A Primer on Drug Addiction

What is drug addiction? Considerable confusion exists regarding the nature of addiction. The most common misunderstanding is that addiction refers to a state of physical dependence on a drug whereby discontinuing drug intake produces a withdrawal syndrome consisting of various somatic disturbances. Addiction is better defined as a behavioral syndrome where drug procurement and use seem to dominate the individual’s motivation and where the normal constraints on behavior are largely ineffective. This condition may or may not be accompanied by the development of physical dependence on the drug. This condition has also been described as a "psychological" addiction (thus distinguishing it from physical dependence archaically termed "physical" addiction), but confusion is minimized by using the term addiction to refer to the behavioral syndrome described above and the term physical dependence to refer to the condition associated with somatic withdrawal reactions. The distinguishing feature of the condition commonly referred to as addiction is the ability of the drug to dominate the individual’s behavior, regardless of whether physical dependence is also produced by the drug.
 

What causes drug addiction? Many factors influence a person’s initial drug use. Personality characteristics, peer pressure, and psychological stress can all contribute to the early stage of drug abuse. These factors are less important as drug use continues and the person repeatedly experiences the potent pharmacological effects of the drug. This chemical action, which stimulates certain brain systems, produces the addiction, while other psychological and social factors become less and less important in influencing the individual’s behavior. When the pharmacological action of a drug dominates the individual’s behavior and the normal psychological and social control of behavior is no longer effective, the addiction is fully developed. This self-perceived "loss of control" is a common feature of drug addiction and reflects the biological nature of the problem.
 

How is drug addiction related to "normal" behavior? Specialized brain systems have evolved to ensure survival of the species. These systems direct behavior by rewarding actions that promote survival of the individual and of the species. Intake of nutrients and procreation are governed by specific brain systems; for example, the interaction of various substances in foods (e.g., sugars, fats) activate taste receptors which in turn activate brain reward mechanisms. Activation of brain reward systems produces changes in affect ranging from slight mood elevation to intense pleasure and euphoria, and these psychological states help direct behavior toward natural rewards. Some chemicals activate brain reward systems directly, bypassing the sensory receptors mediating natural rewards. The caffeine from coffee and tea, the alcohol from fermented beverages, and the nicotine from tobacco all activate brain reward mechanisms directly. Moderate use of these substances has gained widespread acceptance over the centuries, although their use has been periodically prohibited (e.g., alcohol during prohibition) or restricted (e.g., cigarette smoking currently). Other drugs much more potently activate brain reward systems. Initial use of these substances is usually accompanied by mood elevation and other affective changes that lead to their recreational use. (Some drugs have actions that produce other desirable psychological effects, such as relaxation.) Much like moderate caffeine and alcohol use, addictive drugs activate brain reward systems. But the activation is much more intense causing the individual to crave the drug and to focus their activities around taking the drug. The ability of addictive drugs to strongly activate brain reward mechanisms and their ability to chemically alter the normal functioning of these systems can produce an addiction.
 

What are psychoactive drugs? Many drugs interact with brain mechanisms involved in affect, cognition, and behavior. These compounds are termed psychoactive drugs. Drugs are usually classified according to their primary therapeutic actions. Antipsychotic drugs are used to treat schizophrenia and produce a normalization of the disordered thought processes associated with this illness. Antidepressant drugs are used to treat psychological depression and produce a normalization of disturbed affective states characteristic of depression. And antianxiety drugs (i.e., anxiolytics) are used to treat anxiety and produce a calming action in nervous individuals. These and numerous other drugs have important clinical uses and have revolutionized the treatment of many mild to severe mental disorders. Some work at the ASnet and its laboratory facility—the Addiction Research Unit (ARU) at the University at Buffalo—investigates the actions of these drugs, but research focuses on psychoactive drugs that are addictive. Recent work has also investigated the effects of mildly psychoactive compounds found in over-the-counter medicines (e.g., pseudoephedrine, diphenhydramine) and compares their effects with prototypic addictive drugs (e.g., cocaine, heroin). This comparison helps sharpen the distinction between addictive and nonaddictive substance use and is used in comparing the effects of other commonly used substances (i.e., caffeine, nicotine).
 

Why conduct basic scientific research? Although the basic biological actions of some drugs are well understood, many important questions remain to be answered. Why do individuals differ in their vulnerability to addiction? How do psychological factors such as stress interact with brain mechanisms to influence the development of an addiction? And why are some people successful in overcoming their addiction while others are not? (Certainly differences in treatment approaches do not account for the successes, because no single treatment program has a uniquely high success rate.) These and many other questions need to be answered. Considerable progress has been made during the past two decades, but considerable more work needs to be done before drug addiction is fully understood. And understanding addiction is the key to successful treatment.

What is the most effective approach to conducting basic research in drug addiction? Two important considerations direct research at ASnet into basic mechanisms of drug addiction. First, research focuses on prototypic addiction drugs. These are drugs with a high addiction liability (i.e., addiction develops quickly and in a high percentage of individuals after relatively brief use). Prototypic addictive drugs also have well-defined actions on biological systems (i.e., interact with specific brain systems) and have historically shown epidemic patterns of abuse (i.e., abuse patterns showing rapid increases in the number of people using the drug during the past century often followed by a marked decline in use; a cyclic pattern of abuse). The two drug classes that clearly fit these criteria for prototypic addictive drugs are the psychomotor stimulants (e.g., amphetamine, cocaine, methamphetamine) and the opiates (e.g., heroin, morphine). Second, animal models are used to study the underlying biological mechanisms of addiction. Laboratory animals voluntarily self-administer these prototypic addictive drugs, and basic research in drug addiction uses animal models to study the biological mechanisms underlying addiction. (Contrary to popular belief, laboratory animals exposed to addictive drugs usually remain healthy and suffer no adverse effects of these drugs [i.e., low morbidity]. The only experiments where research animals are subjected to any appreciable discomfort involve those studying the effects of psychological stress or continuous exposure to drugs. Few experiments are conducted at the ARU investigating these experimental conditions, and all studies are conducted with laboratory rats.) As basic research studying prototypic addictive drugs in animal models progresses, the principles learned with this approach are extended to other addictive drugs (e.g., alcohol) and to clinical studies (e.g., the treatment of drug addicts).
 

Are there other benefits from studying addiction? Understanding the underlying neural basis of addiction opens the door to not only treating specific drug addictions but to also understanding fundamental relationships between behavior and brain function. Addiction presents a situation where chemical activation of brain mechanisms control the individual's behavior, and understanding this process helps delineate processes involved in normal behavior. In addition, several mental disorders, such as schizophrenia and depression, involve disturbances in the same brain system as that involved in addiction. Basic research provides the key to deciphering the biological basis of addiction and to understanding other types of psychopathology.

Why develop medications for treating addiction? Drug addiction involves disturbances in brain chemistry caused by repeated use of certain psychoactive substances. Although the exact nature of these disturbances is not well understood (and hence, the need for continued basic research), the biological nature of this problem is appreciated by most specialists. Psychological counseling and therapy can help the individual recovering from addiction, but the main problem lies with altered brain chemistry that needs to be treated pharmacologically. A number of medications are currently being investigated in various laboratories, but none are yet very effective. Basic research studying prototypic addictive drugs in animal models can identify the neural mechanisms underlying addiction. This information can then direct the development of medications for the treatment of addiction. These medications are evaluated for their safety and effectiveness using animal models before being prescribed clinically to treat addiction. (This last step is particularly important, considering that heroin was originally developed as a treatment for morphine addiction.)

What's wrong with the current sources of information regarding addiction? A number of agencies and organizations disseminate information about drug addiction (for examples, see the Links on the ARU home page). Most notably, the National Institute on Drug Abuse (NIDA) has been the premier clearing house for information on drug abuse. Many excellent research monographs, pamphlets, and press releases are sponsored by NIDA, but this government organization must also respond to the political realities of all government organizations. When marijuana use in the late 1940s became a national concern, the government was involved in producing a film entitled Reefer Madness to "educate" the public about the dangers of marijuana use. This film remains a classic today, but not as a testimony to unbiased presentation of scientific evidence; rather; this film exemplifies the propaganda expounded by a politically directed organization and has fostered the distrust that many young people have of government information. More recently, NIDA diverted attention from cocaine and heroin addiction when the Surgeon General declared "nicotine more addictive than cocaine." Although this assertion seems to have been quietly accepted by many scientists, the ASnet considers this statement unsubstantiated by the empirical data and socially irresponsible. Dissident opinion has been silenced by the feared repercussions of challenging official government policy. Other, nongovernment organizations providing information regarding drug abuse also have hidden agendas. Most are linked with treatment centers, pharmaceutical firms selling a product, or supported by government grants and contracts. Much of the information disseminated from these sources is accurate, but some of it is not. Although the ASnet is in principle opposed to any illicit substance use, it follows the dictum that unbiased scientific information should be provided to the public. It is the responsibility of science to provide the facts of the individual to decide how to use those facts.
 
 

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