What Addicts Need
Addiction isn't a weakness; it's an illness. Now vaccines and other new
drugs may change the way we treat it.
By Jeneen Interlandi; NEWSWEEK; Feb 23, 2008
Annie Fuller knew she was in trouble a year ago, when in the space of a
few hours she managed to drink a male co-worker more than twice her size
under the table. Of course, she'd been practicing for a quarter of her
life by then; at 47, she was pouring a pint of bourbon, a 12-pack of
beer and a couple of bottles of wine into her 115-pound body each day.
She had come to prefer alcohol to food, sex or the company of friends
and loved ones. Her marriage had ended; she had virtually stopped
leaving the house, except to work and to drink. Fuller had tried and
failed enough times over the years to know that she would not be able to
sober up on her own. The last time she'd stopped drinking her body went
into violent seizures, a common and terrifying symptom of alcohol
withdrawal. But the single mother and mortgage-company VP refused to
sign into rehab. "I live in a small town," she says. "And when you go to
a hospital for something like that, everybody knows about it." So when a
family doctor told her about Vivitrol, a monthly injection that prevents
patients from drinking alcohol by obliterating its ability to
intoxicate, Fuller agreed. She took a sabbatical from work, sent her
15-year-old daughter to stay with relatives and hunkered down to weather
the painful, frightening blizzard of detoxification in the comfort of
her own living room.
What does it mean to be an addict? For a long time the answer was that
someone like Fuller "lacked willpower," a tautology that is pretty much
useless as a guide to treatment. In the current jargon of the recovery
movement, addiction to alcohol, drugs or nicotine is a
"bio-psycho-social-spiritual disorder," a phrase that seems to have been
invented by the treatment industry to emphasize how complex the problem
is and how much more funding it deserves. But the word itself comes from
the Latin addictus, a debtor who was indentured to work off what he
owed; someone addicted to alcohol or drugs is powerless over his or her
fate in the same way-except debtors-as-addicts can never fully balance
the books. It had been years since the pleasure of drinking outweighed
the pain it caused Fuller. Looked at that way, the "social" and
"spiritual" aspects of her problem seem insignificant compared with the
contribution of biology. If you weigh advances in neuroscience over the
last few decades against social and spiritual progress, it's clear which
field is more likely to produce the next breakthrough in treatments.
While the roots of addiction remain a dark tangle of factors-most
experts agree that addicts trying to quit will always need psychological
support-the old white-knuckle wisdom that addicts simply lack resolve
passed out of fashion decades ago. The American Medical Association
recognized addiction as a disease back in 1956. But only now are we
beginning to see treatments that target the underlying biochemistry of
that disease.
The emerging paradigm views addiction as a chronic, relapsing brain
disorder to be managed with all the tools at medicine's disposal. The
addict's brain is malfunctioning, as surely as the pancreas in someone
with diabetes. In both cases, "lifestyle choices" may be contributing
factors, but no one regards that as a reason to withhold insulin from a
diabetic. "We are making unprecedented advances in understanding the
biology of addiction," says David Rosenblum, a public-health professor
and addiction expert at Boston University. "And that is finally starting
to push the thinking from 'moral failing' to 'legitimate illness'."
In laboratories run and funded by the National Institute on Drug Abuse
(NIDA), fMRI and PET scans are forcing that infuriating organ, the
addicted brain, to yield up its secrets. Geneticists have found the
first few (of what is likely to be many) gene variants that predispose
people to addiction, helping explain why only about one person in 10 who
tries an addictive drug actually becomes hooked on it. Neuroscientists
are mapping the intricate network of triggers and feedback loops that
are set in motion by the taste-or, for that matter, the sight or
thought-of a beer or a cigarette; they have learned to identify the
signal that an alcoholic is about to pour a drink even before he's aware
of it himself, and trace the impulse back to its origins in the
primitive midbrain. And they are learning to interrupt and control these
processes at numerous points along the way. Among more than 200
compounds being developed or tested by NIDA are ones that block the
intoxicating effects of drugs, including vaccines that train the body's
own immune system to bar them from the brain. Other compounds have the
amazing ability to intervene in the cortex in the last milliseconds
before the impulse to reach for a glass translates into action. To the
extent that "willpower" is a meaningful concept at all, the era of
willpower-in-a-pill may be just over the horizon. "The future is clear,"
says Nora Volkow, the director of NIDA. "In 10 years we will be treating
addiction as a disease, and that means with medicine."
Volkow's vision of the future, however, is being greeted warily by big
pharmaceutical companies, reluctant to develop products that would
associate their brands with drug addicts. It is also facing resistance
from some elements in the addiction-treatment community, who are wedded
to the 12-Step model pioneered by Alcoholics Anonymous in 1935.
Twelve-Step programs traditionally discourage members from using any
psychoactive substances, on the ground that addicts will simply trade
one dependency for another. That rationale has some unfortunate history
on its side; both opium and cocaine were first introduced to the United
States as cures for alcoholism in the late 1800s. More recently there is
the example of methadone, the synthetic heroin that turned out to be
addictive in its own right, and Antabuse, a drug that makes you throw up
when you drink alcohol-which suffers from the shortcoming that an
alcoholic planning a binge can just skip his dose.
Addictive drugs like cocaine and heroin flood the brain with the
neurotransmitter dopamine, a chemical that induces a sensation of
pleasure and trains the subconscious to remember everything that
preceded that sensation. Together with alcohol, nicotine and
amphetamines, these make up the five drugs generally considered the
hardest to give up; right now, some 22 million Americans are hooked on
at least one of these substances. While each causes a distinct form of
intoxication and a different range of side effects and health problems,
all five hijack the same pathway, deep within the brain. It's the
pathway that conditions us to eat, have sex, form emotional attachments
and carry out the other activities essential to our species' survival.
But the agents of addiction are far more powerful than any of those
natural highs. Just one dose of cocaine, for example, can release two to
10 times the amount of dopamine produced by your favorite meal, person,
song or sight. Take a drug like that consistently enough, and your brain
and body will come to depend on it-first for euphoria, then for
normalcy. Eventually, the pursuit and consumption of drugs will become
as instinctive as the pursuit and consumption of food-only far more
urgent and destructive.
People vary in their innate sensitivity to dopamine, which may partly
explain why addiction runs in families. A gene that codes for a dopamine
receptor designated D2 (one of at least five dopamine receptors that
have been identified so far) comes in several different versions, and
each produces a different concentration of receptors. People with fewer
receptors may receive less stimulation from their naturally occurring
dopamine, and therefore be more inclined to seek an artificial high from
drugs. Unfortunately, tinkering directly with the dopamine system to
control addiction hasn't worked out very well. Dopamine is crucial to
voluntary movement and interfering with it can cause symptoms resembling
Parkinson's.
So far, other neurotransmitters that play a role in addiction have been
easier to tackle. Gamma-aminobutyric acid, or GABA, exerts an inhibitory
effect on neurons, telling the body to stop instead of go. Addicts'
brains are deficient in GABA, so researchers are investigating a drug
called Vigabatrin, which stimulates its production. In December, the
pill cleared its first double-blind, placebo-controlled trial; 30
percent of patients who took Vigabatrin stayed off cocaine during the
nine-week study, compared with just 5 percent in a control group. "It's
the best efficacy signal that we've seen in any clinical trial for
cocaine treatment," says Frank Vocci, director of the pharmacotherapies
division at NIDA. "And it's worked on what many have written off as an
intractable population-hard-core, long-term cocaine addicts." A drug
called Camparal, which is already on the market as a treatment for
alcoholism, works on yet another brain chemical, glutamate. While the
early stages of addiction are driven by pleasure-seeking-hence the
importance of dopamine-the motive eventually shifts to avoiding the pain
of withdrawal; at that point, drug-seeking behavior is fueled by
glutamate. By suppressing this neurotransmitter, Camparal has the
potential to reduce cravings and help prevent relapses during recovery.
Researchers think these drugs hold enormous promise. "The treatment of
depression was revolutionized by medications that manipulate serotonin
concentrations," says Alan Leshner, former head of NIDA, referring to
Prozac and its cousins. "Drugs that act on GABA and glutamate could do
the same thing for addiction."
If you're trying to quit drinking, you are advised not to hang out in
bars, and if you're trying to kick cigarettes, you probably should avoid
French movies from the 1950s. One reason addictions are so hard to break
is that the pleasure of taking the drug becomes associated with all the
situations and activities around it, which then become cues for a
relapse. Researchers at the University of Pennsylvania found that
showing cocaine addicts pictures of drugs or crack pipes for just 33
milliseconds-below the threshold of conscious awareness-was enough to
trigger cravings. Beverly Dyess, 58, learned this last year when, after
six months of sobriety-her longest stretch in 15 years-she went into a
supermarket and discovered that her favorite brand of Scotch was on
sale. She was seeing a therapist daily, but "as soon as I saw the label,
everything else went out the window," she says. For the next two months
she rode a roller coaster of frenzied drinking and crushing guilt. Some
days she would get up early enough to get drunk and then sober up in
time for her evening counseling session. Other days she would run to the
store, buy a bottle of whisky and then, her resolve mysteriously
stiffened, pour it down the sink when she got home. By suppressing the
surge of glutamate that directed her to the Scotch aisle in the first
place, Camparal helped ease the pain of withdrawal and allowed the
counseling and behavioral therapy to work. "I still do the talk
therapy," she says. "But Camparal really helps, because everything is
still a cue for drinking."
Of course, you can't protect yourself against every encounter with a
bottle, or, in some environments, heroin, cocaine or amphetamines. So
researchers are working on ways to break the association that was
Dyess's downfall. A drug called D-cycloserine, or DCS, has the
remarkable effect of helping to erase learned fear responses. The
classic example, in animals, is the association of a particular place
with an electric shock. If you stop giving the shock, the animal
eventually "unlearns" the response and is no longer afraid; DCS makes
this happen faster. It has been successfully tested in people as a
treatment for acrophobia (fear of heights). Now researchers want to see
if it can be used to wipe out the association between visual or social
cues and the impulse to relapse into addiction. So far, it's been tested
only on cocaine, but if it works there it might work for other
addictions as well.
Neuroscientists don't talk about "willpower," which is a philosophical
concept, but they are starting to get a handle on the parts of the brain
involved in self-control, the ability to impose a rational calculus on
behavior. They distinguish three kinds of selfcontrol, and,
unsurprisingly, addicts score poorly on all of them, although it isn't
clear whether taking drugs is the cause or consequence of this
deficiency, and which of the three types plays the biggest role in
addiction has yet to be determined. These are:
* Delayed discounting, the willingness to put off present gratification
in the interest of a bigger long-term reward. Addicts always take the
immediate reward.
* Reflection impulsivity, a measure of how much information is required
to make a decision. Addicts typically act without processing all the
available information.
* Intentional action, the ability to consciously stop a behavior that
has become automatic.
To measure this, NIDA researchers had addicts watch a screen and push
one of two buttons, according to whether a light has flashed on the left
or right side-except when the light was accompanied by a tone. After
several rounds, pushing the button becomes an automatic response that
has to be overridden consciously, and addicts were much less able to do
this than non-addicts. As scientists have known since the 1980s, the
neurons that control movement are activated even before a person is
aware of the intention. Now researchers have identified the part of the
brain-the fronto-median cortex-that is activated when someone stops
himself from executing such automatic behaviors. This is as close as we
have got to finding the seat of willpower in the brain. Put an addict in
an fMRI machine, and you can observe reduced activity in the
fronto-median cortex. But a drug called Provigil, which is ordinarily
used to treat narcolepsy, stimulates that part of the brain and is now
being tested as a treatment for amphetamine addiction. "The idea that we
can restore 'self-control' or 'free will' with medication is a very,
very exciting one," says Vocci of NIDA. "It could be paradigm shifting.
But we need more studies to see how consistently that impacts recovery."
That is a useful caution; these drugs are new and their mechanisms are
still only partially understood. The brain has a way of resisting
attempts to tinker with its chemistry. The discovery in 1960 that
Parkinsonism was caused by a deficiency of dopamine quickly led to the
use of synthetic dopamine precursors, such as L-dopa, which relieved the
symptoms at first, but were not the long-term cure patients had hoped
for.
A more straightforward approach to treating, or preventing, addiction is
to block the action of the drug directly. If it doesn't feel good, the
thinking goes, you won't do it. Naltrexone, a pill that has been around
for a decade, works that way against alcohol, but an addict intent on
getting high can just skip his dose. The solution to that problem is
Vivitrol, a longer-lasting, injectable form of Naltrexone, which came on
the market in 2006. Vivitrol, the drug Annie Fuller took, does not
enhance self-control or stop the craving for liquor, but it does block
liquor's effects. The day Fuller got her shot, her leg swelled to twice
its normal size. The swelling subsided a day or two later, but the next
few weeks were a torment of sweating, shaking, vomiting and tears-side
effects that came from both Vivitrol and alcohol withdrawal. At times
she couldn't walk and needed help to use the bathroom. The only thing
that kept her from drinking was the knowledge that she could not get
drunk. "The shot just took the relapse option off the table," she says.
She got the same injection every month for the rest of the year,
suffering a little less each time, and she is now off the medication and
sober.
Vaccines that would arm the immune system against addictive drugs and
prevent them from making the user high are, potentially, the ultimate
weapons against addiction. A cocaine vaccine is poised to enter its
first large-scale clinical trial in humans this year, and vaccines
against nicotine, heroin and methamphetamine are also in development. In
theory, these addiction vaccines work the same way as the traditional
vaccines used to treat infectious diseases like measles and meningitis.
But instead of targeting bacteria and viruses, the new vaccines zero in
on addictive chemicals. Each of the proposed vaccines consists of drug
molecules that have been attached to proteins from bacteria; it's the
bacterial protein that sets off the immune reaction. Once a person has
been vaccinated, the next time the drug is ingested, antibodies will
latch onto it and prevent it from crossing from the bloodstream into the
brain. Nabi Biopharmaceuticals, a small biotech company in Maryland, has
engineered a nicotine vaccine that is in late-stage clinical trials.
Earlier studies showed that it was twice as effective as a placebo in
helping people quit smoking. The cocaine vaccine, developed by Thomas
Kosten of Baylor College of Medicine, could be on the market as early as
2010. It would have to be given three or four times a year, but
presumably not for life, says Kosten. While the vaccine is being studied
in people who are already addicted to cocaine, it could eventually be
used on others. "You could vaccinate high-risk teens until they matured
to an age of better decision-making," Kosten says. He acknowledges the
obvious civil-liberties issues this raises. "Lawyers certainly want to
argue with us on the ethics of it," he says, "but parent groups and
pediatricians have been receptive to the idea."
The revolution these new drugs promise will have a huge impact on the
addiction-treatment industry (or, as it prefers to think of itself, the
"recovery movement"), which runs the gamut from locked psychiatric wards
in big-city hospitals to spalike mansions in the Malibu Hills of
California. And the reaction there is guarded; the people who run them
have seen panaceas come and go over the years, and the same addicts
return with the same problems. They also, of course, have a large
investment in their own programs, which typically rely on intensive
therapy and counseling based on the 12-Step model. "We need four or five
more years to see how [Vivitrol] does," says staff psychiatrist Garrett
O'Connor at the Betty Ford Center, in Rancho Mirage, Calif. "And we need
to be very cautious, because a failed treatment will set a person back."
The Ford Center and the Hazelden Foundation, in Minnesota, use drugs
sparingly, and mostly just in the first days or weeks of recovery, the
"detox" phase. "Hazelden will never turn its back on pharmaceutical
solutions, but a pill all by itself is not the cure," says William
Moyers, Hazelden's vice president of external affairs. "We're afraid
that people are seeking a medical route that says treatment is the end,
not the beginning." As for Alcoholics Anonymous and its imitators, they
mostly do not forbid members to use medication but there are strong
institutional biases against it. "I'm not judging others, but for
myself, using something like Vivitrol or Camparal feels like a crutch,"
says one longtime AA member, who, following the organization's practice,
asked not to be named. "It's not true sobriety."
The competing view is that of Lisa Torres, a New York lawyer who has
been in recovery from heroin addiction for nearly 20 years, and
continues to take methadone, which she regards as medication for a
chronic condition, analogous to blood-pressure or cholesterol-lowering
drugs. "It's a paradox that some of addicts' biggest advocates have been
the most resistant to new treatments," she says. "But a lot of them come
to the field after recovering from their own addictions, and they can be
very stubborn about what works and what doesn't." More pointedly, she
adds, "some people feel recovery from addiction should not be easy or
convenient."
So for this new paradigm to take hold, a lot of long-held prejudices
will have to change. Doctors (and insurance companies) will have to get
used to the idea of medicating their addicted patients, rather than
handing them a brochure for AA, which a study published in 2005 in The
New England Journal of Medicine found was the most common form of
"treatment" offered. "If you have hypertension and it flares up, you go
to a specialist," says psychologist Thomas McLellan of the University of
Pennsylvania. "The specialist doesn't discharge you to a church
basement. If he did, we would call it malpractice." Addicts, he adds,
are by no means unique in their propensity to relapse. In a study
comparing alcoholics and drug addicts to patients with diabetes, asthma
and hypertension, McLellan found nearly identical rates of noncompliance
and relapse; between 30 and 40 percent of each group failed to follow
even half their doctors' guidelines.
Where doctors go, drug companies are likely to follow. Most of the
research on addiction treatments has been done by NIDA (total 2007
budget: $994 million) or small pharmaceutical companies. "I have been
imploring the bigger companies to work on this," says Volkow. "Their
scientists get it, but the business people are tough to persuade."
Companies with billion-dollar stakes in selling drugs for osteoporosis
or cholesterol don't want their names on a product used by heroin
addicts, says Leshner. Even the relatively unknown Nabi, according to
CEO Raafat Fahim, decided to focus on a vaccine for nicotine "because
it's not illicit and it's not something you can overdose on" (and
afterward sue the company that made the drug that didn't stop you from
taking it). But Steven Paul, the head of research for Eli Lilly,
believes the landscape is changing. There used to be a stigma attached
to depression, too, he says, but the development of Prozac put an end to
that. "Anything that has a large unmet need," says Paul, "is ultimately
going to succeed commercially."
And addicts may need to change their thinking, too. For nearly 75 years,
that thinking has been dominated by the principles laid down by Bill W.,
the founder of Alcoholics Anonymous. The amount of good AA has done in
the world is incalculable; most people reading this article probably can
think of someone they know who owes his or her life to it. Some readers
themselves have surely benefited. But in 1935 AA was, essentially, the
only legitimate option. There were "cures" of various sorts, including
gold chloride injections, but there was virtually no modern neuroscience
or psychopharmacology. Many people are now living in society with mental
illnesses like schizophrenia and bipolar disorder that would have
required institutionalization back then. Addicts, like the rest of the
public, need to recognize the fact that we are entering a new era in
addiction treatment. Viewing her condition as a chronic, recurring
disease that could be treated was precisely what Dyess needed to return
to sobriety. "In the past, when I would relapse," she says, "the
thinking from 12-Step or from family was that I had failed. Now I know
that if it happens, it happens, and I can pick myself up and move on,
instead of assuming it's all over so I might as well keep drinking." The
12 Steps begin with a confession of powerlessness over addiction. But
there's hope that science may some day help put that power within the
reach of anyone who needs it. And then who would choose not to grasp it,
and begin the long war for sobriety-a war without end, but one worth the
fighting.
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