Drug addiction research: moving toward the 21st century.

Advances in science over the last 2 decades have revolutionized our understanding of drug abuse and addiction and continue to significantly impact how we as a Nation approach this major public health problem. We now have strong scientific evidence to show that addiction is a chronic, relapsing disease of the brain that has imbedded behavioral and social context Ž aspects e.g. Leshner, 1997; Nestler and Aghajanian, . 1997; O’Brien, 1997 . Moreover, like other complex brain diseases, addiction’s successful treatment requires what some refer to as ‘whole person treatment’ Ž . Coletti, personal communication attending to all of addiction’s biological, behavioral and social context aspects. We know more about abused drugs and the brain than is known about almost any other aspect of brain function. As discussed throughout this issue, scientists have identified neural circuits that subsume the actions of every known drug of abuse, and they have specified common pathways that are affected by almost all such drugs. Researchers have also identified the primary receptors for every major class of abused drug; identified their genetic code and cloned these receptors; mapped their locations in the brain; and determined the neurotransmitter systems involved. In addition, they have elaborated many of the biochemical cascades within the cell that follow receptor activation by drugs. Moreover, although there appear to be some idiosyncratic effects of each drug taken; there also appears to be some common effects. For example, many studies suggest that independent of a drug’s initial site of action, virtually every drug } be it nicotine, heroin, cocaine, or amphetamine } appears to stimulate increases in dopamine in the nucleus accumbens. This increase in dopamine secretion is believed by many investigators to be a critical element in what continues drug taking behavior. Research has also begun to reveal major differences between the brains of addicted and non-addicted individuals. This is what fundamentally makes addiction a brain disease; it is a condition of changes in brain structure and function. A variety of studies in both humans and other animals have demonstrated that chronic drug use changes the brain in fundamental ways that persist long after the individual has stopped taking the drug. In addition, long-term use of a variety of different drugs has been found to lead to common changes at the cellular and molecular level. We do not yet know which of these changes constitute the switch in state, from voluntary drug use to compulsive, often uncontrollable drug craving, seeking and use, that constitutes addiction. However, we do know that addicted brains are quite different from non-addicted brains and these observable brain changes appear to coincide with the behavioral changes that also occur as addiction develops. It is because of the many recent efforts in clinical neurobiology research that we are able to gain insight into the precise ways in which the brains of human drug abusers are altered. New technologies allow us to observe changes in brain function as individuals move from one state to another or through one phase of abuseraddiction to another. We can now assess in awake and functioning patients many different parameters, such as blood flow, neural activity, receptor and transmitter function, drug pharmacokinetics and pharmacodynamics, as well as some of the neurotoxic effects drugs may have on the human brain. One of the most significant breakthroughs has been the identification of areas of the brain that are specifically involved in the phenomenon of craving. Many clinicians believe that craving is a central factor in many cases of drug relapse, and, therefore, understanding the systems that mediate this phenomenon may provide a foundation for developing much more effective treatments to prevent or reverse the addiction process.