Improving Learning-based Treatment of Cocaine Dependence With Medication

Cocaine dependence is a public health problem with substantial morbidity, however no
effective pharmacotherapy for cocaine dependence has been approved by the FDA. Unlike
previous medication studies that have sought to pharmacologically reduce cocaine
reinforcement, seeking or craving, this exploratory clinical trial will test d-cycloserine
(DCS) for its ability to improve learning-based behavioral treatment of cocaine dependence.
DCS is an NMDA partial agonist that has been shown to robustly improve learning in
preclinical models, including extinction of cocaine conditioned place preference and
blockade of cocaine reacquisition, and to improve extinction-learning based exposure therapy
for multiple anxiety disorders. This Phase II clinical trial will investigate the
pharmacological (DCS) enhancement of a behavioral treatment combining contingency management
(CM) and novel home-environment exposure therapy sessions for cocaine dependence. High
magnitude CM incentives will be used to promote the cocaine abstinence necessary for
extinction in home-based exposure sessions. Participants will be randomized into 2 groups:
1. CM with placebo (CM+PL), and 2. CM with DCS (CM+DCS). For 19 days after group assignment,
participants will report to the laboratory 3 times per week (Mon, Wed, Fri) to provide urine
samples, receive contingent vouchers, and complete assessments of drug use, craving, mood,
withdrawal, and quit self-efficacy. DCS (50 mg) or placebo will be administered on Mon, Wed
and Fri study visits (at the end of the lab visit before returning to the home environment
for exposure sessions during the time of DCS action). Follow-up visits will be conducted at
1 week, 1 month, and 3 months post-CM completion, during which time measures of drug use
(self-reported and urinalysis), craving, mood, and withdrawal will be obtained. Comparison
of continuous abstinence post-CM between the groups will be the primary outcome measure.
During an initial laboratory session, a battery of learning/cognitive tasks will test for
forms of learning/cognition enhanced by DCS that might contribute to the treatment effect.
This project will test the efficacy of a novel intervention for cocaine dependence that was
developed based on a known efficacious cocaine dependence treatment (CM), principles of
extinction learning theory, and a medication shown to improve preclinical learning in
general, including extinction of cocaine conditioning, and clinical learning-based exposure
treatment of anxiety disorders. The study may indicate cost effective additions (home
exposure sessions and DCS) to extend CM benefit after the removal of contingencies, and
therefore may increase the dissemination of CM in community settings.

Inclusion Criteria:

- 18-60 years of age (> 60 due to age-related effects on cognitive functioning)

- Satisfy DSM-IV criteria for cocaine dependence (primarily crack)

- Able to complete all study measures

- Currently seeking treatment for cocaine dependence

Exclusion Criteria:

- Meets DSM-IV criteria for dependence on a drug other than cocaine or nicotine (may
meet abuse criteria for other drugs)

- Pregnant, breast feeding, or planning to become pregnant within 3 months

- If female, do not agree to use an effective means of birth control during the course
of treatment (via phone screen)

- History of seizure disorder, severe hepatic impairment, porphyria, serious head
trauma, dementia, or significant cognitive impairment

- Diagnosis of current major psychiatric disorder besides substance dependence or abuse

- Reported use of DCS in the past year

- Illiteracy, as will be determined during in-person screening

- Concurrently prescribed or using ethionamide or isoniazid (both used to treat
tuberculosis)

- Positive urine result for opioids at screening interview