Investigation of Mifepristone (RU486) on Stress Sensitivity and Relapse Prevention in Cocaine Dependent Patients

This study attempts to reduce relapse risk by blocking glucocorticoid receptors, and thus
allow some of the changes in the brain caused by cocaine to redress themselves

Inclusion Criteria:

1. Age 18 to 60.

2. Male.

3. Meets DSM?IV criteria for current cocaine dependence and is seeking treatment.

4. Identifies life stress (work, interpersonal, financial, etc) as a trigger for cocaine
use or reports uncontrollable craving to use of cocaine.

5. Displays at least one cocaine-positive urine toxicology during screening.

6. Uses cocaine at least 4/30 days in the past month, or reports episodic binges of large
amounts of cocaine (at least $200) at least 2x/month.

7. Able to give informed consent and comply with study procedures.

Exclusion Criteria:

1. Meets DSM-IV criteria for major depression, bipolar disorder, schizophrenia or any
psychotic disorder other than transient psychosis due to drug abuse. Substance Induced
Mood Disorder with Hamilton Depression Scale score ³13 will be excluded.

2. History of seizures in the last 2 years, or history of seizures related to the
substance (cocaine, alcohol, or benzodiazepine) that the patient continues to use.

3. History of allergic, dermatological, or adverse event to mifepristone

4. Chronic organic mental disorder, insufficient proficiency in English that would render
an individual incapable of giving informed consent.

5. Significant current suicidal risks, history of significant suicidal behavior or any
suicide attempt within the past year.

6. Unstable physical disorders, which might make participation hazardous such as
hypertension (>140/90), WBC < 3.5, new diagnosis of hepatitis (patients with chronic
mildly elevated transaminase levels (£2-3 X upper limit of normal will be considered
acceptable if PT/PTT is normal), renal failure (creat > 2; BUN > 40), or diabetes
(HbA1c > 7%), and low Hb (< 12g/dL) or low Hct (<36%).

7. Coronary vascular disease as indicated by history, or suspected by abnormal ECG or
history of cardiac symptoms. Hx of cardiac symptoms (chest pain, chest pressure,
shortness of breath, syncope) during cocaine use.

8. Cardiac conduction system disease as indicated by QRS duration of ³ 0.11 msec.

9. Currently meets DSM-IV criteria for another substance dependence or abuse disorder
other than nicotine, alcohol, or cannabis. If alcohol dependent, must not be in need
of detoxification. Heavy male drinkers (who consume greater than 5 standard alcoholic
drink per day per NIAAA definition) will be excluded.

10. Presents with metabolic indicators of hypoadrenalism such as low serum sodium (<130
mEq/L), high serum potassium (>5.5 mEq/L), Na/K ratio < 30:1, low fasting blood sugar
(<50 mg/dL), or high BUN (>20 mg/dL), or a previous history of Addison's disease or
adrenal insufficiency, or the presence of low K (< 3.5 mEq/L). spot AM cortisol
<5ug/dL, PM cortisol < 3 ug/dL

11. Participants who cannot comply with study procedures during the initial
hospitalization phase.

12. Supplemental exclusion criteria for cold pressor test (CPT): history of frostbite,
open cut or sore on foot to be immersed, history of Raynaud's phenomenon. During the
testing, if sBP > 190 or dBP > 120, or HR > 160, the test will be interrupted. A
second occurrence of these values will stop all further CPT.

13: Patients taking medications metabolized by cytochrome 3A4 (ex: erythromycin, protease
inhibitors) or that inhibit this cytochrome; or consuming grapefruit juice.

14: Patients with an underlying hemorrhagic disorder and those on anti-coagulants. INR >
1.1, PT > 17 msecs, total plt <100x109/L.

15: Use of treatment agents that inhibit steroid biosynthesis by the adrenal cortex, such
as metyrapone, ketoconazole, fluconazole, aminoglutethimide, or etomidate. Patients also
requiring inhaled steroids.

16. Female