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COMPLETEDPHASE1/PHASE2

5HT2CR Balance in Brain Connectivity in Cocaine Dependence

5-HT2AR: 5HT2CR Balance in Brain Connectivity in Cocaine Dependence

NCT03921151•Virginia Commonwealth University

Summary

This project will evaluate the role of the 5-HT2CR:5-HT2AR balance in impulsive action and cue reactivity in cocaine-dependent subjects as compared to non-drug using controls.

Detailed Description

The overall goal of this project is to evaluate the role of molecular interactions between 5-HT2AR and 5-HT2CR in behavioral phenotypes that confer risk for cocaine dependence and relapse. Specifically, this project will evaluate the role of the 5-HT2CR:5-HT2AR balance in impulsive action and cue reactivity in cocaine-dependent subjects as compared to non-drug using controls. Brain and behavioral responses to the 5-HT2AR blocking medication mirtazapine will be compared between subjects who have high and low functioning of the 5-HT2CR based on presence of a specific, functionally-relevant single nucleotide polymorphism (SNP) of the 5-HT2CR (Cys23Ser). The 5-HT2CR Cys23Ser SNP is thought to decrease the function of the protein and a preliminary observation indicates cocaine-dependent subjects carrying the CC genotype (Ser23 protein variant) display significantly higher cue reactivity. For Aims 1 and 2, two fMRI analysis methods will be used: 1) a voxelwise whole brain analysis; 2) a region of interest analysis based on proposed integrative circuitry shown in the model below. Because neuroimaging studies have shown that performance of impulsive action tasks and exposure to cocaine-associated cues (cue reactivity paradigms) activate brain regions in brain circuits in humans, impulsive action and cue reactivity may be engendered in related pathways. To explore this hypothesis, researchers will employ functional magnetic resonance imaging (fMRI)-based dynamic causal modeling (DCM) to ascertain the causal influences of one brain region over another. Employing DCM, researchers will uncover the effective connectivity within nodes of the neurocircuitry involved in impulsive action and cue reactivity. This project will parallel preclinical work studying the relationship between 5-HT2AR and 5-HT2CR on impulsive action and cue reactivity.

Eligibility

Age

18 - 60 years

Sex

ALL

Healthy Volunteers

Yes

Inclusion Criteria

•Cocaine Dependent Subjects
•1. Be English-speaking volunteers
•2. Be aged between 18 and 60 years
•3. Meet DSM-5 criteria for cocaine dependence
•4. Have a self-reported history of using cocaine
•5. Have hematology and chemistry laboratory tests that are within reference limits ( 10%) with the following exceptions: hemoglobin and hematocrit within normal limits (for fMRI).
•6. Have a baseline EKG that demonstrates clinically normal sinus rhythm, clinically normal conduction, and no clinically significant abnormalities
•7. Have a medical history and physical examination demonstrating no clinically significant contraindications for study participation, in the judgment of the admitting physician and the principal investigator.
•8. Have no metal fragments or other bodily metal (e.g., pacemaker) or significant claustrophobia that would put the subjects at risk for MRI scanning.
•Non-Drug Using Controls
+7 more criteria

Exclusion Criteria

•Cocaine Dependent Subjects
•1. Have any history or evidence suggestive of seizure disorder or brain injury.
•2. Have any previous medically adverse reaction to mirtazapine or other antidepressants.
•3. Have neurological or psychiatric disorders, such as (a) psychosis, bipolar illness or major depression as assessed by SCID; (b) organic brain disease or dementia assessed by clinical interview; (c) history of any psychiatric disorder that would require ongoing treatment or that would make study compliance difficult; and (d) history of suicide attempts within the past 3 months and/or current suicidal ideation/plan.
•4. Have evidence of uncontrolled clinically significant heart disease or hypertension, as determined by the PI.
•5. Have evidence of non-psychiatric medical illness including neuroendocrine, autoimmune, renal, hepatic, or active infectious disease.
•6. Use of any medications or drugs that can affect the central nervous system other than cocaine, marijuana, alcohol caffeine and nicotine.
•7. Have a positive HIV test.
•8. Be pregnant or nursing. Other females must either be unable to conceive (i.e., surgically sterilized, sterile, or postmenopausal) or be using a reliable form of contraception (e.g., abstinence, birth control pills, intrauterine device, condoms, or spermicide). All females must provide negative pregnancy urine tests before study entry, weekly during the study, and at the end of study participation.
•9. Have any other illness, condition, or use of psychotropic medications, which in the opinion of the PI and/or the admitting physician would preclude safe and/or successful completion of the study.
+11 more criteria

Locations (1)

Virginia Commonwealth University

Richmond, Virginia, United States

Key Dates

Start Date

May 13, 2014

Primary Completion Date

January 24, 2019

Completion Date

January 24, 2019

Last Updated

November 22, 2021

Enrollment

ACTUAL participants

Conditions

Cocaine Dependence

Interventions

Mirtazapine 15 MG Oral Tablet

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: November 22, 2021Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

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5HT2CR Balance in Brain Connectivity in Cocaine Dependence

Inclusion Criteria

Exclusion Criteria

Safety Study of a Disrupted Adenovirus (Ad) Serotype Cocaine Vaccine for Cocaine-dependent Individuals

Ketamine and Neurofeedback-Training: Effects on Neuroplasticity in Cocaine Addiction

Effect of HF rTMS on Serum BDNF in Cocaine Use Disorder

rTMS and Cognitive-behavioral Therapy for Cocaine Use Disorder

rTMS for Stimulant Use Disorders

Bupropion-Enhanced Contingency Management (CM) for Cocaine Dependence