{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:47:16Z","timestamp":1791953236126,"version":"4.3.4"},"reference-count":60,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,10,28]]},"abstract":"<jats:p>Neurological disorders such as Alzheimer's disease, Parkinson's disease, and neuroinflammatory conditions involve complex, interconnected mechanisms, including neuroinflammation, oxidative stress, cholinergic dysfunction, and synaptic impairment. The cannabinoid type\u20102 receptor (CB2R), primarily expressed in immune and glial cells, has emerged as a promising therapeutic target due to its role in modulating neuroinflammation and providing neuroprotection without the psychoactive effects associated with CB1R activation. Recent research highlights the potential of dual\u2010acting CB2R ligands that also modulate CB1R, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), offering a multitarget approach to neurological disorders. Although CB1R expression was identified in 1993, significant progress in designing receptor modulators began in the 2000s, with recent focus expanding to autoimmune, metabolic, and cancer\u2010related applications. This review summarizes advances in the design, synthesis, and structure\u2013activity relationships of CB2R\u2010targeting ligands, emphasizing dual\u2010 or multitarget agents with cholinesterase inhibitory activity. Key chemical scaffolds include synthetic cannabinoids, heterocyclic compounds, and hybrid molecules integrating cholinesterase pharmacophores. Molecular docking and in silico studies are discussed to elucidate ligand\u2013receptor interactions, binding modes, and determinants of selectivity. Overall, CB2R\u2010centric dual\u2010acting ligands represent a promising strategy for addressing multifactorial neurological disorders.<\/jats:p>","DOI":"10.1002\/cmdc.70521","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:11:41Z","timestamp":1791951101000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond Single\u2010Target Therapy: Dual\u2010Acting Cannabinoid Type\u20102 Receptor Modulation in Neurological Disorders"],"prefix":"10.1002","volume":"21","author":[{"given":"Sandeep","family":"Bindra","sequence":"first","affiliation":[{"name":"Natural Products and Medicinal Chemistry Division CSIR\u2010Indian Institute of Integrative Medicine  Jammu India"},{"name":"Department of Pharmaceutical Chemistry Amrita School of Pharmacy Amrita Vishwa Vidyapeetham  Kochi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5972-1879","authenticated-orcid":false,"given":"T. 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