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While many have studied genetic risk associated with drinking patterns, comprehensive studies identifying dynamic responses to pharmacologic and psychological\/placebo effects underlying binge drinking are lacking. We investigated transcriptome-wide response to binge, medium, and placebo alcohol consumption by 17 healthy heavy social drinkers enrolled in a controlled, in-house, longitudinal study of up to 12\u00a0days. Using RNA-seq, we identified 251 and 13 differentially expressed genes (DEGs) in response to binge drinking and placebo, respectively. Eleven protein-coding DEGs had very large effect sizes in response to binge drinking (Cohen\u2019s d\u2009&gt;\u20091). Furthermore, binge dose significantly impacted the\n                    <jats:italic>Cytokine-cytokine receptor interaction pathway<\/jats:italic>\n                    (KEGG: hsa04060) across all experimental sequences. Placebo also impacted hsa04060, but only when administered following regular alcohol drinking sessions. Similarly, medium-dose and placebo commonly impacted KEGG pathways of\n                    <jats:italic>Systemic lupus erythematosus<\/jats:italic>\n                    ,\n                    <jats:italic>Neutrophil extracellular trap formation<\/jats:italic>\n                    , and\n                    <jats:italic>Alcoholism<\/jats:italic>\n                    based on the sequence of drinking sessions. These findings together indicate the \u201cdose-extending effects\u201d of placebo at a molecular level. Furthermore, besides supporting alcohol dose-specific molecular changes, results suggest that the placebo effects may induce molecular responses within the same pathways regulated by alcohol.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-56900-x","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T07:02:11Z","timestamp":1715324531000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Peripheral blood transcriptomic profiling of molecular mechanisms commonly regulated by binge drinking and placebo effects"],"prefix":"10.1038","volume":"14","author":[{"given":"Amol Carl","family":"Shetty","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Sivinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Cornell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"McCracken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Sadzewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anup","family":"Mahurkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing-Qun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana","family":"Colloca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nageswara","family":"Pilli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen A.","family":"Kane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chamindi","family":"Seneviratne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,10]]},"reference":[{"key":"56900_CR1","unstructured":"https:\/\/www.niaaa.nih.gov\/alcohols-effects-health\/alcohol-topics\/alcohol-facts-and-statistics."},{"key":"56900_CR2","unstructured":"Molina, P. 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