Aprepitant Effects in Intravenous Heroin Dependence

Inclusion Criteria:

1. Male and female subjects ranging in age from 18-55 years who are currently opioid
dependent based on meeting DSM-IV criteria for dependence on heroin and who are
either treatment or non-treatment seeking individuals.

2. Use of intravenous heroin daily for a minimum of 45 days prior to study entry.

3. Urine sample (+) for opioids and prior experience with i.v. drug injection.

4. Female subjects who are not of childbearing potential, (i.e. post-hysterectomy, or
two years post-menopausal) or who are of childbearing potential but will either
abstain from heterosexual intercourse and/or practice a medically accepted form of
contraception for the study duration.

5. Subjects who have experienced significant opioid withdrawal and are familiar with its
effects.

6. Subjects who are willing to follow the protocol requirements, including methadone and
study medication schedules, as evidenced by written informed consent and an ability
to read, understand, and complete the study questionnaires.

Exclusion Criteria:

1. Subjects with any significant current axis-1 psychiatric problems, other than those
related to drug abuse and opioid dependence, based on a structured psychiatric
interview, SCID or MINI, during the screening process.

2. Subjects undergoing active treatment for any illness other than chronic stable
medical conditions (Patients with HIV and/or taking anti-viral HIV medication without
a manifestation of AIDS symptoms are allowed).

3. Subjects with clinically significant abnormal findings as determined by medical
history, physical examination, vital signs (blood pressure, heart rate, and
respiration rate), 02 saturation measure,12-lead ECG, clinical laboratory tests (CBC,
chemistry panel), urine drug screen, alcohol breath test, and urine pregnancy test
(for females of childbearing potential only).

4. Subjects who have any acute organ dysfunction or serious unstable disease states
including symptomatic heart, renal or liver disease, COPD, sleep apnea, or
encephalitis.

5. Subjects with 02 saturation below 90% at screening.

6. Subjects taking any concomitant medications (prescription and over-the-counter
therapy) including psychotropic medications for the treatment of current major
depression, schizophrenia, or mood disorders, as well as medications contraindicated
for use with morphine, naltrexone, aprepitant, or methadone.

7. Subjects who have received any investigational drug or treatment within the thirty
(30) days preceding administration of study medication.

8. Females who are nursing, pregnant (as confirmed by a positive urine pregnancy test),
or at risk of becoming pregnant.

9. Subjects allergic or intolerant to morphine, methadone, naloxone, or aprepitant.