The Efficacy of Doxazosin for Cocaine Users

The NE system, especially the alpha 1-adrenergic receptor, may play an important role in
cocaine addiction in humans. The results of this study will provide medical safety data on
the duration of the induction schedule that will be optimal for attaining our target dose of
8 mg doxazosin daily and will guide future pharmacotherapy trials using Doxazosin or related
alpha 1 receptor antagonists for cocaine addiction.

This 17-week double-blind, placebo controlled clinical trial includes a 13 week medication
trial (weeks 1-13) and up to 4 week washout period(weeks 14-17). Qualifying subjects will be
randomized to receive Doxazosin 8 mg/day, or placebo during the study participation.

Subjects will be receiving 1 mg study medication/placebo capsules at week 1, with 1mg/week
induction rate for 8 weeks, according to their randomized assignments, and are maintained on
these agents through week 13. At the end of the study (weeks 14-17), participants will
undergo discontinuation from active/placebo medication over a 4-week period. Subjects who
wish to be transferred to an appropriate treatment program or treatment-research program will
be helped with referral during the 4 week period (weeks 14-17).

Inclusion Criteria:

- Meets DSM-IV diagnosis criteria for cocaine dependence, as determined by self-reported
use of cocaine at least once weekly for at least 1 month prior to study entry; a
positive urine test for cocaine; and a score greater than 3 on the Severity of
Dependence Scale

- If female, willing to use contraception throughout the study

Exclusion Criteria:

- Meets DSM-IV diagnosis criteria for dependence on any drugs other than cocaine, or
tobacco

- Current major psychiatric illness, including schizophrenia, bipolar disorder, or other
psychotic disorder

- Current suicidal or homicidal ideation

- Current use of a prescribed psychotropic medication that cannot be discontinued

- History of or current major medical illness, including major heart, kidney, endocrine,
or liver disorder; abnormal liver function (SGOT or SGPT levels three times greater
than normal); or high blood pressure or low blood pressure

- High risk factor for heart disease, seizure disorders, or any illness for which
disulfiram or methadone treatment would be inadvisable

- Currently taking metronidazole or clotrimazole

- Pregnant or breastfeeding