Disorders of Reward, Drug Abuse, and their Treatment

• Reward circuits
• Nicotine
• Alcohol
• Opiates
• Stimulants
• Sedative hypnotics
• Marijuana
• Hallucinogens
• Club drugs
• Sexual disorders
• Sexual disorders and reward
• Eating disorders
• Other impulse-control disorders
• Summary

Disorders of Reward, Drug Abuse, and their Treatment

Psychopharmacology is generally defined as the study of drugs that affect the brain. Until now, all the chapters of this book have addressed how psychotropic drugs affect the brain for therapeutic purposes. Unfortunately, psychotropic drugs can also be abused, and this has caused major public health problems throughout the world. Here we will attempt to explain how abuse of psychotropic agents affects the brain. Our approach to this problem is to discuss how nontherapeutic use, short-term abuse (intoxication), and the complications of long-term abuse affect chemical neurotransmission, particularly within reward circuits. We will also discuss the mechanism of action of agents that are now used to treat various substance abuse disorders.

Also covered briefly in this chapter are several other disorders thought to be regulated by reward circuitry, including sexual disorders, eating disorders, and various impulse disorders such as gambling. Reward circuitry has a prominent role in most psychiatric disorders, not just in drug abuse. Indeed, links to the reward circuitry can be seen not only for disorders of impulsivity such as attention deficit hyperactivity disorder (ADHD) (discussed in

Chapter 17), bipolar mania (discussed in Chapters 11 and 13), and anxiety disorders such as obsessive compulsive disorder (OCD) (discussed in Chapter 14), but also for disorders of motivation, such as major depression (discussed in Chapters 11 and 12), apathy in dementia (discussed in Chapter 18) and in schizophrenia (discussed in Chapters 9 and 10), use and abuse of pain medications in chronic pain syndromes (discussed in Chapter 15), and use and abuse of stimulants and sedative hypnotics in sleep/wake disorders (discussed in Chapter 16). In many ways, therefore, abnormalities in the adequate functioning of reward circuitry are key aspects to all the disorders discussed in this text. For that reason, we will discuss what is known about reward circuits in some detail.

New treatments for disorders of reward circuitry are finally entering psychopharmacology and the prospects for future therapeutics that target malfunctioning in this circuitry have never been greater. So far, psychopharmacologists have been reluctant to embrace new therapeutics for substance abuse, and thus the uptake of new treatments into clinical practice is often slow and many new treatments are still used minimally by many clinicians. Perhaps the lack of effective psychopharmacological treatments until relatively recently has allowed the field to develop therapeutic nihilism to psychopharmacological approaches. Even today, available psychopharmacological treatments for substance abuse remain few and limited in efficacy, as we shall see in this chapter.

However, the time might be right for some paradigm-shifting questions to be posed for the field of substance abuse treatment in the modern era (Table 19-1). For example, should professional psychopharmacologists be first-line treaters of substance abuse, or should this be left predominantly to lay counselors and professionals who have triumphed over their own past substance abuse? Since some treatments may blunt rather than stop all drug abuse behavior, particularly at the initiation of treatment, this leads one to ask: Is total abstinence the only desirable goal of treatment? Finally, is it rational to use drugs to treat drug abuse, or should drugs be seen mostly as crutches to be avoided?

Answers to these questions may determine whether more psychopharmacological practitioners become proactive in identifying and treating nicotine addiction; whether more practitioners start to use treatments for heavy drinking and alcoholism, including those that assure compliance for a month but are rarely used; whether more practitioners start to use opiate partial agonists for “middle class” patients dependent upon opiates who have never taken methadone. Perhaps the psychopharmacology of substance abuse and related disorders of reward is poised at the beginning of a new era, analogous to where psychopharmacology stood for the treatment of depression and psychosis in the 1950s, with major new therapeutics just around the corner.

At this point, understanding of the neuroscientific basis of reward circuitry and the pharmacological mechanism of action of substances of abuse and their drug treatments is exploding. What is known about this exciting field is summarized and reviewed briefly in this chapter. Mastering this will empower the modern psychopharmacologist to make decisions about whether to enter this field of new therapeutics.

The goal of this chapter is to provide the biological background that will enable the reader to understand not only how substance abuse is thought to alter reward circuitry but also how currently available treatments for various substance abuse disorders work, including the rationale for current research efforts to discover truly novel and highly effective new treatments for these common and very debilitating illnesses. This chapter therefore provides only a very brief overview of the various substance abuse disorders. Full clinical descriptions and formal criteria for how to diagnose the numerous known diagnostic entities should be obtained by consulting standard reference sources. Some useful definitions of key terms used in this field are given in Table 19-2. The discussion here emphasizes the links between various pathological mechanisms, brain circuits, and neurotransmitters with the various symptoms of substance abuse, from nicotine to alcohol to opiates to stimulants. Brief mention is made of other drugs of abuse and other impulse disorders that do not involve drugs. Finally, a discussion of various types of sexual dysfunction that are hypothetically linked to reward circuitry is included.