Level 2 trauma patients admitted to Westchester Medical Center who consent and meet the inclusion criteria will answer a questionnaire, be tested on Beck Anxiety Index, assessed for vital signs and provide blood and urine samples for biomarker testing. before the intervention.

Part 1 Dose Escalation: Subjects will receive a single infusion NPY or vehicle delivered to the upper nasal cavity with an intranasal device. The administration of intranasal NPY will follow the 3 plus 3 model and Fibonacci dose escalation scheme.

Subjects will be assessed for Acute Stress Disorder (ASD) on the National Stressful Events Survey Acute Stress Disorder Sheet (NSESSS) at 3-7 and at 14-30 days post trauma, At >60 days post trauma to be evaluated with the PTSD Symptom Scale Interview for DSM-5 (PSS-I-5) and given the Beck Anxiety Inventory test.

Part 2 Dose Expansion Cohort: Once the maximal tolerated dose (MTD) is determined, we will follow it by a dose expansion cohort to obtain preliminary evidence of efficacy of intranasal NPY to alter the severity of ASD and inhibit the progression to PTSD and the usefulness of several biomarkers.

Patients admitted to the Westchester Medical Center as a level 2 trauma patient who meet the admission criteria will be asked to join the study and written consent will be obtained. Every patient who consents to participate will fill out a questionnaire of general information including education level, marital status, social support etc. and administered the Beck Anxiety Inventory. They will be asked to collect urine samples until the next morning.

The next morning at about 9-11 AM vital signs will be measured, including standing systolic blood pressure. Blood and the overnight urine samples will be collected for biomarker testing. This will include urinary norepinephrine levels, plasma ACTH and epigenetic changes in the genes for glucocorticoid receptor and norepinephrine transporter.

Subjects will then receive intranasal NPY (GMP-grade) delivered to the upper nasal cavity with an intranasal device from Kurve. We have chosen this device since it appears to be the best delivery system to the upper olfactory region of the nose for delivery to the brain. It has been used most widely, including the earlier clinical trial with intranasal NPY. After the intranasal NPY, patients will be evaluated for potential adverse reactions and vital signs measured at 30 min, 90 min, and every 4 hrs until released from the hospital. 1 and 3 days after the intranasal infusion.

The dose escalation of intranasal NPY will follow the 3 plus 3 model and Fibonacci dose escalation scheme with a starting dose of 9.6mg, selected based on the highest previously studied dose (Sayed et al. 2018). According to this model if no participant has a dose limiting toxicity (DLT), we will proceed to the next dose. If 1/3 has a DLT, 3 additional participants will be enrolled and if more than 1/6 have a DLT the dose escalation will be terminated.

A DLT will be defined as an adverse event or a clinically significant change in vital signs as follows: (1) any serious adverse event experienced at any time during the study that was determined to be at least "possibly" related to the study drug, or (2) a non-serious adverse event rated at least moderate in severity and at least "possibly" related to the study drug, or (3) occurrence of any of the following changes in vital signs with 90 minutes following administration of the NPY: (i) symptomatic hypotension or >20% decrease in systolic blood pressure (SBP) and an absolute SBP < 90; (ii) symptomatic hypertension or >20% increase in SBP and an absolute SBP >170 or diastolic blood pressure (DBP) > 95; (iii) new onset of tachyarrhythmia (defined as a heart rate >100 bpm) or symptomatic bradycardia (heart rate <60 bpm).

Tests for Persistent ASD and Development of PTSD At 3-7 and 14-30 days post trauma, subjects will be asked to fill out the National Stressful Events Survey Acute Stress Disorder Short Scale (NSESSS). After at least 60 days from the trauma they will be given an interview to be evaluated with the PTSD Symptom Scale Interview for DSM-5 (PSS-I-5) as well as the Beck Anxiety Inventory.

Dose escalation cohort After reaching the maximal tolerated dose (MTD) of intranasal NPY or four dose escalation steps without reaching a DLT, we will add a dose escalation cohort. The individuals in this cohort will be randomly assigned to be administered intranasal NPY or vehicle (placebo).

Based on the statistical analysis, we hope to be able to expand to 25-33 individuals per group in order to detect a 15% reduction in incidence of PTSD beyond the influence of the placebo with power of 80%.

Subjects will be tested for: Persistent ASD (NSESS) at days 3-7 and 14-30 after the trauma, PTSD and t 3-7 and 14-30 days post trauma: development of PTSD ( PSS-I-5), > 60 days post trauma); and anxiety (Beck Anxiety Inventory) and compared to groups given no intervention.

The information is expected provide preliminary data on efficacy of intranasal NPY administration to reduce the severity of ASD and attenuate the progression to PTSD. In addition, the results should provide preliminary information on usefulness of several biomarkers to inform on the progression of ASD and PTSD in level 2 trauma patients and on the response to intranasal NPY.

Inclusion Criteria:

• Level 2 trauma patients admitted to the trauma floors or trauma ICU at Westchester Medical Center
• Experienced fear at the time of the trauma

Exclusion Criteria:

• Vulnerable populations, such as pregnant women, prisoners, persons with decisional incapacity.
• History of coronary artery disease, heart failure, prior stroke, heart surgery
• Bood pressure >160/90
• Acutely psychotic
• Current diagnosis of anorexia nervosa, bulimia
• Current diagnosis of cancer
• Drug abuse or dependence in the preceding 3 months,
• Any unstable medical condition
• Active suicidal/homicidal ideation
• Cannot speak, read, write and understand English at least at 8th grade level.