National Institute on Drug Abuse's behavioral research agenda.

Basic behavioral research continues to play an integral role in the National Institute on Drug Abuse's (NIDA's) search for solutions to the complex social and public health problems posed by drug abuse and addiction. Along with NIDA's basic molecular and neuroscience research programs, behavioral research has played an important role in increasing clinician's understanding of the mechanisms and processes that underlie addiction. Much has been learned about the ways in which animals and humans respond to their environment and the role these basic behavioral processes play in drug abuse and other drug-abuse-related phenomena, such as withdrawal, craving, and relapse, but there is still much more to be known. The author discusses how NIDA will continue to build and promote its behavioral research agenda and ensure that behavioral research findings are applied in real-life settings when applicable.

Drug abuse and developmental psychopathology.

Drug abuse research and theory has become much more sophisticated over the last 2 decades, and some of the advancements parallel concepts that are part of the developmental psychopathology approach. The application of the developmental psychopathology perspective to recent drug abuse research findings can provide a greater understanding of that information and point to important areas of future research. Among the drug abuse research areas discussed here and viewed from this perspective are antecedent and co-occurring psychopathological conditions and other problem behaviors; the diversity of the nature of, paths to, and processes and outcomes related to drug abuse; the role of intermediary influences; the interaction of individual and environmental predisposing and protective factors; the role of families and other social institutions in intervention; and developmental stage characteristics. Directions for future research are also discussed.

The disease of addiction.

Drug use is a preventable behavior, and addiction is a treatable disease. More than two decades of scientific research have yielded tremendous understanding concerning the nature of addiction and what to do about it. Many tools that can be used by health care providers to aid in the recognition, referral, and treatment for drug abuse and addiction also have been developed. To assist in these efforts, the National Institute on Drug Abuse recently has published the first ever science-based guide to drug treatment: Principles of Drug Addiction Treatment. This guide articulates some essential characteristics of addiction and its treatment and lays out the principles derived from two decades of scientific research that characterize effective treatment programs. This article elaborates many of those points.

Drugs of abuse and the brain.

New insights into our understanding of drug abuse and addiction have revealed that the desire to use drugs and the process of addiction depend on effects on brain function. Drugs of abuse have been hypothesized to produce their rewarding effects by neuropharmacological actions on a common brain reward circuit called the extended amygdala. The extended amygdala involves the mesolimbic dopamine system and specific subregions of the basal forebrain, such as the shell of the nucleus accumbens, the bed nucleus of the stria terminalis, and the central nucleus of the amygdala. The psychomotor stimulants cocaine and amphetamine activate the mesolimbic dopamine system; opiates activate opioid peptide receptors within and independent of the mesolimbic dopamine system. Sedative hypnotics alter multiple neurotransmitter systems in this circuitry, including: 1) gamma aminobutyric acid; 2) dopamine; 3) serotonin; 4) glutamate; and 5) opioid peptides. Nicotine and tetrahydrocannabinol both activate mesolimbic dopamine function and possibly opioid peptide systems in this circuitry. Repeated and prolonged drug abuse leads to compulsive use, and the mechanism for this transition involves, at the behavioral level, a progressive dysregulation of brain reward circuitry and a recruitment of brain stress systems such as corticotropin-releasing factor. The molecular mechanisms of signal transduction in these systems are a likely target for residual changes in that they convey allostatic changes in reward set point, which lead to vulnerability to relapse.

Addiction is a brain disease, and it matters.

Scientific advances over the past 20 years have shown that drug addiction is a chronic, relapsing disease that results from the prolonged effects of drugs on the brain. As with many other brain diseases, addiction has embedded behavioral and social-context aspects that are important parts of the disorder itself. Therefore, the most effective treatment approaches will include biological, behavioral, and social-context components. Recognizing addiction as a chronic, relapsing brain disorder characterized by compulsive drug seeking and use can impact society's overall health and social policy strategies and help diminish the health and social costs associated with drug abuse and addiction.

Understanding drug addiction: implications for treatment.

The addicted brain is qualitatively different from the nonaddicted brain, in ways that include glucose use, gene expression, and responsiveness to environmental cues. Such discoveries place researchers in the early but hopeful stages of translating fundamental findings into new treatments that address the neurobiologic basis of drug craving--even for cocaine, against which there are currently no pharmacologic interventions.