Marc E. Mooney, Ph.D. - US grants

Studies of cigarette smoking have largely focused on adults, but the majority of smoking begins during adolescence. Nevertheless, comparatively little research has focused on adolescent smoking, and still less work has attempted to determine the genetic and environmental factors contributing to smoking initiation and persistence. The purpose of the current proposal is to examine the development of cigarette smoking in a large sample of twins representing the adolescent period of development. The Minnesota Twin Family Study (MTFS) is a longitudinal study of 1,300 twin pairs born in Minnesota between 1971 and 1981 and their families. Our goal is to apply existing behavior genetic methodology (Hannah, Hopper, & Mathews, 1985; Heath, 1990; Neals & Cardon, 1992) to examine the process of becoming a dependent smoker. The present study will apply existing models for smoking initiation and persistence, examine which environmental variables (e.g., peer pressure to smoke, availability of cigarettes) are most associated with smoking initiation, and model the progression to nicotine dependence with this existing data set. The results of these analyses will help inform the interventions that will be considered for Dr. Harry Lando's "Modifiable Factors in Adolescent Smoking" studies.

[unreadable] DESCRIPTION (provided by applicant): [unreadable] This application requests support for a NIDA Mentored Research Scientist Development Award (K01) to promote the development of the applicant, Marc Mooney, Ph.D., as an independent clinical researcher with expertise in the area of clinical trials and medication development for smoking cessation. Dr. Mooney is currently a post-doctoral fellow at the Substance Abuse Research Center in the Department of Psychiatry and Behavioral Sciences at the University of Texas, Houston. He has developed a specific interest in the potential of combining non-nicotine pharmacotherapies with different mechanisms of action, to enhance treatment outcomes and to better understand the effects of medication on cessation-related processes, such as withdrawal. The proposed research plan will enable Dr. Mooney to develop competency in three specific areas: (1) double-blind, randomized, pharmacotherapy trials of non-nicotine agents for smoking cessation; (2) laboratory measures of cognitive processes and impulsivity that may be incorporated into clinical trials; and (3) sophisticated statistical and methodological techniques for longitudinal clinical trial designs. Under the sponsorship and guidance Drs. Joy Schmitz and John Grabowski, Dr. Mooney will participate in the design, execution, and data analysis of clinical trials of potential pharmacotherapies for multiple drugs of abuse. He will conduct a clinical and laboratory trial evaluating the joint effectiveness of bupropion and naltrexone for smoking cessation. His research training will be supported with didactic training, obtained via course work and also through individualized training with expert consultants. Courses and training will help Dr. Mooney to master statistical techniques for longitudinal research, as well as to gain knowledge of findings and methods in cognitive psychology, impulsivity, and clinical trials methodology. In achieving mastery in these areas, Dr. Mooney will be prepared to become a successful independent investigator of pharmacotherapies for nicotine dependence and other substance use disorders. [unreadable] [unreadable] [unreadable] [unreadable]

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this study is to understand the way varenicline, a novel medication that works like nicotine in the brain, helps smokers to quit, through focused measures of potential psychological and physiological processes and events. Varenicline is an FDA-approved pharmacotherapy for smoking cessation that is believed to provide relief from craving and withdrawal by acting on the brain receptors for the neurotransmitter, acetylchlonie. However, no controlled sutdies have established the physiolocial and psychological processes that explain how varneicline helps smokers to quit. The main goal of the proposed pilot study is to evaluate and compare the effects of varenicline on subjective, cognitive, and physiological outcomes, using a randomized, placebo-controlled, double-blind between-groups design. In general, we expect that compared to placebo, those treated with varenicline will find smoking less reinforcing, will have less impaired cognition, less anxiety, and better stress tolerance, as assessed in the laboratory. A secondary goal is to validate hte utility of the laboratory models for the identification of future medications to help smokers to quit. We are requesting the use of a ventilatied room at the GCRC (since subjects will be smoking during sessions).

This proposal requests support for the ROO phase of the K99/R00 Pathway to Independence Award enabling David Herin, Ph.D, to begin his independent career investigating pharmacological treatments for substance abuse. The first (K99) phase ofthis award has been conducted at the University of Texas Health Science Center at Houston (UTHSC) under Drs. John Grabowski and Joy Schmitz. In this phase, Dr. Herin completed training in clinicai trials metholodology, advanced statistical methods, the responsible conduct of research, as well as u-aining in professional skills. Additionally, Dr. Herin obtained experience in implementation of clinical trials in multiple studies at the UTHSC P50 medication development center, and developed collaborations with departmental faculty. This clinical training has enabled Dr. Herin lo secure a tenure-track faculty position in the Department of Psychiatry at the University of Minnesota. As Dr. Herin launches his independent career, ROO support will enable him to conduct a clinical trial investigating the ability of lisdexamfetamine to treat cocaine dependence. During this ROO period, Dr. Herin will also develop collaborations with his University of Minnesota colleagues in fields such as functional imaging, impulsivity, genetics, and human laboratory studies, enabling submission of future interdisciplinary grant applications to funding agencies. In all, the K99 and ROO awards permit Dr. Herin to begin his independent career and make significant scientific contributions to the field of substance abuse research.