Chronic cocaine use may produce disruption of monoamine systems (including dopamine). This may in turn contribute to measurable dysfunction in important cognitive and behavioral processes. Pharmacotherapy with stimulants that enhance dopamine (DA) function has shown efficacy in treating cocaine dependence and improving behavioral function ~ supporting the notion that these processes are related. In the development of novel pharmacotherapies for cocaine dependence, an important step is a full understanding of the psychopharmacological properties of potential medications for cocaine dependence, including subjective, physiological, discriminative and behavioral effects. Selective adenosine (A2A) receptor antagonists may play a key role in the modulation of DA neurotransmission by indirectly enhancing DA receptor activation. Additionally, A2A antagonists inhibit cannabinoid CBI receptor activation, suggesting a potential mechanism for reducing concurrent marijuana use in cocaine dependent patients. A2A antagonists may provide additional benefit on concurrent marijuana use in cocaine dependence, as dual cocaine-marijuana users present unique treatment challenges. This project proposes to evaluate the novel A2A antagonist SYN 115. Its stimulant-like effects may help with affective and behavioral deficiencies related to (a) DA depletion and (b) DA-CB1 interactions. Accordingly, the project aims to characterize the psychopharmacology of SYN115 in individuals with cocaine dependence, cocaine dependence with concurrent marijuana use, and controls. Employing both acute and chronic dosing designs, three experiments will be conducted using well-established psychopharmacological methods in order to characterize dose-response relationships. A mixed-model strategy will be utilized to (a) leverage the power of within-subject, repeated measures designs, and (b) compare cocaine dependent and healthy matched-control subjects. Measures will include drug discrimination, subjective effects, cardiovascular effects, behavioral inhibition (impulsivity), working memory, reversal learning, and decision making. These data will compliment and provide valuable information to our parallel clinical trials using these agents to treat cocaine dependence.

Public Health Relevance

This project will use current techniques in psychopharmacology to examine the effects of the novel A2A antagonist SYN115 on important behavioral, subjective, and physiological processes in cocaine/marijuana abusers and controls. Examination of dose-response relationships will compliment and provide valuable information to subsequent clinical trials with regard to behavioral markers related to treatment efficacy.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Specialized Center (P50)
Project #
5P50DA009262-20
Application #
8660671
Study Section
Special Emphasis Panel (ZDA1-EXL-T)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
20
Fiscal Year
2014
Total Cost
$169,854
Indirect Cost
$56,618
Name
University of Texas Health Science Center Houston
Department
Type
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
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
Vujanovic, Anka A; Rathnayaka, Nuvan; Amador, Christina D et al. (2016) Distress Tolerance: Associations With Posttraumatic Stress Disorder Symptoms Among Trauma-Exposed, Cocaine-Dependent Adults. Behav Modif 40:120-43
Azadeh, Shabnam; Hobbs, Brian P; Ma, Liangsuo et al. (2016) Integrative Bayesian analysis of neuroimaging-genetic data with application to cocaine dependence. Neuroimage 125:813-24
Vujanovic, Anka A; Wardle, Margaret C; Liu, Shijing et al. (2016) Attentional bias in adults with cannabis use disorders. J Addict Dis 35:144-53
Ramesh, Divya; Keyser-Marcus, Lori A; Ma, Liangsuo et al. (2015) Prevalence of traumatic brain injury in cocaine-dependent research volunteers. Am J Addict 24:341-7
Stotts, Angela L; Vujanovic, Anka; Heads, Angela et al. (2015) The role of avoidance and inflexibility in characterizing response to contingency management for cocaine use disorders: A secondary profile analysis. Psychol Addict Behav 29:408-13
Alcorn 3rd, Joseph L; Rathnayaka, Nuvan; Swann, Alan C et al. (2015) Effects of Intranasal Oxytocin on Aggressive Responding in Antisocial Personality Disorder. Psychol Rec 65:691-703
Stotts, Angela L; Northrup, Thomas F (2015) The Promise of Third-Wave Behavioral Therapies in the Treatment of Substance Use Disorders. Curr Opin Psychol 2:75-81
Ma, Liangsuo; Steinberg, Joel L; Cunningham, Kathryn A et al. (2015) Inhibitory behavioral control: A stochastic dynamic causal modeling study comparing cocaine dependent subjects and controls. Neuroimage Clin 7:837-47
Dias, Nadeeka R; Lane, Scott D; Rathnayaka, Nuvan et al. (2015) Demographic and psychological factors associated with lifetime cocaine use: An exploratory factor analysis of baseline questionnaires. Addict Disord Their Treat 14:70-77

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