The researchers propose to utilize a pharmacological approach involving infusions of the sympathomimetic agent isoproterenol to repeatedly trigger cardiorespiratory sensations and anxiety during meal anticipation, to facilitate the development of tolerance or a reduction of the anxiety/fear response in individuals with anorexia nervosa. The investigators aim to conduct a proof of principle study to assess for evidence of initial efficacy of this new treatment approach. As a comparator condition, the researchers propose using repeated administration of saline infusions.

Individuals with anorexia nervosa (AN) are afraid to eat. Moreover, anxiety is a prominent symptom in AN, with anxiety disorders frequently preceding and/or co-occurring with the illness, and with an increased prevalence of anxiety disorders in first-degree family members. Pre-meal anxiety poses a frequent challenge in treatment settings which require adherence to strict meal plans, particularly since it is associated with lower caloric intake. While problematic under current treatment settings, this illness characteristic also provides a potentially important therapeutic target. Unfortunately, straightforward pre-meal treatment with typically effective anxiolytic medicines such as alprazolam are ineffective in individuals with AN, nor do they increase caloric intake. By contrast, cognitive behavioral therapies for anorexia nervosa utilizing exposure therapy, the most effective psychological intervention for anxiety and anxiety disorders, can promote food intake and increase weight in AN. However, such treatments are slow and have less than ideal response rates, suggesting that they could benefit from further optimization. Exposure therapy involves helping patients to voluntarily engage in repeated and sometimes prolonged confrontation with the stimulus that disproportionately provokes the individual's fear. The aim of this practice is to facilitate the development of tolerance or a reduction of the anxiety/fear response that has become conditionally associated with the relevant stimulus, thereby demonstrating to patients that they can learn to manage effectively in the face of anxiety. In the case of anorexia nervosa, the repeated presentation of food and food cues (mental imagery, pictures, smells) elicits distress and facilitates the subsequent development of tolerance of these symptoms. Unfortunately, the effect size of this intervention in AN is relatively small. Here, the researchers investigate whether the use of an acute pharmacological intervention in the context of aversive learning to enhance exposure training can reduce anxiety associated with eating in individuals with anorexia nervosa.

Inclusion Criteria:

1. Must have a body mass index between 17 to 35 kg/m²
2. Must be able to provide written informed consent and must have sufficient proficiency in the English language to understand and complete interviews, questionnaires, and all other study procedures.
3. Must be capable of performing all tasks during each session of the experiment.

Inclusion criteria (AN participants, n = 50):

Participants (ages 18 to 40) must meet Diagnostic and Statistical Manual (DSM 5) criteria for Anorexia Nervosa, either current or lifetime, or have an Eating Disorder Screen (SCOFF) score ≥ 2 and a current BMI of 17 or greater. Selected medications are allowed, including selective serotonin reuptake inhibitors and benzodiazepines. Mood stabilizers and antipsychotic medications are excluded.

Exclusion Criteria:

1. No telephone or limited access to a telephone

2. Has any of the following DSM 5 disorders:

   1. Schizophrenia Spectrum and Other Psychotic Disorders
   2. Bipolar and Related Disorders
   3. Antisocial Personality Disorder

3. Active suicidal ideation with intent or plan

4. Obesity with a body mass index > 35 preventing scanner entry.

5. Illicit stimulant drugs consumed within the past week including methamphetamine or cocaine, assessed via urine drug screen

6. Active drug or alcohol dependence, or active binge drinking within the last month

7. Pregnancy as detected by a urine test

8. Prescription of a medication outside of the accepted range, as determined by best clinical practices and current research.

9. Change in the dose or prescription of a medication within the 3 weeks before enrolling in the study that could affect subjective responses, e.g., anxiolytics or antidepressants.

10. Presence of unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, or metabolic disease; or any other condition that, in the opinion of the investigator, would make participation not be in the best interest (e.g., compromise the well-being) of the subject or that could prevent, limit, or confound the protocol-specified assessments.

11. Non-correctable vision or hearing problems.

12. Systolic blood pressure > 160 mmHg

13. Diastolic blood pressure > 100 mmHg

Additional AN-specific exclusion criteria (AN participants):

1. Any AN individual reporting a history of cardiac or respiratory disease
2. AN with 12-lead EKG abnormalities other than bradycardia or occasional premature ventricular complexes (PVCs); those with severe bradycardia, e.g. heart rate less than 40 bpm will be excluded.
3. AN reporting a seizure within the past year
4. Active antipsychotic, mood stabilizer, lithium, stimulant, or wellbutrin medication prescription.