Contextual drug-associated memories precipitate craving and relapse in cocaine users. Such associative memories can be weakened through interference with memory reconsolidation, a process by which memories are maintained following memory retrieval-induced destabilization. We hypothesized that cocaine-memory reconsolidation requires cannabinoid type 1 receptor ( CB1R ) signaling based on the fundamental role of the endocannabinoid system in synaptic plasticity and emotional memory processing. Using an instrumental model of cocaine relapse, we evaluated whether systemic CB1R antagonism ( AM251 ; 3 mg/kg, I.P.) during memory reconsolidation altered (a) subsequent drug context-induced cocaine-seeking behavior, as well as (b) cellular adaptations and (c) excitatory synaptic physiology in the basolateral amygdala ( BLA ) in male Sprague-Dawley rats. Systemic CB1R antagonism – during, but not after, cocaine-memory reconsolidation – reduced drug context-induced cocaine-seeking behavior three days, but not three we...