Methamphetamine (MA) use is the fastest growing drug problem in the United States, placing strain on the criminal justice and health care systems and resulting in significant public health consequences, including HIV infection. Understanding of the neurobiological, molecular, and cellular basis of MA dependence has increased, yet no medications effective for MA dependence are available. Pharmacogenomic studies have the potential to accelerate the translation of neurobiological findings into safe and effective pharmacotherapies for MA dependence by identifying genes associated with clinical phenotypes of MA dependence and response to treatment. The goal of this Mentored Patient-Oriented Research Career Development Award is to provide Keith Heinzerling, MD, MPH with the training and experience needed to become an independent clinical investigator in the area of pharmacogenomic approaches to medication development for substance abuse with an emphasis on MA use disorders. Dr. Heinzerling is currently a co investigator with the UCLA Medication Development Unit for Stimulant Abuse, under the mentorship of Drs. Steven Shoptaw &Walter Ling. The proposal will allow Dr. Heinzerling to use the abundant educational and research resources in addiction medicine available at UCLA (S. Shoptaw &W. Ling) and Baylor (T. Kosten) and in genetics at UCLA (S. Nelson &J. McCracken) to obtain advanced training in genetics, translational research, addiction pharmacotherapy, clinical trial methodology, and responsible conduct of research that will allow him to become an independent investigator using new genomic approaches to develop medications to treat substance abuse. During the award period, Dr. Heinzerling will perform a pharmacogenomic study aimed at providing preliminary support for associations between genetic polymorphisms and two important clinical phenotypes of MA dependence, baseline frequency of MA use and treatment response to bupropion, using genotypic and phenotypic data from approximately 600 MA dependent participants undergoing screening for several NIDA-funded medication trials, including 120 participants who will be exposed to bupropion. The study will allow Dr. Heinzerling to establish the infrastructure and expertise within the UCLA Medication Development Unit required to secure R01 funding for future pharmacogenomic studies of MA dependence and response to pharmacotherapy.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DA023558-04
Application #
8039262
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Biswas, Jamie
Project Start
2008-04-01
Project End
2013-03-31
Budget Start
2011-04-01
Budget End
2012-03-31
Support Year
4
Fiscal Year
2011
Total Cost
$169,668
Indirect Cost
Name
University of California Los Angeles
Department
Family Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Cook, Ryan; Quinn, Brendan; Heinzerling, Keith et al. (2017) Dropout in clinical trials of pharmacological treatment for methamphetamine dependence: the role of initial abstinence. Addiction 112:1077-1085
Heinzerling, Keith G; Demirdjian, Levon; Wu, Yingnian et al. (2016) Single nucleotide polymorphism near CREB1, rs7591784, is associated with pretreatment methamphetamine use frequency and outcome of outpatient treatment for methamphetamine use disorder. J Psychiatr Res 74:22-9
Heinzerling, Keith G; Swanson, Aimee-Noelle; Hall, Timothy M et al. (2014) Randomized, placebo-controlled trial of bupropion in methamphetamine-dependent participants with less than daily methamphetamine use. Addiction 109:1878-86
Heinzerling, Keith G; Gadzhyan, Janette; van Oudheusden, Henry et al. (2013) Pilot randomized trial of bupropion for adolescent methamphetamine abuse/dependence. J Adolesc Health 52:502-5
Brensilver, Matthew; Heinzerling, Keith G; Shoptaw, Steven (2013) Pharmacotherapy of amphetamine-type stimulant dependence: an update. Drug Alcohol Rev 32:449-60
Heinzerling, Keith G; Shoptaw, Steven (2012) Gender, brain-derived neurotrophic factor Val66Met, and frequency of methamphetamine use. Gend Med 9:112-20
Ling, Walter; Shoptaw, Steven; Hillhouse, Maureen et al. (2012) Double-blind placebo-controlled evaluation of the PROMETAâ„¢ protocol for methamphetamine dependence. Addiction 107:361-9
Brensilver, Matthew; Heinzerling, Keith G; Swanson, Aimee-Noelle et al. (2012) Placebo-group responders in methamphetamine pharmacotherapy trials: the role of immediate establishment of abstinence. Exp Clin Psychopharmacol 20:430-5
Heinzerling, Keith G; McCracken, James T; Swanson, Aimee-Noelle et al. (2012) COMT Val158Met, BDNF Val66Met, and OPRM1 Asn40Asp and methamphetamine dependence treatment response: preliminary investigation. J Clin Psychopharmacol 32:135-7
Heslin, Kevin C; Stein, Judith A; Heinzerling, Keith G et al. (2011) Clinical correlates of health-related quality of life among opioid-dependent patients. Qual Life Res 20:1205-13

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