This Medications Development Center (MDC) for cocaine pharmacotherapy renewal has evaluated over 25 new medications, introduced many new technologies (fMRI, pharma MRI, SPECT, genetics), and facilitated multidisciplinary collaborations among clinical pharmacology, laboratory medicine, neuroimaging, and molecular genetics. We have 78 publications in the past 4 years, covering cocaine genetics (GABA transporter) to vaccines and opiate and nicotine research collaborations with the Chinese National Institute on Drug Dependence. In our continuation we will focus on medication development by modulating norepinephrine (NE) and dopamine (DA) and propose six Specific Aims 1. To conduct human laboratory cocaine- and methamphetamine (MA)-adminlstration studies with 4 new agents for safety and efficacy: RTI-336 (DA transporter blocker), SY117 (adenosine 2a inhibitor to increase DA activity), and two novel agents, YPK10A and JD-Tic (kappa opiate antagonist) (Proj 1). 2. To conduct two clinical trials of agents modulating NE activity through alpha 1-NE blockade (prazosin and carvedilol) or NE reduction by inhibiting dopamine beta hydroxylase (Proj 2 &3). 3. To test for NE genetic matching of patients to the 3 medications in our two clinical trials. 4. To continue pilot research focused on human genetics for matching new NE and other agents to effective cocaine &MA pharmacotherapies. 5. To attract and train new drug abuse pharmacotherapy investigators through our Center's Core facilities and projects. 6. To disseminate our findings through education and international collaborations

Public Health Relevance

Cocaine- and MA-dependence are major public health problems in the United States. No FDA-approved treatments for cocaine- or methamphetamine-dependence exist. A greater knowledge ofthe basic biology of cocaine- and methamphetamine dependence combined with genetic matching for medication response will lead to improved treatments for the disorder.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Specialized Center (P50)
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Special Emphasis Panel (ZDA1-SXC-E)
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Baylor College of Medicine
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Wachman, Elisha M; Hayes, Marie J; Lester, Barry M et al. (2014) Epigenetic variation in the mu-opioid receptor gene in infants with neonatal abstinence syndrome. J Pediatr 165:472-8
Graham, David P; Nielsen, David A; Kosten, Thomas R et al. (2014) Examining the utility of using genotype and functional biology in a clinical pharmacology trial: pilot testing dopamine ?-hydroxylase, norepinephrine, and post-traumatic stress disorder. Psychiatr Genet 24:181-2
Spellicy, C J; Harding, M J; Hamon, S C et al. (2014) A variant in ANKK1 modulates acute subjective effects of cocaine: a preliminary study. Genes Brain Behav 13:559-64
Mahoney 3rd, James J; De La Garza 2nd, Richard; Jackson, Brian J et al. (2014) The relationship between sleep and drug use characteristics in participants with cocaine or methamphetamine use disorders. Psychiatry Res 219:367-71
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
Mahoney 3rd, James J; Newton, Thomas F; Omar, Yasmine et al. (2013) The relationship between lifetime stress and addiction severity in cocaine-dependent participants. Eur Neuropsychopharmacol 23:351-7
Brewer 3rd, Alex J; Mahoney 3rd, James J; Nerumalla, Chandra S et al. (2013) The influence of smoking cigarettes on the high and desire for cocaine among active cocaine users. Pharmacol Biochem Behav 106:132-6
Kosten, Thomas R; Domingo, Coreen B; Hamon, Sara C et al. (2013) DBH gene as predictor of response in a cocaine vaccine clinical trial. Neurosci Lett 541:29-33
Haile, Colin N; Kosten, Thomas R (2013) Pharmacotherapy for stimulant-related disorders. Curr Psychiatry Rep 15:415
Ross, Elizabeth L; Yoon, Jin H; Mahoney 3rd, James J et al. (2013) The impact of self-reported life stress on current impulsivity in cocaine dependent adults. Prog Neuropsychopharmacol Biol Psychiatry 46:113-9

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