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Marijuana ingredient may stall decline from Alzheimer's

by Society for Neuroscience
New research
shows that a synthetic analogue of the active
component of marijuana may reduce the
inflammation and prevent the mental decline
associated with Alzheimer's disease.
Public release date: 22-Feb-2005

Contact: Elissa Petruzzi
elissa [at] sfn.org <mailto:elissa [at] sfn.org><mailto:elissa [at] sfn.org>
202-462-6688
Society for Neuroscience <http://www.sfn.org/><http://www.sfn.org/>

Marijuana ingredient may stall decline from Alzheimer's

WASHINGTON, DC February 17, 2005 -- New research
shows that a synthetic analogue of the active
component of marijuana may reduce the
inflammation and prevent the mental decline
associated with Alzheimer's disease.

"This research is not only a major step in our
understanding [of] how the brain reacts to
Alzheimer's disease, but may also help open a
route to novel anti-Alzheimer's drugs," says
Raphael Mechoulam, professor emeritus of
medicinal chemistry at Hebrew University in
Jerusalem and discoverer of marijuana's active
component.

To show the preventive effects of cannabinoids on
Alzheimer's disease, researchers at the Cajal
Institute and Complutense University in Madrid,
led by Maria de Ceballos, conducted studies using
human brain tissue, as well as experiments with
rats. The study appears in the February 23, 2005,
issue of The Journal of Neuroscience.

The team first compared the brain tissue of
patients who died from Alzheimer's disease with
that of healthy people who had died at a similar
age. They looked closely at cannabinoid receptors
CB1 and CB2– proteins to which cannabinoids bind,
allowing their effects to be felt – and at
microglia, which activate the brain's immune
response. Micro- glia collect near plaques and,
when active, cause inflammation. The researchers
found a dramatically reduced functioning of
cannabinoid receptors in diseased brain tissue,
meaning that patients had lost the capacity to
experience cannabinoids' protective effects.

In addition, the researchers showed that
cannabinoids prevented cognitive decline through
rat experiments. They injected either amyloid
(which leads to cognitive decline) that had been
allowed to aggregate or control proteins into the
brains of rats for one week. Other rats were
injected with a cannabinoid and either amyloid or
a control protein.

After two months, the researchers trained the
rats over five days to find a platform hidden
underwater. Rats treated with the control protein
– with or without cannabinoids – and those
treated with the amyloid protein and cannabinoid
were able to find the platform. Rats treated with
amyloid protein alone did not learn how to find
the platform.

The researchers found that the presence of
amyloid protein in the rats' brains activated
immune cells. Rats that received the control
protein alone or cannabinoid and a control
protein did not show activation of microglia.
Using cell cultures, the investigators confirmed
that cannabinoids counteracted the activation of
microglia and thus reduced inflammation.

"These findings that cannabinoids work both to
prevent inflammation and to protect the brain may
set the stage for their use as a therapeutic
approach for [Alzheimer's disease]," de Ceballos
says. The scientists will now focus their efforts
on targeting one of the two main cannabinoid
receptors that is not involved in producing the
psychotropic effects, or high, from marijuana.

###

The Journal of Neuroscience is owned and
published by the Society for Neuroscience, an
organization of more than 36,000 basic scientists
and clinicians who study the brain and nervous
system. De Ceballos may be reached at
mceballos [at] cajal.csic.es
<mailto:mceballos [at] cajal.csic.es><mailto:mceballos [at] cajal.csic.es>
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