Targeting Drug Memories With Methylphenidate

Study Overview
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Brief Summary
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This study aims to identify the neural, behavioral, and pharmacological mechanisms promoting diminished expression of drug-related memories in human drug addiction. In this fMRI study with a within-subjects placebo-controlled double-blind cross-over design, oral methylphenidate (20 mg) or placebo will be administered to individuals with cocaine use disorders (CUD) to peak during the retrieval of a drug-cue memory before extinction; in addition to fMRI activations, skin conductance responses (SCR, acquired simultaneously) will serve as the psychophysiological indicators of memory modification. Assessments of interference with the return of drug-cue memories via SCR and craving will be conducted the day following MRI. This pharmocologically-enhanced behavioral approach to decreasing drug memories and craving in iCUD could ultimately be used to develop effective cue-exposure therapies for drug addiction. Procedures include MRI, blood draw, questionnaires and interviews, skin conductance response measures, and behavioral tasks.

Detailed Description
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Cue-exposure therapy has not proven efficacious in reducing relapse in drug addiction, illuminating the need for alternative strategies. Here researchers will test the neural correlates of two strategies, encompassing behavioral and pharmacological approaches, aimed to interfere with the return of drug memories in individuals with cocaine use disorders. Results may pave the way towards enhancing the efficacy of cue-exposure therapy in reducing cue-induced craving and relapse in drug addiction (generalizable across drugs of abuse/behavioral addictions).

Official Title
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Targeting Neural, Behavioral and Pharmacological Mechanisms of Drug Memories in Drug Addiction With Methylphenidate

Conditions
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Substance Use Disorder, Cocaine Use Disorder

Intervention / Treatment
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* Drug: Methylphenidate
* Behavioral: Memory reconsolidation
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Ability to understand and give informed consent Males and females 26-50 years of age DSM-V diagnosis for CUD or otherwise problematic cocaine use as clinically determined Exclusion criteria: DSM-5 diagnosis for schizophrenia or developmental disorder (e.g., autism) Head trauma with loss of consciousness History of neurological disease of central origin including seizures Cardiovascular disease including high blood pressure and/or other medical conditions, including metabolic, endocrinological, oncological or autoimmune diseases, and infectious diseases including Hepatitis B and C or HIV/AIDS Metal implants or other MR contraindications

Ages Eligible for Study
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Minimum Age: 26 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methylphenidate then Placebo<br>20 mg of methylphenidate then matching placebo pill. | Drug: Methylphenidate<br>* Oral administration of 20 mg Methylphenidate<br>Behavioral: Memory reconsolidation<br>* Retrieval of drug-cue memories before extinction.<br>Drug: Placebo<br>* Matching placebo pill<br>|
| Placebo Comparator: Placebo then Methylphenidate<br>Matching placebo pill then 20 mg of methylphenidate. | Drug: Methylphenidate<br>* Oral administration of 20 mg Methylphenidate<br>Behavioral: Memory reconsolidation<br>* Retrieval of drug-cue memories before extinction.<br>Drug: Placebo<br>* Matching placebo pill<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fMRI blood-oxygenation level dependent (BOLD) signal | fMRI blood-oxygenation level dependent (BOLD) signal deactivation in the ventromedial prefrontal cortex in response to retrieval of drug-cue memory. | Day 1 | 
| fMRI blood-oxygenation level dependent (BOLD) signal | fMRI blood-oxygenation level dependent (BOLD) signal deactivation in the ventromedial prefrontal cortex in response to retrieval of drug-cue memory. | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skin Conductance Responses (SCR) | Measure of changes to skin conductance responses in response to retrieval of drug-cue memory. The conductance is measured by placing two electrodes on the fingers and passing a small, 0.5 V electric charge between the two points. An increase in the skin conductance response (SCR) reflects heightened arousal in response to the drug-cue memory, changes in which are monitored following exposure to the drug cues. | 24 hours after each neuroimaging session | 
| Craving | Measure of changes to craving in response to retrieval of drug-cue memory. Self-reported cue-induced craving in response to drug cues will be assessed. | 24 hours after each neuroimaging session |