Caffeine and Cocaine

Study Overview
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Brief Summary
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This study is being done to find out if medicines that affect a neurotransmitter (chemical messenger) in the brain called adenosine improve behavioral problems that are related to drug abuse. Another purpose of the study is to find out how genes related to adenosine change how people respond to these medicines. More information about how these medicines change behaviors may be helpful to come up with new treatments for drug abuse.

Detailed Description
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Specific Aims: Aim 1. To characterize the behavioral and subjective effects of acute caffeine administration in cocaine-dependent subjects, using laboratory measures of impulse control, drug discrimination (with d-amphetamine as the training dose), and subjective effects. Hypotheses related to Aim 1: Subjects will show decreases in impulsivity (delay to reward and response inhibition) after acute oral doses of caffeine compared to placebo. Subjects will show some stimulant-like subjective effects following acute oral doses of caffeine, but not the euphoric effects that would predict abuse potential.

Official Title
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Experiment 1: Adenosine Receptor A2A Antagonists and Cocaine Dependence

Conditions
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Cocaine Dependence

Intervention / Treatment
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* Drug: Caffeine 150 MG
* Drug: Placebo
* Drug: Amphetamine
* Drug: Caffeine 300 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who currently meet DSM-IV criteria for cocaine dependence and healthy controls At least one cocaine positive urine during screening. Current regular consumption of caffeine. Female subjects: a negative pregnancy test. Exclusion Criteria: Current or past DSM-IV Axis I disorder other than substance abuse/ dependence Any significant non-psychiatric medical illness requiring ongoing medical treatment or which would preclude treatment with d-amphetamine or caffeine Substance dependence other than cocaine within the last 3 months. Positive breath alcohol. Positive urine drug screen for drugs other than cocaine or THC at the time of behavioral testing For female subjects: known pregnancy or a positive pregnancy test or current breast feeding. Diagnosis of Adult Attention Deficit Disorder as determined by: a) meeting DSM-IV criteria for childhood ADHD, b) currently has impairing ADHD symptoms, c) ADHD symptoms can not have remitted at any period since childhood. HIV positive. I.Q. below 70.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 Caffeine 150 mg<br>Caffeine 150 mg | Drug: Caffeine 150 MG<br>* Across five separate testing days, subjects were administered two placebo doses, 20 mg amphetamine, 150 mg caffeine, and 300 mg caffeine in counterbalanced fashion<br>* Other names: Vivarin;|
| Placebo Comparator: 2 Placebo<br>Placebo | Drug: Placebo<br>* Across five separate testing days, subjects were administered two placebo doses, 20 mg amphetamine, 150 mg caffeine, and 300 mg caffeine in counterbalanced fashion<br>|
| Experimental: 3 Amphetamine<br>Amphetamine | Drug: Amphetamine<br>* Across five separate testing days, subjects were administered two placebo doses, 20 mg damphetamine,150 mg caffeine, and 300 mg caffeine in counterbalanced fashion<br>|
| Experimental: 4 Caffeine 300 mg<br>Caffeine 300 mg | Drug: Caffeine 300 MG<br>* Across five separate testing days, subjects were administered two placebo doses, 20 mg damphetamine,150 mg caffeine, and 300 mg caffeine in counterbalanced fashion<br>* Other names: Vivarin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scale Subjective Rating of Drug Effects | Visual Analog Scale Rating. Scores range from 0 to 100 with higher scores meaning greater intensity of response being rated. | Immediately after dose | 
| Systolic and Diastolic Blood Pressure | Sitting Blood Pressure | Average across 7 time points: Immediately after dose and every 30 minutes for 3 hours | 
| Heart Rate | Sitting heart rate | Average across 7 time points: Immediately after dose and every 30 minutes for 3 hours | 
| Addiction Research Center Inventory Subjective Rating of Drug Effects | Addiction Research Center Inventory (ARCI 49). T/F scales with 49 items. Includes the following subscales: Morphine-Benzedrine Group (MBG), includes euphoria (0 to +16, higher numbers = more euphoria) Phenobarbital-Chorpromazine-Alcohol Group (PCAG), includes sedation (-3 to +11, higher scores = more sedation) Lysergic Acid Diethylmide Group (LSD) , includes dysphoria and agitation (-4 to +10, higher scores = more dysphoria) Amphetamine Group (A), includes stimulation ( 0 to +11, higher scores = more stimulation) Benzedrine Group (BG), includes energy and intellectual efficiacy (+4 to +9, higher scores = more energy) | Immediately after dose | 
| Drug Effects Questionnaire Rating of Subjective Ratings of Drug Effects | Assessments measured using a 4 item Drug Effects Questionnaire (DEQ) Ranges from 0 to 100 with higher numbers showing greater effect for each scale. | Immediately after dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Probabalistic Feedback Selection Task | Accuracy on a range from 0 to 1 of correctly performing a learning task, with 1 being the highest degree of accuracy. | 75 minutes after dose | 
| Saliva Caffeine and Paraxanthine Levels | Due to insufficient oral volume or breakage during sample transfer, data were lost or incomplete for two cocaine-dependent subjects. Analyses for the saliva data represent 11 cocaine-dependent subjects and 10 controls. | 30 minutes prior to dose, 30/90/150 minutes post dose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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substance abuse, cocaine, caffeine, impulsivity