This is a double-blind, randomized, placebo-controlled, five-period crossover study to examine the likability of a repeated administration of immediate release methylphenidate hydrochloride (IR-MPH 40 mg) and OROS®-MPH (CONCERTA® 72 mg) in healthy adults. Hypotheses are as follows:

• Hypothesis 1: the subjective feelings of detection and likeability will be greater for periods of IR-MPH administration than after OROS-MPH administration irregardless of sequence;
• Hypothesis 2: the greater ratings of feelings of detection and likeability will be associated with the periods of most rapid change in plasma d-MPH and not with the magnitude of plasma d-MPH concentration (other than the OROS-MPH to IR-MPH condition in which they coincide), and
• Hypothesis 3: the subjective feelings of dislike will be greatest for the two conditions in which IR-MPH is the second condition.

The main goal of this study is to assess whether the abuse liability potential of delayed, repeated administrations of different formulations of MPH is moderated by the oral delivery system in which a delivery system with slower onset may be safer than one with more rapid early release. To this end, the investigators will compare repeated administration of orally administered, therapeutic doses of a short (IR-MPH) and a long-acting formulation of MPH (OROS-MPH) in the following areas:

1. pharmacokinetic profile of MPH assessing rate of onset of MPH action (indexed through change in plasma level) and
2. abuse liability (indexed through detection and likeability).

The investigators will test all combinations of initial administration and then delayed (repeated) administration of the two formulations: IR-MPH to IR-MPH; IR-MPH to OROS-MPH; OROS-MPH to IR-MPH; OROS-MPH to OROS-MPH, and placebo to placebo.

Inclusion Criteria:

1. Males or non-pregnant, non-lactating females. With the exception of women who have been post-menopausal for a minimum of 12 months prior to screening and those who have undergone hysterectomy or bilateral oophorectomy, all female subjects must have a negative urine pregnancy test at both screening and at each admission to the research unit. All male and female subjects must have used a medically acceptable form of birth control for at least one month prior to screening and be willing to continue use during the study. Medically acceptable forms of birth control include abstinence, hormonal contraceptives, diaphragm with spermicide, condom with spermicide, intrauterine device, or surgical sterilization (including vasectomy of male partner[s]).
2. Eighteen (18) to 45 years of age, inclusive
3. Based on medical history, limited physical examination (neurologic and cardiac) and/or lab results, are considered healthy and free of any conditions that may interfere with participation in the study. Any abnormalities at screening on results of electrocardiogram (ECG) or any laboratory test must be determined to be not clinically significant by an investigator.
4. Agree to not use prescription stimulants (except for the study medication) during the study
5. Have venous access sufficient for blood sampling as determined by clinical examination
6. Weigh at least 100 pounds at screening
7. Agree and are available to return to the study center for five full-day (approximately 18 hours) study visits held five to 30 days apart within a 22-week period, and willing to complete all protocol-specified assessments.
8. Able to read and comprehend English

Exclusion Criteria:

1. Marked anxiety, tension, and agitation since the drug may aggravate these symptoms

2. Known hypersensitivity to methylphenidate or other components of Concerta or Ritalin

3. Subjects with glaucoma

4. Motor tics or with a family history or diagnosis of Tourette's syndrome

5. Treated with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuation of treatment with MAOIs

6. Presence or history of any medically diagnosed, clinically significant Axis I psychiatric disorder (including substance use disorders, bipolar disorder, any psychotic disorder)

7. Scores of Baseline Scales:

   • Hamilton Depression Scale > 17 (out of a possible 67 on the 21-item scale) (Hamilton 1960)
   • Beck Depression Inventory > 19 (out of a possible 63 on the 21-item scale) (Beck et al 1961)
   • Hamilton Anxiety Scale > 21 (out of a possible 56 on the 14-item scale) (Hamilton 1959)

8. Any clinically significant chronic disease or unstable medical abnormality by history or physical examination, including hypertension, hyperthyroidism, a seizure disorder, history of myocardial infarction or stroke, or history of cardiac arrhythmia or heart murmur (other than uncomplicated mitral valve prolapse)

9. Clinically significant abnormal baseline laboratory values which include the following:

   • Values > 20% above the upper range of the laboratory standard of a basic metabolic screen and complete blood count
   • Exclusionary blood pressure > 140 (systolic) and 90 (diastolic).
   • Exclusionary ECG parameters: QTC > 460 msec, QRS > 120 msec, and PR > 200 msec. Subjects having ECG evidence of ischemia or arrhythmia as reviewed by an independent cardiologist

10. Currently taking or require any of the following medications:

    • Clonidine or other alpha-2 adrenergic receptor agonists
    • Tricyclic antidepressants
    • Selective serotonin reuptake inhibitors (SSRIs)
    • Theophylline
    • Coumarin anticoagulants
    • Anticonvulsants
    • Prescription stimulants

11. Have taken an SSRI in the 35 days before initiation of the study medication

12. Currently physically dependent on benzodiazepines, opiates or alcohol as determined by clinical evaluation or positive urine drug screen at screening

13. Preexisting severe gastrointestinal narrowing (pathologic or iatrogenic, for example: small bowel inflammatory disease, "short gut" syndrome due to adhesions or decreased transit time, past history of peritonitis, cystic fibrosis, chronic intestinal pseudoabsorption, or Meckel's diverticulum)

14. Unable to swallow the study medication whole

15. Have had a significant blood loss (> 500 mL) or donated blood in the 30 days preceding dosing

16. Have a positive urine drug screen at screening

17. Have taken an investigational medication or product within the past 30 days

18. Have taken prescription medications (with the exception of birth control methods) within seven days of screening or is anticipated to need any medications, over-the-counter products (other than acetaminophen), or herbal supplements during the study