The purpose of the study is

1. To establish the feasibility of fMRI studies of the interaction of guanfacine and ketamine.
2. To explore the possibility that guanfacine can ameliorate the negative effects of ketamine on task-related prefrontal activation.
3. To assess the strength of any interaction between guanfacine and ketamine.

Potential subjects will be interviewed over the phone and, if appropriate, will be scheduled for a screening session. Participants who meet study criteria will participate in two study sessions separated by at least two weeks. The sessions will be identical except on one day they will receive guanfacine and on the other, they will receive a placebo.

This study was initially completed in 2014. Upon analysis of the collected data, it was decided to add additional subjects and gather additional data to verify results seen in the collected data. The study was reopened and new data was added beginning in September 2016. Information about the study beginning in 2016 is available in a separate record.

Inclusion Criteria:

• Age between 21 and 45, inclusive
• Right-handed
• Have at least a 12th grade education level or equivalent
• Able to read and write English as a primary language
• Willing to refrain from caffeine and alcohol use for one week prior to each MRI session.

Exclusion Criteria:

• Abnormality on physical examination
• A 12 lead ECG at screening has clinically significant abnormalities as determined by the physician reading the ECG
• A positive pre-study urine drug screen or, at the study physicians' discretion on any drug screens given before the scans
• Abnormality on clinical chemistry or hematology examination at the pre-study medical screening.
• History of positive HIV or Hepatitis B.
• Has received either prescribed or over-the-counter (OTC) centrally active medicine or herbal supplements within the week prior to the MRI scan.
• History of any substance abuse disorder meeting DSM-IV criteria with the exception of nicotine
• Any history of DSM-IV Axis I psychiatric disorders,
• Any history of major medical or neurological disorders
• Any history indicating learning disability, mental retardation, or attention deficit disorder.
• First-degree relative with Axis I DSM-IV disorder including substance abuse or dependence.
• Any clinically significant abnormalities on screening electrocardiogram
• Any history of head injury
• Any evidence of psychosis-like symptoms, as indicated by elevated scores on the Perceptual Aberration-Magical Ideation (Chapman, Chapman et al. 1978; Eckblad, Chapman et al. 1983) and the revised Social Anhedonia scales(Eckblad, Chapman et al. unpublished)
• A positive urine toxicology screen for illicit substance use or positive alcohol breathalyzer test conducted at screening interview and prior to each MRI session
• Known sensitivity to ketamine.
• Body circumference of 52 inches or greater.
• History of claustrophobia
• Any clinically significant impairment of color vision or visual acuity after correction available in the scanner.
• Presence of cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies in vulnerable positions as assessed by a standard pre-MRI screening questionnaire
• Pregnancy or breast-feeding would exclude potential participants and all female subjects will receive a urine pregnancy test at screening and before each MRI scan.
• Donation of blood in excess of 500 mL within 56 days prior to dosing.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• Blood pressure must be higher than 90/70. Pulse must be greater than 40 unless the participant is cleared by a study physician

Baseline population is the number of participants who started the study

Throughout the length of the study (Aproximately 3 years)