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FRONTIERS IN NEUROSCIENCE: THE SCIENCE OF SUBSTANCE ABUSE

Addiction Is a Brain Disease, and It Matters


Alan I. Leshner

Scientific advances over the past 20 years have shown that drug addiction is a chronic, affects both the health of the individual and
relapsing disease that results from the prolonged effects of drugs on the brain. As with the health of the public. The use of drugs
many other brain diseases, addiction has embedded behavioral and social-context has well-known and severe negative conse-
aspects that are important parts of the disorder itself. Therefore, the most effective quences for health, both mental and phys-
treatment approaches will include biological, behavioral, and social-context compo- ical. But drug abuse and addiction also have
nents. Recognizing addiction as a chronic, relapsing brain disorder characterized by tremendous implications for the health of
compulsive drug seeking and use can impact societys overall health and social policy the public, because drug use, directly or
strategies and help diminish the health and social costs associated with drug abuse and indirectly, is now a major vector for the
addiction. transmission of many serious infectious dis-
easesparticularly acquired immunodefi-
ciency syndrome (AIDS), hepatitis, and tu-
berculosisas well as violence. Because ad-
Dramatic advances over the past two dec- drug user or, worse, an addict. The most diction is such a complex and pervasive

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ades in both the neurosciences and the beneficent public view of drug addicts is as health issue, we must include in our overall
behavioral sciences have revolutionized our victims of their societal situation. However, strategies a committed public health ap-
understanding of drug abuse and addiction. the more common view is that drug addicts proach, including extensive education and
Scientists have identified neural circuits are weak or bad people, unwilling to lead prevention efforts, treatment, and research.
that subsume the actions of every known moral lives and to control their behavior Science is providing the basis for such
drug of abuse, and they have specified com- and gratifications. To the contrary, addic- public health approaches. For example, two
mon pathways that are affected by almost tion is actually a chronic, relapsing illness, large sets of multisite studies (3) have dem-
all such drugs. Researchers have also iden- characterized by compulsive drug seeking onstrated the effectiveness of well-delineat-
tified and cloned the major receptors for and use (1). The gulf in implications be- ed outreach strategies in modifying the be-
virtually every abusable drug, as well as the tween the bad person view and the haviors of addicted individuals that put
natural ligands for most of those receptors. chronic illness sufferer view is tremen- them at risk for acquiring the human im-
In addition, they have elaborated many of dous. As just one example, there are many munodeficiency virus (HIV), even if they
the biochemical cascades within the cell people who believe that addicted individu- continue to use drugs and do not want to
that follow receptor activation by drugs. als do not even deserve treatment. This enter treatment. This approach runs
Research has also begun to reveal major stigma, and the underlying moralistic tone, counter to the broadly held view that ad-
differences between the brains of addicted is a significant overlay on all decisions that dicts are so incapacitated by drugs that they
and nonaddicted individuals and to indi- relate to drug use and drug users. are unable to modify any of their behaviors.
cate some common elements of addiction, Another barrier is that some of the peo- It also suggests a base for improved strate-
regardless of the substance. ple who work in the fields of drug abuse gies for reducing the negative health con-
That is the good news. The bad news is the prevention and addiction treatment also sequences of injection drug use for the in-
dramatic lag between these advances in sci- hold ingrained ideologies that, although dividual and for society.
ence and their appreciation by the general usually different in origin and form from the
public or their application in either practice ideologies of the general public, can be just What Matters in Addiction
or public policy settings. There is a wide gap as problematic. For example, many drug
between the scientific facts and public percep- abuse workers are themselves former drug Scientific research and clinical experience
tions about drug abuse and addiction. For users who have had successful treatment have taught us much about what really
example, many, perhaps most, people see drug experiences with a particular treatment matters in addiction and where we need to
abuse and addiction as social problems, to be method. They therefore may zealously de- concentrate our clinical and policy efforts.
handled only with social solutions, particular- fend a single approach, even in the face of However, too often the focus is on the
ly through the criminal justice system. On the contradictory scientific evidence. In fact, wrong aspects of addiction, and efforts to
other hand, science has taught that drug abuse there are many drug abuse treatments that deal with this difficult issue can be badly
and addiction are as much health problems as have been shown to be effective through misguided.
they are social problems. The consequence of clinical trials (1, 2). Any discussion about psychoactive drugs
this gap is a significant delay in gaining con- These difficulties notwithstanding, I be- inevitably turns to the question of whether
trol over the drug abuse problem. lieve that we can and must bridge this a particular drug is physically or psycholog-
Part of the lag and resultant disconnection informational disconnection if we are going ically addicting. In essence, this issue re-
comes from the normal delay in transferring to make any real progress in controlling volves around whether or not dramatic
any scientific knowledge into practice and drug abuse and addiction. It is time to re- physical withdrawal symptoms occur when
policy. However, there are other factors place ideology with science. an individual stops taking a drug, what is
unique to the drug abuse arena that com- typically called physical dependence by pro-
pound the problem. One major barrier is Drug Abuse and Addiction as fessionals in the field. The assumption that
the tremendous stigma attached to being a Public Health Problems often follows is that the more dramatic the
physical withdrawal symptoms, the more
The author is with the National Institute on Drug Abuse, At the most general level, research has serious or dangerous the drug must be.
National Institutes of Health, 5600 Fishers Lane, Room
10-05, Rockville, MD 20857, USA. E-mail: leshner@ shown that drug abuse is a dual-edged This thinking is outdated. From both
nih.gov health issue, as well as a social issue. It clinical and policy perspectives, it does not

www.sciencemag.org z SCIENCE z VOL. 278 z 3 OCTOBER 1997 45


matter much what physical withdrawal phorical switch in the brain seems to be treatment episode. Relapses are more the
symptoms, if any, occur. First, even the thrown as a result of prolonged drug use. norm. Thus, addiction must be approached
florid withdrawal symptoms of heroin ad- Initially, drug use is a voluntary behavior, more like other chronic illnessessuch as
diction can now be easily managed with but when that switch is thrown, the indi- diabetes and chronic hypertensionthan
appropriate medication. Second, and more vidual moves into the state of addiction, like an acute illness, such as a bacterial
important, many of the most addicting and characterized by compulsive drug seeking infection or a broken bone (1). This re-
dangerous drugs do not produce severe and use (11). quirement has tremendous implications for
physical symptoms upon withdrawal. Crack Understanding that addiction is, at its how we evaluate treatment effectiveness
cocaine and methamphetamine are clear core, a consequence of fundamental and treatment outcomes. Viewing addiction
examples: Both are highly addicting, but changes in brain function means that a as a chronic, relapsing disorder means that a
cessation of their use produces few physical major goal of treatment must be either to good treatment outcome, and the most rea-
withdrawal symptoms, certainly nothing reverse or to compensate for those brain sonable expectation, is a significant de-
like the physical symptoms accompanying changes. These goals can be accomplished crease in drug use and long periods of ab-
alcohol or heroin withdrawal. through either medications or behavioral stinence, with only occasional relapses.
What does matter tremendously is treatments [behavioral treatments have That makes a reasonable standard for treat-
whether or not a drug causes what we now been successful in altering brain function ment successas is the case for other
know to be the essence of addiction: com- in other psychobiological disorders (12)]. chronic illnessesthe management of the
pulsive drug seeking and use, even in the Elucidation of the biology underlying the illness, not a cure (1, 2).
face of negative health and social conse- metaphorical switch is key to the develop-

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quences (4). These are the characteristics ment of more effective treatments, partic- Conclusion
that ultimately matter most to the patient ularly antiaddiction medications.
and are where treatment efforts should be Addiction as a chronic, relapsing disease of
directed. These behaviors are also the ele- But Not Just a Brain Disease the brain is a totally new concept for much
ments responsible for the massive health of the general public, for many policymak-
and social problems that drug addiction Of course, addiction is not that simple. ers, and, sadly, for many health care profes-
brings in its wake. Addiction is not just a brain disease. It is a sionals. Many of the implications have been
brain disease for which the social contexts discussed above, but there are others.
Addiction Is a Brain Disease in which it has both developed and is ex- At the policy level, understanding the
pressed are critically important. The case of importance of drug use and addiction for
Although each drug that has been studied the many thousands of returning Vietnam both the health of individuals and the
has some idiosyncratic mechanisms of ac- war veterans who were addicted to heroin health of the public affects many of our
tion, virtually all drugs of abuse have com- illustrates this point. In contrast to addicts overall public health strategies. An accurate
mon effects, either directly or indirectly, on on the streets of the United States, it was understanding of the nature of drug abuse
a single pathway deep within the brain. relatively easy to treat the returning veter- and addiction should also affect our crimi-
This pathway, the mesolimbic reward sys- ans addictions. This success was possible nal justice strategies. For example, if we
tem, extends from the ventral tegmentum because they had become addicted while in know that criminals are drug addicted, it is
to the nucleus accumbens, with projections a setting almost totally different from the no longer reasonable to simply incarcerate
to areas such as the limbic system and the one to which they had returned. At home them. If they have a brain disease, impris-
orbitofrontal cortex. Activation of this sys- in the United States, they were exposed to oning them without treatment is futile. If
tem appears to be a common element in few of the conditioned environmental cues they are left untreated, their recidivism
what keeps drug users taking drugs. This that had initially been associated with their rates to both crime and drug use are fright-
activity is not unique to any one drug; all drug use in Vietnam. Exposure to condi- eningly high; however, if addicted criminals
addictive substances affect this circuit (5). tioned cues can be a major factor in causing are treated while in prison, both types of
Not only does acute drug use modify persistent or recurrent drug cravings and recidivism can be reduced dramatically
brain function in critical ways, but pro- drug use relapses even after successful treat- (14). It is therefore counterproductive to
longed drug use causes pervasive changes in ment (13). not treat addicts while they are in prison.
brain function that persist long after the The implications are obvious. If we un- At an even more general level, under-
individual stops taking the drug. Significant derstand addiction as a prototypical psycho- standing addiction as a brain disease also
effects of chronic use have been identified biological illness, with critical biological, affects how society approaches and deals
for many drugs at all levels: molecular, cel- behavioral, and social-context components, with addicted individuals. We need to face
lular, structural, and functional (6, 7). The our treatment strategies must include bio- the fact that even if the condition initially
addicted brain is distinctly different from logical, behavioral, and social-context ele- comes about because of a voluntary behavior
the nonaddicted brain, as manifested by ments. Not only must the underlying brain (drug use), an addicts brain is different from
changes in brain metabolic activity, recep- disease be treated, but the behavioral and a nonaddicts brain, and the addicted indi-
tor availability, gene expression, and re- social cue components must also be ad- vidual must be dealt with as if he or she is in
sponsiveness to environmental cues. Some dressed, just as they are with many other a different brain state. We have learned to
of these long-lasting brain changes are idio- brain diseases, including stroke, schizophre- deal with people in different brain states for
syncratic to specific drugs, whereas others nia, and Alzheimers disease. schizophrenia and Alzheimers disease. Re-
are common to many different drugs (69). call that as recently as the beginning of this
The common brain effects of addicting sub- A Chronic, Relapsing Disorder century we were still putting individuals with
stances suggest common brain mechanisms schizophrenia in prisonlike asylums, whereas
underlying all addictions (5, 7, 9, 10). Addiction is rarely an acute illness. For now we know they require medical treat-
That addiction is tied to changes in most people, it is a chronic, relapsing dis- ments. We now need to see the addict as
brain structure and function is what makes order. Total abstinence for the rest of ones someone whose mind (read: brain) has been
it, fundamentally, a brain disease. A meta- life is a relatively rare outcome from a single altered fundamentally by drugs. Treatment is

46 SCIENCE z VOL. 278 z 3 OCTOBER 1997 z www.sciencemag.org


ARTICLES
required to deal with the altered brain func-
tion and the concomitant behavioral and
social functioning components of the illness.
Interpreting Dutch Cannabis
Understanding addiction as a brain dis-
ease explains in part why historic policy
Policy: Reasoning by Analogy in
strategies focusing solely on the social or
criminal justice aspects of drug use and
the Legalization Debate
addiction have been unsuccessful. They are
missing at least half of the issue. If the brain Robert MacCoun and Peter Reuter
is the core of the problem, attending to the
brain needs to be a core part of the solution. The Dutch depenalization and subsequent de facto legalization of cannabis since 1976
is used here to highlight the strengths and limitations of reasoning by analogy as a guide
REFERENCES AND NOTES for projecting the effects of relaxing drug prohibitions. While the Dutch case and other
___________________________
analogies have flaws, they appear to converge in suggesting that reductions in criminal
1. C. P. OBrien and A. T. McLellan, Lancet 347, 237
(1996). penalties have limited effects on drug useat least for marijuana but that commercial
2. A. T. McLellan et al., in Treating Drug Abusers Effec- access is associated with growth in the drug-using population.
tively, J. A. Egertson et al., Eds. (Blackwell, Malden,
MA, 1997), pp. 7 40.
3. R. Booth et al., Drug Alcohol Depend. 42, 11 (1996);
H. M. Colon et al., AIDS Educ. Prev. 7, 195 (1995);
Illicit drugs continue to be a major source

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R. C. Stephens et al., in Handbook on Risk of AIDS, The Legalization Debate
B. S. Brown and G. M. Beschner, Eds. (Greenwood,
Westport, CT 1993), pp. 519 556; W. W. Wiebel et of health and social problems in the Unit-
al., J. Acquired Immune Defic. Syndr. 12, 282 (1996). ed States, accounting for 35% of new cases Given the persistence of a major drug prob-
4. American Psychiatric Association, Diagnostic and of acquired immunodeficiency syndrome lem despite expensive, intrusive, and harsh
Statistical Manual of Mental Disorders, (American
Psychiatric Association Press, Washington, DC, ed. 4,
(1) and about $50 billion in criminal in- policies, it is not surprising that there has
1994); Institute of Medicine, Pathways of Addiction come (2). Large declines in prevalence been a continuing debate in the United
(National Academy Press, Washington, DC, 1996). have occurred since the mid-1980s States about the desirability of major
5. G. F. Koob, Trends Pharmacol. Sci. 13, 177 (1992);
G. F. Koob et al., Semin. Neurosci. 6, 221 (1994).
10.7% of the household population report- changes in that policy, indeed a shift in
6. S. E. Hyman, Neuron 16, 901 (1996); E. J. Nestler, ed use of an illicit drug in the previous the basic regime (13). Some press for de-
ibid., p. 897; W. P. Melega et al., Behav. Brain Res. year in 1995, compared with 16.3% in penalization (often misleadingly termed
84, 259 (1997); J. Ortiz et al., Synapse 21, 289 1985 (3) but most measures of adverse decriminalization), the removal of crimi-
(1995); N. D. Volkow et al., Am. J. Psychiatry 147,
719 (1990). consequences have risen or stabilized. nal penalties for the simple possession of
7. E. J. Nestler et al., Mol. Psychiatry 1, 190 (1996); Heroin-related deaths recorded by Medi- drugs; a smaller number press for the more
D. W. Self and E. J. Nestler, Annu. Rev. Neurosci. cal Examiners in 25 metropolitan areas radical step of legalizing the distribution of
18, 463 (1995).
8. E. J. Nestler, J. Neurosci. 12, 2439 (1992); T. E. rose from 1300 in 1985 to 3500 in 1994 any psychoactive substance, subject to civ-
Robinson and K. C. Berridge, Brain Res. Rev. 18, (4). il regulation (14). Few commentators dis-
247 (1993); R. Z. Terwilliger et al., Brain Res. 548, U.S. drug policy is heavily committed tinguish among drugs in debating these
100 (1991).
9. G. F. Koob, Neuron 16, 893 (1996).
to a punishment-based approach. This is recommendations.
10. A. I. Leshner, Hospital Practice: A Special Report reflected in budgets; two-thirds of the fed- The debate about legalization invokes
(McGraw-Hill, Minneapolis, MN, 1997). eral governments $16 billion expendi- conflicts in values, with legalizers empha-
11. The state of addiction both the clinical condition
and the brain stateis qualitatively different from
tures go to supply-reduction programs (5), sizing the threat that prohibition poses to
the effects of large amounts of drugs. The individ- whereas state and local governments, esti- civil liberties (15) and opponents the hedo-
ual, once addicted, has moved from a state where mated to spend $18 billion, probably de- nism and self-centeredness of drug taking
drug use is voluntary and controlled to one where vote 75 to 80% to policing, prosecution, (16). However, the debate also exposes
drug craving, seeking, and use are no longer under
the same kind of voluntary control, and these and corrections (6). About 400,000 indi- gross discrepancies in predictions of the ef-
changes reflect changes in brain function. The ex- viduals are currently incarcerated in jails fects of legalization on levels of drug use.
act mechanisms involved are not known. For ex- or prisons for violation of drug laws (7). Legalizers point to the failure of increasing
ample, it is not clear whether that change in state
reflects a relatively precipitous change in a singe
Moreover, treatment and prevention pro- enforcement to raise prices or decrease
mechanism or multiple mechanisms acting in con- grams are frequently required to show that availability as evidence that legalization
cert, or whether the shift to addiction represents they are cost-effective, a standard never would not much increase use or dependence
the sum of more gradual neuroadaptations. More- imposed on drug enforcement (8). Penal- (17), while their opponents emphasize the
over, there are individual differences in the vulner-
ability to becoming addicted and the speed of be- ties have increased whenever a drug be- importance of symbolic and real barriers to
coming addicted. For some individuals, the meta- comes more prominent, as for example in initiation associated with prohibition to
phorical switch moves quickly, whereas for others the new federal methamphetamine statute suggest that legalization would produce
the changes occur quite gradually (6 10).
12. L. B. Baxter et al., Semin. Clin. Neuropsychiatry 1, 32 (9). The probability of a cocaine or heroin massive increases in these rates (18).
(1996). seller being incarcerated has risen sharply There are three general strategies for
13. A. R. Childress et al., Natl. Inst. Drug Abuse Res. since about 1985 (10), but that has led projecting the likely consequences of a
Monogr. 84, 25 (1988); D. C. Daley and G. A.
Marlatt, in Substance Abuse: A Comprehensive
neither to increased price (11) nor re- change in the legal regime for drugs. First,
Textbook, J. H. Lowinson et al., Eds. ( Williams & duced availability (12). one can draw upon existing theory and
Wilkins, Baltimore, ed. 3, 1997), pp. 458 467; research. But for a variety of reasons (19),
C. P. OBrien, Pharmacol. Rev. 27, 535 (1975); research on variations in drug law enforce-
C. P. OBrien et al., Addict. Behav. 15, 355 (1990); R. MacCoun is at the Richard and Rhoda Goldman School
S. Grant et al., Proc. Natl. Acad. Sci. U.S.A. 93, of Public Policy, University of California, Berkeley, CA ment within a prohibition regime cannot be
12040 (1996). 94720 7320, USA. E-mail: maccoun@socrates.berkeley. extrapolated outside that regime, and exist-
14. J. A. Inciardi et al., J. Drug Issues 27, 261 (1997); edu ing theories provide an uncertain guide to
H. K. Wexler and D. S. Lipton, in Drug Treatment and P. Reuter is at the School of Public Affairs and Depart-
Criminal Justice, J. A. Inciardi, Ed. (Sage, Newbury ment of Criminology, University of Maryland, MD 20742, the net consequences of such interventions.
Park, CA, 1993), pp. 261278. USA. Legal change is far more fundamental than

www.sciencemag.org z SCIENCE z VOL. 278 z 3 OCTOBER 1997 47


Addiction Is a Brain Disease, and It Matters
Alan I. Leshner (October 3, 1997)
Science 278 (5335), 45-47. [doi: 10.1126/science.278.5335.45]

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