NCT03921151

5HT2CR Balance in Brain Connectivity in Cocaine Dependence

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

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 90 (actual)
• Sponsor: Virginia Commonwealth University · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

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.

Conditions

• Cocaine Dependence

Interventions

Type	Name	Description
DRUG	Mirtazapine 15 MG Oral Tablet	The intervention will be a 15mg of mirtazapine oral tablet given to participants prior to their treatment scan and assessments. In order to ensure that biases or social desirability do not contaminate baseline assessments, all participants will also be given a tablet consisting of dextrose in gelatin prior to their baseline scan and assessment.

Timeline

• Start date: 2014-05-13
• Primary completion: 2019-01-24
• Completion: 2019-01-24
• First posted: 2019-04-19
• Last updated: 2021-11-22
• Results posted: 2021-11-22

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study