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Serotonin 2A receptors (5\u2010HT2AR) have been involved in psychosis and, like Akt kinase, are known to be modulated by THC. Likewise, endocannabinoid system dysregulation has been suggested in schizophrenia. The presence of these molecules in blood makes them interesting targets, as they can be evaluated in patients by a minimally invasive technique. The aim of the present study was to evaluate 5\u2010HT2AR protein expression and the Akt functional status in platelet homogenates of subjects diagnosed with schizophrenia, cannabis use disorder, or both conditions, compared with age\u2010 and sex\u2010matched control subjects. Additionally, endocannabinoids and pro\u2010inflammatory interleukin\u20106 (IL\u20106) levels were also measured in the plasma of these subjects. Results showed that both platelet 5\u2010HT2AR and the active phospho (Ser473)Akt protein expression were significantly increased in schizophrenia subjects, whereas patients with a dual diagnosis of schizophrenia and cannabis use disorder did not show significant changes. Similarly, plasma concentrations of anandamide and other lipid mediators such as PEA and DEA, as well as the pro\u2010inflammatory IL\u20106, were significantly increased in schizophrenia, but not in dual subjects. Results demonstrate that schizophrenia subjects show different circulating markers pattern depending on the associated diagnosis of cannabis use disorder, supporting the hypothesis that there could be different underlying mechanisms that may explain clinical differences among these groups. Moreover, they provide the first preliminary evidence of peripherally measurable molecules of interest for bigger prospective studies in these subpopulations.<\/jats:p>","DOI":"10.1111\/adb.13233","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T15:24:04Z","timestamp":1663169044000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Cannabis use selectively modulates circulating biomarkers in the blood of schizophrenia patients"],"prefix":"10.1111","volume":"27","author":[{"given":"In\u00e9s","family":"Ibarra\u2010Lecue","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of the Basque Country UPV\/EHU  Leioa Bizkaia Spain"},{"name":"Department of Psychiatry, College of Physicians and Surgeons, Columbia University New York and New York State Psychiatric Institute  New York New York USA"},{"name":"New York State Psychiatric Institute  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Unzueta\u2010Larrinaga","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of the Basque Country UPV\/EHU  Leioa Bizkaia Spain"},{"name":"Biocruces Bizkaia Health Research Institute  Barakaldo Bizkaia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"Barrena\u2010Barbadillo","sequence":"additional","affiliation":[{"name":"Department of Nursing University of the Basque Country UPV\/EHU  Leioa Bizkaia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aitor","family":"Villate","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry University of the Basque Country UPV\/EHU  Leioa Bizkaia Spain"},{"name":"PiE\u2010UPV\/EHU, Plentzia Itsas Estazioa  Areatza Pasealekua Plentzia Bizkaia 48620 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Horrillo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of the Basque Country UPV\/EHU  Leioa Bizkaia Spain"},{"name":"Biocruces Bizkaia Health Research Institute  Barakaldo Bizkaia Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"Mendivil","sequence":"additional","affiliation":[{"name":"Uribe Mental Health Center  Osakidetza Bizkaia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Landabaso","sequence":"additional","affiliation":[{"name":"Uribe Mental Health Center  Osakidetza Bizkaia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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