Addiction Is a Brain Disease, and It Matters

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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,

relapsing disease that results from the prolonged effects of drugs on the brain. As with

many other brain diseases, addiction has embedded behavioral and social-context

aspects that are important parts of the disorder itself. Therefore, the most effective

treatment approaches will include biological, behavioral, and social-context compo-

nents. Recognizing addiction as a chronic, relapsing brain disorder characterized by

compulsive drug seeking and use can impact society’s overall health and social policy

strategies and help diminish the health and social costs associated with drug abuse and

addiction.

Dramatic advances over the past two dec-

ades in both the neurosciences and the

behavioral sciences have revolutionized our

understanding of drug abuse and addiction.

Scientists have identified neural circuits

that subsume the actions of every known

drug of abuse, and they have specified com-

mon pathways that are affected by almost

all such drugs. Researchers have also iden-

tified and cloned the major receptors for

virtually every abusable drug, as well as the

natural ligands for most of those receptors.

In addition, they have elaborated many of

the biochemical cascades within the cell

that follow receptor activation by drugs.

Research has also begun to reveal major

differences between the brains of addicted

and nonaddicted individuals and to indi-

cate some common elements of addiction,

regardless of the substance.

That is the good news. The bad news is the

dramatic lag between these advances in sci-

ence and their appreciation by the general

public or their application in either practice

or public policy settings. There is a wide gap

between the scientific facts and public percep-

tions about drug abuse and addiction. For

example, many, perhaps most, people see drug

abuse and addiction as social problems, to be

handled only with social solutions, particular-

ly through the criminal justice system. On the

other hand, science has taught that drug abuse

and addiction are as much health problems as

they are social problems. The consequence of

this gap is a significant delay in gaining con-

trol over the drug abuse problem.

Part of the lag and resultant disconnection

comes from the normal delay in transferring

any scientific knowledge into practice and

policy. However, there are other factors

unique to the drug abuse arena that com-

pound the problem. One major barrier is

the tremendous stigma attached to being a

drug user or, worse, an addict. The most

beneficent public view of drug addicts is as

victims of their societal situation. However,

the more common view is that drug addicts

are weak or bad people, unwilling to lead

moral lives and to control their behavior

and gratifications. To the contrary, addic-

tion is actually a chronic, relapsing illness,

characterized by compulsive drug seeking

and use (1). The gulf in implications be-

tween the “bad person” view and the

“chronic illness sufferer” view is tremen-

dous. As just one example, there are many

people who believe that addicted individu-

als do not even deserve treatment. This

stigma, and the underlying moralistic tone,

is a significant overlay on all decisions that

relate to drug use and drug users.

Another barrier is that some of the peo-

ple who work in the fields of drug abuse

prevention and addiction treatment also

hold ingrained ideologies that, although

usually different in origin and form from the

ideologies of the general public, can be just

as problematic. For example, many drug

abuse workers are themselves former drug

users who have had successful treatment

experiences with a particular treatment

method. They therefore may zealously de-

fend a single approach, even in the face of

contradictory scientific evidence. In fact,

there are many drug abuse treatments that

have been shown to be effective through

clinical trials (1, 2).

These difficulties notwithstanding, I be-

lieve that we can and must bridge this

informational disconnection if we are going

to make any real progress in controlling

drug abuse and addiction. It is time to re-

place ideology with science.

Drug Abuse and Addiction as

Public Health Problems

At the most general level, research has

shown that drug abuse is a dual-edged

health issue, as well as a social issue. It

affects both the health of the individual and

the health of the public. The use of drugs

has well-known and severe negative conse-

quences for health, both mental and phys-

ical. But drug abuse and addiction also have

tremendous implications for the health of

the public, because drug use, directly or

indirectly, is now a major vector for the

transmission of many serious infectious dis-

eases—particularly acquired immunodefi-

ciency syndrome (AIDS), hepatitis, and tu-

berculosis—as well as violence. Because ad-

diction is such a complex and pervasive

health issue, we must include in our overall

strategies a committed public health ap-

proach, including extensive education and

prevention efforts, treatment, and research.

Science is providing the basis for such

public health approaches. For example, two

large sets of multisite studies (3) have dem-

onstrated the effectiveness of well-delineat-

ed outreach strategies in modifying the be-

haviors of addicted individuals that put

them at risk for acquiring the human im-

munodeficiency virus (HIV), even if they

continue to use drugs and do not want to

enter treatment. This approach runs

counter to the broadly held view that ad-

dicts are so incapacitated by drugs that they

are unable to modify any of their behaviors.

It also suggests a base for improved strate-

gies for reducing the negative health con-

sequences of injection drug use for the in-

dividual and for society.

What Matters in Addiction

Scientific research and clinical experience

have taught us much about what really

matters in addiction and where we need to

concentrate our clinical and policy efforts.

However, too often the focus is on the

wrong aspects of addiction, and efforts to

deal with this difficult issue can be badly

misguided.

Any discussion about psychoactive drugs

inevitably turns to the question of whether

a particular drug is physically or psycholog-

ically addicting. In essence, this issue re-

volves around whether or not dramatic

physical withdrawal symptoms occur when

an individual stops taking a drug, what is

typically called physical dependence by pro-

fessionals in the field. The assumption that

often follows is that the more dramatic the

physical withdrawal symptoms, the more

serious or dangerous the drug must be.

This thinking is outdated. From both

clinical and policy perspectives, it does not

The author is with the National Institute on Drug Abuse,

National Institutes of Health, 5600 Fishers Lane, Room

10-05, Rockville, MD 20857, USA. E-mail: leshner@

nih.gov

FRONTIERS IN NEUROSCIENCE: THE SCIENCE OF SUBSTANCE ABUSE

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matter much what physical withdrawal

symptoms, if any, occur. First, even the

florid withdrawal symptoms of heroin ad-

diction can now be easily managed with

appropriate medication. Second, and more

important, many of the most addicting and

dangerous drugs do not produce severe

physical symptoms upon withdrawal. Crack

cocaine and methamphetamine are clear

examples: Both are highly addicting, but

cessation of their use produces few physical

withdrawal symptoms, certainly nothing

like the physical symptoms accompanying

alcohol or heroin withdrawal.

What does matter tremendously is

whether or not a drug causes what we now

know to be the essence of addiction: com-

pulsive drug seeking and use, even in the

face of negative health and social conse-

quences (4). These are the characteristics

that ultimately matter most to the patient

and are where treatment efforts should be

directed. These behaviors are also the ele-

ments responsible for the massive health

and social problems that drug addiction

brings in its wake.

Addiction Is a Brain Disease

Although each drug that has been studied

has some idiosyncratic mechanisms of ac-

tion, virtually all drugs of abuse have com-

mon effects, either directly or indirectly, on

a single pathway deep within the brain.

This pathway, the mesolimbic reward sys-

tem, extends from the ventral tegmentum

to the nucleus accumbens, with projections

to areas such as the limbic system and the

orbitofrontal cortex. Activation of this sys-

tem appears to be a common element in

what keeps drug users taking drugs. This

activity is not unique to any one drug; all

addictive substances affect this circuit (5).

Not only does acute drug use modify

brain function in critical ways, but pro-

longed drug use causes pervasive changes in

brain function that persist long after the

individual stops taking the drug. Significant

effects of chronic use have been identified

for many drugs at all levels: molecular, cel-

lular, structural, and functional (6, 7). The

addicted brain is distinctly different from

the nonaddicted brain, as manifested by

changes in brain metabolic activity, recep-

tor availability, gene expression, and re-

sponsiveness to environmental cues. Some

of these long-lasting brain changes are idio-

syncratic to specific drugs, whereas others

are common to many different drugs (6–9).

The common brain effects of addicting sub-

stances suggest common brain mechanisms

underlying all addictions (5, 7, 9, 10).

That addiction is tied to changes in

brain structure and function is what makes

it, fundamentally, a brain disease. A meta-

phorical switch in the brain seems to be

thrown as a result of prolonged drug use.

Initially, drug use is a voluntary behavior,

but when that switch is thrown, the indi-

vidual moves into the state of addiction,

characterized by compulsive drug seeking

and use (11).

Understanding that addiction is, at its

core, a consequence of fundamental

changes in brain function means that a

major goal of treatment must be either to

reverse or to compensate for those brain

changes. These goals can be accomplished

through either medications or behavioral

treatments [behavioral treatments have

been successful in altering brain function

in other psychobiological disorders (12)].

Elucidation of the biology underlying the

metaphorical switch is key to the develop-

ment of more effective treatments, partic-

ularly antiaddiction medications.

But Not Just a Brain Disease

Of course, addiction is not that simple.

Addiction is not just a brain disease. It is a

brain disease for which the social contexts

in which it has both developed and is ex-

pressed are critically important. The case of

the many thousands of returning Vietnam

war veterans who were addicted to heroin

illustrates this point. In contrast to addicts

on the streets of the United States, it was

relatively easy to treat the returning veter-

ans’ addictions. This success was possible

because they had become addicted while in

a setting almost totally different from the

one to which they had returned. At home

in the United States, they were exposed to

few of the conditioned environmental cues

that had initially been associated with their

drug use in Vietnam. Exposure to condi-

tioned cues can be a major factor in causing

persistent or recurrent drug cravings and

drug use relapses even after successful treat-

ment (13).

The implications are obvious. If we un-

derstand addiction as a prototypical psycho-

biological illness, with critical biological,

behavioral, and social-context components,

our treatment strategies must include bio-

logical, behavioral, and social-context ele-

ments. Not only must the underlying brain

disease be treated, but the behavioral and

social cue components must also be ad-

dressed, just as they are with many other

brain diseases, including stroke, schizophre-

nia, and Alzheimer’s disease.

A Chronic, Relapsing Disorder

Addiction is rarely an acute illness. For

most people, it is a chronic, relapsing dis-

order. Total abstinence for the rest of one’s

life is a relatively rare outcome from a single

treatment episode. Relapses are more the

norm. Thus, addiction must be approached

more like other chronic illnesses—such as

diabetes and chronic hypertension—than

like an acute illness, such as a bacterial

infection or a broken bone (1). This re-

quirement has tremendous implications for

how we evaluate treatment effectiveness

and treatment outcomes. Viewing addiction

as a chronic, relapsing disorder means that a

good treatment outcome, and the most rea-

sonable expectation, is a significant de-

crease in drug use and long periods of ab-

stinence, with only occasional relapses.

That makes a reasonable standard for treat-

ment success—as is the case for other

chronic illnesses—the management of the

illness, not a cure (1, 2).

Conclusion

Addiction as a chronic, relapsing disease of

the brain is a totally new concept for much

of the general public, for many policymak-

ers, and, sadly, for many health care profes-

sionals. Many of the implications have been

discussed above, but there are others.

At the policy level, understanding the

importance of drug use and addiction for

both the health of individuals and the

health of the public affects many of our

overall public health strategies. An accurate

understanding of the nature of drug abuse

and addiction should also affect our crimi-

nal justice strategies. For example, if we

know that criminals are drug addicted, it is

no longer reasonable to simply incarcerate

them. If they have a brain disease, impris-

oning them without treatment is futile. If

they are left untreated, their recidivism

rates to both crime and drug use are fright-

eningly high; however, if addicted criminals

are treated while in prison, both types of

recidivism can be reduced dramatically

(14). It is therefore counterproductive to

not treat addicts while they are in prison.

At an even more general level, under-

standing addiction as a brain disease also

affects how society approaches and deals

with addicted individuals. We need to face

the fact that even if the condition initially

comes about because of a voluntary behavior

(drug use), an addict’s brain is different from

a nonaddict’s brain, and the addicted indi-

vidual must be dealt with as if he or she is in

a different brain state. We have learned to

deal with people in different brain states for

schizophrenia and Alzheimer’s disease. Re-

call that as recently as the beginning of this

century we were still putting individuals with

schizophrenia in prisonlike asylums, whereas

now we know they require medical treat-

ments. We now need to see the addict as

someone whose mind (read: brain) has been

altered fundamentally by drugs. Treatment is

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required to deal with the altered brain func-

tion and the concomitant behavioral and

social functioning components of the illness.

Understanding addiction as a brain dis-

ease explains in part why historic policy

strategies focusing solely on the social or

criminal justice aspects of drug use and

addiction have been unsuccessful. They are

missing at least half of the issue. If the brain

is the core of the problem, attending to the

brain needs to be a core part of the solution.

REFERENCES AND NOTES

___________________________

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2. A. T. McLellan et al.,inTreating Drug Abusers Effec-

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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);

R. C. Stephens et al.,inHandbook on Risk of AIDS,

B. S. Brown and G. M. Beschner, Eds. (Greenwood,

Westport, CT 1993), pp. 519–556; W. W. Wiebel et

al., J. Acquired Immune Defic. Syndr. 12, 282 (1996).

4. American Psychiatric Association, Diagnostic and

Statistical Manual of Mental Disorders, (American

Psychiatric Association Press, Washington, DC, ed. 4,

1994); Institute of Medicine, Pathways of Addiction

(National Academy Press, Washington, DC, 1996).

5. G. F. Koob, Trends Pharmacol. Sci. 13, 177 (1992);

G. F. Koob et al., Semin. Neurosci. 6, 221 (1994).

6. S. E. Hyman, Neuron 16, 901 (1996); E. J. Nestler,

ibid., p. 897; W. P. Melega et al., Behav. Brain Res.

84, 259 (1997); J. Ortiz et al., Synapse 21, 289

(1995); N. D. Volkow et al., Am. J. Psychiatry 147,

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9. G. F. Koob, Neuron 16, 893 (1996).

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11. The state of addiction—both the clinical condition

and the brain state—is qualitatively different from

the effects of large amounts of drugs. The individ-

ual, once addicted, has moved from a state where

drug use is voluntary and controlled to one where

drug craving, seeking, and use are no longer under

the same kind of voluntary control, and these

changes reflect changes in brain function. The ex-

act mechanisms involved are not known. For ex-

ample, it is not clear whether that change in state

reflects a relatively precipitous change in a singe

mechanism or multiple mechanisms acting in con-

cert, or whether the shift to addiction represents

the sum of more gradual neuroadaptations. More-

over, there are individual differences in the vulner-

ability to becoming addicted and the speed of be-

coming addicted. For some individuals, the meta-

phorical switch moves quickly, whereas for others

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Interpreting Dutch Cannabis

Policy: Reasoning by Analogy in

the Legalization Debate

Robert MacCoun and Peter Reuter

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

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

penalties have limited effects on drug use—at least for marijuana—but that commercial

access is associated with growth in the drug-using population.

Illicit drugs continue to be a major source

of health and social problems in the Unit-

ed States, accounting for 35% of new cases

of acquired immunodeficiency syndrome

(1) and about $50 billion in criminal in-

come (2). Large declines in prevalence

have occurred since the mid-1980s—

10.7% of the household population report-

ed use of an illicit drug in the previous

year in 1995, compared with 16.3% in

1985 (3)—but most measures of adverse

consequences have risen or stabilized.

Heroin-related deaths recorded by Medi-

cal Examiners in 25 metropolitan areas

rose from 1300 in 1985 to 3500 in 1994

(4).

U.S. drug policy is heavily committed

to a punishment-based approach. This is

reflected in budgets; two-thirds of the fed-

eral government’s $16 billion expendi-

tures go to supply-reduction programs (5),

whereas state and local governments, esti-

mated to spend $18 billion, probably de-

vote 75 to 80% to policing, prosecution,

and corrections (6). About 400,000 indi-

viduals are currently incarcerated in jails

or prisons for violation of drug laws (7).

Moreover, treatment and prevention pro-

grams are frequently required to show that

they are cost-effective, a standard never

imposed on drug enforcement (8). Penal-

ties have increased whenever a drug be-

comes more prominent, as for example in

the new federal methamphetamine statute

(9). The probability of a cocaine or heroin

seller being incarcerated has risen sharply

since about 1985 (10), but that has led

neither to increased price (11) nor re-

duced availability (12).

The Legalization Debate

Given the persistence of a major drug prob-

lem despite expensive, intrusive, and harsh

policies, it is not surprising that there has

been a continuing debate in the United

States about the desirability of major

changes in that policy, indeed a shift in

the basic regime (13). Some press for de-

penalization (often misleadingly termed

decriminalization), the removal of crimi-

nal penalties for the simple possession of

drugs; a smaller number press for the more

radical step of legalizing the distribution of

any psychoactive substance, subject to civ-

il regulation (14). Few commentators dis-

tinguish among drugs in debating these

recommendations.

The debate about legalization invokes

conflicts in values, with legalizers empha-

sizing the threat that prohibition poses to

civil liberties (15) and opponents the hedo-

nism and self-centeredness of drug taking

(16). However, the debate also exposes

gross discrepancies in predictions of the ef-

fects of legalization on levels of drug use.

Legalizers point to the failure of increasing

enforcement to raise prices or decrease

availability as evidence that legalization

would not much increase use or dependence

(17), while their opponents emphasize the

importance of symbolic and real barriers to

initiation associated with prohibition to

suggest that legalization would produce

massive increases in these rates (18).

There are three general strategies for

projecting the likely consequences of a

change in the legal regime for drugs. First,

one can draw upon existing theory and

research. But for a variety of reasons (19),

research on variations in drug law enforce-

ment within a prohibition regime cannot be

extrapolated outside that regime, and exist-

ing theories provide an uncertain guide to

the net consequences of such interventions.

Legal change is far more fundamental than

R. MacCoun is at the Richard and Rhoda Goldman School

of Public Policy, University of California, Berkeley, CA

94720–7320, USA. E-mail: [email protected].

edu

P. Reuter is at the School of Public Affairs and Depart-

ment of Criminology, University of Maryland, MD 20742,

USA.

ARTICLES

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