The purpose of this study is to test the safety and efficacy of repeated doses of ketamine as compared to placebo to reduce symptoms of Posttraumatic Stress Disorder (PTSD) among Veteran receiving Prolonged Exposure Therapy.

In this single site clinical trial, intended to evaluate the safety and efficacy of repeated doses of ketamine in conjunction with prolonged exposure (PE) therapy for PTSD. Veterans who meet criteria for PTSD and the additional inclusion and exclusion criteria will be randomized to one of two treatment arms (placebo plus PE vs ketamine plus PE). Participants receive the study drug via intravenous infusion once per week for 3-weeks.

Inclusion Criteria:

• male or female Veterans between the ages of 18 and 75 years
• diagnosis of PTSD
• ability to provide written informed consent

Exclusion Criteria:

• females who are currently pregnant or breastfeeding
• current high risk for suicide
• history of moderate/severe head injury
• history of psychosis
• current episode of mania/hypomania
• severe substance and/or alcohol use disorder in the last 6 months

The investigators will use a sequentially numbered, opaque, sealed envelopes, pharmacy-controlled allocations, and coded identical containers for adequate concealment allocation. Administration of study drugs and infusion monitoring will be conducted by research nurse keeping blinding from investigators and independent outcome assessors.