The goal of the proposed SNRP at UHM-John A. Burns School of Medicine (JABSOM) is to develop a critical mass of neuroscientists who will focus their research efforts on health problems that are highly prevalent in Hawai'i, particularly among the under-represented minority populations. These neuroscientists are trained in a variety of disciplines and will contribute to and collaborate on five interdisciplinary projects proposed in this application. The scientific issues to be explored in the proposed research program will involve the understanding of neurotoxic effects of the major drugs of abuse in Hawaii [i.e. methamphetamine (Meth) and marijuana] and to learn whether prenatal methamphetamine exposure might affect neonatal brain development. The problems of Meth and marijuana abuse affect the underserved minorities, specifically Pacific islanders, and Asians, in Hawai'i more than other populations. Furthermore, although the population infected with HIV is relatively smaller compared to some major metropolitan areas, the rising infection rate among the Asian Pacific Islanders is a concern to the local Department of Health. Therefore, we will also explore possible mechanisms of brain injury in HIV. To achieve this goal, the following are the scientific objectives: 1) To evaluate changes in brain function in individuals with substance-dependence (specifically with methamphetamine and with marijuana);2) to evaluate possible brain changes in neonates with prenatal methamphetamine exposure;3) to develop in vivo markers of oxidative stress and determine whether changes in these markers are related to neurotoxicity in HIV subjects with or without Meth abuse. We also propose the following programmatic objectives: 1) to build strong interdisciplinary teams of researchers to study brain-related changes associated with substance abuse (especially methamphetamine and marijuana, which are highly prevalent in Hawaii) and with HIV/AIDS;2) to provide mentoring to junior investigators and graduate students, including medical students, residents and fellows, for their career development;3) to provide a forum for inter-disciplinary learning through bi-monthly research seminars and bi-monthly journal clubs. These scientific and programmatic objectives will be achieved through the four interdisciplinary projects, an administrative-clinical-training core and a technical core proposed in this application.