大麻がアルツハイマー病の記憶障害に効果あり?/マリファナ THC

 マリファナは記憶に良いとはされず、短期的には記憶呼び出し障害をきたすとされている。いくつかの研究では、長期大量服用で記憶障害を引きおこすとされる。
画像 しかし、新たな研究で、マリファナの有効成分であるTHC(テトラヒドロカンナビノール)がアルツハイマー病の記憶障害を予防し、改善する可能性もあるという。
 THCと同じ脳受容器に影響する化合物が年長のマウス(人でいうと65-70才に相当)で脳の炎症を抑え、記憶を改善するとわかった。アルツハイマー病では脳内の炎症は痴呆をきたす過程で重要な役割を果たす。
 イブプロフェンなどの抗炎症剤であるNSAIDsは若い脳には効果を示すが、老人脳にはWIN-55・212-2化合物と異なり効果がない。
 WIN-55,212-2化合物は老人マウスで新たな脳細胞の成長を促進する。神経再生という驚異的な発見であり、こうした働きをする薬剤はプロザックのようなSSRI抗うつ剤のみである。
 記憶を障害させるとはっきりしている薬剤が長期的にみて記憶を保護する作用を持っているのは、若年脳と老化脳の学習方法の違いによると仮説を立てている。
 神経伝達物質グルタミン酸glutamateが新たな細胞とその接続の成長させ、古いものを壊す過程で記憶保持に関係している。memantineなどのいくつかのアルツハイマー病治療薬はTHC同様、グルタミン酸に影響を及ぼしている。
 このプロセスは若いときはバランスがとれているため、成長と破壊を妨げると記憶障害をおこし、年をとると破壊のプロセスを妨げることで障害よりも補助に役立つと考えている。
 マリファナのちょうど一服が最適量ではないかと概算される。夜寝る前の一服なら、長期使用によっても障害は少ないだろう。

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大麻の成分が乳ガンに効果あり
http://kurie.at.webry.info/200711/article_31.html
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Marijuana's Memory Paradox
Are pot smokers less likely to get Alzheimer's? A compound similar to the active ingredient in cannabis shows promise as a potential memory protector.
By Maia Szalavitz for MSN Health & Fitness
http://health.msn.com/health-topics/alzheimers-disease/articlepage.aspx?cp-documentid=100230518


Marijuana isn't known for being a friend to memory; its short-term effects notoriously impair recall. And although the data is conflicting, some studies link cannabis with memory deficits in those who use excessive doses for long periods of time

But new research suggests that one of the active ingredients in marijuana―THC―and similar compounds could possibly prevent or even reverse one of the most devastating memory disorders of all: Alzheimer's disease.

In a paper published in the December 2008 issue of the journal Neurobiology of Aging, researchers found that a compound that affects the same brain receptors as THC reduced brain inflammation and improved memory in older rats. (The rodents were the human equivalent of age 65 to 70.) Although there's debate over the role played by inflammation in Alzheimer's, many researchers believe it's an important part of the process that causes dementia.

"We were shocked and surprised that it worked," says Gary Wenk, Ph.D., one of the study's authors and a professor of psychology and neuroscience at Ohio State University.

Wenk and his colleagues traced the anti-inflammatory effect of the compound (which has the awkward name "WIN-55,212-2") to its activation of cannabinoid receptors on brain cells―the same receptors activated by THC.

Other anti-inflammatory compounds studied in rats and humans like NSAID drugs (ibuprofen, etc.) showed effects on young brains, but unlike WIN-55,212-2 did not improve aged brains.

Wenk has also found in these older rats that the WIN-55,212-2 compound promotes the growth of new brain cells―a process that declines and may even stop in older animals. "The most amazing thing we saw was that it re-initiates neurogenesis―usually, the only drugs that do that are the SSRI antidepressants [selective serotonin re-uptake inhibitors, the class of drugs that includes Prozac]."

Timing is everything

How could a drug that clearly impairs memory while people are under its influence function to protect users' recall in the long term? Wenk theorizes that this could be due to differences in the way young and old brains learn.

Research shows that the neurotransmitter glutamate is involved in storing memory in a process that involves growing both new cells and connections between them, and destroying old ones. Some current Alzheimer's drugs like memantine affect glutamate―as does THC.

Early in life, this process is in balance, and so interfering with either the growth or the "pruning back" of brain cells and connections―as might occur from using marijuana―might impair memory. But, says Wenk, "The same systems involved in pruning neurons at the beginning of life could be killing them at the end." Therefore, interfering with the pruning process later in life might actually help, rather than harm.

No need for a high

Rest assured, Wenk and his colleagues aren't advocating a stoner lifestyle.

Because WIN-55,212-2, like THC, produces a high, the researchers looked for the lowest effective dose. They estimate that that dose is the equivalent to just one toke of marijuana. "A puff is enough," Wenk says.

Though that dose wouldn't get someone high, it could, admittedly, have some psychoactive effect. But this wouldn't necessarily rule out medical use. The drug could be taken before bedtime, for example. And with long-term use, tolerance to these psychoactive effects can develop, so impairment might be minimal with a steady dose anyway.

Cannabis research is controversial

To find out if THC has a protective effect on humans, scientists could study marijuana smokers as they age. If the theory holds, such users might be expected to develop Alzheimer's disease at lower rates than non-users―although the timing and extent of use would almost certainly also matter.

Given the controversy that would likely arise if a protective effect were to be discovered, however, no one has funded the epidemiological studies that would be needed to show this.

It's even hard to get experimental research published, according to Kim Janda, Professor of Chemistry at the Scripps Research Institute in California. In 2006, he published a paper demonstrating that THC interfered with another process implicated in the pathology of Alzheimer's disease: the formation of amyloid-beta plaques and fibrils.

Janda's THC research was rejected by several big-name journals and eventually published in the journal Molecular Pharmacology; it's now one of his most frequently cited articles by fellow scientists. Unfortunately, the article was also denounced in the press by the likes of Rush Limbaugh as an example of politicized science by hidden supporters of legalization―despite the fact that Janda also works on anti-cocaine addiction vaccines.

Although Janda would like to investigate further, he currently does not have grants to enable him to do so.

Why further marijuana studies should be funded

Bill Thies, Ph.D., chief medical and scientific Officer of the Alzheimer's Association, says of Wenk's research, "The authors of the paper make the case that one way to modulate the inflammatory reaction is to activate cannabinoid receptors. I think that's perfectly reasonable basic science."

Thies notes, however, that it's a long way from basic science to a usable drug, and pleads for a rational discussion. "The issue of marijuana is highly emotional and political and the minute it's put in context of legalizing marijuana, the discussion loses all sensible aspects."

Don Abrams, M.D., chief of hematology/oncology at San Francisco General Hospital, has studied medical marijuana use in people with HIV for more than a decade. He says, "I think the safety profile of marijuana compares very favorably to many other prescribed drugs," noting that there have not been any reported overdoses, and that most research does not support a link between smoking the drug and lung cancer (which may be because marijuana users tend to not smoke nearly as much as cigarette smokers).

"Cannabis is anti-inflammatory and it is also an antioxidant, and those are two things that we seek in treating neurodegenerative disorders," he says, "It's there, it's in nature, if the research does find that it has these benefits, why not take advantage of it?"

With five million Americans currently living with Alzheimer's and no highly effective treatment or prevention method known, any promising lead―even one as politically fraught as marijuana and related synthetics―could be worth following.

Comment: Do we need more research on marijuana's potential medicinal effects?


Maia Szalavitz is a journalist and author who covers the intersection between mind, brain and behavior. She is a senior fellow at Stats.org, a media watchdog organization, which investigates coverage of science and statistics. Her own experience as a former heroin and cocaine addict brings a unique perspective to her work. She's a regular contributor to Brain & Body. Her most recent book, co-written with leading child trauma expert Bruce D. Perry, M.D., Ph.D., is The Boy Who Was Raised as a Dog and Other Stories from a Child Psychiatrist's Notebook: What Traumatized Children Can Teach Us About Loss, Love and Healing (Basic, 2007).

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Cannabinoid receptor stimulation is anti-inflammatory and improves memory in old rats
Neurobiology of Aging, Volume 29, Issue 12, December 2008, Pages 1894-1901
Yannick Marchalant, Francesca Cerbai, Holly M. Brothers, Gary L. Wenk

Abstract
The number of activated microglia increase during normal aging. Stimulation of endocannabinoid receptors can reduce the number of activated microglia, particularly in the hippocampus, of young rats infused chronically with lipopolysaccharide (LPS). In the current study we demonstrate that endocannabinoid receptor stimulation by administration of WIN-55212-2 (2 mg/kg day) can reduce the number of activated microglia in hippocampus of aged rats and attenuate the spatial memory impairment in the water pool task. Our results suggest that the action of WIN-55212-2 does not depend upon a direct effect upon microglia or astrocytes but is dependent upon stimulation of neuronal cannabinoid receptors. Aging significantly reduced cannabinoid type 1 receptor binding but had no effect on cannabinoid receptor protein levels. Stimulation of cannabinoid receptors may provide clinical benefits in age-related diseases that are associated with brain inflammation, such as Alzheimer's disease.
Article Outline

1. Introduction
2. Methods

2.1. Subjects and surgical procedures
2.2. Water pool testing
2.3. Histological procedures
2.4. Double immunofluorescence staining
2.5. Western blots
2.6. [3H] SR141716A in vitro binding

3. Results

3.1. Behavior
3.2. Histology
3.3. Regional microglia cell counts
3.4. CB1 receptors
3.5. No co-localization between CB1 receptors and resting or activated microglial cells
3.6. No co-localization between CB1 and astrocytes
3.7. Co-localization between CB1 and neurons

4. Discussion
Conflict of interest
Disclosure statement
Acknowledgements
References

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