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However, the majority of studies have been performed in animal models. The aim of the present study was to assess the state of the<jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content><jats:sub>1<\/jats:sub>receptor, the enzymes fatty acid amide hydrolase (<jats:styled-content style=\"fixed-case\">FAAH<\/jats:styled-content>) and monoacylglycerol lipase (<jats:styled-content style=\"fixed-case\">MAGL<\/jats:styled-content>), and the extracellular signal\u2010regulated kinase (<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>) and cyclic\u2010<jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content>response element\u2010binding protein (<jats:styled-content style=\"fixed-case\">CREB<\/jats:styled-content>) in the post\u2010mortem prefrontal cortex of alcoholic subjects. Experiments were performed in samples from 44 subjects classified in four experimental groups: (1) non\u2010suicidal alcoholic subjects (<jats:italic>n<\/jats:italic>\u2009=\u200911); (2) suicidal alcoholic subjects (<jats:italic>n<\/jats:italic>\u2009=\u200911); (3) non\u2010alcoholic suicide victims (<jats:italic>n<\/jats:italic>\u2009=\u200911); and (4) control subjects (<jats:italic>n<\/jats:italic>\u2009=\u200911). We did not observe statistically significant differences in<jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content><jats:sub>1<\/jats:sub><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>relative expression among the four experimental groups. Conversely, our results showed an increase in<jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content><jats:sub>1<\/jats:sub>receptor protein expression in the prefrontal cortex of the suicidal alcoholic group (127.2\u2009\u00b1\u20097.3%), with no changes in functionality with regard to either G protein activation or the inhibition of adenylyl cyclase. In parallel, alcoholic subjects presented lower levels of<jats:styled-content style=\"fixed-case\">MAGL<\/jats:styled-content>activity, regardless of the cause of death. A significant decrease in the active form of<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">CREB<\/jats:styled-content>levels was also observed in both alcoholic groups. Taken together, our data are consistent with a role for the<jats:styled-content style=\"fixed-case\">ECS<\/jats:styled-content>in the neurobiological mechanisms underlying alcoholism. Moreover, the alterations reported here should be of great interest for the therapeutic treatment of this chronic psychiatric disease.<\/jats:p>","DOI":"10.1111\/adb.12160","type":"journal-article","created":{"date-parts":[[2014,7,8]],"date-time":"2014-07-08T08:09:00Z","timestamp":1404806940000},"page":"773-783","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["The endocannabinoid system is altered in the post\u2010mortem prefrontal cortex of alcoholic subjects"],"prefix":"10.1111","volume":"20","author":[{"given":"Amaia M.","family":"Erdozain","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of the Basque Country UPV\/EHU Bizkaia Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Rubio","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Faculty of Medicine Complutense University Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa M.","family":"Valdizan","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM) Madrid Spain"},{"name":"Department of Physiology and Pharmacology Institute of Biomedicine and Biotechnology IBBTEC (Universidad de Cantabria\u2010CSIC\u2010IDICAN) Santander Cantabria Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Pazos","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM) Madrid Spain"},{"name":"Department of Physiology and Pharmacology Institute of Biomedicine and Biotechnology IBBTEC (Universidad de Cantabria\u2010CSIC\u2010IDICAN) Santander Cantabria Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Javier","family":"Meana","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of the Basque Country UPV\/EHU Bizkaia Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM) Madrid Spain"},{"name":"BioCruces Health Research Institute Bizkaia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Fern\u00e1ndez\u2010Ruiz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Faculty of Medicine Complutense University Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Madrid Spain"},{"name":"Instituto Ram\u00f3n y Cajal de Investigaciones Sanitarias (IRYCIS) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P. 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