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.