Drug Discrimination in Methadone-Maintained Humans Study 3

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 and \<3 individual therapy sessions in the two months 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 (e.g., major, unstable cardiovascular, renal, endocrine or hepatic disease) or stable medical condition requiring treatment that would interact with study medications (e.g., controlled hypertension on an antihypertensive) or ability to participate in study sessions, (e.g.,chronic back pain that would preclude being able to sit for long periods, etc), to be determined by history provided by the prospective subject or laboratory evaluation and physical examination as outlined below. These would be determined by the study physician alone or in consultation with the PI. 2. Current diagnosis of other drug or alcohol physical dependence (other than tobacco). 3. History of major psychiatric disorder (psychosis, schizophrenia, bipolar) or current psychiatric disorder that requires medication (e.g., current major depression). 4. Pregnancy, plans to become pregnant or inadequate birth control (adequate birth control includes an IUD, condoms, birth control pills, etc). Male participants are encouraged to use condoms because little has been studied on the effects of these drugs on the male reproductive system. 5. Present or recent use of over-the-counter psychoactive drug, prescription psychoactive drug (antidepressants, anxiolytics, antipsychotics and anticonvulsants that may also be used for mood stabilization or sleep disruption) or drug (e.g., ciprofloxacin, fluvoxamine) that would have major interaction with drugs to be tested. 6. Liver function tests greater than 3 times normal, BUN and Creatinine outside normal range, or thyroid function tests outside normal range. 7. A supine or semi-recumbent blood pressure of 100/65mmHg, a seated blood pressure of 90/60mmHg, or orthostatic change of \>20mmHg systolic or \>10mmHg diastolic on standing or heart rate less than 60 beats/min. 8. EKG abnormalities including but not limited to: bradycardia (\<60 bpm); prolonged QTc interval (\>450 msec); Wolff-Parkinson White syndrome; wide complex tachycardia; 2nd degree, Mobitz type II heart block; 3rd degree heart block; left or right bundle branch block. 9. Participants who become arrested and/or incarcerated will not be allowed to continue to participate.