Studies of Opioid Seeking Behavior: Yohimbine and Hydrocortisone Effects

Phase 1: Participants will first be an outpatient and must come to the Tolan Park Medical
Building 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.

Phase 2: Participants will then live on an inpatient research unit (located in Detroit
Michigan) for at least 16 consecutive nights and possibly up to 18 consecutive nights.
Participants will continue on the same dose of buprenorphine as in phase 1.

During this stay they will participate in a total of 11 experimental sessions. Participants
will take part in multiple trials in which they have the opportunity to choose drug,
hydromorphone, or money. Hydromorphone is a heroin-like opioid. During the first two test
sessions, participants will receive a sample of the drug doses that can be chosen. Before
each of the final 9 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 be given
a capsule that contains either different doses of the drug hydrocortisone or a placebo
(blank). Hydrocortisone is also a drug that can produce a "stress"-like response in humans.
Then participants will have the opportunity 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.

Phase 3: After participants have completed the experimental procedures, they will again come
to the Tolan Park Medical Building 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.

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, or Benzodiazepines will not be excluded, but
participants must provide an alcohol free breath specimen, and a benzodiazepine free
urine sample.

- 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.