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Addiction is a Brain Disease

By   ALAN I. LESHNER, MD

A core concept evolving with scientific advances over the past decade is that drug addiction is a brain disease that develops over time as a result of the initially voluntary behavior of using drugs.  (Drugs include alcohol.)

The consequence is virtually uncontrollable compulsive drug craving, seeking, and use that interferes with, if not destroys, an individual’s functioning in the family and in society.  This medical condition demands formal treatment.

  • We now know in great detail the brain mechanisms through which drugs acutely modify mood, memory, perception, and emotional states.
  • Using drugs repeatedly over time changes brain structure and function in fundamental and long-lasting ways that can persist long after the individual stops using them.
  • Addiction comes about through an array of neuro-adaptive changes and the lying down and strengthening of new memory connections in various circuits in the brain.

The Highjacked Brain
We do not yet know all the relevant mechanisms, but the evidence suggests that those long-lasting brain changes are responsible for the distortions of cognitive and emotional functioning that characterize addicts, particularly including the compulsion to use drugs that is the essence of addiction.

It is as if drugs have highjacked the brain’s natural motivational control circuits, resulting in drug use becoming the sole, or at least the top, motivational priority for the individual.

Thus, the majority of the biomedical community now considers addiction, in its essence, to be a brain disease:

This brain-based view of addiction has generated substantial controversy, particularly among people who seem able to think only in polarized ways.

  • Many people erroneously still believe that biological and behavioral explanations are alternative or competing ways to understand phenomena, when in fact they are complementary and integrative.

Modern science has taught that it is much too simplistic to set biology in opposition to behavior or to pit willpower against brain chemistry.

  • Addiction involves inseparable biological and behavioral components.  It is the quintessential bio-behavioral disorder.

Many people also erroneously still believe that drug addiction is simply a failure of will or of strength of character.  Research contradicts that position.

Responsible For Our Recovery
However, the recognition that addiction is a brain disease does not mean that the addict is simply a hapless victim.  Addiction begins with the voluntary behavior of using drugs, and addicts must participate in and take some significant responsibility for their recovery.

  • Thus, having this brain disease does not absolve the addict of responsibility for his or her behavior.

But it does explain why an addict cannot simply stop using drugs by sheer force of will alone.

The Essence of Addiction
The entire concept of addiction has suffered greatly from imprecision and misconception.  In fact, if it were possible, it would be best to start all over with some new, more neutral term.

The confusion comes about in part because of a now archaic distinction between whether specific drugs are “physically” or “psychologically”addicting.

The distinction historically revolved around whether or not dramatic physical withdrawal symptoms occur when an individual stops taking a drug; what we in the field now call “physical dependence.”

  • However, 20 years of scientific research has taught that focusing on this physical versus psychological distinction is off the mark and a distraction from the real issues.

From both clinical and policy perspectives, it actually does not matter very much what physical withdrawal symptoms occur.

  • Physical dependence is not that important, because even the dramatic withdrawal symptoms of heroin and alcohol addiction can now be easily managed with appropriate medications.
  • Even more important, many of the most dangerous and addicting drugs, including methamphetamine and crack cocaine, do not produce very severe physical dependence symptoms upon withdrawal.

What really matters most is whether or not a drug causes what we now know to be the essence of addiction, namely

  • The uncontrollable, compulsive drug craving, seeking, and use, even in the face of negative health and social consequences.

This is the crux of how the Institute of Medicine, the American Psychiatric Association, and the American Medical Association define addiction and how we all should use the term.

It is really only this compulsive quality of addiction that matters in the long run to the addict and to his or her family and that should matter to society as a whole.

Thus, the majority of the biomedical community now considers addiction, in its essence, to be a brain disease:

  • A condition caused by persistent changes in brain structure and function.

This results in compulsive craving that overwhelms all other motivations and is the root cause of the massive health and social problems associated with drug addiction.

The Definition of Addiction
In updating our national discourse on drug abuse, we should keep in mind this simple definition:

  • Addiction is a brain disease expressed in the form of compulsive behavior.

Both developing and recovering from it depend on biology, behavior, and social context.

It is also important to correct the common misimpression that drug use, abuse and addiction are points on a single continuum along which one slides back and forth over time, moving from user to addict, then back to occasional user, then back to addict.

Clinical observation and more formal research studies support the view that, once addicted, the individual has moved into a different state of being.

  • It is as if a threshold has been crossed.

Very few people appear able to successfully return to occasional use after having been truly addicted.

The Altered Brain - A Chronic Illness
Unfortunately, we do not yet have a clear biological or behavioral marker of that transition from voluntary drug use to addiction.

However, a body of scientific evidence is rapidly developing that points to an array of cellular and molecular changes in specific brain circuits.  Moreover, many of these brain changes are common to all chemical addictions, and some also are typical of other compulsive behaviors such as pathological overeating.

  • Addiction should be understood as a chronic recurring illness.
  • Although some addicts do gain full control over their drug use after a single treatment episode, many have relapses.

The complexity of this brain disease is not atypical, because virtually no brain diseases are simply biological in nature and expression.  All, including stroke, Alzheimer's disease, schizophrenia, and clinical depression, include some behavioral and social aspects.

What may make addiction seem unique among brain diseases, however, is that it does begin with a clearly voluntary behavior- the initial decision to use drugs.  Moreover, not everyone who ever uses drugs goes on to become addicted.

  • Individuals differ substantially in how easily and quickly they become addicted and in their preferences for particular substances.

Consistent with the bio-behavioral nature of addiction, these individual differences result from a combination of environmental and biological, particularly genetic, factors.

In fact, estimates are that between 50 and 70 percent of the variability in susceptibility to becoming addicted can be accounted for by genetic factors.  Although genetic characteristics may predispose individuals to be more or less susceptible to becoming addicted, genes do not doom one to become an addict.

  • Over time the addict loses substantial control over his or her initially voluntary behavior, and it becomes compulsive.  For many people these behaviors are truly uncontrollable, just like the behavioral expression of any other brain disease.

Schizophrenics cannot control their hallucinations and delusions.  Parkinson’s patients cannot control their trembling.  Clinically depressed patients cannot voluntarily control their moods.

Thus, once one is addicted, the characteristics of the illness- and the treatment approaches- are not that different from most other brain diseases.  No mater how one develops an illness, once one has it, one is in the diseased state and needs treatment.

Environmental Cues
Addictive behaviors do have special characteristics related to the social contexts in which they originate.

  • All of the environmental cues surrounding initial drug use and development of the addiction actually become “conditioned” to that drug use and are thus critical to the development and expression of addiction.

Environmental cues are paired in time with an individual’s initial drug use experiences and, through classical conditioning, take on conditioned stimulus properties.

  • When those cues are present at a later time, they elicit anticipation of a drug experience and thus generate tremendous drug craving.

Cue-induced craving is one of the most frequent causes of drug use relapses, even after long periods of abstinence, independently of whether drugs are available.

The salience of environmental or contextual cues helps explain why reentry to one’s community can be so difficult for addicts leaving the controlled environments of treatment or correctional settings and why aftercare is so essential to successful recovery.

  • The person who became addicted in the home environment is constantly exposed to the cues conditioned to his or her initial drug use, such as the neighborhood where he or she hung out, drug-using buddies, or the lamppost where he or she bought drugs.
  • Simple exposure to those cues automatically triggers craving and can lead rapidly to relapses.

This is one reason why someone who apparently overcame drug cravings while in prison or residential treatment could quickly revert to drug use upon returning home.

In fact, one of the major goals of drug addiction treatment is to teach addicts how to deal with the cravings caused by inevitable exposure to these conditioned cues.

Implications
It is no wonder addicts cannot simply quit on their own.

They have an illness that requires biomedical treatment.

  • People often assume that because addiction begins with a voluntary behavior and is expressed in the form of excess behavior, people should just be able to quit by force of will alone.
  • However, it is essential to understand when dealing with addicts that we are dealing with individuals whose brains have been altered by drug use.

They need drug addiction treatment.

We know that, contrary to common belief, very few addicts actually do just stop on their own.

Observing that there are very few heroin addicts in their 50s or 60s, people frequently ask what happened to those who were heroin addicts 30 years ago, assuming that they must have quit on their own.

  • However, longitudinal studies find that only a very small fraction actually quit on their own.  The rest have either been successfully treated, are currently in maintenance treatment, or (for about half) are dead.

Consider the example of smoking cigarettes:  Various studies have found that between 3 and 7 percent of people who try to quit on their own each year actually succeed.

Science has at last convinced the public that depression is not just a lot of sadness; that depressed individuals are in a different brain state and thus require treatment to get their symptoms under control.  It is time to recognize that this is also the case for addicts.

The Role of Personal Responsibility
The role of personal responsibility is undiminished but clarified.

Does having a brain disease mean that people who are addicted no longer have any responsibility for their behavior or that they are simply victims of their own genetics and brain chemistry?  Of course not.

Addiction begins with the voluntary behavior of drug use, and although genetic characteristics may predispose individuals to be more or less susceptible to becoming addicted, genes do not doom one to become an addict.

This is one major reason why efforts to prevent drug use are so vital to any comprehensive strategy to deal with the nation’s drug problems.  Initial drug use is a voluntary, and therefore preventable, behavior.

Moreover, as with any illness, behavior becomes a critical part of recovery.  At a minimum, one must comply with the treatment regimen, which is harder than it sounds.

  • Treatment compliance is the biggest cause of relapses for all chronic illnesses, including asthma, diabetes, hypertension, and addiction.
  • Moreover, treatment compliance rates are no worse for addiction than for these other illnesses, ranging from 30 to 50 percent.

Thus, for drug addiction as well as for other chronic diseases, the individual’s motivation and behavior are clearly important parts of success in treatment and recovery.

Alcohol/ Drug Treatment Programs
Maintaining this comprehensive bio-behavioral understanding of addiction also speaks to what needs to be provided in drug treatment programs.

  • Again, we must be careful not to pit biology against behavior.

The National Institute on Drug Abuse’s recently published Principles of Effective Drug Addiction Treatment provides a detailed discussion of how we must treat all aspects of the individual, not just the biological component or the behavioral component.

As with other brain diseases such as schizophrenia and depression, the data show that the best drug addiction treatment approaches attend to the entire individual, combining the use of medications, behavioral therapies, and attention to necessary social services and rehabilitation.

  • These might include such services as family therapy to enable the patient to return to successful family life, mental health services, education and vocational training, and housing services.

That does not mean, of course, that all individuals need all components of treatment and all rehabilitation services. Another principle of effective addiction treatment is that the array of services included in an individual's treatment plan must be matched to his or her particular set of needs. Moreover, since those needs will surely change over the course of recovery, the array of services provided will need to be continually reassessed and adjusted.

We believe holistic approaches ranging from brain wave biofeedback to yoga and acupuncture are an important part  of the "array of  services" to which he refers.

Recommended Reading
J. D. Berke and S. E. Hyman, "Addiction, Dopamine, and the Molecular Mechanisms of Memory," Neuron 25 (2000): 515~532 (http://www.neuron.org/cgi/content/full/25/3/515/).

H. Garavan, J. Pankiewicz, A. Bloom, J. K. Cho, L. Sperry, T. J. Ross, B. J. Salmeron, R. Risinger, D. Kelley, and E. A. Stein, "Cue-Induced Cocaine Craving: Neuroanatomical Specificity for Drug Users and Drug Stimuli," American Journal of Psychiatry 157 (2000): 1789~1798 (ajp.psychiatryonline.org/article.aspx?articleid=174425).

A. I. Leshner, "Science-Based Views of Drug Addiction and Its Treatment," Journal of the American Medical Association 282 (1999): 1314~1316
(jama.jamanetwork.com/article.aspx?articleid=191976).

A. T. McLellan, D. C. Lewis, C. P. O'Brien, and H. D. Kleber, "Drug Dependence, a Chronic Medical Illness," Journal of the American Medical Association 284 (2000): 1689~1695 (jama.ama-assn.org/cgi/content/abstract/284/13/1689).

National Institute on Drug Abuse, Principles of Drug Addiction Treatment: A Research-Based Guide (National Institutes of Health, Bethesda, MD, July 2000) (www.nida.nih.gov/PODAT/PODATindex.html).

National Institute on Drug Abuse, Preventing Drug Use Among Children and Adolescents: A Research-Based Guide (National Institutes of Health, Bethesda, MD, March 1997) (www.nida.nih.gov/Prevention/Prevopen.html).

E. J. Nestler, "Genes and Addiction," Nature Genetics 26 (2000): 277~281 (www.nature.com/cgi-taf/DynaPage.taf?file=/ng/journal/v26/n3/full/ng1100_277.html).

Physician Leadership on National Drug Policy, position paper on drug policy (PLNDP Program Office, Brown University, Center for Alcohol and Addiction Studies, Providence, R.I.: January 2000) (plndp.org/Resources/resources.html).

F. S. Taxman and J. A. Bouffard, "The Importance of Systems in Improving Offender Outcomes: New Frontiers in Treatment Integrity," Justice Research and Policy 2 (2000): 37~58.


Alan I. Leshner is the former director of the National Institute on Drug Abuse at
The National Institutes of Health.