Ketamine as a Treatment for Post-Traumatic Stress Disorder (PTSD)

Ketamine is an approved medication in several countries for the induction of general
anesthesia and for use as adjunct to other anesthetics. Intravenous ketamine is being
developed and tested for the treatment of posttraumatic stress disorder (PTSD).

All subjects will be administered the study medication by the study anesthesiologists and
under the direct supervision of the investigator or designee. On all dosing days, all
subjects must remain at the clinical site until at least 4 hours post-dose (or longer if
required for study procedures) and will be accompanied by a responsible adult when discharged
from the clinical site. The end of study will occur when the last subject in the trial
completes his/her last study assessment.

Inclusion Criteria:

- Men or women, 18-65 years of age;

- 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;

- Participants must fulfill DSM-5 criteria for current civilian or combat-related PTSD

- 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);

- Women of childbearing potential must have a negative pregnancy test at screening and
prior to each intravenous infusion;

- 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:

- Women who plan to become pregnant, are pregnant or are breast-feeding

- 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;

- Clinically significant abnormal findings of laboratory parameters, physical
examination, or ECG;

- Renal impairment, as reflected by a BUN >20 mg/dL, and/or creatinin clearance of >1.3
mg/dL;

- Thyroid impairment, as reflected by TSH> 4.2 mU/L Patients with uncorrected
hypothyroidism or hyperthyroidism;

- Hormonal treatment (e.g., estrogen) started in the 3 months prior to the first
infusion day;

- Use of evidence-based individual psychotherapy (such as prolonged exposure) during the
study;

- History of autism, mental retardation, pervasive developmental disorders, or
Tourette's syndrome; History of one or more seizures without a clear and resolved
etiology;

- History of (hypo)mania;

- Past or current presence of psychotic symptoms, or diagnosis of a lifetime psychotic
disorder including schizophrenia or schizoaffective disorder;

- Drug or alcohol abuse or dependence within the preceding 3 months

- Previous recreational use of ketamine or PCP;

- Current diagnosis of bulimia nervosa or anorexia nervosa;

- Diagnosis of schizotypal or antisocial personality disorder

- Patients judged clinically to be at serious and imminent suicidal or homicidal risk.

- A blood pressure of one reading over 160/90 or two separate readings over 140/90 at
screen or baseline visits

- Patients who report current treatment with a benzodiazepine, an opioid medication, or
a mood stabilizer (such as valproic acid or lithium) within 2 weeks prior to
randomization