HIGH TIMES FOR ALZHEIMERS

'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 (A=DF) 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 A=DF 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 A=DF killing cells.

"My basic hypothesis," he says, "is that A=DF 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 A=DF. When he added cannabinoids to the brew, A=DF 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."

Note: Sophie Petit-Zeman on the way cannabinoids could alleviate
symptoms of degenerative diseases.

Alzheimer's Society helpline: 0845 300 0336

Source: Guardian Unlimited, The (UK)
Author: Sophie Petit-Zeman
Published: Thursday, September 26, 2002
Copyright: 2002 Guardian Newspapers Limited
Contact: letters@guardian.co.uk
Website: http://www.guardian.co.uk/