Effects of Pioglitazone, a PPARgamma Receptor Agonist, on the Abuse Liability of Oxycodone

This 9-week investigation will use an inpatient/outpatient design in which participants will
be maintained on ascending doses of pioglitazone (3 weeks on placebo followed by 3 weeks on
PIO 15 mg followed by 3 weeks on PIO 45 mg). At the end of each maintenance period the
effects of oxycodone (0, 10, and 20 mg) will be examined during a single laboratory session
using a cumulative dosing procedure.

Inclusion Criteria:

1. Recreational use of prescription opioids at least once per month within the past year

2. No current major mood, psychotic, or anxiety disorder

3. Physically healthy

4. aspartate aminotransferase (AST) or alanine aminotransferase (ALT) within normal
limits

5. Able to perform study procedures 6.21-45 years of age

7.Blood glucose concentration between 70-145 mg/dl for men and 70-125 mg/dl for women
(fasting) 8.Hb > 13 for men and Hb > 11 for women with no other evidence of medical
disorder resulting in blood loss or anemia/hematological disease

Exclusion Criteria:

1. Physical dependence on any drugs, excluding nicotine and caffeine

2. Participants requesting treatment

3. Participants on parole or probation

4. Pregnancy or lactation: Female participants must agree to the use of a barrier
control method of contraception (e.g. male and female condoms, diaphragms, cervical
caps and contraceptive sponges used in combination with spermicide)

5. Current or recent history of significant violent behavior (within the past 6 months)

6. Current major Axis I psychopathology that might interfere with ability to participate
in the study

7. Significant suicide risk

8. Current chronic pain

9. Current or history of congestive heart failure, edema, or diabetes mellitus

10. Sensitivity, allergy, or contraindication to opioids or pioglitazone

11. Unstable physical disorders that might make participation hazardous, such as
end-stage AIDS, hypertension (blood pressure > 140/90), or heart disease (please note
that participants will be asked about previous visits to a cardiologist, chest pain,
or strong palpitations; if these exist, they will be referred to a cardiologist and
excluded unless cleared for participation by a cardiologist)