Pharmacologic MRI in Cocaine Addiction

Study Overview
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Brief Summary
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In the proposed study, the investigators will assess the brain response to medication probes the investigators have previously studied with SPECT. The brain response to ondansetron and lidocaine infusions will be measured Arterial Spin Labeling and functional connectivity MRI (fcMRI).

Detailed Description
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An extensive effort has been mounted to understand the neurobiologic mechanisms involved in the development and persistence of cocaine addiction and tendency to relapse. Although the last two decades have resulted in an explosion in our understanding of the biological mechanisms of reward, establishing the relevance of this knowledge to the addictive process has been problematic. Most importantly, this information has been of limited utility in offering new pharmacologic treatment approaches to addicted patients - particularly those with cocaine addiction. Over the past 15 years our laboratory has published multiple studies using pharmacologic probes to explore the biologic underpinnings of cocaine addiction using single photon emissions computerized tomography (SPECT) technology. More recently, however, functional magnetic resonance imaging (fMRI) has offered several advantages over SPECT and is now a favored approach, e.g. fMRI allows the continuous measurement of neural responses rather than a very limited time period with SPECT (1-3 minutes every 48 hours). Using fMRI [including both ASL (Arterial Spin Labeling) and fcMRI (functional connectivity], the neural response can be measured throughout the 60 min that follows infusion, allowing identification and capture of the maximal brain response period that may occur at any time during this 60 min. In the proposed study, we will assess the brain response to two of the probes (scopolamine and lidocaine) we have previously studied with SPECT.

Official Title
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Pharmacologic MRI in Cocaine-addiction

Conditions
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Cocaine Dependence

Intervention / Treatment
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* Drug: ondansetron, lidocaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cocaine dependence (cocaine patients) identify cocaine as their present primary drug of use Patients must have used cocaine within the previous 4 weeks (by patient history) and be abstinent for at least 1 week. No drug dependence (healthy control population). Exclusion Criteria: Other medical or psychiatric disorders that may effect neural functioning. Medications that may effect brain functioning

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 64 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cocaine-Addicted Participants<br>Group of participants diagnosed with cocaine dependence | Drug: ondansetron, lidocaine<br>* Ondansetron: Ondansetron (0.15 mg/kg) will be administered through the IV line over 15 min at a constant rate of infusion. Lidocaine: Lidocaine will be administered as a 2mg/kg initial bolus over 5 minutes followed by a continuous intravenous infusion of lidocaine at a rate of 2mg/kg/hour for 55 min (60 min total infusion).<br>* Other names: Zofran, Xylocaine;|
| Control Participants<br>healthy control volunteers | Drug: ondansetron, lidocaine<br>* Ondansetron: Ondansetron (0.15 mg/kg) will be administered through the IV line over 15 min at a constant rate of infusion. Lidocaine: Lidocaine will be administered as a 2mg/kg initial bolus over 5 minutes followed by a continuous intravenous infusion of lidocaine at a rate of 2mg/kg/hour for 55 min (60 min total infusion).<br>* Other names: Zofran, Xylocaine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| blood-oxygen-level-dependent contrast (BOLD) | change in BOLD response to drug infusion (ondansetron, lidocaine). | 60 minutes after drug infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cocaine addiction, neuroimaging, functional magnetic resonance imaging (fMRI)