The purpose of this open-label, pilot study is to evaluate fMRI as a biomarker of opioid antagonism in adolescents with ED. Modulation of brain activation will be examined in regions of interest by fMRI using a food-specific and general reward task in adolescents with ED in a pre/post design.

This is an open-label, interventional trial to evaluate reward system modulation (detected by neuroimaging) in response to opioid antagonism (i.e., naltrexone) in adolescents aged 13-21 years with an eating disorder characterized by the target behaviors of binge eating and/or purging (e.g., AN-BP, BN, BED). A pre/post design completed on the same day will be employed to quantify within-individual change while reducing potential confounding due to known neuroimaging variables (e.g., menstrual phase, treatment changes) that may occur with time elapsed between study visits. Self-report data regarding will be captured via electronic surveys using validated instruments (where possible), structured interview, study records.

Reward System Modulation by fMRI. Each scan will last approximately 1 hour and involve two reward activation paradigms: passive food view (PFV) and monetary incentive delay (MID). These two reward activation paradigms provide distinct insight and will generate pilot data to support the choice of the optimal paradigm for further testing of reward system modulation in adolescents with eating disorders. PFV provides a paradigm that is relevant to the target behaviors (i.e., binge eating, purging), has been evaluated in ED patients, in response to naltrexone in adults, and is expected to activate food cue-reactivity regions (e.g., prefrontal cortex). MID is a widely used paradigm in adolescents to detect reward anticipation and receipt particularly in the striatum and is currently being used to study the developmental trajectory of reward processing in the longitudinal Adolescent Brain Cognitive Development (ABCD) trial. To the greatest extent possible, we will harmonize our fMRI parameters with those published for ABCD.

Opioid Antagonism and exposure-response linkage. A single oral dose of naltrexone hydrochloride 50 mg tablet will be administered. Plasma and urine will be obtained to measure systemic exposure to naltrexone and it primary, active metabolite, 6-beta-naltrexol, using a validated UPLC-MS/MS assay.

Inclusion Criteria:

• Eating disorder diagnosis per DSM-V criteria that is characterized by binge eating (defined as loss of control of eating resulting in large amount of food consumed in a short period of time) and/or purging (e.g., vomiting, excessive exercising, laxative use)
• Stable medication regimen (no dose or drug changes in the past 4 weeks)
• Participant and parent/legal guardian (if under 18 years) are willing and able to provide informed permission/assent/consent for the study

Exclusion Criteria:

• Pregnant (via UCG)
• Prior hypersensitivity reaction to naltrexone (e.g., anaphylaxis)
• Non-removable metal in the body
• Current naltrexone use
• Self-reported opioid use in the past 7 days
• A language barrier (e.g., non-English speaking) for the participant that precludes communication and/or ability to complete all study-related requirements.

1 day (single study visit)