ADDICTION AND DEPENDENCE

While addiction has been called a victimless crime, nothing could be further from the truth. Research consistently demonstrates that acts of violence against self and others, accidents, decreased productivity, health problems, and a number of other social ills have links to alcohol and drug abuse and addiction. Every day we read about, hear about, or know someone who is a victim of a crime caused by those who use or seek drugs. For some, it is tempting to ignore the ravages of addiction by rationalizing their lack of substance use. However, much like recent findings on secondhand smoke, researchers are identifying other deleterious secondhand effects of substance abuse and dependence. These events include dealing with noise from intoxicated partiers, assault from intoxicated persons, and encountering intoxicated drivers (Wechsler, Lee, Nelson et al.).

Few people disagree that substance abuse and dependence are destructive health behaviors, yet there seems to be a vast sea of confusion surrounding these behaviors. The facts are clear: Addiction to and dependence on tobacco, alcohol, illicit and legal drugs, and possibly biologically driven behaviors such as sex and eating, and social activities such as gambling, are widespread and very destructive.

Addiction has wide-ranging consequences. In 1998 over 500,000 full-time college students were unintentionally injured under the influence of alcohol and over 600,000 were hit or assaulted by another student who had been drinking (Hingson, et al.). Over 1,400 students died from unintentional alcohol injuries (Hingson, et al.), 42 percent of adolescents admitted to a trauma center tested positive for drugs or alcohol and 72 percent of adolescents who were victims of gunshot wounds tested positive for substance use (Madan, et al.). Young persons are not the only ones affected by drug and alcohol abuse. For example, almost half of patients over 65 years old who were treated at trauma centers tested positive for alcohol (Zautcke et al.).

As can be seen from the above data, drug and alcohol abuse puts an extreme burden on the healthcare system. Over the past eighteen years, persons admitted to level I trauma centers testing positive for alcohol has declined by about one-third. However, during this same period, the number of patients testing positive for cocaine has increased 212 percent and for opioids, 543 percent. (Soderstrom et al.)

Drug and alcohol abuse and dependence cut across all geographic, ethnic, and social boundaries although some groups have rates higher than other ethnic groups (National Household Survey on Drug Abuse, 2000). According to the Drug Enforcement Agency (DEA), the total sales of illicit drugs in the United States in 1993 amounted to $100 billion. This makes the sale of illicit drugs as large a business as a top ten company on the Fortune 500 list.

Despite concerted efforts at education and interdiction, drug use is still commonplace in the United States. For example, National Household Survey on Drug Abuse data indicate that 14 million Americans (6.3% of the population age twelve and older) used an illicit drug in the month prior to the survey. Marijuana was the most commonly used drug (4.8%). National rates for other drugs were as follows: cocaine (0.5%), hallucinogens (0.4%), and inhalants (0.3%). Approximately 130,000 Americans (0.1%) are heroin users. MDMA (Ecstasy) use between 1999 and 2000 increased by almost 25 percent to 6.4 million persons (National Household Survey on Drug Abuse, 2000). This statistic is particularly alarming given the propensity of Ecstasy to cause permanent brain damage in its users.

The business community is so concerned about substance abuse and dependence that pre-employment drug screening of prospective employees has become commonplace. The majority of Fortune 500 companies have some sort of drug-testing program. Drug testing is the norm in the U.S. armed forces, and many court cases in the early twenty-first century are examining if and when the government has the right to test its employees. In 2002 the U.S. Supreme Court, in Board of Education of Independent School District No. 92 of Pottawatomie County et al. v. Earls et al., held that drug testing of students is a reasonable means of preventing and deterring drug use among school children and is not a violation of Fourth Amendment rights.

The death toll from health problems caused by smoking is staggering. A study published in the Journal of the American Medical Association (JAMA) in 2000, estimated that almost 400,000 Americans die each year from smoking related illnesses (Thun, et al.).

Beyond the health consequences for adults, smoking is a serious threat to young people on several levels. Despite widespread antismoking programs, 14.9 percent of teenagers smoke on a regular basis. Unfortunately, many youth perceive low risk of dangers from smoking and others start smoking tobacco cigarettes after smoking safe marijuana.

Smoking is not the only potential threat from addictive substances to young people. The National Household Survey on Drug Abuse estimates that 27.5 percent of twelve- to twenty-year-olds have used alcohol in the past month. The 2000 Household Survey found that 6.6 percent of the household population, ages twelve to seventeen, had used marijuana in the preceding month while 9.8 percent reported using some illicit drug during the same period.

Why would anyone engage in such behavior in the face of such obvious and dire consequences? What are the root causes of such behavior? Why is there any debate about drug use when the frightening consequences are known? Part of the answer comes from exploring the question of what addiction really means.

What Is Addiction?

The concept of addiction—whether to alcohol, cigarettes, heroin, or sexual behavior—is widely misunderstood. Although there is room for debate about the levels of addiction caused by different substances, and perhaps about the rights of people to use addictive substances, there is no debate about what constitutes addiction. Addictive disease is defined by compulsion, loss of control, and continued, repeated use despite adverse consequences. Even though a person knows what will happen, he or she will use the addictive substance again. Thus, addiction is a disease characterized by repetitive and destructive use of one or more substances, and stems from a biological vulnerability exposed or induced by environmental factors such as drug taking.

Until scientists learned how popular recreational drugs such as cocaine affected the brain, it was thought that addiction required a physical withdrawal syndrome. That is not necessarily true. While a mild withdrawal has been described, positive effects drive compulsive use of cocaine. This information has contributed to research that clearly indicates there is no valid distinction between physical and psychological addiction.

Anyone who uses any chemical in the way described above is suffering from addictive disease. Users are distinguished by the type of drug, genetic vulnerabilities, individual predisposition to addiction, and the setting in which the drug is used.

Addiction includes preoccupation with the acquisition of a drug. In general, when obtaining a drug plays a central role in a person's life, addiction is present or near. Many studies have shown that addicts rank finding and using their drug above work, family, religion, hunger, sex, and survival. Even when the high is no longer achieved, the drug and its use are paramount. Drug taking fools the brain, giving the user a false sense of accomplishment that is at odds with reality, to the point that denial is common.

Since drugs cause a chronic disease in an otherwise healthy person, staying clean, or straight, becomes a daily problem. Relapse, therefore, is another significant and expected part of addictive disease. It is common for addicts to have relatively long periods of abstinence intermingled with drug-use binges. Chemical addiction does not happen overnight. Addicts are not moral failures but victims of a disease.

If addiction is understood as defined above, it is easy to see why it can be called a process: Use leads to brain changes; tolerance leads to abuse, which leads to loss of control, chemical dependence, and addiction.

Who Becomes Addicted?

Who becomes addicted is a complex disease process that is best understood in a biopsychosocial model where biological, environmental, and social influences create this brain disease (Tsung et al.). While research in this area is ongoing, several findings are clear. First, genetics plays a powerful role in who becomes addicted and to what. For example, approximately 10 percent of the population has a preexisting biological, or genetic, predisposition to drug and alcohol dependency. This genetic relationship is supported by the higher concordance rates (likelihood of one twin having the condition if the other has) of substance dependence among identical twins (those who share the same genetic material), compared to fraternal twins (those with non-identical genetic material). Genetic factors underlie neurotransmitter receptor patterns in the brain that predispose a person to addiction (Rose et al.). Genetic factors are important in explaining why one person can have a drink and walk away and another person cannot stop drinking until he or she passes out.

Second, there is clearly a drug effect. That is, while all drugs impact upon similar reward properties of the brain, the pharmacological properties of some drugs are more addictive than others. Some substances such as cocaine or narcotics can cause addiction in almost anyone, regardless of genetic predisposition, if they are used frequently for a long enough time.

Third, environmental factors and drug use expectancies (i.e., motivation and intent) also play a role in the addiction process (Jang et al.). For example, rarely do cancer patients become addicts despite taking powerful doses of narcotic pain medication. Similarly, while an estimated 20 percent of American soldiers in Vietnam developed heroin addiction, 90 percent were able to give up heroin once they returned from Vietnam. An outcome rate much higher than typically seen among heroin users. Finally, as Russian physiologist Ivan Pavlov (1849–1936) proved, whether it is food and a bell or a drug and a bell, salivation is salivation. Drugs are powerful conditioners shaping behavior and responses.

Despite all of this evidence of addiction, the fields of psychiatry in particular and medicine in general have been slow to respond to the medical and societal challenges posed by addiction. Even the 2000 Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-R), the bible of psychiatric diagnosis, does not mention addiction, per se, but instead discusses dependence.

What Is Dependence?

What is meant by dependence? Is there a real distinction between dependence and addiction or is the difference only semantic? Examination of the DSM-IV-TR criteria for Substance Dependence reveals that the above criteria cited for addiction (e.g., compulsive use, loss of control, and continued use despite adverse consequences) are included in the Dependence criteria. However, the Substance Dependence criteria also include the additional factors of tolerance and withdrawal. Thus, traditional distinctions that viewed dependence as a stage below addiction, where the choice to continue taking drugs or alcohol or to continue certain behaviors can be stopped if the person really wants to stop, may be of reduced utility (Kleiman).

In any event, once a person's drug use progresses from abuse to dependence, the capacity for voluntary control is significantly reduced. The addicted brain becomes an impaired brain because the original drug free condition has been replaced by a drug present new normality. As drug policy expert Mark A. R. Kleiman explains, people act and make decisions differently when they are intoxicated than when they are sober. Making decisions such as having another round, Kleiman points out, may lead to further bad choices. The nature of the drug—to reduce inhibition when intoxicated—brings about drugged choices.

Is Addiction a Real Disease?

In addition to genetics, addiction as a disease is supported by the common signs and symptoms among the homeless and physician drug addicts. The target for drugs of abuse is the brain and changes in the neuroanatomy of the brain occur in all addicts and underlie the disease of addiction. Recent research in neuroscience has identified a specific area of the brain described as the reward center. This area of the brain makes essential survival behaviors such as eating, drinking and sex pleasurable, reinforcing, and thus likely to reoccur. It has become evident that virtually all drugs of abuse target this same area of the brain and result in neurotransmitter brain reward. The problem is that the neurotransmitter changes caused by these drugs far exceed those produced by the natural reinforcers. Animals will press a lever for a drug injection or a puff of cocaine. Once they learn that pressing the lever gives them cocaine, they press and press and press, frequently at the expense of eating, drinking, and ultimately their lives. Unfortunately, the same is true in humans where it is not uncommon to see addicts lose family, careers, and even their lives because of their addiction.

This same area has connections to the emotional areas of the brain (i.e., limbic system). Thus, drug use and addiction can be seen as a disease of brain reward with significant physical and psychological consequences. To truly understand the concept of addiction, one must look at issues of both positive and negative reinforcement. The pleasure effects of the drugs obviously result in positive reinforcement. However, continued drug use ultimately leads to changes in neurotransmitter levels and a host of negative states and emotions (e.g., depression, anxiety, fatigue, etc.). In these cases, continued use of the drug leads to a decrease in these unpleasant effects and results in what is called negative reinforcement (e.g., removal of unpleasant feelings) and the subsequent return to a normal (in this case, drugged brain) state. Research has led to a new understanding of addiction that is not based solely on withdrawal effects.

To understand this process in more detail let us examine the drug cocaine. Drugs like cocaine trick the limbic system by triggering the reward response through the release of neurotransmitters. Neurotransmitters are chemical messengers between nerve cells that are intricately involved in regulating moods. Cocaine use, for example, acutely leads to the increased availability of the neurotransmitter dopamine. Dopamine causes specific nerve cells to fire, and the result is endogenous brain reward or euphoria. Since cocaine uses brain systems normally reserved for species survival reward, the user feels as if he or she has just accomplished something important. The euphoria and brain reward produced by cocaine make the brain view the drug as a substance critical for survival. Hence the brain asks for more cocaine and excessive amounts of dopamine are released. Normally, any surplus dopamine released by the nerve cells is reabsorbed by them; however, cocaine interferes with this reabsorption. Finally, the brain's store of dopamine is depleted. With their supply of neurotransmitters depleted, cocaine users experience intense depression and cravings for more cocaine. In addition, the limbic system remembers cocaine's pleasurable response, a memory that can be triggered by talking about the drug, or smelling it, or even a visual stimulus such as talcum powder. It is believed that the action of drugs in a section of the brain called the nucleus accumbens is primarily responsible for the feelings of positive reinforcement that result from use of virtually all substances of abuse.

Other factors besides the pharmacological effects of drugs may lead to positive reinforcement. For example, drug use may enhance a person's social standing, encourage approval by drug-using friends, and convey a special status to the user. Recent research has shown that environmental factors can account for a considerable amount of the variance attributed to whether teens decide to use or abstain from alcohol (Rose et al.).

Given enough repetitions, drug and alcohol use become as entrenched as the desire for food, water, or sex. Furthermore, the dopamine pathways have many other influences, from the hypothalamus and hormones to the frontal lobe of the brain—the area responsible for judgment and insight. Not only do drugs cause the addict's brain to demand more drugs; the addict's ability to handle this demand rationally in the context of other everyday demands (such as work, family responsibilities, health and safety concerns) is distorted. Tormented by the acquired drive for the drug, memory of euphoria, and denial of obvious consequences, the addict becomes out of control.

Obviously, the complexity of the body and the brain means that no simple answer for the cause of addiction will be found. However, researchers are using sophisticated diagnostic examinations to uncover more information in an attempt to understand better the effects of drugs upon the brain. While it is doubtful that these procedures will provide a definitive, simple answer to the cause of addiction, the information gleaned from them may result in more effective treatment and prevention strategies.

What Is Tolerance?

Tolerance may occur when the brain environment redefines normal and resets that level of feeling due to continued drug use. If drugs are taken to seek pleasure, they develop a life of their own as the brain redefines normal to require their presence in expected quantities. In other words, it takes more and more just to feel normal.

Interestingly, the emphasis on drug reward in the addiction process paves the way for other conditions, such as eating disorders and even sexual or gambling disorders, to be considered addictions. Eating disorders, in particular, share common behavioral symptoms, biological reward pathways, high relapse rates, and treatment strategies with other forms of substance abuse. More research is necessary to establish the legitimate inclusion of sexual and gambling behaviors with other expressions of addiction.

Drug Triggers: The Brain Learns

Drug use provides a quick and powerful means of changing one's moods and sensations. In a cost-benefit analysis, the user seeks the immediately gratifying effects as a benefit that outweighs the long-term cost of drug use. Other users may be influenced by physical or psychological states such as depression, pain, or stress that may be temporarily relieved by drug consumption. Drug use is such a powerful reinforcer and shaper of behavior that drug paraphernalia and virtually all of the events associated with finding and using drugs become reinforcers.

A variety of nondrug factors, including psychological states such as depression or anxiety, and/or environmental factors (such as drug paraphernalia and drug-using locations or friends) can become so associated with drug taking that merely being depressed or seeing drug paraphernalia may trigger the urge to use drugs.

WITHDRAWAL. While significant evidence supports the role of dopamine in the reward process, the neuroanatomy of withdrawal is not as clearly defined. However, a wide variety of abused drugs, with apparently little in common pharmacologically, have common withdrawal effects in certain areas of the brain. Opiates, benzodiazepines, nicotine, and alcohol have all had their withdrawal symptoms treated effectively with clonidine, a medication that works in an area of the brain called the locus coeruleus.

Unlike opiate and alcohol withdrawal, symptoms of cocaine withdrawal are relatively mild and disappear relatively quickly. This dearth of withdrawal symptoms helps to explain the episodic pattern of use reported by many cocaine addicts: Periods of intense bingeing alternate with intervals of abstinence. The intense craving and high relapse rate associated with cocaine use appear to derive more from a desire to repeat a pleasurable experience than to avoid the discomfort of withdrawal.

In fact, for all drugs, reward may be more important than withdrawal in the persistence of addiction and relapse, in that successful treatment of withdrawal has not generally improved recovery.

TREATMENT IMPLICATIONS. The disease model of addiction is supported by the high degree of addiction that various substances of abuse cause and the likelihood that someone addicted to one drug often will be using more than one drug. This multiple addiction is a major factor and plays a significant role in the treatment of addiction. Treatment strategies aimed at eliminating one specific form of addiction, such as cocaine abuse, without addressing other mood-altering substances, have usually failed. The addict who abuses only one drug is very rare. The Epidemiologic Catchment Area study of over 20,000 respondents found that 16 percent of the general population experienced alcoholism at some point during their lifetime—with 30 percent of these alcoholics also abusing other drugs. Alcoholics were 3.9 times more likely than nonalcoholics to have comorbid drug abuse. Similarly, the rates of alcohol abuse among other drug addicts were high: 36 percent of cannabis addicts, 62 percent of amphetamine addicts, 67 percent of opiate addicts, and 84 percent of cocaine addicts were also alcoholics. These studies, combined with clinical observations regarding the concurrent use of multiple substances, suggest common biological determinants for all addiction (Miller and Gold).

The success of Alcoholics Anonymous, with its broad ban of all mood-altering substances, lends further support to the unified disease concept of addiction. Similarly, naltrexone, a medication known previously for its efficacy in helping opiate addicts to recover, has been used successfully to treat alcoholism, cocaine addiction, and eating disorders. Although naltrexone can block the effects only of opiates, it appears to be effective against other drugs of abuse primarily because of the involvement of the opiate system in reward. According to this theory, naltrexone's opiate inhibition makes other drug use less reinforcing and ultimately prevents full-blown relapse to drug use as the addict's body learns not to associate drug use with reward. However, even with the use of Alcoholics Anonymous and viable pharmacological therapies like naltrexone, addiction remains difficult to treat primarily because drug use is so intertwined with the biological reward system.

For an addict, drug use becomes an acquired drive state that permeates all aspects of life. Withdrawal from drug use activates separate neural pathways that cause withdrawal events to be perceived as life threatening, and the subsequent physiological and psychological reactions often lead to renewed drug consumption. The treatment research consensus is that time in treatment and/or abstinence is the greatest predictor of treatment success and may reflect the time required to reinstate predrug neural homeostasis, fading of memory of euphoria and conditioned cues, and the reemergence of endogenous reinforcement for work, friends, shelter, food, water, and sex.

Drug reinforcement is so powerful that even when it is eliminated by pharmacological blockade (e.g., naltrexone), humans quickly identify themselves as opiate available or unavailable and change their behavior without changing their attachment to the drug and its effects. Once pharmacological intervention is discontinued, the addict will often resume self-administration.

Moods and other mental states, such as drug craving and anxiety, can become conditioned stimuli that may lead to drug use. Clinicians have used relaxation training, in which patients are taught relaxation and breathing techniques, to use in the presence of drug-related stimuli or the mental states they would normally associate with the need to use drugs.

Clearly, relapse prevention and successful treatment of addiction require much more than the alleviation of withdrawal symptoms. It is well known that patients with higher pretreatment levels of social support, employment, and productivity have a better prognosis for successful response to initial treatment and long-term abstinence. Treatment outcomes for these patients may improve because they perceive the long-term cost of drug use (loss of family or job) as outweighing the short-term benefit of drug use. Educational efforts that stress the risks associated with drug abuse help individuals to avoid drug use. No pharmacological or nonpharmacological treatment strategy can match the success of prevention. Research has shown that treatment efforts and relapse prevention are especially effective in impaired professionals (i.e., healthcare and other professionals whose licenses are controlled by state agencies). It appears as though these individuals have access to necessary inpatient and residential care to reverse the patterns of this devastating disease. These programs use a carrot and stick approach and rely on abstinence verification through objective urinalysis testing. Lessons from treatment of these patients can be used to improve the treatment of all patients with addiction.

The disease model of addiction should not be used to excuse the addict's responsibility; abuse has to begin somewhere. The addict remains culpable for the initial decision to use the drug and for continuing to use it despite adverse consequences. Nevertheless, an understanding of addiction and the addiction process allows us to comprehend the existence of addiction as well as why abstinence in treatment is difficult to achieve.

Summary

All abuse-prone drugs are used, at least initially, for their positive effects and because the user believes the short-term benefits of this experience surpass the long-term costs. Once initiated, drug use permits access to the reinforcement reward system, which is believed to be anatomically distinct from the negative/withdrawal system in the brain. This positive reward system provides the user with an experience that the brain equates with profoundly important events like eating, drinking, and sex.

While studies have confirmed an encouraging decline in the number of illicit drug users, substance abuse continues to be a national problem. National Household Survey suggests that over 14 million Americans are users of illicit drugs (National Household Survey, 2000). Estimates of the presence of drugs like cocaine and opiates in trauma victims has increased several hundredfold from less than two decades before. Ecstasy use among adolescents jumped almost 25 percent between 1999 and 2000. In 2001, 5.2 percent of 8th graders, 8.0 percent of 10th graders, and 11.7 percent of high school seniors had used Ecstasy in their lifetimes (NIDA Infofax). Increased use has resulted in a dramatic increase in emergency room visits. According to data from the Substance Abuse and Mental Health Services Administration's Drug Abuse Warning Network, Ecstasy-related hospital emergency room incidents increased from 253 in 1994 to over 4,500 in 2000. The number of MDMA related deaths has also been increasing. (Goldberger and Gold).

Better news is increased understanding of the role that genetics and inheritance play in possible predisposition to addiction. And the best news of all is the widespread acceptance of the biological nature of drug addiction and the disease model, which brings hope to millions of people who think they are at fault because they cannot overcome their body's desires. The future will bring greater understanding of the biological pathways and, with that, cures for addiction and dependence.

mark s. gold (1995)

revised by mark s. gold

michael j. herkov

SEE ALSO: Alcoholism; Freedom and Free Will; Harmful Substances, Legal Control of; Health and Disease: History of Concepts; Impaired Professionals; Maternal-Fetal Relationship; Organ Transplants; Smoking

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INTERNET RESOURCES

NIDA Infofax. Available from <http://www.nida.nih.gov/Infofax/HSYouthtrends.html>.

Substance Abuse and Mental Health Services Administration's Drug Abuse Warning Network. July 2001. Available from <http://www.samhsa.gov/oas/dawn.htm>.