The Sustained Effects of Ketamine
Condition: Mental Disorders
MeSH terms: Mental Disorders
Intervention: Ketamine; Lamotrigine; Placebo
Intervention description: The subanesthetic dose of ketamine (0.23mg/kg bolus followed by 0.58mg/kg infusion over approximately 60 minutes) will be administered via intravenous infusion; lamotrigine (300 mg oral dose) or the matched-placebo control about 2-hours prior to the start of the infusion of ketamine; oral dose placebo
Intervention MeSH terms: Lamotrigine; Ketamine
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of the study is to characterize the effects of a single, sub-anesthetic dose of
      ketamine in rs-fMRI in healthy subjects. Post-ketamine rs-fMRI data will demonstrate a
      pattern of increased global brain connectivity (GBC) in fronto-temporal cortex.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female between the ages of 21-65 years. Females will be included if they are
             not pregnant and agreed to utilize a barrier method contraceptive (e.g., condom or
             diaphragm with spermicide) tubal ligation, abstinence, or partner with vasectomy) or
             if post-menopausal for at least 1 year, or surgically sterile.

          -  Able to provide written informed consent according to Yale HIC guidelines.

          -  Agree to refrain from elective surgeries (including dental) for a 2-week period
             following study drug.

          -  Able to read and write English as a primary language.

        Exclusion Criteria:

          -  Personal history of mood, anxiety, or psychotic axis I DSM-IV disorders confirmed
             after comprehensive psychiatric evaluation.

          -  Any history of serious medical or neurological illness.

          -  Any signs of major medical or neurological illness on examination or as a result of
             ECG screening or laboratory studies.

          -  A first-degree family member with history of schizophrenia.

          -  Lifetime history of psychoactive substance or alcohol dependence or substance or
             alcohol abuse (other than nicotine or caffeine abuse), or drinking more that 5
             drinks/week during the last year.

          -  Abnormality on physical examination. A subject with a clinical abnormality may be
             included only if the study physician considers the abnormality will not introduce
             additional risk factors and will not interfere with the study procedure (e.g.
             uncontrolled hypertension, hyperthyroidism, or hypothyroidism will be excluded).

          -  A positive pre-study (screening) urine drug screen or, at the study physician's
             discretion on any drug screens given before the scans.

          -  Pregnant or lactating women or a positive urine pregnancy test for women of
             child-bearing potential at screening or prior to any imaging day.

          -  Positive HIV or Hepatitis B/C tests. This test will take place at the screening visit.
             Subjects will be invited back either for their next study visit or for a HIV/Hep
             debriefing session. A study clinician will inform them in person of the results. They
             will be given access to counselling and advised of the appropriate next steps.

          -  Has received either prescribed or over-the-counter (OTC) centrally active medicine or
             herbal supplements within the week prior to the MRI scan. Subjects who have taken OTC
             medication or herbal supplements may still be entered into the study, if, in the
             opinion of the principal/co-investigator, the medication received will not interfere
             with the study procedures or compromise safety.

          -  Any history indicating learning disability, mental retardation, or attention deficit
             disorder.

          -  Known sensitivity to ketamine.

          -  Known sensitivity to lamotrigine.

          -  Body weight of 250 pounds or greater.

          -  History of claustrophobia.

          -  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.

          -  Donation of blood in excess of 500 mL within 56 days prior to dosing.

          -  History of sensitivity to heparin or heparin-induced thrombocytopenia.

          -  Resting blood pressure lower than 90/60 or higher than 150/90, or resting heart rate
             lower than 45/min or higher than 100/min.