The majority of pharmaceutical drugs on the market target G protein coupled receptor (GPCRs); however, GPCR signaling and regulation adapt in response to environmental stimuli. One GPCR gaining attention due to the increasing legalization of cannabis is the cannabinoid 1 receptor (CB1R). Cannabis legalization is leading to increased use to treat pain and other ailments, including pain caused by inflammation. Studies presented throughout this dissertation investigate adaptations in synaptic CB1R suppression of GABA release after persistent inflammation induced by Complete Freund?s Adjuvant (CFA).