Adding Trauma-focused Psychotherapy to Ketamine Treatment for Chronic PTSD

Inclusion Criteria: 1. Men or women, 18-70 years of age; 2. Participants must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign a written informed consent document; 3. Participants must fulfill DSM-5 criteria for current civilian or combat-related PTSD, based on clinical assessment by a study psychiatrist and on the CAPS-5, and a past-month total CAPS5 score ≥ 30 at screening - this is done to ensure at least moderate severity and to safeguard against high placebo response rates; 4. Women must be using a medically accepted reliable means of contraception (if using an oral contraceptive medication, they must also be using a barrier contraceptive) or not be of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year); 5. Women of childbearing potential must have a negative pregnancy test at screening and prior to each intravenous infusion; 6. Men who are sexually active with women of childbearing potential must use a medically accepted reliable means of contraception and must agree not to donate sperm for a period of 90 days after receiving the last dose of ketamine; 7. Participants must be able to identify a family member, physician, or friend (i.e. someone who knows them well) who will participate in a Treatment Contract (and e.g. contact the study physician on their behalf in case manic symptoms or suicidal thoughts develop). Exclusion Criteria: 1. Women who plan to become pregnant, are pregnant or are breast-feeding (because the medical risk of using ketamine during pregnancy and breast-feeding is unknown); 2. Serious, unstable medical illnesses such as hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease, including gastro-esophageal reflux disease, obstructive sleep apnea, history of difficulty with airway management during previous anesthetics, ischemic heart disease and uncontrolled hypertension, and history of severe head injury; 3. Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG; 4. Renal impairment, as reflected by a BUN \>20 mg/dL, and/or creatinine clearance of \>1.3 mg/dL; 5. Clinically significant uncorrected hypothyroidism or hyperthyroidism, as indicated by a TSH value 25% above or below the normal range; 6. A Body Mass Index (BMI) \>40; 7. Hormonal treatment (e.g., estrogen) started in the 3 months prior to the first infusion day; 8. History of a neurodevelopmental disorder (e.g., autism, pervasive developmental disorder) ; 9. History of one or more seizures without a clear and resolved etiology; 10. Lifetime history of bipolar I or II disorder; 11. Presence of psychotic symptoms, or diagnosis of a lifetime psychotic disorder including schizophrenia or schizoaffective disorder; 12. Drug or alcohol use disorder within the preceding 3 months 13. Previous recreational use of ketamine or PCP on more than one occasion, or any recreational use of ketamine or PCP within the last two years; 14. Previous non-response to clinical or research ketamine or esketamine administration; 15. Current diagnosis of bulimia nervosa or anorexia nervosa; 16. Patients judged clinically to be at serious and imminent suicidal or homicidal risk; 17. SBP \>165 and DBP \>95 at infusion days - higher BP allowed to account for stress or anxiety; 18. Concurrent treatment with opioid medication, or with long-acting or daytime short-acting benzodiazepines within two weeks of study start; 19. Current cognitive impairment, as defined by a score \<23 on the Montreal Cognitive Assessment (MoCA); 20. Estimated IQ \<80; 21. Currently receiving evidence-based psychotherapy for PTSD (e.g., prolonged exposure, cognitive processing therapy); Note: Concurrent treatment with other psychotropic medications (including a short-acting benzodiazepine at bedtime only) will be permitted, but dose must be stabilized for at least three months before study start.