Text: Selective serotonin reuptake inhibitors (SSRIs) have been a focus of research in development of medication for cocaine dependence, in part because preclinical studies have shown that manipulation of the serotonin (5-HT) system affects cocaine self administration and drug reinstatement. Some of the strongest human data supporting examination of one particular SSRI for cocaine dependence comes from a clinical trial completed by our research group. In a preliminary 12-week, double blind, placebo controlled trial of citalopram for cocaine dependence, citalopram produced a significant reduction in cocaine positive urines compared to placebo. Based on what is known regarding the role of the orbito-frontal cortex (OFC) and striatum in addiction and the effects of 5-HT manipulation on OFC function, there is evidence supporting the hypothesis that the reduction in cocaine use achieved by citalopram is related to change in striatal dopamine function mediated in part by changes in OFC serotonin. Combined with the positive preliminary findings from our previous clinical study with citalopram, this provides a strong rationale for further studies of citalopram as a treatment for cocaine dependence. This study builds upon compelling evidence supporting citalopram as a treatment medication for cocaine dependence, based on a conceptual model of prefrontal-striatal interactions. In the context of a randomized, double-blind, placebo-controlled, intent-to-treat, 3-arm, parallel design, single site study, with a sample size of N=125 cocaine dependent subjects, we expect to confirm the hypothesis that citalopram reduces cocaine use during treatment and increases abstinence rates at the end of treatment compared to placebo. Secondary analyses will test behavioral markers as predictors of treatment response based on the conceptual model of citalopram on fronto-striatal function.

Public Health Relevance

In spite of the significant public health concerns regarding cocaine dependence, there is as yet no FDA approved medication for the disorder. If a greater understanding of the basic neurobiology of the effects of chronic cocaine use on the human brain can be gained from this study it would be significant and could lead to the development of new medications for cocaine dependence.

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National Institute on Drug Abuse (NIDA)
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Special Emphasis Panel (ZDA1-EXL-T)
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University of Texas Health Science Center Houston
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D'Souza MA, Johann M; Wardle PhD, Margaret; Green PhD, Charles E et al. (2018) Resting Heart Rate Variability: Exploring Associations With Symptom Severity in Adults With Substance Use Disorders and Posttraumatic Stress. J Dual Diagn :1-6
Vujanovic, Anka A; Wardle, Margaret C; Bakhshaie, Jafar et al. (2018) Distress tolerance: Associations with trauma and substance cue reactivity in low-income, inner-city adults with substance use disorders and posttraumatic stress. Psychol Addict Behav 32:264-276
Miller, William R; Fox, Robert G; Stutz, Sonja J et al. (2018) PPAR? agonism attenuates cocaine cue reactivity. Addict Biol 23:55-68
Vujanovic, Anka A; Smith, Lia J; Green, Charles E et al. (2018) Development of a novel, integrated cognitive-behavioral therapy for co-occurring posttraumatic stress and substance use disorders: A pilot randomized clinical trial. Contemp Clin Trials 65:123-129
Ma, Liangsuo; Steinberg, Joel L; Wang, Qin et al. (2017) A preliminary longitudinal study of white matter alteration in cocaine use disorder subjects. Drug Alcohol Depend 173:39-46
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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