It is inside the brain that cocaine triggers euphoria and
along with it, for some, a terrible craving that leads to the
destruction of job, family, and self. Inside the brain is
where Dr. Michael Kuhar's development will act if it is successful.
His efforts�including the recent CTAC-sponsored
phase�to create anticocaine medication span 15 years and
have encompassed the testing and evaluation of some 500
chemical compounds. A dozen of the best
of the 500 were administered to rats and
then the best two of the 12 were chosen to
be given to monkeys. In the Yerkes Primate
Center at Emory University, Atlanta,
Kuhar and his team are at the cusp of
what could be a major breakthrough.
"These two compounds have been injected
into primate subjects thousands of times
with no observable side effects and the
subjects stop performing the tasks required
to receive the cocaine, strongly suggesting
that these medications eliminate the desire for the
drug.
When we move into human subject trials, we will be watching
very closely not only for evidence of effectiveness but
against negative side effects including toxicity." The scientific
community is closely watching Kuhar's pioneering
work. A new pharmaceutical company focused solely on
creating substances to heal drug abusers is negotiating to
license and further develop Kuhar's compounds. Licensing
by a company is essential for bringing new medications to
market. There is reason to believe that if Kuhar (photo
above) and Landry both succeed, then their drugs could be
used together to help cocaine addicts. Both researchers
have done remarkable work, but it would be a mistake to
assume that effective, safe anticocaine medication will be
available soon; there's lots more testing before that day
arrives�if it ever does.
Much of CTAC's research and development budget supports
bold new efforts to obtain crucial information for the demand reduction
side
of the National
Drug
Control
Strategy. In
direct pursuit of that goal,
CTAC is
funding the
construction
of brain imaging
centers
to learn
everything
we can about the interactions of drugs of abuse as they
enter the brain, and ways to block those destructive effects.
Research institutions receiving these state-of-the-art scanners
promise to give top priority access to scientists who
are working right now on drug abuse questions and to train
the next generation of brain researchers to focus on drugs
of abuse.
A massive, CTAC-sponsored Functional Magnetic Resonance
Imaging machine, powered by a 7-Tesla coil magnet
seen under construction in photos (left)��has been
installed at Massachusetts General Hospital. It's the most powerful brain scanner in the world, according to Dr. Bruce
Rosen (top right), who directs the use of the new FMRI.
The hospital's chief clinician on this project, Hans Breiter,
M.D. (above), sees the enormous machine's equally huge
mission as, "Mapping the neurochemistry of human behavior
itself and creating a virtual stethoscope for treatment
professionals, ultimately allowing them to easily, reliably
measure the effectiveness of everything they do on behalf
of their patients." Other CTAC-supported advanced neuroimaging
system installations are complete or scheduled at
NIDA in Baltimore, Brookhaven National Laboratory on
Long Island, University of Pennsylvania in Philadelphia,
Harvard's McLean Hospital outside Boston, and at UCLA.
Neuroscientists working on drug abuse today routinely discuss
the role in cocaine dependence of a brain area called
the nucleus accumbens. But it wasn't until 1997 that Dr.
Edythe London (in lab coat, photo below) of the National
Institute on Drug Abuse, was able to visualize�with high
resolution�the function of this nucleus in the human brain
of a cocaine addict by using a state-of-the-art Positron
Emission Tomography (PET) scanner sponsored by CTAC
for use at NIDA's Addiction Research Center in Baltimore.
The PET instrument at NIDA will now be used by Dr. Diana
Fishbein under CTAC sponsorship to conduct basic
research leading to better management of recovering
addicts. Today, Dr. London is based at UCLA
where her new work focuses on methamphetamine
dependence. The photos (right) show a
young woman in a UCLA treatment research
program, who consented to brain scanning, an
interview and to be photographed. She told
Dr. London that she believes her years of
doing meth have damaged her brain, resulting
in changed behavior.
Dr. London hopes that this line of study will
result in new knowledge leading to the development
of effective medications and behavioral
therapies for people whose lives are
being destroyed by meth. Also at UCLA, investigators
at the Crump Institute on Molecular
Imaging are bringing state-of-the-art techniques
to bear on the problem of drug abuse
from another unique perspective. With CTAC's
sponsorship, Dr. Simon Cherry and his colleagues
are developing a small PET scanner
with resolution fine enough to literally see
gene expression in discreet nuclei of a monkey
brain. This new instrument will allow
injection of DNA and selective probes that can
alter gene expression in specific monkey brain
regions critical to the reward effects of
cocaine and other abused drugs. The effects of
such genetic manipulations on brain function
will be studied at the molecular level with
PET, and ultimately can be related to drug
abuse behaviors in nonhuman primates. For
the first time, the links between drug abuse
and brain function will be linked to the
expression of certain genes that can then be
monitored externally. While this may sound
like science fiction, it is excitingly real and
feasible and the implications for the development
of counterdrug medications for humans
could be breathtaking.
