Project Summary: Cocaine intoxication is known to produce alterations in cognitive function and is commonly thought to produce clinically significant cognitive deficits as a consequence of long-term abuse. However, past quasi-experimental studies have yielded mixed findings and no experimental studies have been conducted to examine neuropsychological effects of cocaine bingeing, a common pattern of abuse. The goal of this mentored research scientist award is to enhance the developing experimental research skills of Nehal P. Vadhan, Ph.D. In July, 2005, Dr. Vadhan joined the Division on Substance Abuse faculty at Columbia University as an Assistant Professor of Clinical Psychology in Psychiatry. To gain facility with behavioral pharmacology techniques and become an independent substance abuse researcher, Dr. Vadhan will need mentoring and formal course work. Under the sponsorship of Dr. Richard W. Foltin, and with guidance from other senior researchers, Dr. Vadhan will train in methodology, safety and ethics of conducting research with psychoactive substances in the human laboratory, methodology of studying neuropsychological function in laboratory settings, biostatistics, and current concepts and theory in neurobiology. Over the next five years, Dr. Vadhan plans to conduct mentored research on the neuropsychological effects of binge-smoked cocaine in human abusers. His application proposes three studies: a cross-sectional study comparing neuropsychological function in cocaine users with high and low levels of previous experience with cocaine to a non-cocaine-using control group, and two experimental studies, where neuropsychological function will be examined in cocaine-dependent human volunteers while they smoke cocaine during binges of varying length in the laboratory and during periods of abstinence. These studies will comprise a systematic and comprehensive investigation of the neuropsychological effects of cocaine "bingeing", and will identify patterns of cocaine use that warrant special clinical attention. This training plan will allow Dr. Vadhan to develop an independent clinical and experimental research career focused on his goal to understand the neuropsychology of substance abuse disorders. Relevance: The proposed projects will allow for a greater understanding of cocaine's effects on cognitive ability, an area of significant public health concern. Knowledge of such effects may also assist in clinical treatment of cocaine-abusing individuals.