Glutamate Enhancing
Agent Found to Blunt Cocaine High
January / February 2004
In a controlled study, Penn Behavioral Health psychiatrists
demonstrated that a glutamate-enhancing agent blunts the
cocaine
high experienced by cocaine addicts. A subsequent open-label
study also indicated that the drug promotes cocaine abstinence
and reduces craving. “About 16 percent of people who
try cocaine become addicted and this addiction is driven
by
a cycle of euphoria and craving which often leads to a binge
pattern of use,” says Charles
A. Dackis, MD, addiction specialist and chief of psychiatry
at the Penn Presbyterian Medical Center.
In addition to regular craving, cocaine addicts experience
cue craving, an intense craving that occurs when they see
something that reminds them of their addiction, such as a
person, place or thing. Studies at the Hospital of the University
of Pennsylvania demonstrated that when shown videos of cocaine
paraphernalia, participants who were addicted to cocaine
underwent tremendous metabolic changes in the brain.
“Although
cocaine acutely stimulates the brain, over time a chronically
exposed person will experience dysregulation of the pleasure
centers in the brain, which appears to include the depletion
of two neurotransmitters, glutamate and dopamine,” adds
Dr. Dackis, who also works in the University of Pennsylvania
Center for Studies on Addiction. “Chronic exposure
to cocaine puts cocaine addicts in a negative mood state,
termed
‘hedonic dysregulation,’ that involves malfunctioning
pleasure circuitry, and they complain that they can’t
enjoy life or anything without cocaine.”
Cocaine addicts also have markedly reduced activity in the
frontal lobe of the brain, which is largely comprised of glutamate-containing
pyramidal cells. Neuropsychological tests that examine frontal
lobe function find deficits in cocaine addicts who have impaired
executive function, decision-making, ability to weigh risks
against benefits, and ability to suppress impulses.
Despite 20 years of intensive research, no drug has been
identified with proven ability in cocaine addiction. However,
modafinil is the first glutamate enhancing agent to be tested.
“The preliminary open-label results are very promising
and we are currently testing modafinil in a controlled study.
Modafinil is a novel, awakening drug that enhances executive
function and concentration. Since it reaches the pleasure
centers of the brain, we believe it may reverse some of the
long-term affects of cocaine,” explains Dr. Dackis.
“And, even more importantly, it has demonstrated an
ability to block the cocaine high.”
In the open-label study, 17 cocaine-dependent individuals
(with severe cocaine withdrawal) were randomized to receive
either 200 or 400 mg/day of modafinil for a period of eight
weeks. When compared to a group of placebo-treated subjects
from another study, those who received modafinil had significantly
higher abstinence (47 percent vs. 6.5 percent) and treatment
retention. Both dosages were well tolerated and the four participants
who used cocaine in combination with modafinil reported absent
or diminished euphoria.
Penn psychiatrists are currently conducting a double blind
placebo controlled clinical trial studying modafinil and
its
affect on cocaine dependence. In addition, the National Institute
on Drug Abuse is soon launching a multi-center study (which
will likely include Penn as a site) on modafinil and cocaine.
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