Nitrous Oxide for PTSD

Phase 2

Terminated

Interventions: Drug: Midazolam
Drug: Nitrous Oxide
Drug: Oxygen
Drug: Nitrogen
Drug: Saline

Brief 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.

Detailed Description: The proposed projects will examine the efficacy of nitrous oxide in relieving Veteran's PTSD symptoms and in parallel, explore whether nitrous oxide improves cognitive and pain outcomes. Specifically, the investigators will first assess whether nitrous oxide treatment improves PTSD symptoms within 1 week. In parallel, the investigators will explore whether the treatment improves co-existing depression and pain. In addition, the investigators will explore nitrous oxide's effects on a PTSD-associated impairment that is often overlooked - disruption in cognitive control, a core neurobiological process critical for regulating thoughts and for successful daily functioning.

Recruitment & Eligibility

Inclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
Nitrous Oxide	Oxygen	PTSD participants in this arm will receive and admixture of up to 50%nitrous oxide and 50% oxygen plus intravenous saline
Nitrous Oxide	Saline	PTSD participants in this arm will receive and admixture of up to 50%nitrous oxide and 50% oxygen plus intravenous saline
Midazolam	Oxygen	PTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam
Midazolam	Midazolam	PTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam
Nitrous Oxide	Nitrous Oxide	PTSD participants in this arm will receive and admixture of up to 50%nitrous oxide and 50% oxygen plus intravenous saline
Midazolam	Nitrogen	PTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam

Primary Outcome Measures

Name	Time	Method
Improvement in the Severity of PTSD as Measured by the Clinician Administered PTSD Scale DSM5 (CAPS-5)	1 week	Improvement in PTSD severity is measured by the Clinician Administered PTSD Scale DSM-5 (CAPS-5). It measures frequency and intensity of PTSD-related symptoms. For the CAPS-5 the minimum units are 0 and maximum units are 80. The higher the number on the CAPS-5, the more severe the PTSD symptoms. Response is defined as a change in the CAPS-5 of at least 12 points, which represents meaningful improvement in clinical PTSD symptoms.

Secondary Outcome Measures