©
2002 Psychiatric Times. All rights reserved.
Addiction Is a Disease
by John H. Halpern,
M.D.
Psychiatric Times 
October 2002 Vol. XIX Issue 10
(Please see Point
article by Jeffrey A. Schaler, Ph.D.)
The practice of medicine obligates physicians to accept
the responsibility of promoting the overall health of their
patients. When dealing with patients who abuse substances,
we can find direct and indirect adverse consequences from
such use. Lung cancer, although rare in the general
population, is linked to chronic tobacco smoking, for
example. Cigarette smokers who begin this addiction in their
teen years appear to have a higher incidence of adult
depression (Goodman and Capitman, 2000); so, either early
tobacco use is a marker for later mental illness or, more
ominously, this legal drug of abuse may promote the
development of mental illness. Multiple warning labels
describing tobacco's toxicity and other risks to health have
been printed for decades on each pack of cigarettes sold,
yet more than 20% of Americans continue to "choose" to smoke
(Centers for Disease Control and Prevention [CDC], 2001).
Despite the hundreds of millions of dollars spent in
anti-tobacco messages and education, the ever-increasing
state and federal "sin" taxes collected on every pack of
tobacco product sold, the harsh restrictions on tobacco
advertisements by legislative mandate, and the high-profile
lawsuits and settlements, the median prevalence figures of
current tobacco use in the United States have held steady
for the last five years.
Perhaps, then, "choice" has little to do with the
decision to continue tobacco use. Cigarette smokers are so
concerned about their drug use that each year some 1 million
of them attempt to quit; but, sadly, less than 15% succeed
in abstinence for a full year (Rose, 1996). Despite
understanding that risks outweigh perceived benefits,
addicted individuals compulsively continue their drug use in
a chronic, relapsing fashion. It is not that these
individuals are devoid of any choice when engaging in
behaviors that support and reinforce continued drug use;
rather, we must accept that not all choices are equally easy
to make, especially when there exists a host of genetic,
environmental and non-environmental factors supporting
continued drug use.
Clinical research reveals that some individuals may be
more vulnerable to drug dependence than others due to
genetic and developmental risk factors. The best-validated
risks are family history and male gender (Hyman, 2001).
Studies of separated, adopted twins, for example, have found
the risk for alcoholism and other addictive drugs is greater
for those twins whose biological parents also had drug
dependence, regardless of drug use status in the adoptive
parents (Cadoret et al., 1995; Kendler et al., 2000; Tsuang
et al., 1996). Drug craving and relapse are triggered by
exposure to drug-related cues (e.g., photos of drugs and
paraphernalia), as well as stress. Neuroimaging studies of
former cocaine-dependent individuals have, for example,
identified neural correlates of cue-induced craving for
cocaine (Childress et al., 1999; Wexler et al., 2001).
Preclinical studies also indicate that repeated exposure
to highly addictive substances alters, perhaps permanently,
a number of molecular and neurochemical indices, thereby
changing physiologic homeostasis. In other words, even after
detoxification, an individual may be sensitized to relapse
because of changes in the brain from prior repeated use. We
know the molecular targets in the central nervous system for
most of the addictive drugs. As examples, opioids are
agonists at µ opioid receptors; alcohol is an agonist at
g-alphabutyric acid-A (GABA-A) receptors and an antagonist
at 
-methyl-D-aspartate
(NMDA) glutamate receptors; and tobacco's nicotine is an
agonist at nicotinic acetylcholine receptors (Hyman, 2001).
We also know that the principal CNS pathway for processing
reward, punishment and reinforcement extends from the
ventral tegmental area (VTA) to the nucleus accumbens (NAc),
mediated, in particular, by the release of the
neurotransmitter dopamine (Spanagel and Weiss, 1999).
Preclinical evidence supports the "final common pathway"
theory that addictive drugs, despite discordant molecular
targets, all result in an increased release and
dysregulation of synaptic dopamine in this region of the
brain (Nestler, 2001). For example, the same dose of cocaine
administered weekly to monkeys results in increased
extracellular release of dopamine in the CNS, a phenomenon
called neurochemical sensitization. When a second
dose of cocaine is administered after the first dose is
wearing off, a decreased release of extracellular dopamine
is found in the CNS, a phenomenon called acute
tolerance (Bradberry, 2000). As tolerance builds,
increased amounts of the drug are ingested in an attempt to
achieve the same rewards, which, in turn, will also further
drive molecular changes in the brain. Drug dependence, then,
is reinforced at the cellular level as the CNS adjusts to
continued drug exposure. Such conditioning may be unmasked
by abrupt cessation of drug use, resulting in a period of
observable and reproducible symptoms of withdrawal.
Chronic exposure to addictive substances also shifts
signal transduction pathways within neurons, thereby
altering gene expression (Matsumoto et al., 2001; Walton et
al., 2001). New or different concentrations of regulatory
proteins, in turn, are synthesized, directing neurons to
form new synaptic branches and altered concentrations of
cellular receptor density. Cocaine, for example, has been
found to increase spine density and dendritic branching of
neurons in the NAc and prefrontal cortex of rats (Robinson
and Kolb, 1999). The remodeling of neurons involved with the
maintenance of the brain's reward center also may continue
long after drug use has ceased (Hyman and Malenka, 2001;
Ungless et al., 2001). There are probably hundreds of
transcription factors involved in gene regulation; already
the cyclic-AMP response-element-binding protein (CREB) and
FosB are
implicated in addiction (Nestler, 2001). Interestingly,
biochemically modified isoforms of FosB appear
only slightly after acute drug exposure, but they accumulate
over time with repeated drug administration. Other
regulatory proteins of the Fos family rapidly break down
after synthesis, but FosB is highly
stable, persisting for months after drug withdrawal. Here,
then, is one example of a molecular mechanism for
drug-induced changes in gene expression persisting long
after last use. Preclinical models reveal that chronic, but
not acute, administration of cocaine, amphetamine,
phencyclidine, alcohol, nicotine and opiates induces FosB release
in the NAc and dorsal striatum (Kelz and Nestler, 2000).
In short, both human and preclinical data converge to
suggest that addiction is associated with frank biological
abnormalities that cannot be easily explained by a simple
hypothesis of "choice." It is a strange set of societal
circumstances that people may still consider the ingestion
of some drugs as outside the purview of physicians, when
clearly the practice of medicine deals with the impact of
exogenous substances upon the human body and mind. Those
individuals who abuse drugs do so absent the legal
mechanisms for which society provides, i.e., a prescription
or recommendation from a physician. Whether legal or not,
all addictive substances should be carefully reviewed with
our patients precisely because physicians must obtain all
information that may assist in the diagnosis and treatment
of disease and in the improved preventive health of
patients.
Drug dependence changes the lives of users and those
around them. Tobacco, for example, is the single greatest
cause of preventable death in the United States (CDC, 2001).
Certainly, then, tobacco is a menace to public health and
its continued popularity supports nicotine dependence as a
chronic, relapsing disease in which volitional choice
becomes but one negotiable variable in the struggle to
achieve good health throughout the life cycle.
Moral rejectionists mislabel drug dependence as a failure
of volition only and, thereby, claim a right to assign
judgment and blame. The absurdity of looking through such a
narrow lens is that if addiction really were merely a
choice, people would stop after experiencing more harm than
perceived benefits!
Accepting drug dependence as another mental illness does
not typically abrogate responsibility for an addict's
actions: Thousands each year are arrested, prosecuted and
sentenced to serve jail time for simple drug possession,
and, as for mental illness in general, consider that the two
psychiatric inpatient facilities in the United States in
which the largest numbers of patients reside are the Los
Angeles County Jail and New York City Rikers Island Prison
(Geller, 2000; Torrey, 1999; Watson et al., 2001).
Obviously, such individuals' moment-to-moment
decision-making can have long-term consequences that were
never wished for or accurately anticipated.
Not all choices can be equally entertained at every given
moment either, and sometimes other options are not even
known. For example, a young woman, supporting herself and
her drug habit through prostitution, may not know of the
different "ethical" choices available to her, especially
when as a child she had been introduced to both drugs and
her career by her mother's example. The reasons for
experimenting with addictive drugs, then, may be quite
different from the motivations fueling continued use.
Relapse is not due to an absolute loss of volitional control
but rather to loss of a perspective that cherishes good
health and mental well-being above other, less healthy
choices. In high-risk situations, this long-term desire for
maintaining better health through abstinence is overwhelmed
by the cued wish to re-experience a known, anticipated
"high" available at that moment.
Stigmatization of illness continues against many patients
afflicted with brain pathology. Substance dependence is
particularly stigmatized by those who wish to make this
illness a debate over volition while denying the biological
underpinnings of behavior. Moreover, demands for precise
linguistic definitions of addiction and disease, as if they
must forever be hermetically sealed within specific
denotations of legalese and ethics, is of little value to
physicians charged with the observation and treatment of
pathology. History reveals many examples of debates over
illness versus individual responsibility: Hansen's disease
("leprosy" from Mycobacterium leprae), seizure
disorders ("epilepsy"), cancer and major depression are some
examples of medical disorders now vindicated with the
discovery of effective medications and procedures.
Physicians, and psychiatrists in particular, are needed now
more than ever to stand up and explain to the lay public how
substance abuse and dependence can significantly alter brain
function and physical health and that a variety of treatment
modalities are available.
Effective management of drug dependence requires a
medical model so as to tailor therapy according to the
condition of the individual. Faith-based support groups,
Alcoholics Anonymous and its affiliates, and long-term
residential programs have a long history of assisting people
in achieving and maintaining abstinence via a combination of
direct therapy, education, cognitive skill-building
exercises, expanded non-drug social supports and providing a
drug-free environment. Contingency management skills can be
taught to provide individuals with extra time to anticipate
the high-risk situations and emotions for relapse and then,
hopefully, re-script behavior to minimize such exposures
(Carroll et al., 2001). This helps individuals learn to
avoid night clubs or other users because such settings and
people may make the choice for continued abstinence appear
less valuable than the immediate reward anticipated with
use.
Current pharmacotherapy for drug dependence includes
screening for an underlying psychiatric condition after the
patient has successfully completed detoxification. People
may choose to self-medicate with an addictive drug, all the
while unaware that they have a treatable psychiatric
illness. For example, rates for alcoholism and other drug
abuse are much higher in people with untreated bipolar
disorder and depression. For motivated individuals,
disulfiram (Antabuse) may particularly aid in maintaining
sobriety from alcohol. Smoking tobacco while on the
antidepressant buproprion (Zyban, Wellbutrin) is another
aversive treatment, as the drug induces an undesirable taste
when some smokers relapse. Agonist replacement medications
assist with detoxification and/or offer a stable, safer
maintenance therapy for those who repeatedly fail pure
abstinence (e.g., methadone for opiate dependence, nicotine
gum or patch for tobacco dependence). Many new medications
are also in development including more opiate antagonists
for the treatment of alcoholism and opiate dependence and
NMDA antagonists such as acamprosate [Campral] for
alcoholism (Tempesta et al., 2000). One day, perhaps there
will even be a vaccine to confer natural immunity against
cocaine (Schabacker et al., 2000). As Krystal et al. (2001)
reported regarding the efficacy of naltrexone (ReVia), an
opioid antagonist, in the treatment of alcoholism, sometimes
medications do not prove to be as effective as promised.
Evidence still suggests, however, that naltrexone may be
quite effective if taken intermittently on the days that the
individual feels at greater risk for relapse, rather than
ingesting it every day (Boening et al., 2001).
Whether addiction is a disease or merely a choice, the
utility of the medical model is needed to address resultant
risks to public and individual health. A careful review of
this growing body of scientific literature should offer hope
that real solutions are possible. All other models for
addressing drug dependence have, to date, proven to be
costly failures, and doctors are not going to ignore viable
treatment options for healing those suffering with drug
dependence. Defining addiction as a choice only abdicates
our responsibility for seeking health and true healing for
our patients and, instead, leaves crushed lives dehumanized
by a chronic relapsing condition with no hope for cure. As
every doctor knows, "Remember to do some good" should
quickly follow the first rule to "do no harm."
Dr. Halpern is an instructor in psychiatry at Harvard
Medical School and on staff at McLean Hospital and Brigham
& Women's Hospital. He is the recipient of a Career
Development Award (K23) from the National Institute on Drug
Abuse for ongoing research at McLean Hospital's Alcohol and
Drug Abuse Research Center.
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