Effects of Buprenorphine/Naloxone Dose on Experimental Stress Reactivity and Opioid Abstinence

If participants meet all the criteria, their involvement in the study (Phases 1 and 2
described below) will last for 10-13 weeks. Participants will be asked to stay at the
research site for a minimum of 2 nights on 4 separate weeks and will have 22 office visits
During that time, participants can't leave the unit unescorted or have visitors.

Participants will receive a medication called Buprenorphine/Naloxone. Buprenorphine/Naloxone
is approved by the Food and Drug Administration (FDA) to treat opioid addiction, and is a
safe and effective alternative to methadone. Participants will receive this medication every
day. When participants are not living on the inpatient unit they will come to the research
clinic every day to receive the medication.

On Day 1, one single 1-mL (0.2 teaspoon) blood sample will be collected to assess the effect
of the Buprenorphine/Naloxone medication dose on gene expression pattern.

On the 8 days while participants are an inpatient they will participate in experimental
sessions that involve drug administration. On some days participants will receive morphine
and on some days participants will receive oral medications called yohimbine and
hydrocortisone that will be used to study stress responses. Each afternoon study staff will
collect one blood sample (10 mL or 2 teaspoons) from a vein in the participant's arm; these
samples will be used to measure biological signals of stress.

At the end of the study participants will be detoxified from the Buprenorphine/Naloxone
medication over a 3-week outpatient period.

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

- Participants must be in generally good health to be eligible. All candidates will
receive a routine medical exam (history and physical) with standard laboratory tests
(including blood and urine samples, EKG, mandatory TB testing, and voluntary HIV
testing).

Exclusion Criteria:

- No candidate who has a current DSM-IV Axis I disorder other than Drug Dependence or a
history of serious psychiatric problems (e.g. psychosis, bipolar or major depression)
will be allowed to participate.

- Candidates meeting criteria for opioid or nicotine dependence will not be excluded,
but those with other Substance Dependence disorders will be excluded. Those with Abuse
of Alcohol, Cannabis, Cocaine, will not be excluded, but participants must provide an
alcohol free breath specimen.

- No candidate with medical (neurological, cardiovascular, pulmonary or systemic)
disorders will be allowed to participate. This will be determined with history and
physical exam, standard laboratory testing (blood and urine), EKG, and TB tests (to
avoid transmitting this communicable disease on the residential unit or in the
laboratory).

- Candidates with evidence of cognitive impairment (based on reading ability and
comprehension, will be excluded.

- Female candidates who are pregnant (urine pregnancy test), lactating, or not using
adequate birth control methods (self-report) will be excluded.

- Candidates with injection phobia, or seeking treatment for opioid dependence will be
excluded.