Targeting Brain Circuits for Addiction, Relapse

Could a once-a-month alcoholism shot keep some
of the highest-risk heroin addicts from relapse? A drug that wakes up
narcoleptics treat cocaine addiction? An old antidepressant fight
methamphetamine?

This
is the next frontier in substance abuse: Better understanding of how
addiction overlaps with other brain diseases is sparking a hunt to see
if a treatment for one might also help another.

We're
not talking about attempts just to temporarily block an addict's high.
Today's goal is to change the underlying brain circuitry that leaves
substance abusers prone to relapse.

It's
"a different way of looking at mental illnesses, including substance
abuse disorders," says National Institute on Drug Abuse Director Dr.
Nora Volkow, who on Monday urged researchers at the American
Psychiatric Association's annual meeting to get more creative in the
quest for brain-changing therapies for addiction.

Rather
than a problem in a single brain region, scientists increasingly
believe that psychiatric diseases are a result of dysfunctioning
circuits spread over multiple regions, leaving them unable to properly
communicate and work together. That disrupts, for example, the balance
between impulsivity and self-control that plays a crucial role in
addiction.

These
networks of circuits overlap, explaining why so many mental disorders
share common symptoms, such as mood problems. It's also a reason that
addictions — to nicotine, alcohol or various types of legal or illegal
drugs — often go hand-in-hand with post-traumatic stress disorder,
depression, schizophrenia and other mental illnesses.

Think
of it as if the brain were an orchestra, its circuits the violins and
the piano and the brass section, all smoothly starting and stopping
their parts on cue, Volkow told The Associated Press.

"That
orchestration is disrupted in psychiatric illness," she explains.
"There's not a psychiatric disease that owns one particular circuit."

So
NIDA, part of the National Institutes of Health, is calling for more
research into treatments that could target circuits involved with
cognitive control, better decision-making and resistance to impulses.
Under way:

— Manufacturer Alkermes
Inc. recently asked the Food and Drug Administration to approve its
once-a-month naltrexone shot — already sold to treat alcoholism — to
help people kick addiction to heroin and related drugs known as
opioids. Scientists have long known that naltrexone pills can block
heroin's effects, but the pills last only a day so skipping a dose lets
addicts get high again. Alkermes' studies show the monthly version,
named Vivitrol, can help reduce heroin use long-term.

But
Volkow points to a study in Russia that found naltrexone shots also
reduced cravings for the illegal drug. That's important, she says,
because the treatment may be extinguishing too-active reward circuitry
in the brain that conditioned people to keep using, and thus may
prevent relapse.

With NIDA funding, Dr.
Charles O'Brien of the University of Pennsylvania is studying that
question in a tough-to-treat population, prison parolees. They quickly
relapse as they return home and so-called "cue-induced cravings"
reawaken, strong desires triggered by seeing friends they once did
drugs with or simply passing by their old seller's street corner. At
five sites around the Northeast, O'Brien's study will test if six
months of Vivitrol can stop that cycle.


Studies at several hospitals around the country suggest modafinil, used
to fend off the sudden sleep attacks of narcolepsy, also can help
cocaine users abstain. It may act as a mild stimulant that reduces
their desire for the drug. But back to those brain circuits, cocaine
causes damage in networks involved in reasoning, weighing decisions and
overcoming impulses. Some research suggests modafinil counters that
problem by improving what scientists call executive function,
higher-order decision-making that involves those capabilities.


An old antidepressant, bupropion, that's already used for smoking
cessation now is being tested for methamphetamine addiction, based on
early-stage research suggesting it somehow blunts the high. But Volkow
says addiction makes the brain more sensitive to stressors that in turn
trigger negative mood circuitry, so she wants antidepressants also to
be tested in combination with other addiction medications.

Medication
isn't the only option. Biofeedback teaches people with high blood
pressure to control their heart rate. O'Brien's colleagues at Penn are
preparing to test if putting addicts into MRI machines for real-time
brain scans could do something similar, teaching them how to control
their impulses to take drugs.

"It's controlling your own brain," O'Brien says. While the idea is extremely early-stage, "we think that it's very promising."