"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 email@example.com.