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