Study of Intranasal Ketamine for Social Impairment in Autism Spectrum Disorder

Inclusion Criteria: * Ages 12 to 30 years old. * Weight equal to or greater than 50 kg. * General good health as determined by physical exam, medical history, laboratory work up, and EKG. * Diagnostic and Statistical Manual of Mental Disorders 5th Edition diagnosis of autism spectrum disorder (not associated with Fragile X Syndrome or other known genetic syndrome) as confirmed by the Autism Diagnostic Observation Schedule at screen or previous (within last 5 years) if available. * Valid Intelligence Quotient (IQ) score greater than or equal to 50 as confirmed via testing (Leiter-3) at screen or previous (within last 5 years, any valid testing acceptable). * Clinical Global Impressions-Severity score of 4 (Moderately Ill). * Score of 10 on the Social Withdrawal subscale of the Aberrant Behavior Checklist. * Stable dosing of all concomitant psychotropic medications for five half-lives prior to screening visit and during the study. * Presence of parent/guardian or significant other or caregiver willing to serve as informant for behavioral outcome measures. Exclusion Criteria: * Presence of co-morbid schizophrenia, schizoaffective disorder, bipolar disorder with psychosis, bipolar disorder or psychosis not otherwise specified. Comorbid diagnoses determined by psychiatrist clinical interview and use of Diagnostic and Statistical Manual of Mental Disorders 5th Edition diagnostic criteria. * History of drug or alcohol abuse. * Presence of cardiac disease including coronary artery disease, congestive heart failure, or uncontrolled hypertension per medical history (individuals with ≥ 2 blood pressure readings of ≥140/90 during screen/baseline will be excluded). * Airway instability, tracheal surgery, or tracheal stenosis per medical history. * Central nervous system masses or hydrocephalus per medical history. * Porphyria, thyroid disorder, or thyroid medication use per medical history. * Glaucoma or other cause of increased intraocular pressure per medical history. * Allergy to ketamine. * Current use of drugs with concomitant modification of non-competitive N-methyl-D-aspartate glutamate activity (acamprosate, amantadine, memantine, d-cycloserine etc.) * For female subjects of child bearing potential, a positive pregnancy test. * Any major chronic medical or chronic respiratory illness considered to be uncontrolled by the Principal Investigator. * Inability to tolerate study procedures or study drug per the discretion of the Principal Investigator.