Marijuana may stave off Alzheimer's - U.S. study
05 Oct 2008
By Andy Sullivan

WASHINGTON, Oct 5 (Reuters) - Good news for aging hippies: smoking pot may stave off Alzheimer's disease.

New research shows that the active ingredient in marijuana may prevent the progression of the disease by preserving levels of an important neurotransmitter that allows the brain to function.

Researchers at the Scripps Research Institute in California found that marijuana's active ingredient, delta-9-tetrahydrocannabinol, or THC, can prevent the neurotransmitter acetylcholine from breaking down more effectively than commercially marketed drugs.

THC is also more effective at blocking clumps of protein that can inhibit memory and cognition in Alzheimer's patients, the researchers reported in the journal Molecular Pharmaceutics.

The researchers said their discovery could lead to more effective drug treatment for Alzheimer's, the leading cause of dementia among the elderly.

Those afflicted with Alzheimer's suffer from memory loss, impaired decision-making, and diminished language and movement skills. The ultimate cause of the disease is unknown, though it is believed to be hereditary.

Marijuana is used to relieve glaucoma and can help reduce side effects from cancer and AIDS treatment.

Possessing marijuana for recreational use is illegal in many parts of the world, including the United States, though some states allow possession for medical purposes.
source: http://www.alertnet.org/thenews/newsdesk/N05247208.htm

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Alzheimer's Disease


Alzheimer’s disease (AD) is a neurological disorder of unknown origin that is characterized by a progressive loss of memory and learned behavior. Patients with Alzheimer’s are also likely to experience depression, agitation, and appetite loss, among other symptoms. Over 4.5 million Americans are estimated to be afflicted with the disease. No approved treatments or medications are available to stop the progression of AD, and few pharmaceuticals have been FDA-approved to treat symptoms of the disease.

A review of the recent scientific literature indicates that cannabinoid therapy may provide symptomatic relief to patients afflicted with AD while also moderating the progression of the disease.

Writing in the February 2005 issue of the Journal of Neuroscience, investigators at Madrid's Complutense University and the Cajal Institute in Spain reported that the intracerebroventricular administration of the synthetic cannabinoid WIN 55,212-2 prevented cognitive impairment and decreased neurotoxicity in rats injected with amyloid-beta peptide (a protein believed to induce Alzheimer’s). Additional cannabinoids were also found to reduce the inflammation associated with Alzheimer's disease in human brain tissue in culture. "Our results indicate that … cannabinoids succeed in preventing the neurodegenerative process occurring in the disease," investigators concluded.[1]

Investigators at The Scripps Research Institute in California in 2006 reported that THC inhibits the enzyme responsible for the aggregation of amyloid plaque — the primary marker for Alzheimer's disease — in a manner "considerably superior" to approved Alzheimer's drugs such as donepezil and tacrine. "Our results provide a mechanism whereby the THC molecule can directly impact Alzheimer's disease pathology," researchers concluded. "THC and its analogues may provide an improved therapeutic [option] for Alzheimer's disease [by]... simultaneously treating both the symptoms and the progression of [the] disease."[2]

Most recently, investigators at Ohio State University, Department of Psychology and Neuroscience, reported that older rats administered daily doses of WIN 55,212-2 for a period of three weeks performed significantly better than non-treated controls on a water-maze memory test. Writing in the journal Neuroscience in 2007, researchers reported that rats treated with the compound experienced a 50 percent improvement in memory and a 40 to 50 percent reduction in inflammation compared to controls.[3]

Previous preclinical studies have demonstrated that cannabinoids can prevent cell death by anti-oxidation.[4] Some experts believe that cannabinoids’ neuroprotective properties could also play a role in moderating AD.[5] Writing in the September 2007 issue of the British Journal of Pharmacology, investigators at Ireland's Trinity College Institute of Neuroscience concluded, "[C]annabinoids offer a multi-faceted approach for the treatment of Alzheimer's disease by providing neuroprotection and reducing neuroinflammation, whilst simultaneously supporting the brain's intrinsic repair mechanisms by augmenting neurotrophin expression and enhancing neurogenesis. ... Manipulation of the cannabinoid pathway offers a pharmacological approach for the treatment of AD that may be efficacious than current treatment regimens."[6]

In addition to potentially modifying the progression of AD, clinical trials also indicate that cannabinoid therapy can reduce agitation and stimulate weight gain in patients with the disease. Most recently, investigators at Berlin Germany’s Charite Universitatmedizin, Department of Psychiatry and Psychotherapy, reported that the daily administration of 2.5 mg of synthetic THC over a two-week period reduced nocturnal motor activity and agitation in AD patients in an open-label pilot study.[7]

Clinical data presented at the 2003 annual meeting of the International Psychogeriatric Association previously reported that the oral administration of up to 10 mg of synthetic THC reduced agitation and stimulated weight gain in late-stage Alzheimer’s patients in an open-label clinical trial.[8] Improved weight gain and a decrease in negative feelings among AD patients administered cannabinoids were previously reported by investigators in the International Journal of Geriatric Psychiatry in 1997.[9] Additional study of the use of cannabinoids and Alzheimer’s would appear to be warranted.

REFERENCES

[1] Ramirez et al. 2005. Prevention of Alzheimer’s Disease pathology by cannabinoids. The Journal of Neuroscience 25: 1904-1913.

[2] Eubanks et al. 2006. A molecular link between the active component of marijuana and Alzheimer's disease pathology. Molecular Pharmaceutics (E-pub ahead of print).

[3] Marchalant et al. 2007. Anti-inflammatory property of the cannabinoid agonist WIN-55212-2 in a rodent model of chronic brain inflammation. Neuroscience 144: 1516-1522.

[4] Hampson et al. 1998. Cannabidiol and delta-9-tetrahydrocannabinol are neuroprotective antioxidants. Proceedings of the National Academy of Sciences 95: 8268-8273.

[5] Science News. June 11, 1998. “Marijuana chemical tapped to fight strokes.”

[6] Campbell and Gowran. 2007. Alzheimer's disease; taking the edge off with cannabinoids? British Journal of Pharmacology 152: 655-662.

[7] Walther et al. 2006. Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia. Physcopharmacology 185: 524-528.

[8] BBC News. August 21, 2003. “Cannabis lifts Alzheimer’s appetite.”

[9] Volicer et al. 1997. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease. International Journal of Geriatric Psychiatry 12: 913-919.

source: http://www.norml.org/index.cfm?Group_ID=7003

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Prevention of Alzheimer's Disease Pathology by Cannabinoids: Neuroprotection Mediated by Blockade of Microglial Activation

Belén G. Ramírez,1 Cristina Blázquez,2 Teresa Gómez del Pulgar,2 Manuel Guzmán,2 and María L. de Ceballos1

1Neurodegeneration Group, Cajal Institute, Consejo Superior de Investigaciones Científicas, 28002 Madrid, Spain, and 2Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040 Madrid, Spain

Alzheimer's disease (AD) is characterized by enhanced {beta}-amyloid peptide ({beta}A) deposition along with glial activation in senile plaques, selective neuronal loss, and cognitive deficits. Cannabinoids are neuroprotective agents against excitotoxicity in vitro and acute brain damage in vivo. This background prompted us to study the localization, expression, and function of cannabinoid receptors in AD and the possible protective role of cannabinoids after {beta}A treatment, both in vivo and in vitro. Here, we show that senile plaques in AD patients express cannabinoid receptors CB1 and CB2, together with markers of microglial activation, and that CB1-positive neurons, present in high numbers in control cases, are greatly reduced in areas of microglial activation. In pharmacological experiments, we found that G-protein coupling and CB1 receptor protein expression are markedly decreased in AD brains. Additionally, in AD brains, protein nitration is increased, and, more specifically, CB1 and CB2 proteins show enhanced nitration. Intracerebroventricular administration of the synthetic cannabinoid WIN55,212-2 to rats prevent {beta}A-induced microglial activation, cognitive impairment, and loss of neuronal markers. Cannabinoids (HU-210, WIN55,212-2, and JWH-133) block {beta}A-induced activation of cultured microglial cells, as judged by mitochondrial activity, cell morphology, and tumor necrosis factor-{alpha} release; these effects are independent of the antioxidant action of cannabinoid compounds and are also exerted by a CB2-selective agonist. Moreover, cannabinoids abrogate microglia-mediated neurotoxicity after {beta}A addition to rat cortical cocultures. Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.

Key words: Alzheimer's disease; {beta}-amyloid; cannabinoids; microglia; neurotoxicity; neuroprotection

Received Sep 9, 2004; revised December 28, 2004; accepted December 30, 2004.

source: http://www.jneurosci.org/cgi/content/abstract/25/8/1904

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Marijuana could prevent Alzheimer's

NEW 1/27/09

A puff a day might keep Alzheimer's away, according to marijuana research by professor Gary Wenk and associate professor Yannic Marchalant of the Ohio State Department of Psychology.

Wenk's studies show that a low dosage in the morning of a certain canavanoid, a component in marijuana, reversed memory loss in older rats' brains. In his study, an experimental group of old rats received a dosage, and a control group of rats did not. The old rats that received the drugs performed better on memory tests, and the drug slowed and prevented brain cell death. However, marijuana had the reverse effect on young rats' brains, actually impairing mental ability.

Alzheimer's is a disease unique to humans and the memory loss in the rats was a natural decline, but rat brains are similar enough to human brains to serve as partial models for humans, Wenk said.

Research on marijuana as a treatment for Alzheimer's disease began because of the drug's success in slowing progression of multiple sclerosis and reducing patients' pain, Wemk said. Alzheimer's affects a similar part of the brain that MS does.

Other research has shown that young people who take Advil regularly for arthritis, drink alcohol in moderation or smoke cigarettes reduce their risks of developing Alzheimer's as they age, but marijuana is the first substance that has worked on older brains in experiments.

Alzheimer's screening is available for people in their 30s, but it is expensive and many people do not recognize the warning signs. "People get diagnosed [with Alzheimer's] in their 60s, and they need something now," Wenk said.

Separating the benefits of marijuana from the high is a problem the researchers encountered, and Wenk said that it might not be possible. "That poses a problem, because you can't be making people with memory loss high," he said.

Research involving marijuana or any other illegal drug is controversial, and Wenk's findings are no exception. He said it is difficult to get work published, and his findings have received criticism that he is advocating a "stoner life," and praise for contributing to science. MSN, Yahoo and WBNS have all featured his research. The American Association for the Advancement of Science has recently elected Wenk as a fellow for his contributions to Alzheimer's research. "I am God and I am the devil," Wenk said.

Graduate student Holly Brothers, who worked on the research with Wenk and Marchalant, said that the scientific community does have sway on policy makers' decisions on drug use, but it is a slow process. "We accept medical use of cocaine and morphine, which are just as illicit as marijuana and extremely addictive," she said.

The FDA maintains that marijuana has no medical use. Despite this, 13 states have legalized medical marijuana.

source: http://media.www.thelantern.com/media/stor...s-3598061.shtml

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Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice.

Kuchibhotla KV, Lattarulo CR, Hyman BT, Bacskai BJ

Massachusetts General Hospital, Department of Neurology/Alzheimer's Disease Research Laboratory, 114 16th Street, Charlestown, MA 02129, USA.

Although senile plaques focally disrupt neuronal health, the functional response of astrocytes to Alzheimer's disease pathology is unknown. Using multiphoton fluorescence lifetime imaging microscopy in vivo, we quantitatively imaged astrocytic calcium homeostasis in a mouse model of Alzheimer's disease. Resting calcium was globally elevated in the astrocytic network, but was independent of proximity to individual plaques. Time-lapse imaging revealed that calcium transients in astrocytes were more frequent, synchronously coordinated across long distances, and uncoupled from neuronal activity. Furthermore, rare intercellular calcium waves were observed, but only in mice with amyloid-beta plaques, originating near plaques and spreading radially at least 200 micrometers. Thus, although neurotoxicity is observed near amyloid-beta deposits, there exists a more general astrocyte-based network response to focal pathology.

source: http://alzheimersdisease.researchtoday.net/

 

 

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