The National Institute of Neurological Disorders and Stroke (NINDS) awarded a $675,107 Project Grant under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) to Northeastern University. The grant supports a 5-year research project to design and evaluate novel non-opioid, non-addictive analgesics for treating neuropathic pain. The key objectives are to: 1) synthesize and optimize a series of cannabinoid CB1 receptor allosteric agonist-positive allosteric modulators (CB1 AGO-PAMs) combined with CB2 receptor agonists; 2) conduct in vitro and in vivo studies to characterize the pharmacological properties and drug-like profiles of lead CB1/CB2 AGO-PAM compounds; and 3) evaluate the efficacy of optimized CB1/CB2 AGO-PAMs in suppressing nociception across different neuropathic pain models. The research aims to develop a first-in-class therapeutic strategy utilizing the unique properties of dualsteric ligands to provide effective pain relief without the side effects associated with orthosteric CB1 agonists.
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