Prazosin for ETOH or Cocaine Craving

1. Objective of the project: To evaluate the efficacy of prazosin on the reduction of
craving in alcohol and cocaine dependent individuals. The investigators hypothesize that
prazosin will be more effective than placebo in the reduction of craving that is
stimulated by exposure to visual cues or to intolerance to stress in individuals
dependent on cocaine and in individuals dependent on alcohol.

Specifically, the investigators hypothesize that in this laboratory study:

- Subjects in the prazosin condition will report a reduction in craving induced in
the laboratory by exposure to visual cues compared to subjects in the placebo
condition.

- Subjects in the prazosin condition will show less reaction of the noradrenergic
system when craving is induced in the laboratory by exposure to visual cues
compared to subjects in the placebo condition.

- Subjects will be less likely to relapse to their drug of choice while they are in
the prazosin condition compared to when they are in the placebo condition. Most
individuals who are able to achieve sobriety in chemical dependency treatment
eventually relapse. Until the investigators can prevent the cravings for drugs,
which usually precedes relapse, it is unlikely that the investigators will have
more effective treatment for drug addiction. Our final hypothesis is that the
alpha-1, adrenergic antagonist, prazosin, will prove to be an effective
pharmacological agent for treatment of drug dependency.

2. Research plan study design: The proposed study will be a double-blind,
placebo-controlled, crossover study of prazosin in subjects who are either dependent on
alcohol or on cocaine, and who have been able to achieve one month of sobriety while in
intensive outpatient treatment. The double-blind, crossover protocol will last 8 weeks
and will include 32 subjects; 16 of whom are alcohol-dependent, and 16 of whom are
cocaine-dependent. The focus of this first study will be on subjective and physiological
measures of craving that will be induced in a controlled setting by exposure to visual
cues.

3. Methodology Setting: This study will occur in room 6A-107 in Building 1 at the Veterans
Administration Puget Sound Health Care System in Seattle. This is a soundproof room
specifically designed and constructed for studies of this type. Participants: 16
alcohol-dependent adults and 16 cocaine-dependent adults presenting for chemical
dependency treatment at the VA Puget Sound Health Care System (VAPSHCS) Addiction
Treatment Center. Study Procedures: Once potential subjects have provided their consent
to participate in the study, they will undergo a 2 hour baseline assessment that
consists of some pencil and paper questionnaires, providing a medical and psychiatric
history, and a physical exam. They will provide blood for some basic screening labs to
insure they are healthy enough to proceed with the study, and have their baseline vital
signs measured. Veterans who are screened for the study will then be enrolled once their
lab results and the screening process have determined that they do not meet any medical
exclusion criteria. At that point, participants will be randomized to either the study
medication or placebo. During the course of the study, participants continue with their
outpatient chemical dependency treatment through the Addiction Treatment Center at the
VA Puget Sound. During the eight weeks of the study, participants will have weekly
orthostatic vital sign and adverse events monitoring by the study nurse or physician.
All serious or unexpected adverse events will be reported to the FDA and UW Human
Subjects Committee in accordance with requirements. Participants will also provide
self-reports of drug or alcohol use and urine drug analysis specimens at these weekly
visits. At the end of week 4, each participant will be tested in a 1 hour craving
session in room 6A-107 at VA Puget Sound. Subjects will have their heart rate and skin
conductance response continuously measured, and have their blood pressure measured every
5 minutes. They will be shown 5 1-minute films, 3 of which are designed to be neutral
and 2 of which are designed to provoke craving for their drug of choice. They will be
asked to complete a subjective scale of craving prior to each video and after the last
video. Participants will not be permitted to leave the craving lab after the last film,
until they feel that they have subjectively returned to a level of normal physiological
arousal and are no longer experiencing any craving.

4. Findings: No findings to date.

Inclusion Criteria:

- Age 18-70 years

- Current DSM-IV diagnosis of alcohol dependence or cocaine dependence with no use in
last 30 days

- Capacity to provide informed consent

- Actively enrolled in chemical dependency treatment at VA Puget Sound English fluency

Exclusion Criteria:

- Evidence of significant abuse of opiates, PCP, sedatives or anxiolytics

- Suicidal ideation

- DSM IV diagnosis of bipolar mood disorder, schizophrenia or schizoaffective disorder

- Significant acute or chronic medical illness, including unstable angina, recent
myocardial infarction, history of congestive heart failure, preexisting hypotension
(systolic < 110), or orthostatic hypotension (systolic drop > 20mmHg after two minutes
standing or any drop with dizziness), insulin-dependent diabetes mellitus; chronic
renal or hepatic failure, pancreatitis, gout, M ni re's disease, benign positional
vertigo, narcolepsy

- Concomitant use of alpha-1 antagonists History of prazosin-sensitivity Women who are
pregnant, nursing infant(s), or of childbearing potential and not using a
contraceptive method judged by the investigator to be effective

- Non-compliance with outpatient chemical dependency treatment