BACKGROUND Over a third of patients with Post-Traumatic Stress Disorder (PTSD) do not respond to current interventions. Ketamine is one potential treatment avenue, however its effects are temporary. Administering ketamine alongside psychotherapy is one potential means of prolonging its effects, however, there are few studies investigating this treatment method to date, and none testing ketamine with electronic Cognitive Behavioural Therapy (e-CBT). OBJECTIVE The present study is an open label

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... ndomized controlled trial assessing the efficacy of a combined treatment of sub-anesthetic IV ketamine in conjunction with e-CBT to treat patients with PTSD. METHODS Twenty participants with refractory PTSD will be randomly assigned either to an experimental group receiving a combination of ketamine and e-CBT over 14 weeks, or they will be assigned to a waitlist-control group at the end of which they will receive the experimental treatment. Both groups will be assessed for symptoms of PTSD and comorbid disorders before treatment, midway, and at the end of the experiment. RESULTS Symptoms of PTSD for participants in the experimental group are expected to improve significantly more than participants in the waitlist-control group with at least a moderate effect size. CONCLUSIONS This will be the first experiment assessing the relationship between e-CBT and Ketamine and their combined ability to treat refractory PTSD. If successful, this study will open online/asynchronous therapeutic options to patients with PTSD and will provide new insights into the functional role of glutamate in trauma-related disorders as well as in learning, memory, and fear-extinction. CLINICALTRIAL ClinicalTrials.gov database - NCT04771767