(90)90308-Y"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40519-018-0599-6"},{"key":"e_1_2_8_22_1","first-page":"1245","article-title":"Effect of ghrelin on serum metabolites in Alzheimer\u2019s disease model rats; a metabolomics studies based on 1H\u2010NMR technique","volume":"21","author":"Goshadrou F.","year":"2018","journal-title":"Iranian Journal of Basic Medical Sciences"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(97)00071-5"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.7b04424"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2019.107711"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2018.05.010"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12373"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0196850"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2mb25073j"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2013.55"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15030"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.14485"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.13035"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.21049"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)41573-1"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)38103-6"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2002.tb02611.x"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2011.26"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo10040135"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2011.11.005"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-019-0280-9"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2018.03.007"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v082.i13"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0064-y"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0000000000000616"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1369-1600.2010.00308.x"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2014.03.019"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2018.02.004"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-2638"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr100885w"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.03.007"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)02550-0"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-1593"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2017.00617"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.13781"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2016.10.016"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2005.04.025"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2012.01885.x"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agx022"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2010.03886.x"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12280"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom7010016"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-007-0082-2"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.060426"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25811"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201901433R"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3393"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0531-2"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.2337\/db08-0025"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agz030"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1089"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyw175"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.irn.2017.08.002"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.14334"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-28720-6_149"}],"container-title":["Alcoholism: Clinical and Experimental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acer.14719","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acer.14719","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acer.14719","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T06:02:27Z","timestamp":1693202547000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acer.14719"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,30]]},"references-count":74,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1111\/acer.14719"],"URL":"https:\/\/doi.org\/10.1111\/acer.14719","archive":["Portico"],"relation":{},"ISSN":["0145-6008","1530-0277"],"issn-type":[{"value":"0145-6008","type":"print"},{"value":"1530-0277","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,30]]},"assertion":[{"value":"2021-06-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}