Nitrous Oxide for Posttraumatic Stress Disorder (PTSD): A Phase IIa Trial
Phase: PHASE2
Conditions: PTSD
Sponsor: VA Office of Research and Development

Title: Nitrous Oxide for 
Posttraumatic Stress Disorder 
(PTSD):  A Phase IIa Trial
Protocol ID # 53017 
PD: Carolyn Rodriguez, MD, PhD 
Approval Period: 06/21/2022 - 02/01/2023 
NCT04378426
Date: 01/18/2023
PROTOCOL APPLICATION FORM 
Human Subjects Research Stanford 
University

Clinical Study
Purpose: 
PTSD seriously disrupts the lives of many Veterans. Current first-line pharmacological treatments 
often fail to bring meaningful improvement, leaving these Veterans with distressing and impairing 
symptoms. Developing more effective and more rapidly effective therapeutic options is critical. The 
purpose of the study is to assess efficacy of nitrous oxide in PTSD and the duration of its short-term 
therapeutic effects.
Objectives:
1. To determine the efficacy of nitrous oxide in PTSD 
2. To examine the safety of nitrous oxide administration in PTSD
Design: 
The clinical study design is a randomized placebo-controlled clinical trial including two groups: 
Group 1) “Active Treatment” Nitrous oxide group, and, Group 2) “Active Comparator/Placebo 
group.”
Methods:
The study’s first phase is the Screening phase, to assess eligibility via inclusion and exclusion criteria. 
During the Baseline phase, participants will be rated for PTSD. Participants will then enter the 
Randomization phase and be randomized (1:1) to receive either an admixture of up to 50% nitrous 
oxide and 50% oxygen plus IV saline ("active treatment") plus IV saline or 50% nitrogen and 50% 
oxygen plus 0.045mg/kg midazolam ("active comparator") for 1 hour. During the Treatment phase, 
the gas mixture will be administered via facemask connected to a standard anesthesia machine at 4-8 
L/min. Participants will be continuously monitored (EKG, BP, O2) during treatment per the 
American Society of Anesthesiologists standard and observed for an additional four hours of 
recovery supervised by an attending-level anesthesiologist. To examine changes in PTSD, symptoms 
will be reassessed 7 days (1 week) post-administration. Unexpected adverse effects of nitrous oxide 
will be recorded at each time point.