Based on the current research findings on the therapeutic effectiveness of trauma focus psychotherapy and of ketamine combining the two treatments may yield a promising new rapid week-long treatment for PTSD. As PTSD symptoms' structure is comprised of several unique clusters which include re-experiencing, avoidance, depression and hypervigilance the investigators hypothesize that by combining Ketamine with trauma-focused psychotherapy the proposed intervention can address these PTSD symptoms clusters more effectively than existing treatments. This proposed clinical trial has the potential to produce a significant therapeutic effect that otherwise would take months to occur by tapping on the enhanced neuroplasticity and the antidepressant effect of ketamine (which lasts between 24hrs to 7 days), to promote rapid changes in learning and memory when applying psychotherapy within a unique window of opportunity of neurophysiological changes produced by the investigative drug.~During the first visit participants will undergo a clinical interview to establish a PTSD diagnosis and other eligibility criteria. If found eligible participants will be invited to take part in this 7-day rapid treatment trial for PTSD.~On the first therapy visits, participants will be educated about the psychological treatment that will be provided and the potential benefit of ketamine or midazolam that may enhance the psychotherapy outcomes.~On the second day of the study, participants will receive an infusion of ketamine or midazolam and will undergo a magnetic resonance imaging (MRI) to assess their brain reactivity to PTSD before the treatment.~On days 3-6 participants will attend a 60-90 minutes psychotherapy session to address their PTSD symptoms.~A second ketamine or midazolam infusion will take place on day 4 of the study to enhance the drug therapeutic effect for the study duration.~Day 7 will include another MRI scan to assess treatment effect on PTSD.~Participants will need to attend two follow up MRI scans and clinical evaluation at 30 and 90 days post-treatment to assess the long-term effectiveness of the intervention.
The purpose of this study is to test if the combination of ketamine, vs midazolam, with an intensive trauma-focused psychotherapy will be more effective in relieving post-traumatic stress disorder (PTSD). This week-long treatment has the potential to produce a significant therapeutic effect that otherwise would take months to occur. The study will also focus on learning about the neurophysiological changes produced by the proposed clinical trial.