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Preclinical studies have found that pharmacological blockade of cannabinoid receptor 1 leads to reductions in alcohol intake. Furthermore, variations in endocannabinoid metabolism between individuals may be associated with the presence and severity of alcohol use disorder. However, little is known about the acute effects of alcohol on the endocannabinoid system in humans. In this study, we evaluated the effect of acute alcohol administration on circulating endocannabinoid levels by analysing data from two highly\u2010controlled alcohol administration experiments. In the first within\u2010subjects experiment, 47 healthy participants were randomized to receive alcohol and placebo in a counterbalanced order. Alcohol was administered using an intravenous clamping procedure such that each participant attained a nearly identical breath alcohol concentration of 0.05%, maintained over 3\u2009h. In the second experiment, 23 healthy participants self\u2010administered alcohol intravenously; participants had control over their exposure throughout the paradigm. In both experiments, circulating concentrations of two endocannabinoids, N\u2010arachidonoylethanolamine (AEA) and 2\u2010arachidonoylglycerol (2\u2010AG), were measured at baseline and following alcohol exposure. During the intravenous clamping procedure, acute alcohol administration reduced circulating AEA but not 2\u2010AG levels when compared to placebo. This finding was confirmed in the self\u2010administration paradigm, where alcohol reduced AEA levels in an exposure\u2010dependent manner. Future studies should seek to determine whether alcohol administration has similar effects on brain endocannabinoid signalling. An improved understanding of the bidirectional relationship between endocannabinoid signalling and alcohol intake may deepen our understanding of the aetiology and repercussions of alcohol use disorder.<\/jats:p>","DOI":"10.1111\/adb.13197","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T12:28:43Z","timestamp":1656505723000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The effects of acute alcohol administration on circulating endocannabinoid levels in humans"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2172-8802","authenticated-orcid":false,"given":"Matthew E.","family":"Sloan","sequence":"first","affiliation":[{"name":"Addictions Division Centre for Addiction and Mental Health  Toronto Ontario Canada"},{"name":"Division of Neurosciences and Clinical Translation, Department of Psychiatry University of Toronto  Toronto Ontario 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