Effects of Methylphenidate (Ritalin®) on the Neural Basis of Anxiety

Inclusion Criteria:

- Healthy male subjects, 18 to 40 years of age, inclusive.

- In good general health (as determined by medical history, blood pressure, and ECG),
especially no findings (including concomitant medications) that would constitute
contraindications for treatment with any of the study drugs.

- A weight of > 120 lbs (55 kg) and a BMI between 18 to 30 kg/m2, inclusive.

- Participants must be willing to drink only alcohol-free liquids and no
xanthine-containing liquids (such as coffee, black or green tea, red bull, chocolate)
the day before and during the study day.

- Subjects able to participate and willing to give written informed consent and to
comply with the study restrictions.

Exclusion Criteria:

- History of any hematological, hepatic, respiratory, cardiovascular (including
structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities,
coronary artery disease or myocardial infarction), renal or CNS disease (including
seizures), gallbladder removal or other medical or surgical condition that could
alter the absorption, metabolism or elimination of drugs.

- Family history of sudden death or ventricular arrhythmia.

- Any major illness (as judged by the study physician) within 1 month prior to first
dose.

- Current or history of any psychiatric disorder, marked anxiety, tension and
agitation.

- History of glaucoma.

- History (including family history) of motor tic or diagnosis of Tourette's syndrome.

- History of psychotropic medicine and/or alcohol dependence.

- Active suicidal ideation, history of suicidal behavior, or otherwise considered at
high suicidal risk by trained study staff using the C-SSRS.

- Positive urine toxicology (drugs of abuse as determined by a positive urine test) at
screening and before each drug administration.

- Use of any medications or herbal remedies, including psychotropic medicines and
regular sleep medications, taken within 14 days or 6 times the elimination half-life
of the medication (whichever is longer) prior to the first dose and throughout the
study, with the exception of acetaminophen for minor pains, occasional use of
sleeping medication as long as it is not taken the evening prior to a visit,
medications explicitly approved by the investigator and the sponsor.

- Past intolerance (including allergic) to any of the study medications or components
thereof.

- Supine systolic blood pressure (BP) >140 or >90 mmHg, diastolic BP <90 mmHg or <50
mmHg (mean of two measurements at screening) and current or past history of
clinically significant hypertension.

- Current smoker (> 10 cigarettes/day); habitual caffeine consumption of more than 400
mg/d (approximately 4 cups of coffee or equivalent).

- QTcF > 450 msec based on the average interval on triplicate ECGs. Notable resting
bradycardia (mean HR < 45 bpm) or notable resting tachycardia (mean HR > 90 bpm).

- Contraindication to magnetic resonance imaging.

- Participation in a clinical trial with an investigational drug or a device within 30
days prior to dosing in the first period.

- Volunteers who do not have sufficient command of the English language, or who have
any other impairment that would prevent them from reading and understanding the
informed consent form(s) and completing the study procedures including clinical
testing.

- Any other reason why, per study physician, the subject should not participate in this
study, including concomitant disease or condition that could interfere with, or for
which the study drug might interfere with, the conduct of the study, or that would,
in the opinion of the principal investigator, pose an unacceptable risk to the
subject in this study.