Addiction Research: An Historical Perspective
Avram Goldstein, M.D.
Stanford University, Stanford, CA
Modern research into drug addiction began at NIDA's precursor organization, the Lexington "narcotics farm." There, 50 to 60 years ago, Himmelsbach, Isbell, Fraser, Wikler, and Martin gained the first systematic scientific knowledge about drug tolerance, physical dependence, reinforcement, and the behavior of addicts of their day. My historical overview will discuss how far we have come, into what blind alleys we have strayed, what triumphs NIDA's quarter century can rightfully claim, where we stand today, and what lessons the past holds for the future.
Emotions and Vulnerability to Addiction: The Challenge of Integrating Molecular and Behavioral Approaches
Huda Akil, Ph.D.
University of Michigan, Ann Arbor, MI
This work has focused on two research areas: the brain biology of stress and depression, and the biology of endorphins and other molecules related to substance abuse. Each of these areas takes a broad-based approach, examining the system at a cellular, molecular, and integrative level. This is most clearly demonstrated in our most recent work, which has been focusing on the effects of stress on the acquisition of drug-taking behavior and on the neurobiological basis of individual differences in this interaction. The feature that most clearly characterizes this research approach is the integration of numerous tools and research strategies in an effort to understand the biological bases of emotional behavior and to use this understanding to approach the study of human emotions, in both health and disease.
Neuroimaging: A Window Into the Addicted Brain
Hans Breiter, M.D.
Massachusetts General Hospital, Charlestown, MA
Not available at press time
The Future of Addiction Treatment Research
Herbert D. Kleber, M.D.
College of Physicians and Surgeons of Columbia University, New York, NY
Future treatment approaches for drug abusers will continue to involve the combination of pharmacological and behavioral interventions. Current pharmacotherapies, both successful and failed, have generally relied on medications developed for non-drug abuse indications, while successful behavioral interventions have derived either from preclinical laboratory data or cognitive psychology. Although more recent testing of pharmacological interventions has had the theoretical underpinnings of neuroscience research (e.g., the dopamine theory for cocaine abusers), to date no successful medication has arisen from the research.
Future pharmacological treatment research will have to rely on new compounds screened and developed with specific brain mechanisms in mind, and with an awareness of the complexity of action of various drugs of abuse—not just dopamine, for example, but the D1 or D2 receptor, or modulators of the dopamine system such as the excitatory and inhibitory amino acids. Large-scale screening remains risky, however, without a demonstration of proof of concept.
The next few decades should witness development of agents to block existing drugs of abuse, including vaccines and receptor antagonists; agents that repair the brain changed by chronic compulsive drug use; and subtle agonists that mimic some effects without abuse liability. Since human nature will not have changed, however, the majority of addicts will want nothing to do with any of these. Thus, better behavioral interventions will be critical. They will need to be targeted rather than general—an intervention to increase compliance with a blocker, another to better provide the skills to avoid relapses while on an agonist or reparative agent. We will need to reach out to new disciplines and knowledge bases to craft these new behavioral tools. Finally, a mechanism to test rapidly these new pharmacotherapies and behavioral interventions on a large enough scale with sharing of data in real time will need to be assembled.
Preventing Drug Abuse and Addiction: Directions for Future Research
Mary Ann Pentz, Ph.D.
University of Southern California, Los Angeles, CA
Research indicates that school- and community-based prevention programs aimed at counteracting social influences to use drugs can achieve 2 to 5 percent actual reductions in adolescent drug use, which translate to 40 to 60 percent net reductions. Additional, recent research indicates that programs aimed at building academic and social competence, which are considered protective factors against drug use, can increase academic and social competence skills in children, which affect drug use later in adolescence. However, effects of these risk and protective programs depend on several factors, including quality of program implementation, inclusion of boosters and/or other support components such as parent education or media, and the complementarity of programs with school and other local policies. Furthermore, generalization of effects from research to field settings depends on the success of technology transfer, that is, the adoption, use, and dissemination of programs. Compared with research that has yielded significant information about the main and mediating effects of prevention programs, relatively little is known about factors that can maximize effectiveness in diverse settings and populations, thereby increasing the probability that we can achieve nationwide reductions in drug use morbidity and mortality.
These gaps in knowledge translate to specific directions for future prevention research. First is the specificity of a prevention program. For example, does a tobacco-specific prevention program receive more support than a general life skills or drug abuse prevention program in some communities, which translates to better implementation and effects? Community priorities for specific types of prevention and general community readiness for prevention could be studied in prevention trials, using block designs and community as the unit of assignment to different priority or readiness blocks. Second is the study of factors that may explain why some communities continue to implement programs that are ineffective and factors that may help to increase community adoption of effective programs. Variables such as "sunk" costs, political support, and available resources for implementation could be treated as covariates in analyses of retention of ineffective programs, and change toward adoption of effective programs. Third is the study of "reinvention," or tailoring of programs to fit community or population needs. Analysis of reinvention in implementation analyses of prevention programs could yield factors that improve prevention effects.
Fourth is the relationship of prevention programs to local policies and policy changes that occur in a community. Specifically, more preventive interventions need to be developed and evaluated which include complementary, cross-referencing of prevention messages in programs and policies. Fifth is the study of differential prevention effects with subpopulations of youth who have different natural trajectories of drug use that might reflect addiction potential. For example, research could examine whether universal drug abuse prevention programs are effective with youth who may have elevated risk based on a genetic or neurophysiological factor, e.g., ADHD with conduct disorder. Finally, relatively little is known about how to combine protective with risk factor prevention programs. More prevention trials could be developed which deliberately bridge at least two developmental periods for intervention, for example, late childhood and early adolescence, and which sequence developmentally appropriate protective and risk factor prevention programs.
HIV Infection: Prevention and Progression
David Vlahov, Ph.D.
The New York Academy of Medicine, New York, NY
Blood-borne infections, including HIV, among illicit drug users remain a major public health problem. Studies of injection drug users have identified key risk factors that center on multiple person re-use of syringes. More recent studies have focused attention on the especially high risk for infection among newly initiated injection drug users, suggesting that programs to prevent acquisition of HIV and other blood-borne infections need to be targeted early. A comprehensive approach to prevention program development including drug treatment, needle exchange, outreach education, and behavioral interventions has shown promising results. In the past few years, the advances in development of combination antiretroviral therapy, which can reduce HIV viral load to undetectable levels, have provided a new strategy for HIV prevention through case identification and management of infected individuals. This strategy requires strict adherence on the part of infected individuals, and considerable attention is directed at achieving this. Numerous studies show that injection drug users can be accessed for interventions and that comprehension of and adherence to study protocols are achievable. More information is needed on the interactions of the antiretroviral therapies and both the pharmacologic treatments for drug dependence and the effects of chronic viral hepatitis that are commonly found in this population. Prior research from NIDA has addressed many important questions, and as strategies for prevention and management of HIV and other blood-borne infections develop, NIDA will continue to play a key role in advancing public health.
The Science of Substance Abuse: Surprises, Challenges, and Opportunities
Floyd E. Bloom, M.D.
The Scripps Research Institute, La Jolla, CA
In keeping with the incremental nature of the NIDA anniversary celebration, this presentation will look back on the 25 years of involvement with research on the neuroscience of substance abuse. From the first molecular demonstration of the stereoselective opiate binding site in the brain to today's unexpectedly grand expansion of endogenous opioid signals and their receptors, the precision of sites engaged with psychostimulants, and the characterization of the effects of cannabinoids, the field of NIDA's mission has been a continual series of surprises and new research opportunities. Along this path have been many notable opportunities for new therapeutic extensions to the problems of the human addict. The major challenge for this scientist remains a double-headed enigma, in which one strives for scientific advances that can affect social policy, while hoping that prematurely set social policies do not place new barriers in the path of rapidly progressing scientific research.
Prevention and Treatment of Adolescent Drug Abuse: What Does the Future Hold?
José Szapocznik, Ph.D.
University of Miami School of Medicine, Miami, FL
This Nation has seen an alarming increase in adolescent problems such as drug use, crime, and violence. Seriously troubled youth are involved with drugs, and drugs exacerbate their antisocial behaviors. Increasing numbers of troubled adolescents and increasing severity of these problems are a response to our changing environment.
There is much known about the prevention and treatment of adolescent drug abuse and related antisocial behaviors. However, as in other health fields such as cancer, although much is known, much remains to be learned. Children are influenced by messages in their environment and their social relations. The single most important influence in children's lives is their parents. The critical role of parents in the prevention and treatment of adolescent drug abuse will be discussed in detail. The role of other sectors of society will also be discussed because all sectors of society need to be involved in reversing the national trends in troubled drug-using youth.
To prevent drug abuse from occurring, to treat those who are already troubled, and to prevent relapse for those who have already been treated, society must allow science to guide decisions about environments that encourage or discourage healthy adolescent development. We have the knowledge to correct the social influences that are encouraging youth to use drugs and engage in other antisocial behaviors. Do we have the will to do what it takes?