Establishing and Eliminating Cue-drug Associations in Human Cocaine Addiction

Study Overview
=================
Brief Summary
-----------------
We will develop a procedure for conditioning cue-cocaine associations in human drug users. Next, we will reactivate that learning and intervene pharmacologically to prevent the reconsolidation of cue-drug memories. We hypothesize that a combined behavioral and pharmacological approach will have significant potential for persistently inhibiting relapse.

Official Title
-----------------
Establishing and Eliminating Cue-drug Associations in Human Cocaine Addiction

Conditions
-----------------
Cocaine Dependent Subjects

Intervention / Treatment
-----------------
* Drug: cocaine hydrochloride
* Drug: propranolol
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 - 50 years voluntary, written, informed consent physically healthy by medical history, physical, neurological, ECG, and laboratory examinations DSM-IV criteria for Cocaine Abuse (305.60) or Cocaine Dependence (304.20) recent street cocaine use in excess of that administered in the current study intravenous and/or smoked (crack/freebase) use positive urine toxicology screen for cocaine for females, non-lactating, no longer of child-bearing potential (or agree to practice effective contraception during the study), and a negative serum pregnancy (-HCG) test able to read English and complete study evaluations. Exclusion Criteria: Other drug dependence (except nicotine) a primary major DSM-IV psychiatric diagnosis (schizophrenia, bipolar disorder, etc.), unrelated to cocaine a history of significant medical (cardiovascular) or neurological illness (e.g., prior myocardial infarction, current active symptoms of cardiovascular disease / angina, evidence of cocaine-related cardiovascular symptoms, prior arrythmias of clinical significance, and/or need for cardiovascular resuscitation, neurovascular events such as transient ischemic attacks, stroke, and/or seizures) current use of psychotropic and/or potentially psychoactive prescription medication seeking treatment for drug abuse/dependence those having contraindications to beta-blocker administration, including diagnoses of asthma, bronchitis, emphysema, or a history of adverse reactions to beta-blockers (including propranolol), as well as those with bradycardia and/or first-degree or greater heart block by ECG

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cocaine hydrochloride<br>cocaine hydrochloride | Drug: cocaine hydrochloride<br> <br> Drug: propranolol<br> <br> Drug: placebo<br> <br> |
| Experimental: propranolol<br>propranolol | Drug: cocaine hydrochloride<br> <br> Drug: propranolol<br> <br> |
| Placebo Comparator: placebo<br>placebo | Drug: cocaine hydrochloride<br> <br> Drug: propranolol<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total number of patient controlled analgesic (PCA) pump activations (responses) | Data on cocaine self-administration (total number of responses) will be checked for normality prior to analysis using Kolmogorov-Smirnov statistics and normal probability plots. Data that is not normally distributed will be log transformed. If it remains highly skewed after transformation, it will be analyzed using non-parametric approaches (e.g., a non-parametric, ANOVA-Type Statistic). Normally distributed data will be analyzed employing a mixed model design, 3-way ANOVA with co-factors of placebo vs propranolol (between subjects), non-cocaine predicting cues vs. cocaine predicting cues (within subjects) and non-reactivated cocaine cues vs. reactivated cocaine cues (within subjects). | 3 days |