Behavioral Effects of Drugs: Inpatient (35)

Study Overview
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Brief Summary
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This study will determine the influence of methylphenidate (Metadate®) and duloxetine (Cymbalta®), alone and in combination, on the reinforcing, subjective and physiological effects of cocaine.

Official Title
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Influence of Methylphenidate and Duloxetine Maintenance on Pharmacodynamic Effects of Cocaine

Conditions
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Cocaine Use Disorder

Intervention / Treatment
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* Drug: Cocaine
* Drug: Placebo oral capsule
* Drug: Methylphenidate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recent cocaine use Exclusion Criteria: Abnormal screening outcome (e.g., ECG, blood chemistry result) that study physicians deem clinically significant Current or past histories of substance abuse or dependence that are deemed by the study physicians to interfere with study completion History of serious physical disease, current physical disease, impaired cardiovascular functioning, chronic obstructive pulmonary disease, history of seizure or current or past histories of serious psychiatric disorder that in the opinion of the study physician would interfere with study participation will be excluded from participation Females not currently using effective birth control Contraindications to cocaine, methylphenidate or duloxetine

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: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Subjects will be maintained on oral placebo. Subjects will be maintained on placebo and methylphenidate during placebo maintenance. Cocaine will be administered acutely during placebo maintenance. Placebo will be administered acutely during placebo maintenance. | Drug: Cocaine<br>* The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and duloxetine.<br>Drug: Placebo oral capsule<br>* The pharmacodynamic effects of placebo will be determined during maintenance on placebo and duloxetine.<br>Drug: Methylphenidate<br>* The pharmacodynamic effects of methylphenidate maintenance will be determined during maintenance on placebo and duloxetine.<br>* Other names: Metadate®;|
| Active Comparator: Duloxetine<br>Subjects will be maintained on oral duloxetine. Subjects will be maintained on duloxetine and methylphenidate during placebo maintenance. Cocaine will be administered acutely during duloxetine maintenance. Placebo will be administered acutely during duloxetine maintenance. | Drug: Cocaine<br>* The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and duloxetine.<br>Drug: Placebo oral capsule<br>* The pharmacodynamic effects of placebo will be determined during maintenance on placebo and duloxetine.<br>Drug: Methylphenidate<br>* The pharmacodynamic effects of methylphenidate maintenance will be determined during maintenance on placebo and duloxetine.<br>* Other names: Metadate®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reinforcing Effects of Cocaine Following Placebo Maintenance. | Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement. | Following at least 4 days of maintenance on placebo during inpatient admission. | 
| Reinforcing Effects of Cocaine Following Duloxetine Maintenance. | Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement. | Following at least 4 days of maintenance on duloxetine during inpatient admission. | 
| Reinforcing Effects of Cocaine Following Methylphenidate Maintenance. | Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement. | Following at least 4 days of maintenance on duloxetine during inpatient admission. | 
| Reinforcing Effects of Cocaine Following Methylphenidate and Duloxetine Maintenance. | Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement. | Following at least 4 days of maintenance on methylphenidate and duloxetine during inpatient admission. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjective Rating Scale-Sedative | Subjects will complete the adjective rating scale during nine sessions while they are admitted to our inpatient unit. Responses to 16 items are summed (total score=0-64; Higher values=more sedation) to calculate scores on a sedative subscale. | Nine times over approximately four weeks inpatient admission. | 
| Adjective Rating Scale-Stimulant | Subjects will complete the adjective rating scale during nine sessions while they are admitted to our inpatient unit. Responses to 16 items are summed (total score=0-64; Higher values=more stimulation) to calculate total scores on a stimulant subscale. | Nine times over approximately four weeks inpatient admission. | 
| Drug Effect Questionnaire | Subjects will complete the drug effect questionnaire during nine sessions while they are admitted to our inpatient unit. The items (total scores=0-100; Higher scores=greater drug effect) on this scale categorize the constellation of drug effects endorsed by subjects. | Nine times over approximately four weeks inpatient admission. | 
| Heart rate | Beats per minute. Measured daily during inpatient admission. | Daily over approximately four week inpatient admissions. | 
| Blood pressure | mmHg.Measured daily during inpatient admission. | Daily over approximately four week inpatient admissions. | 
| Temperature | Degrees fahrenheit. Measured daily during inpatient admission. | Daily over approximately four week inpatient admissions. | 
| Side effects | Subjects will complete a side effects questionnaire daily while they reside on the inpatient unit. Side Effects questions will query subjects about common effects of centrally active medications. | Daily over approximately four week inpatient admissions. | 
| Delay Discounting Task | Subjects will complete the delay discounting task during nine sessions while they are admitted to our inpatient unit. Responses will be used to calculate discounting slope (i.e., K). | Nine times over approximately four weeks inpatient admission. | 
| Attentional Bias | Subjects will complete attentional bias during nine sessions while they are admitted to our inpatient unit. Time attending to drug stimuli will be used to evaluate attentional bias. | Nine times over approximately four weeks inpatient admission. | 
| Inhibitory Control | Subjects will complete an inhibitory control task during nine sessions while they are admitted to our inpatient unit. Ability to inhibit prepotent responding will be used to calculate inhibitory control. | Nine times over approximately four weeks inpatient admission. |