Cocaine dependence is an important public health problem with over 1.7 million users in the US alone. In spite of ongoing efforts, no medications have been approved for the treatment of cocaine dependence yet. Thus, development of effective pharmacotherapies for cocaine dependence remains an important goal. Among potentialtargets for cocainepharmacotherapy, the gamma-aminobutyric acid (GABA) system has received increasing attention in both preclinical and clinical studies. In preclinical studies, medications which increased GABA effects attenuated cocaine self-administration. Similarly, a number of clinical trials testing the efficacy of GABA medications for cocaine dependence showed promising findings. These preclinical and clinical studies suggest that medications act on the brain GABA system may have utility for cocaine pharmacotherapy. The goal of this proposal is to determine the potential utility of selected GABA medications for cocaine pharmacotherapy by examining their interactions with cocaine in human laboratory settings. The GABA medications included in this proposal are tiagabine, topiramate, valproic acid, baclofen and progesterone. In each study, 12 cocaine users will have experimental sessions following placebo and active medication treatment. The medications will be given in escalating doses over 3 days to attain therapeutic levels while maintainingmedical safety and minimizing side effects. During the sessions, subjects will receive escalating doses of cocaine to examine the effects of GABA medications on the cardiovascular and subjective-rewarding responses to cocaine. The medications selected have diverse effects on the GABA system and are potential medications for future cocaine pharmacotherapy trials. Theproposed studies will provide essential safety information for selected GABA medications by systematically examining their interactions with dose-dependent cardiovascular and subjective-rewarding effects of cocaine. The results of this study willprovide new insight on the interaction between the GABA system and cocaine effects and will guide future pharmacotherapy trials using GABA medications.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Specialized Center (P50)
Project #
1P50DA018197-01
Application #
6830605
Study Section
Special Emphasis Panel (ZDA1-KXA-N (22))
Project Start
2004-09-01
Project End
2009-06-30
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
1
Fiscal Year
2004
Total Cost
$143,344
Indirect Cost
Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Cao, Bo; Bauer, Isabelle E; Sharma, Ajaykumar N et al. (2016) Reduced hippocampus volume and memory performance in bipolar disorder patients carrying the BDNF val66met met allele. J Affect Disord 198:198-205
Shorter, Daryl; Nielsen, David A; Hamon, Sara C et al. (2016) The α-1 adrenoceptor (ADRA1A) genotype moderates the magnitude of acute cocaine-induced subjective effects in cocaine-dependent individuals. Pharmacogenet Genomics 26:428-35
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
Li, Xiaofan; Shorter, Daryl; Kosten, Thomas R (2016) Buprenorphine Prescribing: To Expand or Not to Expand. J Psychiatr Pract 22:183-92
Brewer 3rd, Alex J; Nielsen, David A; Spellicy, Catherine J et al. (2015) Genetic variation of the dopamine transporter (DAT1) influences the acute subjective responses to cocaine in volunteers with cocaine use disorders. Pharmacogenet Genomics 25:296-304
Shorter, Daryl; Hsieh, John; Kosten, Thomas R (2015) Pharmacologic management of comorbid post-traumatic stress disorder and addictions. Am J Addict 24:705-12
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
Patriquin, Michelle A; Bauer, Isabelle E; Soares, Jair C et al. (2015) Addiction pharmacogenetics: a systematic review of the genetic variation of the dopaminergic system. Psychiatr Genet 25:181-93
Newton, Thomas F; Haile, Colin N; Mahoney 3rd, James J et al. (2015) Dopamine D3 receptor-preferring agonist enhances the subjective effects of cocaine in humans. Psychiatry Res 230:44-9
Bauer, Isabelle E; Soares, Jair C; Nielsen, David A (2015) The role of opioidergic genes in the treatment outcome of drug addiction pharmacotherapy: A systematic review. Am J Addict 24:15-23

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