Targeting Drug Memories With Methylphenidate

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

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.

Study Overview

• Status: Recruiting
• Conditions: Substance Use Disorder; Cocaine Use Disorder
• Intervention / Treatment: Drug: Methylphenidate; Behavioral: Memory reconsolidation; Drug: Placebo

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Natalie E McClain, BA; Phone Number: 5023034101; Email: natalie.mcclain@mssm.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Rita Z Goldstein, PhD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2023
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: July 28, 2023
• First Submitted That Met QC Criteria: July 28, 2023
• First Posted (Actual): August 7, 2023

Study Record Updates

• Last Update Posted (Actual): August 7, 2023
• Last Update Submitted That Met QC Criteria: July 28, 2023
• Last Verified: July 18, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Methylphenidate
• Other Study ID Numbers: GCO 20-2707; R21DA054281 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Immediately following publication. No end date.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal. Any purpose. Proposals should be directed to rita.goldstein@mssm.edu. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No