SFN: Going to Pot May Lower Alzheimer's Risk

ATLANTA, Oct. 19 -- Those years of pot smoking a generation ago may have created an unexpected legacy for baby boomers -- a lower risk of Alzheimer's disease.

That's the implication of animal research presented by Gary Wenk, Ph.D., of Ohio State University in Columbus at the Society for Neuroscience meeting here.

As the boomers hit the age where Alzheimer's begins to show itself, it may be that if "they smoked marijuana in the '60s and '70s they don't get the disease, because of that behavior," said Dr. Wenk.

He based the assertion on research he and colleagues have done with rats, not usually known for developing Alzheimer's, nor for that matter, for smoking marijuana.

But as the animals age, Dr. Wenk said, they develop inflammation in parts of the brain analogous to the parts damaged by inflammation in people with Alzheimer's.

Recent research in other fields suggested that cannabinoids -- the active ingredients in marijuana -- can cross the blood-brain barrier, even at low doses, and can reduce inflammation, Dr. Wenk said.

So, in young rats, Dr. Wenk and colleagues created brain inflammation by infusing nanogram quantities of lipopolysaccharide and then treated them with a synthetic cannabinoid called WIN-55212-2.

"We saw an 80% to 90% drop in the inflammation in the brain," he said, "and also the impairment in memory that inflammation produces could be reversed."

But that "wasn't actually a big surprise," Dr. Wenk said. Many anti-inflammatory agents have been shown to have the same effect, but only in young rats. In older animals, the effects are usually muted, perhaps by the loss of the appropriate receptors in the brain.

What was both surprising and exciting, he said, was what happened when 24-month-old rats -- equivalent to about 70 years old in human terms -- were given the cannabinoid, as doses of either 0.5 or 2.0 mg/kg of body weight.

The old rats -- like old humans -- had inflammation in some areas of the brain, as shown by activated microglia. Dr. Wenk said. When they were given the cannabinoid, "we saw a 50% to 90% drop in the number of activated microglia, depending on the area you looked at," he said.

What's more, he said, the mice improved their performance on a standard memory test -- the water maze -- by about 50%.

In the test, rats are placed in a tank of water that has a submerged platform on which they can rest. Rats usually take one or two minutes to find the platform the first time, but young rats only take a few seconds to find it again when they are subsequently replaced in the tank.

Old rats, on the other hand "typically never really get it," Dr. Wenk said.

But when treated with the cannabinoid, their performance would drop from perhaps 300 seconds to 150, he said -- an improvement, even though they weren't as quick as young rats.

The implication of the study is that treatment with an anti-inflammatory agent can restore some cognitive function and may stop the long decline in cognition that is characteristic of Alzheimer's, Dr. Wenk said.

The challenge for researchers, he said, is to find a dose of the cannabinoid that has beneficial effects but doesn't leave patients stoned.

"It's not going to do Alzheimer's patients any good if I reduce brain inflammation but leave a psychoactive drug running wild," Dr. Wenk said.