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This article belongs to the Special Issue Translational Biomarkers in Addictive Disorders., The pharmacological modulation of the cannabinoid receptor 2 (CB2r) has emerged as a promising potential therapeutic option in addiction. The purpose of this review was to determine the functional involvement of CB2r in the effects produced by drugs of abuse at the central nervous system (CNS) level by assessing evidence from preclinical and clinical studies. In rodents, several reports suggest the functional involvement of CB2r in the effects produced by drugs of abuse such as alcohol, cocaine, or nicotine. In addition, the discovery of CB2r in brain areas that are part of the reward system supports the relevance of CB2r in the field of addiction. Interestingly, animal studies support that the CB2r regulates anxiety and depression behavioral traits. Due to its frequent comorbidity with neuropsychiatric disorders, these pharmacological actions may be of great interest in managing SUD. Preliminary clinical trials are focused on exploring the therapeutic potential of modulating CB2r in treating addictive disorders. These promising results support the development of new pharmacological tools regulating the CB2r that may help to increase the therapeutic success in the management of SUD., The preparation of the manuscript was supported by ‘Instituto de Salud Carlos III, Fondos FEDER, Red de Trastornos Adictivos’ (RTA, RD16/0017/0014 to J.M.) and ‘Ministerio de Sanidad, Delegación del Gobierno para el Plan Nacional Sobre Drogas’ (PNSD, 2019I012 to J.M.).

This article belongs to the Special Issue Gut Microbiota and Immunity., Alcohol binge drinking (BD) and poor nutritional habits are two frequent behaviors among many adolescents that alter gut microbiota in a pro-inflammatory direction. Dysbiotic changes in the gut microbiome are observed after alcohol and high-fat diet (HFD) consumption, even before obesity onset. In this study, we investigate the neuroinflammatory response of adolescent BD when combined with a continuous or intermittent HFD and its effects on adult ethanol consumption by using a self-administration (SA) paradigm in mice. The inflammatory biomarkers IL-6 and CX3CL1 were measured in the striatum 24 h after BD, 3 weeks later and after the ethanol (EtOH) SA. Adolescent BD increased alcohol consumption in the oral SA and caused a greater motivation to seek the substance. Likewise, mice with intermittent access to HFD exhibited higher EtOH consumption, while the opposite effect was found in mice with continuous HFD access. Biochemical analyses showed that after BD and three weeks later, striatal levels of IL-6 and CX3CL1 were increased. In addition, in saline-treated mice, CX3CL1 was increased after continuous access to HFD. After oral SA procedure, striatal IL-6 was increased only in animals exposed to BD and HFD. In addition, striatal CX3CL1 levels were increased in all BD- and HFD-exposed groups. Overall, our findings show that adolescent BD and intermittent HFD increase adult alcohol intake and point to neuroinflammation as an important mechanism modulating this interaction., This research was funded by Spanish Ministry of Health, Social Affairs and Equality, Government Delegation for the National Drugs Plan (2018/013 to MRA and PNSD 2016I016 to JMa); Generalitat Valenciana, Conselleria de Educación, Dirección General de Universidades, Grupos de Investigación de excelencia, PROMETEOII/2018/132 to JMi; Ministerio de Economía y Competitividad’ (FIS, PI14/00438) to JMa. Instituto de Salud Carlos III, Red de Trastornos Adictivos (RD16/0017/0007 to JMi) and Unión Europea, Fondos FEDER “una manera de hacer Europa”.