National Institute on Drug Abuse RESEARCH MONOGRAPH SERIES Residual Effects of Abused Drugs on Behavior U.S. Department of Health and Human1 Services 0 • Public Health Service 1 • National Institutes of Health Residual Effects of Abused Drugs on Behavior Editors: John W. Spencer, Ph.D. Division of Clinical Research National Institute on Drug Abuse John J. Boren, Ph.D. Division of Clinical Research National Institute on Drug Abuse Research Monograph 101 1990 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Alcohol, Drug Abuse, and Mental Health Administration National Institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 For sale by the Superintendent of Documents, U.S. Government Printing Office, Washington, DC 20402 Residual Effects of Abused Drugs on Behavior ACKNOWLEDGMENT This monograph is based on the papers and discussion from a technical review on “Residual Effects of Abused Drugs on Behavior: Clinical- Research Integration” held on February 23 and 24, 1989, in Rockville, MD. The review meeting was sponsored by the Office of Science and the Division of Clinical Research, National Institute on Drug Abuse. COPYRIGHT STATUS The National Institute on Drug Abuse has obtained permission from the copyright holders to reproduce certain previously published material as noted in the text. Further reproduction of this copyrighted material is permitted only as part of a reprinting of the entire publication or chapter. For any other use, the copyright holder’s permission is required. All other material in this volume except quoted passages from copyrighted sources is in the public domain and may be used or reproduced without permission from the Institute or the authors. Citation of the source is appreciated. Opinions expressed in this volume are those of the authors and do not necessarily reflect the opinions or official policy of the National Institute on Drug Abuse or any other part of the U.S. Department of Health and Human Services. The U.S. Government does not endorse or favor any specific commercial product or company. Trade, proprietary, or company names appearing in this publication are used only because they are considered essential in the context of the studies reported herein. DHHS publication number (ADM)90-1719 Printed 1990 NIDA Research Monographs are indexed in the Index Medicus. They are selectively included in the coverage of American Statistics Index, BioSciences Information Service, Chemical Abstracts, Current Contents, Psychological Abstracts, and Psychopharmacology Abstracts. iv Contents Page Preface vii Methodological Issues Why Evaluate for Residual Drug Effects 1 John Spencer The Long-Term Neurobehavioral Consequences of Substance Abuse: Conceptual and Methodological Challenges for Future Research 10 Robert Reed and Igor Grant Use of Complex Behavioral Baselines to Monitor Residual Drug Effects in Animals 57 Merle Paule Clinical and Laboratory Investigations of Residual Drug Effects Clinical-Behavioral Observations of the Long-Term Effects of Drug Abuse 71 George E. Woody, A. Thomas McLellan, and Charles P. O’Brien Adaptive Behavior in Recovering Female Phencyclidine/Polysubstance Abusers 86 Judy Howard Leila Beckwith, and Carol Rodning Long-Term Marijuana Use and Subsequent Effects on Learning and Cognitive Functions Related to School Achievement: Preliminary Study 96 Robert I. Block, Sara Farnham, Kathleen Braverman, Russell Noyes, Jr., and M.M. Ghoneim v Residual Effects of Alcohol 112 Peter E. Nathan Hepatic, Nutritional, and Genetic Influences on Cognitive Process in Alcoholics 124 Ralph E. Tarter, Howard Moss, Amelia Arria, and David Van Thiel Learning and Memory Deficits in Detoxified Alcoholics 136 Marlene Oscar-Berman Persisting Neurotoxic Consequences of Solvent Abuse: A Developing Animal Model for Toluene-Induced Neurotoxicity 156 Gordon Pryor Cognitive Deficits in Abstaining Cocaine Abusers 167 Ronald I. Herning, Barbara J. Glover, Bonnie Koeppl, William Weddington, and Jerome H. Jaffe Abstinence Symptomatology and Neuropsychological Deficits in Chronic Cocaine Abusers 179 Stephanie S. O’Malley and Frank H. Gawin List of NIDA Research Monographs 191 vi Preface During the past decade, there has been a disturbing rise in the abuse of various addictive drugs. What has become increasingly clear is the com- plexity of use of substances such as methamphetamine, marijuana, phency- clidine, cocaine or crack, and alcohol; often two or more drugs are taken concurrently at high doses. Not only is the degree of possible toxicity poorly understood, but so are the residual central nervous system and behavioral effects following drug discontinuation. Determining long-term drug effects is important if their possible adverse consequences to physical and mental functioning are to be fully understood. For example, the extent to which long-term drug use specifically impairs cognition, e.g., the ability to think and reason, or exacerbates a long-lasting psychiatric or dementialike disorder is either not known or the information is incomplete. The ramification of residual drug effects extends beyond the individual to include the family, various legal and educational institutions, and even newborn infants. Estimates of the financial costs of treatment and rehabilitation of indigent substance abusers as well as postnatal care given to babies born to addicted mothers are escalating yearly. A technical review entitled “Residual Effects of Abused Drugs on Behavior: A Clinical-Research Integration” was held at the National Institute on Drug Abuse in Rockville, MD, on February 23 and 24, 1989. The two major goals were: (1) to evaluate the current state of knowledge on the residual effects of chronic substance abuse on behavior, and (2) to foster an inter- disciplinary research effort to study and understand long-term drug effects by involving both laboratory researchers and clinicians. vii The papers presented at this technical review form the basis for the present monograph. John W. Spencer, Ph.D. John J. Boren, Ph.D. Clinical and Behavioral Pharmacology Branch Division of Clinical Research National Institute on Drug Abuse Rockville, MD 20857 viii Why Evaluate for Residual Drug Effects John W. Spencer INTRODUCTION If illegal drugs such as cocaine and crack, phencyclidine, marijuana, or methamphetamine are repeatedly abused for an indefinite period of time, are there long-lasting effects on behavior following discontinuation of use? Can either temporary or permanent brain damage or brain dysfunction be de- scribed? If some type of behavioral deficit does exist, can it be directly attributable to the use of the drug itself? Despite over 20 years of research, answers to these questions are either not known or are incomplete. What has been described in the research literature is that following alcohol withdrawal and, to some extent, inhalant abuse, certain individuals may have a behavioral, cognitive impairment in the initiation and flexibility of think- ing and reasoning, a loss in memory function, or both (Nathan, this vol- ume). These longer lasting, persistent impairments in behavior extending beyond any detoxification period have been termed “residual effects.” Studies that have attempted to establish whether residual effects exist for any illegal drug of abuse have been more equivocal (Reed and Grant, this volume). The major points that will be described and developed in this chapter are that, following repeated abuse of any substance, it will first be necessary to evaluate and establish whether residual drug effects exist; then the careful profiling or classifying of residual effects into type, degree of severity, and duration of effect or recovery for a specific population (children, adults) can provide a directed focus of research into the consequences of long-term illegal drug usage. STEPS IN CLINICAL EVALUATION Clinically, it is important to describe the presence of any detrimental behav- ioral deficits following long-term substance abuse. The neuropsychologist is 1 often presented with assessment referrals that request evaluation of detoxi- fied drug abusers. A major job is the thorough indexing of performance impairments. Data collected helps to describe behaviorally what tasks the individual can or cannot perform. It is useful to analyze both level and quality of performance. This information can reveal how deficient the client is when compared to a drug-nonabusing subject, as well as reflecting the degree of accuracy and speed on specific items. Areas that need to be measured include motor dexterity, sensory processing (visual, auditory, and tactile), reaction time, attention and concentration, language functioning and verbal reasoning, visual-spatial analysis and construction, verbal and non- verbal memory, and degree of abstraction, planning, and problem-solving skills. Many of these perceptual and cognitive functions overlap in the skills required for successful performance. Memory may involve both verbal stimuli and visual-spatial configurations and depend upon adequate sensory processing ability. Concentration deficits can impair the ability to reason, as well as the ability to make judgments. Motivational deficits also may contribute to impairment at all levels of functioning. As will be dis- cussed later in this chapter, more specific types of neurobehavioral responses may need to be evaluated. Neuropsychological evaluations should not only help describe cognitive impairments but should also list perfor- mance strengths that are not adequately used by the abstinent substance