The purpose is to study the extent to which stress and other factors, including money, the amount of drug available and the amount of work effort, affect drug choice.

This study will assess whether exposure to yohimbine, a drug stressor, increases opioid craving- and -seeking behavior. We will determine whether these behavioral outcomes are associated with biobehavioral stress markers: increased saliva cortisol levels, cardiovascular response (heart rate and blood pressure), and negative mood state.

Physical, environmental, and pharmacological stressors have been repeatedly shown to increase self-administration of various abused substances in both preclinical and human studies. The primary aim of the proposed work is to assess the effects of yohimbine, a pharmacological agent, used to create an objectively-measured stress response, upon opioid-seeking behavior and craving.

Participants will first be an outpatient and must come to the Jefferson Avenue Research Program daily to receive buprenorphine doses. This phase will last at least 10 days or longer. Three times per week during the first two weeks (i.e., on 6 different days), participants will be asked to provide urine samples and to complete questionnaires that ask about opiate withdrawal symptoms.

Next, participants will live on an inpatient research unit for at least 11 consecutive nights and possibly up to 15 consecutive nights. During this stay they will participate in a total of eight experimental sessions. Participants will take part in multiple trials in which they have the opportunity to choose drug, hydromorphone (HYD), or money. HYD is a drug that is currently used as a cough suppressant and to relieve pain. During the first two test sessions, participants will receive a sample of the drug doses that can be chosen. Before each of the final 6 test sessions begin, participants will be given a capsule containing either different doses of the drug yohimbine or a placebo (blank). Yohimbine is a drug that has been shown to produce a "stress"-like response in humans. Then participants will have 12 opportunities to choose either drug or money by using a computer to earn choices. Respiration rate, oxygen saturation, heart rate, and blood pressure will be monitored throughout choice trials. Self-report questionnaires will be completed at different times during the study.

After participants have completed the experimental procedures, they will again come to the Jefferson Ave. Research Program daily to receive buprenorphine doses. The dose of buprenorphine will be gradually decreased so that they will eventually be free from medication. This will take three weeks. We will administer questionnaires and collect urine samples three times each week to assess using illicit drugs.

Inclusion Criteria:

• Opioid dependent, as determined by structured clinical interview for DSM-IV (SCID) and Addiction Severity Index (ASI)
• Positive urine test for opiates
• Willing to use an adequate form of contraception for the duration of the study.
• Reads and writes English

Exclusion Criteria:

• Psychiatric illness, as determined by the DSM-IV criteria
• History of or current neurological disease, including structural abnormalities, seizures, infection, peripheral neuropathy, and head traumas
• History of cardiovascular disease, myocardial infarction, chest pain, or edema
• Systolic blood pressure greater than 160mm HG or less than 95 mm HG: PR diastolic blood pressure greater than 95 mm HG.
• Pulmonary disease, including obstructive pulmonary disease, Cor pulmonale, tuberculosis, and asthma
• Systemic disease (e.g. endocrinopathies, liver or kidney failure, myxedema, hypothyroidism, Addison's disease, autoimmune disease)
• Current alcohol or sedative drug dependence
• Pregnant or breast feeding
• Currently receiving treatment for opioid dependence
• Known phobia of injections

Heroin dependent research volunteers