Pubdate: Wed, 25 Sep 2002 Source: Guardian, The (UK) Copyright: 2002 Guardian Newspapers Limited Contact: http://www.guardian.co.uk/guardian/ Details: http://www.mapinc.org/media/175 Author: Sophie Petit-Zeman HIGH TIMES FOR ALZHEIMER'S Sophie Petit-Zeman On The Way Cannabinoids Could Alleviate Symptoms Of Degenerative Diseases 'A younger sibling of mine accidentally let grandma eat the wrong brownies... You could tell she had AD [Alzheimer's disease] but nothing so prominent. It was like it took her back 3-4 years." Postings such as this one on the Alzforum website intrigued Dr Nathaniel Milton, a biochemist at London's Royal Free and University College medical school. He was already actively researching compounds which prevent the brain cell death that occurs in Alzheimer's disease, and, with research partner Insight Biotechnology, had taken out patents on some capable of doing this. He was also aware of a few reports suggesting that cannabis preparations, in the hands of doctors, could do for their patients much of what the brownies did for grandma. The brain of an Alzheimer's sufferer contains abnormal deposits called "tangles" and "plaques." Associated with these deposits are proteins, or bits of them, called tau and amyloid-beta (Ass) respectively. Healthy tau plays a structural role in brain cells, but there is good evidence that in Alzheimer's disease, it becomes festooned with atoms of phosphorus and oxygen, like lights on a Christmas tree. It is thought to be this that tips tau into tangles. Milton has evidence that something similar happens to Ass in plaques, and that this, in turn, makes it toxic to brain cells. In research to be published in the journal Neuroscience Letters, and which he will also present at next month's neurobiology of aging conference in Florida, he reports that cannabinoids - cannabis-like compounds that occur naturally in the brain - can stop Ass killing cells. "My basic hypothesis," he says, "is that Ass is taken up into neurons, where it is phophorylated [garlanded, like tau, with phosphorus and oxygen] and kills them. It's this toxic action that cannabinoids prevent." Milton discovered this by incubating human neurons in culture, and then poisoning them with Ass. When he added cannabinoids to the brew, Ass was apparently no longer toxic. Milton describes a complex "protective signalling pathway inside neurons" that he thinks is activated by the cannabinoids. Other compounds with similar properties do exist, and one of particular interest is corticotrophin releasing hormone (CRH). Like cannabinoids, CRH is made within the brain and is reportedly reduced in people with Alzheimer's disease. This is of particular interest to Milton because, he says: "If it turns out that reduced CRH is fundamental to the disease process, then the brain may be losing one of its innate protective mechanisms. People with high natural levels of cannabinoids in their brains might then be protected against Alzheimer's disease." And the next question follows like, well, smoke after lighting up: Are we set to see a generation, or indeed generations, of cannabis smokers immune to Alzheimer's disease? Milton says not, because his research shows not only the ability of cannabinoids to protect against brain cell death in Alzheimer's disease, but also that too much of them is toxic. Dr Richard Harvey, director of research at the Alzheimer's Society, says: "There's no epidemiological data on whether exposure to cannabis in humans affects the risk of developing dementia, and it may be difficult to collect such data." But Harvey calls Milton's research "very interesting", adding that: "Clearly in the test tube, cannabinoids have the ability to block at least one of the probable causal mechanisms in Alzheimer's disease and so become a potential treatment or preventative agent that needs to be tested in humans." . Alzheimer's Society helpline: 0845 300 0336 - --- MAP posted-by: Beth