ObjectiveThe neurobehavioral underpinnings of binge‐eating disorder (BED), co‐occurring with obesity (OB), are largely unknown. This research project conceptualizes BED as a disorder with dysfunctional emotion regulation (ER) linked with changes in central noradrenaline (NA) transmission and NA‐modulated neuronal networks.MethodsWe expect abnormalities in NA activity in both BED and OB, but most pronounced in BED. We expect these abnormalities to be modifiable through state‐of‐the‐art ER intervention, specifically in BED. To assess the role of NA transmission, we will quantify changes in NA transporter (NAT) availability using the highly NAT‐specific [11C]methylreboxetin (MRB) and positron emission tomography‐magnetic resonance imaging (PET‐MRI) that allows measuring molecular and neuronal changes before and after an ER intervention. Individual 12‐session smartphone‐supported acceptance‐based behavioral therapy will be conducted to improve ER. Thirty individuals with OB and BED (OB + BED), 30 individuals with OB without BED (OB ‐ BED), and 20 individuals with normal weight will undergo assessments of NAT availability and neuronal network activity under rest and stimulated conditions, clinical interviews, self‐report questionnaires on eating behavior, ER, mental and physical health, and quality of life, and neuropsychological tests on executive function. Afterwards, in an experimental randomized‐controlled design, individuals with OB + BED and OB ‐ BED will be allocated to smartphone‐supported ER intervention versus a waitlist and re‐assessed after 10 weeks.DiscussionBy obtaining biological and behavioral markers, the proposed study will disentangle the involvement of NAT and the central NA system in the modulation of emotion‐supporting neuronal networks that influence eating behavior. Neurobehavioral mechanisms of change during an ER intervention will be determined.Trial RegistrationGerman Clinical Trials Register (DRKS): DRKS00029367.Public SignificanceThis study investigates the central noradrenaline system by using hybrid brain imaging in conjunction with emotion regulation as a putative core biological mechanism in individuals with obesity with or without binge‐eating disorder that is targeted by emotion regulation intervention. The results will provide a molecular signature beyond functional imaging biomarkers as a predictive biomarker toward precision medicine for tailoring treatments for individuals with binge‐eating disorders and obesity.