Progesterone Treatment for Cocaine-dependent Women: A Pilot Study

Primary Aims: The primary aims will be directed at treatment efficacy. Relatively unique
to cocaine treatment trials, one of the principal outcome measures will be time to cocaine
relapse. We hypothesize that maintenance on PROG will increase the time to cocaine relapse
compared to maintenance on placebo (PBO). Another cocaine-related efficacy endpoint will be
the proportion of patients who achieve at least 2 consecutive weeks of cocaine abstinence
(based on urine toxicology results) during the double-blind treatment phase. Lastly, the
proportion of cocaine-negative urines collected throughout the treatment trial will be
measured. We hypothesize that women in the PROG group will show a greater reduction in
cocaine use compared to those in the PBO group.

Secondary Aims: 1) Determine if response to laboratory stressors will predict treatment
outcome. We hypothesize that those women with the greatest stress response will do worse in
treatment and that maintenance on PROG will reduce stress/anxiety and thereby improve
treatment outcome. 2) Determine if treatment retention is better in the PROG group compared
to the PBO group and determine if maintenance on PROG improves overall functioning compared
to maintenance on PBO based on the Clinical Global Inventory (CGI). We hypothesize that
women in the PROG group will have better treatment retention and improvement in CGI scores
compared to women in the PBO group.

Tertiary Aims: To conduct exploratory analyses to determine whether 1) trauma history is
related to treatment outcomes and 2) improvements in treatment outcome measures are related
to decreases in HIV high-risk behaviors.

Inclusion Criteria:

- 1. Women between the ages of 18-45 who meet criteria for current cocaine dependence
(DSM-IV-TR). Volunteers may meet criteria for abuse or dependence on nicotine,
marijuana or alcohol, as long as the dependence is secondary to cocaine dependence
and does not require any medical intervention (see additional exclusions for alcohol
dependence below).

2. Use cocaine by the smoked or intranasal route at least four days in the past
month, with at least weekly cocaine use.

3. Women with regular menstrual cycles (24-45 days) who are not pregnant, based on
the results of a blood pregnancy test drawn at the time of screening. They must
agree to use a barrier method of contraception with proven efficacy and agree not to
become pregnant during the study. To confirm this, urine pregnancy tests will be
conducted weekly.

4. Women must be capable of giving informed consent and capable of complying with
study procedures.

Exclusion Criteria:

- 1. Meets DSM-IV-TR criteria for bipolar disorder, Schizophrenia, or any psychotic
disorder other than transient psychosis due to drug abuse.

2. Individuals with any current Axis I psychiatric disorder as defined by DSM-IV-TR
supported by the SCID-I/P that in the investigator's judgment are unstable or would
be disrupted by study medication. Disorders that are stable on psychotherapy or
pharmacotherapy will not be exclusionary. Individuals will be permitted to take
prescribed zolpidem and zaleplon or other medications for insomnia if there is no
evidence of dependence on these substances.

3. Individuals with current major depressive disorder.

4. Individuals physiologically dependent on any other drugs (excluding nicotine or
cannabis) that require medical intervention will be excluded and referred for
treatment. Individuals with severe alcohol dependence , even without physiological
dependence, or with any known alcohol-related diseases will also be excluded.

5. Females who have any of the following medical contraindications: undiagnosed
abnormal genital bleeding, known or suspected history of breast or genital cancer,
active deep vein thrombosis, pulmonary embolism, or history of these conditions,
active or recent (within last year) arterial thromboembolic diseases (e.g., stroke,
myocardial infarction), liver dysfunction.

6. Females who are cognitively impaired or have a chronic organic mental disorder.

7. Individuals with current suicidal risk.

8. Individuals with coronary vascular disease as indicated by history or suspected by
abnormal ECG or history of cardiac symptoms.

9. Unstable physical disorders which might make participation hazardous such as
uncontrolled hypertension (SBP > 150, DBP> 90, or HR > 100 when sitting quietly),
acute hepatitis (patients with chronic mildly elevated transaminases < 3x upper limit
of normal are acceptable), or uncontrolled diabetes.

10. Individuals with a history of seizures.

11. Women who are pregnant or nursing.

12. Individuals who are legally mandated (e.g., to avoid incarceration, monetary or
other penalties, etc.) to participate in substance abuse treatment program.

13. Females with a known or suspected hypersensitivity to oral micronized
progesterone.