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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Specialized Center (P50)
Project #
5P50DA009262-19
Application #
8474733
Study Section
Special Emphasis Panel (ZDA1-EXL-T)
Project Start
Project End
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
19
Fiscal Year
2013
Total Cost
$248,589
Indirect Cost
$92,791
Name
University of Texas Health Science Center Houston
Department
Type
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
Lindsay, Jan A; Minard, Charles G; Hudson, Sonora et al. (2014) Using prize-based incentives to enhance daily interactive voice response (IVR) compliance: a feasibility study. J Subst Abuse Treat 46:74-7
Sharma, Jyoti; Rathnayaka, Nuvan; Green, Charles et al. (2014) Bradycardia as a Marker of Chronic Cocaine Use: A Novel Cardiovascular Finding. Behav Med :1-8
Schmitz, Joy M; Green, Charles E; Stotts, Angela L et al. (2014) A two-phased screening paradigm for evaluating candidate medications for cocaine cessation or relapse prevention: modafinil, levodopa-carbidopa, naltrexone. Drug Alcohol Depend 136:100-7
Narayana, Ponnada A; Herrera, Juan J; Bockhorst, Kurt H et al. (2014) Chronic cocaine administration causes extensive white matter damage in brain: diffusion tensor imaging and immunohistochemistry studies. Psychiatry Res 221:220-30
Farris, Samantha G; Zvolensky, Michael J; Beckham, Jean C et al. (2014) Trauma exposure and cigarette smoking: the impact of negative affect and affect-regulatory smoking motives. J Addict Dis 33:354-65
Hasan, Khader M; Moeller, F Gerard; Narayana, Ponnada A (2014) DTI-based segmentation and quantification of human brain lateral ventricular CSF volumetry and mean diffusivity: validation, age, gender effects and biophysical implications. Magn Reson Imaging 32:405-12
Fineberg, Naomi A; Chamberlain, Samuel R; Goudriaan, Anna E et al. (2014) New developments in human neurocognition: clinical, genetic, and brain imaging correlates of impulsivity and compulsivity. CNS Spectr 19:69-89
Lane, Scott D; Green, Charles E; Schmitz, Joy M et al. (2014) Comparison of Caffeine and d-amphetamine in Cocaine-Dependent Subjects: Differential Outcomes on Subjective and Cardiovascular Effects, Reward Learning, and Salivary Paraxanthine. J Addict Res Ther 5:176
Liu, Shijing; Green, Charles E; Lane, Scott D et al. (2014) The influence of dopamine ?-hydroxylase gene polymorphism rs1611115 on levodopa/carbidopa treatment for cocaine dependence: a preliminary study. Pharmacogenet Genomics 24:370-3
Anastasio, N C; Liu, S; Maili, L et al. (2014) Variation within the serotonin (5-HT) 5-HT?C receptor system aligns with vulnerability to cocaine cue reactivity. Transl Psychiatry 4:e369

Showing the most recent 10 out of 55 publications