The UT Houston Substance Abuse Research-Medication Development Center (SAR-MDC) is currently in its 15th year of funding. During the previous funding period, the focus of the Center was on """"""""agonist"""""""" or """"""""replacement"""""""" therapy for cocaine dependence using stimulant and stimulant-like medications. For this competing renewal of our Center, the theme advances to examining behavioral and neurochemical mechanisms of replacement therapy to drive novel medication development for cocaine dependence. The research is a collaborative, interdisciplinary effort in behavioral laboratory, brain imaging, and outpatient clinical trials using novel medications, novel imaging methodologies, and novel clinical trial designs that will provide a greater understanding of the behavioral neurobiology of cocaine dependence and lead to effective pharmacotherapies for the disorder.
The aims of the Center will be achieved through two cores and five projects. The Administrative Core (F. Gerard Moeller PI) serves as a general resource for the other projects and the Advanced Clinical Design and Statistical Analysis Core. The Advanced Clinical Design and Statistical Analysis Core (Charles Green PI) will provide advanced statistical analysis and study design support to the other projects of the Center as well as other NIDA funded projects outside the Center. Project 1 (Joy M. Schmitz PI) is a Phase II adaptive design clinical trial using the selective adenosine A2A receptor antagonist SYN115 alone and in combination with the dopamine precursor L-Dopa. Project 2 (Scott D. Lane PI) is a behavioral laboratory study that characterizes the psychopharmacological properties of novel medications including the adenosine A2A receptor antagonist SYN115. Measurement will focus on drug discrimination, subjective effects, behavioral inhibition and decision making. Project 3 (Joy M. Schmitz PI) is a Phase II clinical trial that will study the efficacy of combination serotonin/dopamine pharmacotherapy in cocaine dependent subjects with Bayesian subgroup analyses. Project 4 (F. Gerard Moeller PI) is a human imaging project utilizing fMRI and DTI as predictors of treatment response of subjects in Projects 1 and 3. Project 5 (Ponnada A. Narayana PI) is a rodent imaging project utilizing DTI and brain neurohistology to study effects of chronic cocaine administration on brain structure and potential amelioration of these effects using the adenosine A2A receptor antagonist SYN115.

Public Health Relevance

Cocaine dependence continues to be a significant public health problem in the United States, with 2.1 million current cocaine users aged 12 and older in the United States in 2007. Cocaine dependence is also associated with risky sexual behavior and impulsivity, which increase the risk of HIV transmission. The overall goal of this Center is to gain a greater understanding of the basic neurobiology of chronic cocaine use and through this knowledge to develop effective pharmacotherapies for cocaine dependence.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Specialized Center (P50)
Project #
2P50DA009262-16A1
Application #
7994529
Study Section
Special Emphasis Panel (ZDA1-EXL-T (05))
Program Officer
Bough, Kristopher J
Project Start
1997-09-01
Project End
2015-05-31
Budget Start
2010-08-01
Budget End
2011-05-31
Support Year
16
Fiscal Year
2010
Total Cost
$2,079,960
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Psychiatry
Type
Schools of Medicine
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
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Schmitz, Joy M; Green, Charles E; Hasan, Khader M et al. (2017) PPAR-gamma agonist pioglitazone modifies craving intensity and brain white matter integrity in patients with primary cocaine use disorder: a double-blind randomized controlled pilot trial. Addiction 112:1861-1868
Wardle, Margaret C; Vincent, Jessica N; Suchting, Robert et al. (2017) Anhedonia Is Associated with Poorer Outcomes in Contingency Management for Cocaine Use Disorder. J Subst Abuse Treat 72:32-39
Ahn, Woo-Young; Ramesh, Divya; Moeller, Frederick Gerard et al. (2016) Utility of Machine-Learning Approaches to Identify Behavioral Markers for Substance Use Disorders: Impulsivity Dimensions as Predictors of Current Cocaine Dependence. Front Psychiatry 7:34
Azadeh, Shabnam; Hobbs, Brian P; Ma, Liangsuo et al. (2016) Integrative Bayesian analysis of neuroimaging-genetic data with application to cocaine dependence. Neuroimage 125:813-824
Sharma, Jyoti; Rathnayaka, Nuvan; Green, Charles et al. (2016) Bradycardia as a Marker of Chronic Cocaine Use: A Novel Cardiovascular Finding. Behav Med 42:1-8

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