Cocaethylene as a Treatment for Cocaine Dependence - 1

Currently, there are no medications available to specifically treat cocaine addiction.
Cocaethylene is an active metabolite of cocaine and has a similar chemical structure to
cocaine. The purpose of this study is to determine whether substitution therapy with
cocaethylene is a safe and effective treatment for cocaine dependence.

This double-blind, placebo-controlled trial will occur in 3 parts. In Part 1, the individual
pharmacokinetics of an intravenous dose of cocaethylene will be determined in order to
estimate individualized cocaethylene infusion rates and pharmacokinetic parameters. This
will provide important information on how cocaethylene is processed by the body. In Part 2,
an infusion of cocaethylene, producing a venous plasma concentration of 200 ng/ml, will be
administered over an 8-hour period. Clinical monitoring and blood sampling will occur in
order to determine the safety profile of cocaethylene. During Part 3, the ability of
cocaethylene to modify the acute effects of intravenous cocaine will be determined.
Cocaethylene will be administered in plasma concentrations of 0 ng/ml, 50 ng/ml, or 200
ng/ml over an 8-hour period. Participants will be randomly assigned to receive a challenge
intravenous dose of cocaine (0.5 mg/kg or 1 mg/kg) or placebo at the 4-hour mark of
cocaethylene infusion. Following the initial 8-hour period, cocaethylene infusion will be
continued for an additional 5 hours. Behavioral and physiological measures will be collected
throughout the study sessions at predetermined times to evaluate whether tolerance to
cocaethylene develops. These measures will also help to determine whether cocaethylene
modifies or produces tolerance to the effects of an acute dose of cocaine.

Inclusion Criteria:

- Meets DSM-IV criteria for cocaine dependence

- Cocaine use of at least 0.5 grams each week during the three months prior to
enrollment, confirmed by a positive urine test for cocaine metabolite

- Females are eligible if currently using adequate contraception, not planning to
become pregnant, or surgically sterilized

- Females of child-bearing potential must have a negative pregnancy test prior to study
entry

- Currently not physiologically dependent on alcohol, but may meet DSM-IV criteria for
alcohol abuse or dependence

Exclusion Criteria:

- Meets DSM-IV criteria for dependence on any drugs (other than nicotine or alcohol)
within the year prior to enrollment

- Currently abuses other substances such as opiates, sedative-hypnotics, or
amphetamines (excluding marijuana or nicotine) more than twice a week

- History of a serious medical illness or indication of a serious medical illness such
as seizures, hypertension, heart disease, an abnormal ECG, anemia, diabetes, or
abnormal blood flow sounds

- Meets DSM-IV criteria for a current major mental disorder, including major
depression, bipolar disorder, schizophrenia, schizophreniform disorder,
schizoaffective disorder, mental retardation, or organic mental syndrome

- Currently being treated with psychotropic medication

- At risk for suicide, as determined by a psychiatrist

- Greater than two times the normal level for liver or kidney function tests

- Currently seeking treatment for drug abuse

- Participants with liver function tests equal to or greater than three times the
normal level will be discontinued from the study