{"doi":"10.3389/fpsyt.2023.1171959","title":"Editorial: Unravelling the role of CB2r in neuropsychiatric diseases","abstract":"expressed in immune cells was challenged, as many studies now indicate neuronal, glial, and endothelial cells expression of CB2Rs beyond immuno-cannabinoid activity (1,(3)(4)(5). Thus, neuroinflammation, an indicator and modulator of neurodegeneration is emerging as a key component underlying the effects of CB2Rs that are associated with immune responses.Therefore, CB2Rs could be considered as targets for the reduction of neuroinflammatory processes for the reduction of M1 neurotoxic state and induction of M2 neuroprotective state (9).While there exists some controversy, ambiguity and lingering debate about functional neuronal expression of CB2Rs, a number of studies demonstrate that CB2Rs are expressed at low basal levels in the CNS, but that they are dynamic, inducible and can be upregulated in neuropsychiatric and neurological disorders (2,3,7). This provides a potential role of CB2Rs in neuropsychiatric and neurodegenerative disorder, as CB1R ligands are associated with CNS side effects. Moreover progress in the treatment of neuropsychiatric disorders have been limited, but novel approaches in genetic and epigenetic techniques with imaging of signaling in brain circuits are contributing to unraveling new biomarkers and therapeutic targets for neuropsychiatric disorders. The concerns and probable limitations for the use of CB2R ligands in neuropsychiatric disorders could be associated with peripheral side effects where they are expressed abundantly. However, it is noteworthy that the determination of CB1R and CB2R crystal structures, along with the quantum and chemometric methods to construct partial least squares model may be used to design and generate compounds binding to both CB1R and CB2R in a therapeutic way without psychoactivity (8). This is a special research topic and contributions of studies, \"Unraveling the role of CB2r in neuropsychiatric diseases\". Advances on the role of CB2Rs in preclinical and clinical research studies is presented, including two review articles and three clinical research studies, focusing not only on CB1Rs and CB2Rs, but also on the components of the eCBome studies in neurodegenerative and neuropsychiatric diseases. The shifting landscape and increasing new knowledge on cannabis/cannabinoid medicalization and recreational use provided an opportunity for Ishiguro et al, to review and summarize the potential role of CB2Rs in neuropsychiatric and neurodegenerative disorders. The review focused on CB2Rs that presents therapeutic advantages over the CB1Rs that is associated with a number of physiological effects, including psycho-activity that limits their use. The initial excitement of targeting CB1R antagonist as an anti-obesity drug was withdrawn, due to severe side effects, including suicides. In their review, Morcuende et al, The significant progress and advances in the expanded ECS, the eCBome is unraveling the molecular basis not only of the CNR2 genomic structure, its polymorphic nature, sub-type specificity, and variations (SNPs and CNVs) but also of the components of eCBome. This offers opportunities for continued studies and clinical trials targeting microbiome and elements of eCBome crosstalk that is revealing a bidirectional gut-brain communication in neuropsychiatric disease.","journal":"Frontiers in Psychiatry","year":2023,"id":394332,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9504,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":414617,"name":"Emmanuel S. Onaivi","orcid":"0000-0002-7561-8927","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-19T01:19:10.334330Z","pmid":"37020728","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}