Effectiveness of Amantadine and Propranolol for Treating Cocaine Dependence - 2

Cocaine withdrawal symptoms are a major contributing factor for why outpatient cocaine
dependence treatment programs often fail. Individuals with severe cocaine withdrawal
symptoms often experience anxiety, shaking, and muscle pain. Amantadine is a medication
currently used to improve muscle control, reduce shaking, and lessen stiffness. Therefore,
it may help reduce the muscle pain that some cocaine addicts experience. By enhancing
activity of the brain chemical dopamine, amantadine may also reduce other symptoms
associated with cocaine withdrawal. Propranolol is a medication currently used to treat high
blood pressure and irregular heart rhythms. It may reduce anxiety and lessen cocaine
cravings in individuals addicted to cocaine. The purpose of this study is to evaluate the
effectiveness of amantadine and propranolol, alone and in combination, for treating cocaine
addicts with severe cocaine withdrawal symptoms.

A 2-week baseline evaluation period will be followed by an 8-week treatment phase. During
the baseline evaluation, cocaine use will be measured with urine tests, three times each
week. Only participants who are experiencing severe withdrawal symptoms and who use cocaine
at least twice during the first 2 weeks will continue in the study. Eligible individuals
will then be randomly assigned to receive amantadine alone, propranolol alone, a combination
of amantadine and propranolol, or placebo. Treatments will begin at Week 3 and study visits
will occur three times each week. Cocaine levels will be monitored throughout the study with
urine tests.

Inclusion Criteria:

- Male and females, 18 to 60 years old.

- Meets DSM-IV diagnosis criteria for cocaine dependence as determined by the
Structured Clinical Interview for DSM-IV (SCID)

- Score of at least (> or =) 22 on the Initial Cocaine Selective Severity Assessment
(CSSA)

- Lives within commuting distance of the Treatment Research Center (TRC) and the
Penn/VA Center for Studies of Addiction, University of Pennsylvania

- If female, willing to use contraception throughout the study

- Continued use of cocaine during a two week evaluation phase prior to medication
treatment as demonstrated by at least 2 new uses of cocaine documented by
quantitative urine toxicology screen obtained three times weekly according to new use
rules

Exclusion Criteria:

- Meets DSM-IV/SCID diagnosis criteria for dependence on any drugs other than cocaine,
marijuana, or nicotine. Cocaine dependent subjects who identify cocaine dependence as
their primary addiction but who also meet criteria for alcohol dependence will be
accepted as long as the alcohol dependence is not severe enough to require
medications for alcohol detoxification.

- Concomitant treatment with psychotropic medications.

- Patients mandated to treatment based upon a legal decision or as a condition of
employment. This will be assessed by the patient's self-report.

- Current severe psychiatric symptoms (e.g., psychosis, dementia, suicidal or homicidal
ideation, mania or depression requiring antidepressant medication)

- Sensitivity to propranolol or amantadine

- Use of any investigational medication within the past 30 days.

- History of significant heart disease (an arrhythmia which required medication,
Wolff-Parkinson -White Syndrome, angina pectoris, documented history of myocardial
infarction, heart failure).

- History of chest pain associated with cocaine use which has prompted a visit to a
physician.

- Current use of reserpine, verapamil, theophylline, trimethoprim, cimetidine,
haloperidol, benzodiazepines, or anticonvulsants

- Bronchospastic disease

- Hyperthyroidism

- Diabetes mellitus

- Patients with known AIDS or other serious illnesses which may require hospitalization
during the study.

- Female subjects who are pregnant or lactating, or female subjects of child bearing
potential who are not using acceptable methods of birth control. Acceptable methods
of birth control include:

1. barrier (diaphragm or condom) with spermicide

2. intrauterine progesterone contraceptive system

3. levonorgestrel implant

4. medroxyprogesterone acetate contraceptive injection

5. oral contraceptives.

- Patients with impaired renal function as indicated by corrected creatinine clearance
below 80 ml/min/70 kg as determined by the modified Cockcroft equation (CDC, 1986).

- Clinical laboratory tests (CBC, blood chemistries, urinalysis) outside normal limits
that are clinically unacceptable to the Principal Investigator. EKG 1st degree heart
block, sinus tachycardia, left axis deviation, and nonspecific ST or T wave changes
are allowed; liver function tests [LFTs] <5 x ULN are acceptable). A complete list of
exclusionary lab results are included in the appendix 1