Drug Discrimination in Methadone-Maintained Humans Study 2 (OMDD2)

• Self-report Ratings [ Time Frame: Every Session ] [ Designated as safety issue: No ]
• Vital Signs [ Time Frame: Every Session ] [ Designated as safety issue: Yes ]
• ECG [ Time Frame: Test Sessions ] [ Designated as safety issue: Yes ]

This study involves giving psychoactive drugs intramuscularly (injected into the muscle of the upper arm or the hip) and/or orally, and measuring the subject's ability to tell the difference between one drug and another, as well as measuring the effects of the drugs on mood, physiology (e.g., heart rate, blood pressure, respiration rate) and behavior. Each subject will receive 2-4 of the listed interventions.

Inclusion Criteria:

1. Must be between the ages of 18-65.
2. Participation in the UAMS Substance Abuse Treatment Clinic Methadone Maintenance Program or the Catar Clinic Little Rock with maintenance on a stable dose of methadone (+ or - 10 mg) for at least 1 month prior to study entry.
3. Subjects would have to be in "good standing" in the methadone maintenance program in order to participate; i.e., compliance with scheduled medication and group therapy session hours. This would be defined as < 3 missed methadone medications and missed < 3 group or <3 individual therapy sessions in the month prior to study participation
4. Subjects must submit a urine sample negative for illicit drugs prior to study entry.
5. Subjects must be able to read and understand English.

Exclusion Criteria:

1. Unstable medical condition or stable medical condition that would interact with study medications or participation.
2. Current diagnosis of other drug or alcohol physical dependence (other than tobacco).
3. History of major psychiatric disorder (psychosis, schizophrenia, bipolar, depression)
4. Pregnancy, plans to become pregnant or inadequate birth control.
5. Present or recent (< 1 week) use of over-the-counter psychoactive drug, prescription psychoactive drug or drug that would have major interaction with drugs to be tested. Recent use will be defined based upon the pharmacokinetics of the drug and dosing schedule. Thus, a short-acting antihistamine taken as needed (e.g., once the night before) will not necessarily rule out a participant; however,
6. History of severe reaction to Narcan challenge, which may have been given as part of admission into the Methadone Maintenance Program or to reverse overdose.
7. Liver function tests (ALT, AST) greater than 3 times normal, BUN and Creatinine outside normal range, or thyroid function tests outside normal range.
8. ECG abnormalities including but not limited to: bradycardia (<60 bpm); Wolff-Parkinson White syndrome; wide complex tachycardia; 2nd degree, Mobitz type II heart block; 3rd degree heart block; left or right bundle branch block.