The purpose of this study is to find out how an anti-anxiety drug or placebo affects the activity of your brain when you are at rest and when you are viewing emotional material, such as, emotional faces and pictures.

This is an exploratory study to evaluate the usefulness of fMRI as a biomarker to measure the response to a known, FDA approved marketed anxiolytic. As such, this is not a study testing safety and efficacy of an approved medicine; it is a study to evaluate the usefulness of fMRI (a non-significant risk device procedure) to correlate the clinical/behavioral effects of a marketed anxiolytic with brain activity assessed by magnetic resonance imaging. fMRI is a more direct measure of brain function than behavior, outcomes are quantitative and objective. As such, it may be more specific, i.e., may be more sensitive to drug effects or show them earlier than clinical endpoints and enable determination of efficacy in smaller or shorter studies than those required to show effects on clinical endpoints. Finally, imaging may allow differentiation of placebo responders from true drug responders.

Inclusion Criteria:

1. Male or female between 18 - 65 years of age, inclusive

2. In good general health (as determined by medical history, physical examination, laboratory assessments and electrocardiogram (ECG)), especially no findings (including concomitant medications) that would constitute contraindications for treatment with alprazolam

3. Diagnostic and Statistical Manual-IV criteria for Generalized Anxiety Disorder (GAD) (exception: at least 3 months of symptoms)

4. Hamilton Anxiety Scale at screening >/= 20

5. Montgomery-Asberg Depression Rating Scale (MADRS) at screening < 25

6. Prior medications washout:

   • 2-week medication washout prior to randomization for most psychotropic medications
   • If prior history of fluoxetine use, this drug must have been discontinued at least 5 weeks before randomization

7. For females of non-childbearing potential: either postmenopausal for the past year (confirmed by an follicle stimulating hormone level greater than 40 mIU/mL unless the subject is receiving hormone replacement therapy), or surgically sterile (e.g., tubal ligation, hysterectomy)

8. Males and female subjects of child-bearing potential may be included if using appropriate contraceptive methods:

   • must use abstinence or two methods of contraception throughout the trial:

     • should include one primary (e.g., systemic hormonal contraception, vasectomy of the male partner) AND one secondary barrier method (e.g., latex condoms, spermicide) OR
     • a double barrier method (e.g., latex condom plus spermicide (foam, suppository, gel, cream)) may be used

9. GAD should be the clinically predominant disorder, as judged by the investigator, considering relative severity and impact on functioning

Exclusion Criteria:

1. Axis I disorder other than stated above with the exception of the following permitted comorbidities:

   • history of (within past 6 months) or current dysthymia
   • current (within past 6 months) depressive episode with MADRS at baseline < 25
   • history of major depression as long as no current depressive episode as defined above

2. Drug or alcohol dependence in the past 6 months

3. Positive urine toxicology (drugs of abuse as determined by clinician's assessment of positive urine test)

4. Active suicidal ideation (determined by clinician)

5. For females of childbearing potential: Pregnancy or intent to become pregnant or currently breastfeeding

6. Current use of beta-blockers or stimulants (e.g., Methylphenidate, d-Amphetamine, modafinil, and illicit drugs like cocaine or 3,4-methylenedioxy-N-methylamphetamine [MDMA])

7. Current regular use of antihistamines (except for inhalants which are permitted)

8. Current use of herbal medication for mood or anxiety disorders and unwillingness to discontinue use for the duration of the study

9. Current use of fluoxetine

10. Concomitant psychotropic medications including regular use of sleeping medications (also herbals)

    • occasional use of sleeping medication, with the exception of benzodiazepines, is permitted as long as it is not taken the evening prior to a visit

11. Past intolerance (including allergic) to, or clear history of non-response to the study medication

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

13. Body mass index > 32.5 kg/m2

14. Contraindication to magnetic resonance imaging based on a standard fMRI screening forms

15. Concurrent participation in an institutional review board (IRB) approved investigational drug trial

16. Any other reason why, per clinician, the patient should not participate in this study (to be included in this assessment are all considerations, warnings, precautions as per current FDA-approved drug label for Xanax®)

From day 0 (baseline) to day 28.