Normal healthy volunteers

Inclusion Criteria:

• Age range: 18-45 years old
• Race or ethnicity: no restrictions
• Health status: subjects must have no clinically significant diseases or clinically significant abnormal laboratory values as assessed during the screening medical history, physical exam, and laboratory evaluations.
• Must have no history of significant psychiatric illness or substance use.
• Written Informed Consent as well as Health Insurance Portability and Accountability Act (HIPAA) authorization forms must be signed by the eligible subject prior to the initiation of any study procedures.

Exclusion Criteria:

Any of the following conditions are cause for exclusion and/or discontinuation from the study:

• The presence of any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion.
• A positive urine pregnancy test
• The use of oral contraceptives
• The lack of use of acceptable barrier methods of birth control unless abstinent
• The use of any concomitant medication including herbal medications, over-the-counter (OTC) supplements, or a history of hypersensitivity to DM, ALPZ, TOL, or caffeine (CAF) and any history of sensitivity to milk thistle or any of its components.
• Subjects genotyped as poor metabolizers of CYP2D6 at screening
• Active smoking or use of CAF containing beverage (coffee, certain colas) for one week prior and during the study period due to known effects on CYP1A2 activity.
• Subjects expressing inability to conform to dietary restrictions required for the study
• The use of any illicit drugs or habitual consumption of large quantities of ethanol (> 3 drinks/day)