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Selective agents including agonists, antagonists, inverse agonists, and novel allosteric modulators targeting either CB1 or CB2 have been developed to inhibit or augment their basal tone. As a result, the role these receptors play in human physiology and their potential therapeutic applications in disease states are being elucidated. The CB1 receptor, although ubiquitous, is densely expressed in the brain, and CB2 is largely found on cells of immune origin. This minireview highlights the role of CB1 in excitotoxic assaults in the brain and its potential to limit addiction liability. In addition, it will examine the relationship between receptor activity and stimulation of insulin release from pancreatic \u03b2-cells, insulin resistance, and feeding behavior leading toward obesity. The roles of CB2 in the neuropathology of amyotrophic lateral sclerosis and in the central manifestations of chronic HIV infection potentially converge at inflammatory cell activation, thereby providing an opportunity for intervention. Last, CB2 modulation is discussed in the context of an experimental model of postmenopausal osteoporosis. Achieving exquisite receptor selectivity and elucidating the mechanisms underlying receptor inhibition and activation will be essential for the development of the next generation of cannabinergic-based therapeutic agents.<\/jats:p>","DOI":"10.1210\/me.2015-1062","type":"journal-article","created":{"date-parts":[[2015,4,13]],"date-time":"2015-04-13T17:44:06Z","timestamp":1428947046000},"page":"801-813","source":"Crossref","is-referenced-by-count":48,"title":["Minireview: From the Bench, Toward the Clinic: Therapeutic Opportunities for Cannabinoid Receptor Modulation"],"prefix":"10.1210","volume":"29","author":[{"given":"Robert P.","family":"Picone","sequence":"first","affiliation":[{"name":"Clinical Development (R.P.P.), Medical and Regulatory Affairs, Novo Nordisk Inc, Plainsboro, New Jersey 08536"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra A.","family":"Kendall","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences (D.A.K.), 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