Archive for the ‘Alzheimer’s’ Category

Marijuana Ingredient May Help Alzheimer’s

Chemical Counters Brain Problems in Alzheimer’s Disease, Says Spanish Study
By Miranda Hitti
WebMD Health News

Feb. 23, 2005 — New clues about Alzheimer’s disease have emerged from a Spanish study of marijuana. The drug’s active ingredients — cannabinoids — help prevent brain problems seen in Alzheimer’s, say the scientists.

There is no cure for Alzheimer’s disease, which progressively damages brain areas involved in memory, judgment, language, and behavior. Alzheimer’s disease is the most common form of mental decline, or dementia, in older adults.

The new study didn’t test cannabinoids on people living with Alzheimer’s disease. Instead, the researchers focused on human brain tissue samples and conducted cannabinoid experiments on rats.

The findings showed that “cannabinoids work both to prevent inflammation and to protect the brain,” says researcher Maria de Ceballos in a news release. That “may set the stage for [cannabinoids'] use as a therapeutic approach for [Alzheimer's disease].”

A staff member at Madrid’s Cajal Institute, de Ceballos conducted the study with colleagues from nearby Complutense University. Their results appear in the Feb. 23 edition of The Journal of Neuroscience.

Marijuana, Alzheimer’s Disease, and the Human Brain

The researchers studied human brain tissue samples, some of which were from deceased Alzheimer’s patients and some from normal brain tissue.

The typical features seen in the brain tissue of Alzheimer’s disease are called plaques. Plaques are protein clumps that are seen outside brain cells, and they have been shown to activate inflammation seen in brain tissue of Alzheimer’s disease patients.

Besides the typical plaques seen with Alzheimer’s disease, the brain tissues taken from Alzheimer’s patients also had many fewer cannabinoid receptors.

Significant changes in the location, expression, and function of cannabinoid receptors may play a role in Alzheimer’s disease, write the researchers.

That could mean that the patients had lost the capacity to experience cannabinoids’ protective effects, says the news release.

Marijuana and Alzheimer’s Mental Decline

The researchers also injected rats with a protein called beta-amyloid, which gave the rats an Alzheimer’s-like brain condition.

Some of the same rats were also injected with a cannabinoid. For comparison, other rats got injections of an unrelated protein along with beta-amyloid.

After two months, the rats were tested for learning, memory, and mental functions. The researchers tried to train them to find a platform in a tank of water. The rats had two minutes to find the platform. If they failed, the researchers briefly put the rats on the platform. Four times a day for five days, the rats practiced.

By the fifth day, the rats that received the cannabinoid injections were able to find the platform on their own. Those that didn’t get the cannabinoid injections didn’t learn to find the platform.

Another interesting result also surfaced. The cannabinoids completely prevented activation of cells that trigger inflammation. These cells gather near plaque and are believed to be involved in the development of Alzheimer’s disease.

“Our results indicate that cannabinoid receptors are important in the pathology of Alzheimer’s disease and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease,” write the researchers in the journal.

They plan to focus future studies on a cannabinoid receptor that’s unrelated to marijuana’s “high,” says the news release.

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Marijuana may block Alzheimer’s

The active ingredient in marijuana may stall decline from Alzheimer’s disease, research suggests. Scientists showed a synthetic version of the compound may reduce inflammation associated with Alzheimer’s and thus help to prevent mental decline.

They hope the cannabinoid may be used to developed new drug therapies.

The research, by Madrid’s Complutense University and the Cajal Institute, is published in the Journal of Neuroscience.

o Marijuana may block Alzheimers
start quote rb Marijuana may block Alzheimers We would warn the public against taking marijuana as a way of preventing Alzheimer’s end quote rb Marijuana may block Alzheimers
Dr Susanne Sorensen

The scientists 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 brain cell receptors to which cannabinoids bind, allowing their effects to be felt.

They also studied structures called microglia, which activate the brain’s immune response.

Microglia collect near the plaque deposits associated with Alzheimer’s disease and, when active, cause inflammation.

The researchers found a dramatically reduced functioning of cannabinoid receptors in diseased brain tissue.

This was an indication that patients had lost the capacity to experience cannabinoids’ protective effects.

The next step was to test the effect of cannabinoids on rats injected with the amyloid protein that forms Alzheimer’s plaques.

Those animals who were also given a dose of a cannabinoid performed much better in tests of their mental functioning.

The researchers found that the presence of amyloid protein in the rats’ brains activated immune cells.

However, rats that also received the cannabinoid showed no sign of microglia activation.

Using cell cultures, the researchers confirmed that cannabinoids counteracted the activation of microglia and thus reduced inflammation.

Drug target

Researcher Dr Maria de Ceballos said: “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.”

Dr Susanne Sorensen, head of research at the Alzheimer’s Society, said: “This is important research because it provides another piece of the jigsaw puzzle on the workings of the brain.

“There is no cure for Alzheimer’s disease, so the identification of another target for drug development is extremely welcome.

“The Alzheimer’s Society looks forward to seeing further research being carried out on cannabinoid receptors as drug targets for Alzheimer’s disease but would warn the public against taking marijuana as a way of preventing Alzheimer’s.

“It is now generally recognised that as well as providing a ‘high’, long-term use of marijuana can also lead to depression in many individuals.”

Different receptors

Harriet Millward, of the Alzheimer’s Research Trust, said there were two main types of cannabinoid receptor, CR1 and CR2.

“It is CR1 that produces most of the effects of marijuana, including the harmful ones.

“If it is possible to make drugs that act only on CR2, as suggested by the authors of this study, they might mimic the positive effects of cannabinoids without the damaging ones of marijuana.

“However, this is a fairly new field of research and producing such selective drugs is not an easy task.

“There is also no evidence yet that cannabinoid-based drugs can slow the decline in human Alzheimer’s patients.”

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Marijuana reduces memory impairment

The more research they do, the more evidence Ohio State University scientists find that specific elements of marijuana can be good for the aging brain by reducing inflammation there and possibly even stimulating the formation of new brain cells.

The research suggests that the development of a legal drug that contains certain properties similar to those in marijuana might help prevent or delay the onset of Alzheimer’s disease. Though the exact cause of Alzheimer’s remains unknown, chronic inflammation in the brain is believed to contribute to memory impairment.

Any new drug’s properties would resemble those of tetrahydrocannabinol, or THC, the main psychoactive substance in the cannabis plant, but would not share its high-producing effects. THC joins nicotine, alcohol and caffeine as agents that, in moderation, have shown some protection against inflammation in the brain that might translate to better memory late in life.

“It’s not that everything immoral is good for the brain. It’s just that there are some substances that millions of people for thousands of years have used in billions of doses, and we’re noticing there’s a little signal above all the noise,” said Gary Wenk, professor of psychology at Ohio State and principal investigator on the research.

Wenk’s work has already shown that a THC-like synthetic drug can improve memory in animals. Now his team is trying to find out exactly how it works in the brain.

The most recent research on rats indicates that at least three receptors in the brain are activated by the synthetic drug, which is similar to marijuana. These receptors are proteins within the brain’s endocannabinoid system, which is involved in memory as well as physiological processes associated with appetite, mood and pain response.

This research is also showing that receptors in this system can influence brain inflammation and the production of new neurons, or brain cells.

“When we’re young, we reproduce neurons and our memory works fine. When we age, the process slows down, so we have a decrease in new cell formation in normal aging. You need those cells to come back and help form new memories, and we found that this THC-like agent can influence creation of those cells,” said Yannick Marchalant, a study coauthor and research assistant professor of psychology at Ohio State.

Marchalant described the research in a poster presentation Wednesday (11/19) at the Society for Neuroscience meeting in Washington, D.C.

Knowing exactly how any of these compounds work in the brain can make it easier for drug designers to target specific systems with agents that will offer the most effective anti-aging benefits, said Wenk, who is also a professor of neuroscience and molecular virology, immunology and medical genetics.

“Could people smoke marijuana to prevent Alzheimer’s disease if the disease is in their family? We’re not saying that, but it might actually work. What we are saying is it appears that a safe, legal substance that mimics those important properties of marijuana can work on receptors in the brain to prevent memory impairments in aging. So that’s really hopeful,” Wenk said.

One thing is clear from the studies: Once memory impairment is evident, the treatment is not effective. Reducing inflammation and preserving or generating neurons must occur before the memory loss is obvious, Wenk said.

Marchalant led a study on old rats using the synthetic drug, called WIN-55212-2 (WIN), which is not used in humans because of its high potency to induce psychoactive effects.

The researchers used a pump under the skin to give the rats a constant dose of WIN for three weeks – a dose low enough to induce no psychoactive effects on the animals. A control group of rats received no intervention. In follow-up memory tests, in which rats were placed in a small swimming pool to determine how well they use visual cues to find a platform hidden under the surface of the water, the treated rats did better than the control rats in learning and remembering how to find the hidden platform.

“Old rats are not very good at that task. They can learn, but it takes them more time to find the platform. When we gave them the drug, it made them a little better at that task,” Marchalant said.

In some rats, Marchalant combined the WIN with compounds that are known to block specific receptors, which then offers hints at which receptors WIN is activating. The results indicated the WIN lowered the rats’ brain inflammation in the hippocampus by acting on what is called the TRPV1 receptor. The hippocampus is responsible for short-term memory.

With the same intervention technique, the researchers also determined that WIN acts on receptors known as CB1 and CB2, leading to the generation of new brain cells – a process known as neurogenesis. Those results led the scientists to speculate that the combination of lowered inflammation and neurogenesis is the reason the rats’ memory improved after treatment with WIN.

The researchers are continuing to study the endocannabinoid system’s role in regulating inflammation and neuron development. They are trying to zero in on the receptors that must be activated to produce the most benefits from any newly developed drug.

What they already know is THC alone isn’t the answer.

“The end goal is not to recommend the use of THC in humans to reduce Alzheimer’s,” Marchalant said. “We need to find exactly which receptors are most crucial, and ideally lead to the development of drugs that specifically activate those receptors. We hope a compound can be found that can target both inflammation and neurogenesis, which would be the most efficient way to produce the best effects.”

The National Institutes of Health supported this work.

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A TOKE A DAY KEEPS MEMORY LOSS AT BAY

Small Doses of Marijuana Improve the Function of Aging Brains, Scientists Find

Turns out a few dances with Mary Jane can do wonders for an aging brain.

Yes, a daily toke in later-middle and old age can help slow memory loss, or the onset of diseases such as Alzheimer’s, Parkinson’s and multiple sclerosis, a new study suggests.

It’s a pre-emptive strike, one not effective at reversing previous memory loss.  But aging boomers still shouldn’t go overboard, researchers say.  In tests on lab rats, all it took was the equivalent of one human puff.

“We are not trying to make anyone high,” said Gary Wenk, professor of psychology and neuroscience at Ohio State University.  “We are trying to tease out the positive aspects of this plant.”

The benefit was found in a synthetic compound identical to tetrahydrocannabinol, or THC, the psychoactive substance in marijuana, which researchers say activated areas of aged brains in rats affected by memory loss, and stimulated the formation of new brain cells.

Prof.  Wenk, who presented the research in Washington, yesterday at the annual meeting of the Society for Neuroscience, was motivated to look into the effects of marijuana on aging brains after repeatedly noticing the drug mentioned on the blogs of patients with MS who use it to curb pain.  Memory impairment is connected to such chronic brain inflammation.

“There was discussion of smoking a little pot to reduce inflammation, which makes their disease less painful,” Prof.  Wenk said.

Pot is popular among older sufferers, because conventional anti-inflammatory medications are not effective in older brains.

“Millions of people have used this plant for thousands of years,” Prof.  Wenk said.  “There is a lot of evidence that there are some interesting things going on in the brains of these people.”

So, while testing with rats, researchers used a THC-like drug, called WIN-55212-2, to activate receptors in the brain’s endocannabinoid system – usually stimulated by smoking marijuana – which involves memory, appetite, mood and pain response.

After three weeks, the rats were given a memory test where they were placed in a small swimming pool to determine how well they used visual cues to find a platform hidden under the surface of the water.

The treated rats were given enough of the drug to boost brain cells, though not enough to get high, and did better in the swimming-pool test than the control – strait-laced rats without THC – in learning and remembering how to find the hidden platform.

“Old rats are not very good at that task,” said Yannick Marchalant, co-author of the study and assistant professor of psychology at Ohio State.  “When we gave them the drug, it made them a little better at that task.”

They also experienced reduced inflammation and growth of new brain cells.

The researchers hope their findings could lead to the development of a drug to stave off memory loss in people with a history of degenerative disease in their families.

“The model could be used for anyone at risk,” Prof.  Marchalant said.  “Perhaps 20 years before the usual onset of the decline in memory.”

Cannabis joins a long list of taboo substances now shown to reduce brain inflammation.  Nicotine, alcohol and caffeine have also been shown to do so, possibly leading to reduced memory loss later in life.

“What is it about coffee, what is it about smoking and what is it about marijuana that is causing us to see these effects?” Prof.  Wenk asked.  “Different compounds that may be bad for one part of the brain may be good for another.”

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