|Study Helps Unravel Mysteries of Brainís
NIDA research could lead to better treatment for pain
and marijuana addiction
New research funded by the National Institute on Drug Abuse (NIDA),
part of the National Institutes of Health, has identified a new
mechanism for the processing of endocannabinoids, natural brain
compounds similar to THC, the active ingredient in marijuana. The
results of this study, led by researchers from Stony Brook University,
were published March 16 in the Proceedings of the National Academy
Endocannabinoids are known to play a role in numerous physiological
processes including appetite, memory, and pain. Researchers had
long suspected that endocannabinoids needed a specific transporter
that would ferry them to the location where they are broken down.
This study successfully identified a couple of previously known
fatty acid binding proteins (FABPs) as capable of carrying the
endocannabinoid anandamide (also known as AEA) from the cell membrane,
through the cell interior, to the location where it is destroyed.
"This finding is important because it significantly expands
the range of potential targets for developing medications that
could help fight pain, addiction, and other disorders," said
NIDA Director Dr. Nora D. Volkow. "For example, the manipulation
of the endocannabinoid system has the potential to provide sorely
needed therapeutics for the management of severe pain that are
devoid of the side effects of opiate analgesics."
The breakdown of AEA requires two factors. First, because AEA
is a fatty compound and thus unable to move inside the watery cellular
environment, there needs to be a mechanism for transporting AEA
to the location where it is inactivated. Second, the cell must
express an enzyme called FAAH, which is responsible for breaking
down and inactivating AEA. In the laboratory, the researchers coaxed
a non-neuronal cell type (Cos-7) to express FAAH. These FAAH-expressing
Cos7 cells were able to break down AEA efficiently, indicating
that the intracellular AEA transport mechanism was already present
and operational in these cells. The researchers identified these
carriers as two different, previously known fatty-acid binding
proteins (FABPs). By specifically inhibiting FABPs, they were able
to decrease the breakdown of AEA by about 50 percent.
"Inhibiting FABPs could potentially raise the levels of AEA
in the brainís synapses," said Dr. Dale Deutsch, lead author
of the study. "Naturally occurring AEA levels have been shown
to curb pain without the negative side effects, such as motor coordination
problems, of molecules like THC that can also bind the cannabinoid
receptor. So itís advantageous to try and target AEA for therapeutic
"From a theoretical viewpoint, this approach could be used
for treating marijuana addiction," said Dr. Volkow. "Compounds
that inhibit FABPs could produce an effect similar to nicotine
patches for smokers or methadone for opiate replacement. This line
of research may also be important for other types of addiction,
such as chronic alcohol abuse, which also affects AEA levels," she
In addition to pain control, researchers are also examining manipulation
of the endocannabinoid system for treating anxiety, obsessive-compulsive
disorder, traumatic brain injury, and other substance abuse disorders.
The National Institute on Drug Abuse is a component of the National
Institutes of Health, U.S. Department of Health and Human Services.
NIDA supports most of the worldís research on the health aspects
of drug abuse and addiction. The Institute carries out a large variety
of programs to inform policy and improve practice. Fact sheets on
the health effects of drugs of abuse and information on NIDA research
and other activities can be found on the NIDA home page at www.drugabuse.gov.
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Online ordering is available at http://drugpubs.drugabuse.gov.
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Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
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