Pubdate: Thu, 24 Feb 2005
Source: Jerusalem Post (Israel)
Copyright: 2005 The Jerusalem Post
Author: Judy Siegel-Itzkovich
Bookmark: (Cannabis - Medicinal)


New Spanish and Israeli research shows that a synthetic analogue of the 
active component of marijuana can reduce the inflammation and prevent the 
mental decline associated with Alzheimer's disease. Although it was 
conducted on human brain tissue in the lab and in a rat model -- but not in 
living humans -- the research is regarded as a major step not only in 
understanding how the brain reacts to Alzheimer's disease, but also in 
helping to develop novel drugs for Alzheimer's and even Parkinson's disease.

Prof. Raphael Mechoulam, a medicinal chemistry expert who discovered 
marijuana's active component (called THC), conducted the study with 
researchers at the Cajal Institute and Complutense University in Madrid, 
led by Maria de Ceballos. The study appears in Wednesday's issue of The 
Journal of Neuroscience, which is published by the Society for 
Neuroscience, an organization of more than 36,000 basic scientists and 
clinicians who study the brain and nervous system.

To show the preventive effects of cannabinoids on Alzheimer's disease, 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 atmicroglia, 
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.

Meshoullam said that the discovery was important, since most drugs given 
for neurodegenerative diseases like Alzheimer's and Parkinson's are work 
merely against symptoms and not the cause and essence of the 
neurodegeneration. It is not necessary to smoke marijuana to conduct 
trials, but to use the synthetic versions of the active ingredient, he told 
The Jerusalem Post.

Clinical trials have not yet been scheduled or a request made for approval. 
It is very complicated and expensive to run clinical trials, he said, but 
he hoped they would be carried out due to the massive threat to human 
health of Alzheimer's and other neurodegenerative disorders.

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 said. 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. 
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MAP posted-by: Richard Lake