A Drug Treatment for Cocaine Users Who Are Also on Methadone Maintenance Treatment

This will be an approximately 13 to 14 week double-blind, placebo-controlled clinical trial
testing the safety and feasibility of atomoxetine (40 or 80 mg/day) treatment, compared to
placebo, in methadone-stabilized stimulant users. The study will have 3 phases: 1) a oneto
two week- methadone-induction phase; 2) an 8-week "treatment" phase; and 3) 1 week
atomoxetine taper and about a 4-week methadone "taper and detoxification or transfer"
phase. Subjects will be randomized to three treatment arms: 40 mg (n=15) atomoxetine, or 80
mg (n=15) atomoxetine, or placebo (n=15). During the methadone induction phase, subjects
will be stabilized on methadone. During induction onto methadone, participants will be
administered increasing doses of methadone starting at 30 mg daily, and this dose will be
increased for stabilization of opiate withdrawal symptoms from 40 mg up to 140 mg depending
on individual need. Based on the clinic schedule between 1 to 2 weeks after methadone
treatment is initiated , atomoxetine treatment will be started at 40 mg/day. For those
assigned to 80 mg of atomoxetine, the dose will be titrated up to 80 mg/day on the second
week of treatment phase. At the end of the treatment-phase, subjects will undergo
detoxification from methadone over a 4-week period based on an individual's needs, and they
will concurrently be tapered off atomoxetine. All participants will receive a weekly
one-hour of individual psychotherapy (Cognitive Behavioral Therapy) with experienced
clinicians specifically trained to deliver the therapy, and who will receive ongoing
supervision.

Inclusion Criteria:

- • Men and women between 18 and 65 years old.

- Current opioid dependence as evidenced by 1) documentation of prior treatment
for opioid dependence or signs of withdrawal, 2) self-reported history of opioid
dependence for 12 consecutive months and, 3) a positive urine toxicology screen
for opiates.

- Diagnosis of opioid dependence and cocaine dependence by DSM-IV-criteria as well
as laboratory confirmation of recent cocaine use in the form of positive urine
toxicology during the month prior to study entry.

- For those who recently participated in a research study, at least 2 weeks of
washout period before enrollment.

- A history of cocaine use,( a minimum of 1/2 gram during the preceding 30 days).

- Must be seeking treatment for opioid and cocaine use.

- For women of childbearing age, a negative pregnancy test at screening with
agreement to use adequate contraception to prevent pregnancy and monthly
pregnancy tests.

Exclusion Criteria:

- • Serious medical illnesses including hypertension, tachycardia, bradycardia, or
other arrhythmias and major cardiovascular, cerebrovascular, renal, endocrine, or
hepatic disorders;

- Serious psychiatric illness, history of psychosis, schizophrenia or bipolar type
I disorder.

- Current major depression. Subjects with current depressive symptoms not meeting
criteria will be included in the study, with the exception of those endorsing
suicidal and homicidal thoughts, will be excluded even if full criteria for
major depression are not met.

- Current diagnosis of alcohol or drug dependence other than opiates, cocaine,
nicotine and cannabis.

- Current use of over-the-counter or prescription psychoactive drugs
(antidepressant, anxiolytics, antipsychotics, mood stabilizers,
psychostimulants) or drugs that would be expected to have major interactions
with drugs to be tested, e.g., benzodiazepines, codeine, percocet, and other
opiate drugs that will interact with methadone.

- Has not been treated with monoamine oxidase inhibitors within the last fourteen
days.

- Liver function tests (ALT or AST) greater than 3 times normal.

- Known allergy or intolerance to atomoxetine.