Clinical Textbook of Addictive Disorders 3rd ed - R. Frances, S. Miller, A. Mack (Guilford, 2005) WW

4 I. FOUNDATIONS OF ADDICTIONWhile the individual patient, rather than his or her disease, is the appropriatefocus of treatment for substance abuse, an understanding of the neurobiologyof dependence and addiction can clarify the rationales for treatment methodsand goals. Patients who are informed about the brain origins of addictionalso can benefit from understanding that their addiction has a biological basisand does not mean that they are “bad” people.Brain abnormalities resulting from chronic use of nicotine, stimulants,opioids, alcohol, hallucinogens, inhalants, cannabis, and many other abusedsubstances are underlying causes of dependence (the need to keep taking drugsto avoid a withdrawal syndrome) and addiction (intense drug craving and compulsiveuse). Most of the abnormalities associated with dependence resolveafter detoxification, within days or weeks after the substance use stops. Theabnormalities that produce addiction, however, are more wide-ranging, complex,and long-lasting. They may involve an interaction of environmentaleffects—for example, stress, the social context of initial opiate use, and psychologicalconditioning—and a genetic predisposition in the form of brain pathwaysthat were abnormal even before the first dose of opioid was taken. Suchabnormalities can produce craving that leads to relapse months or years afterthe individual is no longer opioid-dependent.In this chapter we describe how drugs affect brain processes to produce drugliking, tolerance, dependence, and addiction. Although these processes arehighly complex, like everything that happens in the brain, we try to explain themin terms that can be understood by patients. We also discuss the treatment implicationsof these concepts. Pharmacological therapy directly offsets or reversessome of the brain changes associated with dependence and addiction, greatlyenhancing the effectiveness of behavioral therapies. Although researchers do notyet have a comprehensive understanding about how these medications work, it isclear that they often renormalize brain abnormalities that have been induced bychronic, high-dose abuse of various substances.ORIGINS OF DRUG LIKINGMany factors, both individual and environmental, influence whether a particularperson who experiments with drugs will continue taking them long enoughto become dependent or addicted. For individuals who do continue, the drug’sability to provide intense feelings of pleasure is a critical reason.When abused drugs travel through the bloodstream to the brain, theyattach to specialized proteins on the surface of neurons that may be receptors,transporters, or even structural elements of the neurons. For example, opiatessuch as heroin bind to mu opioid receptors, which are on the surfaces of opiatesensitiveneurons, and have their effects by inhibiting the cyclic adenosinemonophosphate (cyclic AMP) second messenger system. Inhibition occurs