Nitrous Oxide for PTSD
Condition: PTSD
MeSH terms: Stress Disorders, Post-Traumatic
Intervention: Nitrous Oxide; Midazolam; Nitrogen; Oxygen; Saline
Intervention description: PTSD participants in this arm will receive and admixture of up to 50% nitrous oxide and 50% oxygen plus intravenous saline; PTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam; PTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam; inhaled gas; Placebo infusion
Intervention MeSH terms: Midazolam; Nitrous Oxide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized placebo-controlled clinical trial including two groups: Experimental (admixture of up to 50% nitrous oxide and 50% oxygen plus IV saline) and Active Comparator (admixture of up to 50% nitrogen and 50% oxygen plus 0.045mg/kg midazolam).
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking description: Blinding Protections: First, the investigators will separate personnel and location of the team providing study drug from the team performing psychiatric evaluations. Independent evaluators (IEs) blind to treatment assignment will assess participants . Second, records for drug administration will be kept separate from psychiatric assessment case report forms until completion of the study. Third, all participants will be blinded as to the nature of the inhaled gas and IV drug at each session; all participants will be informed that they will receive either nitrous oxide and IV saline or an air mixture with a high nitrogen component and IV midazolam. Integrity of the blinding will be assessed by recording each patient's guess as to which drug was received.
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: PTSD; Nitrous Oxide

Summary:

      Post-traumatic stress disorder (PTSD) seriously disrupts the lives of many Veterans. Current
      first-line treatments, serotonin reuptake inhibitors or prolonged exposure therapy, take
      weeks to months to bring meaningful improvement, leaving Veterans experiencing prolonged
      suffering. A promising new treatment approach for rapidly reducing PTSD symptoms is nitrous
      oxide, an inhalation anesthetic and putative glutamate modulator that diminishes depression
      symptoms within 1 day and has limited side effects. If shown to be similarly effective in
      PTSD, nitrous oxide may add dramatically to the treatment armamentarium by bringing rapid
      symptom decrease before longer-term therapies take hold. The proposed projects test the
      efficacy of nitrous oxide in relieving Veteran's PTSD symptoms and, in parallel, explore how
      nitrous oxide may modify cognitive and pain outcomes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Veteran

          -  primary diagnosis of PTSD

          -  sufficient severity of PTSD symptoms

          -  capacity to provide informed consent

        Exclusion Criteria:

          -  psychiatric or medical conditions that make participation unsafe

          -  pregnant or nursing females

          -  concurrent use of any medications that might increase the risk of participation (e.g.
             drug interactions