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Considering olfactory dysfunction as outcome of altered, damaged and\/or inefficient olfactory processing, in the current review, we analyze how olfactory processing interacts with the endocannabinoid signaling system. In the human body, endocannabinoid synthesis is a natural and on\u2010demand response to a wide range of physiological and environmental stimuli. Our current understanding of the response dynamics of the endocannabinoid system is based in large part on research advances in limbic system areas, such as the hippocampus and the amygdala. Functional interactions of this signaling system with olfactory processing and associated pathways are just emerging but appear to grow rapidly with multidimensional approaches. Recent work analyzing the crystal structure of endocannabinoid receptors bound to their agonists in a signaling complex has opened avenues for developing specific therapeutic drugs that could help with neuroinflammation, neurodegeneration, and alleviation\/reduction of pain. We discuss the role of endocannabinoids as signaling molecules in the olfactory system and the relevance of the endocannabinoid system for synaptic plasticity.<\/jats:p>","DOI":"10.1111\/ejn.15186","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T08:23:40Z","timestamp":1615883020000},"page":"1002-1014","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Endocannabinoid\u2010mediated neuromodulation in the main olfactory bulb at the interface of environmental stimuli and central neural processing"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4347-2131","authenticated-orcid":false,"given":"Thomas","family":"Heinbockel","sequence":"first","affiliation":[{"name":"Department of Anatomy Howard University College of Medicine  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naina","family":"Bhatia\u2010Dey","sequence":"additional","affiliation":[{"name":"Department of Anatomy Howard University College of Medicine  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vonnie D. 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