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

12 I. FOUNDATIONS OF ADDICTIONTHE IMPORTANT ROLE OF STRESSThat drug abuse patients are more vulnerable to stress than the general populationis a clinical truism. Numerous preclinical studies have documented thatphysical stressors (e.g., foot shock or restraint stress) and psychological stressorscan cause animals to reinstate drug use (e.g., Shaham, Erb, & Stewart, 2000).Furthermore, stressors can trigger drug craving in addicted humans (Sinha,Catapano, & O’Malley, 1999). One potential explanation for these observationsis that abused drugs, including opiates and stimulants, raise levels ofcortisol, a hormone that plays a primary role in stress responses; cortisol, inturn, raises the level of activity in the mesolimbic reward system (Kreek &Koob, 1998). By these mechanisms, stress may contribute to the abuser’s desireto take drugs in the first place, as well as to his or her subsequent compulsion tokeep taking them.PHARMACOLOGICAL INTERVENTIONSAND TREATMENT IMPLICATIONSIn summary, the various biological models of drug addiction are complementaryand broadly applicable to chemical addictions. We next illustrate how longtermpharmacotherapies for opioid dependence, such as methadone, naltrexone,and buprenorphine, can counteract or reverse the abnormalitiesunderlying dependence and addiction. These agents are particularly informative,because they are an agonist, antagonist, and partial agonist, respectively.We do not review short-term treatments for relieving withdrawal symptomsand increasing abstinence but refer readers elsewhere for detailed neurobiologicalexplanations for various abstinence initiation approaches (see Kosten &O’Connor, 2003).Methadone, a long-acting opioid medication with effects that last for days,causes dependence, but because of its sustained stimulation of the mu receptors,it alleviates craving and compulsive drug use. In addition, methadone therapytends to normalize many aspects of the hormonal disruptions found in addictedindividuals (Kling et al., 2000; Kreek, 2000; Schluger, Borg, Ho, & Kreek,2001). For example, it moderates the exaggerated cortisol stress response (discussedearlier) that increases the danger of relapse in stressful situations.Naltrexone is used to help patients avoid relapse after they have beendetoxified from opioid dependence. Its main therapeutic action is to occupy muopioid receptors in the brain with a 100-fold higher affinity than agonists suchas methadone or heroin, so that addictive opioids cannot link up with themand stimulate the brain’s reward system. Naltrexone does not activate the G-protein-coupled cyclic AMP system and does not increase or decrease levels ofcyclic AMP inside the neuron, and it does not promote these brain processes