The marijuana component cannabidiol inhibits beta-amyloid-induced tau protein hyperphosphorylation through Wnt/beta-catenin pathway rescue in PC12 cells.

“Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder. A massive accumulation of beta-amyloid (Abeta) peptide aggregates has been proposed as pivotal event in AD. Abeta-induced toxicity is accompanied by a variegated combination of events including oxidative stress… Cannabidiol, a non-psychoactive marijuana component, has been recently proposed as an antioxidant neuroprotective agent in neurodegenerative diseases. Moreover, it has been shown to rescue PC12 cells from toxicity induced by Abeta peptide. Here, we report that cannabidiol inhibits hyperphosphorylation of tau protein in Abeta-stimulated PC12 neuronal cells, which is one of the most representative hallmarks in AD… These results provide new molecular insight regarding the neuroprotective effect of cannabidiol and suggest its possible role in the pharmacological management of AD, especially in view of its low toxicity in humans.”

http://www.ncbi.nlm.nih.gov/pubmed/16389547

 

Effects of cannabinoids on the immune system and central nervous system: therapeutic implications.

“Cannabinoids possess immunomodulatory activity, are neuroprotective in vivo and in vitro and can modify the production of inflammatory mediators… Cannabinoid-induced immunosuppression may have implications for the treatment of neurological disorders that are associated with excess immunological activity, such as multiple sclerosis and Alzheimer’s disease. There is anecdotal evidence that cannabis use improves the symptoms of multiple sclerosis, and studies with animal models are beginning to provide evidence for the mechanism of such effects. The development of nonpsychotropic cannabinoid analogues and modulators of the metabolism of endogenous cannabinoid ligands may lead to novel approaches to the treatment of neurodegenerative disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/18031185

Microglial interaction with beta-amyloid: implications for the pathogenesis of Alzheimer’s disease.

Abstract

“The etiology of Alzheimer’s disease (AD) involves a significant inflammatory component as evidenced by the presence of elevated levels of a diverse range of proinflammatory molecules in the AD brain. These inflammatory molecules are produced principally by activated microglia, which are found to be clustered within and adjacent to the senile plaque. Moreover, long-term treatment of patients with non-steroidal anti-inflammatory drugs has been shown to reduce risk and incidence of AD and delay disease progression. The microglia respond to beta-amyloid (Abeta) deposition in the brain through the interaction of fibrillar forms of amyloid with cell surface receptors, leading to the activation of intracellular signal transduction cascades. The activation of multiple independent signaling pathways ultimately leads to the induction of proinflammatory gene expression and production of reactive oxygen and nitrogen species. These microglial inflammatory products act in concert to produce neuronal toxicity and death. Therapeutic approaches focused on inhibition of the microglial-mediated local inflammatory response in the AD brain offer new opportunities to intervene in the disease.”

http://www.ncbi.nlm.nih.gov/pubmed/11455613

Cannabis and Alzheimer’s disease

“‘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.”

Dr Richard Harvey, research director of the Alzheimer’s Society

Read more: http://www.alzheimers.org.uk/site/scripts/news_article.php?newsID=123

Marijuana may help stave off Alzheimer’s – NBCNews

“Active ingredient in pot may help preserve brain function.

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 formation of deposits in the brain associated with the degenerative disease.

Researchers at the Scripps Research Institute in California found that marijuana’s active ingredient, delta-9-tetrahydrocannabinol, or THC, can prevent an enzyme called acetylcholinesterase from accelerating the formation of “Alzheimer plaques” in the brain 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.”

http://www.msnbc.msn.com/id/15145917/ns/health-alzheimers_disease/t/marijuana-may-help-stave-alzheimers/

Marijuana May Slow Alzheimer’s Memory Loss

“New evidence from animal models suggests marijuana may contain compounds that slow the memory loss associated with Alzheimer’s disease. Older rats treated with a synthetic chemical similar to marijuana significantly improved their ability to navigate a maze. Researchers believe the strong anti-inflammatory effects of marijuana slow Alzheimer’s progression.”

marijuanaleaves

“The link between chronic inflammation and the progression of Alzheimer’s is compelling, said Gary Wenk, a study co-author and a professor of psychology at Ohio State University.

“Inflammation in the brain is part of aging,” Wenk said. “It happens to almost all of us as we age. But in some cases, this inflammation gets out of hand and causes serious damage.”

Treatment with a synthetic compound similar to marijuana reduced inflammation in older rats in addition to making the animals “smarter,” said Wenk, who is also a professor of neuroscience and molecular virology, immunology and medical genetics.

“The compound substantially improved the memories of the older rats,” he said. “These animals were able to hold on to key details of a specific task. Untreated older rats, on the other hand, were not.”

The researchers presented their findings at the annual Society for Neuroscience meeting.

Evidence suggests that people who regularly smoked marijuana in the 1960s and 1970s rarely develop Alzheimer’s disease, said Wenk, adding that researchers are eager to develop a drug with the anti-inflammatory properties of marijuana, but without the drug’s psychoactive effects.”

Read more: http://psychcentral.com/news/2006/10/23/marijuana-may-slow-alzheimers-memory-loss/350.html

Cannabinoid Treatments: Amyotrophic Lateral Sclerosis (ALS)

“Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a fatal neurodegenerative disorder that is characterized by the selective loss of motor neurons in the spinal cord, brain stem, and motor cortex. An estimated 30,000 Americans are living with ALS, which often arises spontaneously and afflicts otherwise healthy adults. More than half of ALS patients die within 2.5 years following the onset of symptoms.

A review of the scientific literature reveals an absence of clinical trials investigating the use of cannabinoids for ALS treatment. However, recent preclinical findings indicate that cannabinoids can delay ALS progression, lending support to anecdotal reports by patients that cannabinoids may be efficacious in moderating the disease’s development and in alleviating certain ALS-related symptoms such as pain, appetite loss, depression and drooling.

Writing in the March 2004 issue of the journal Amyotrophic Lateral Sclerosis & Other Motor Neuron Disorders, investigators at the California Pacific Medical Center in San Francisco reported that the administration of THC both before and after the onset of ALS symptoms staved disease progression and prolonged survival in animals compared to untreated controls.

Additional trials in animal models of ALS have shown that the administration of other naturally occurring and synthetic cannabinoids can also moderate ALS progression but not necessarily impact survival. One recent study demonstrated that blocking the CB1 cannabinoid receptor did extend life span in an ALS mouse model, suggesting that cannabinoids’ beneficial effects on ALS may be mediated by non-CB1 receptor mechanisms.

As a result, experts are calling for clinical trials to assess cannabinoids for the treatment of ALS. Writing in the American Journal of Hospice & Palliative Medicine in 2010, a team of investigators reported, “Based on the currently available scientific data, it is reasonable to think that cannabis might significantly slow the progression of ALS, potentially extending life expectancy and substantially reducing the overall burden of the disease.” They concluded, “There is an overwhelming amount of preclinical and clinical evidence to warrant initiating a multicenter randomized, double-blind, placebo-controlled trial of cannabis as a disease-modifying compound in ALS.”

By braatahon December 25, 2012| From braatah.com
 
 
 
 

Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid.

Abstract

“Effective treatment for amyotrophic lateral sclerosis (ALS) remains elusive. Two of the primary hypotheses underlying motor neuron vulnerability are susceptibility to excitotoxicity and oxidative damage. There is rapidly emerging evidence that the cannabinoid receptor system has the potential to reduce both excitotoxic and oxidative cell damage. Here we report that treatment with Delta(9)-tetrahydrocannabinol (Delta(9)-THC) was effective if administered either before or after onset of signs in the ALS mouse model (hSOD(G93A) transgenic mice). Administration at the onset of tremors delayed motor impairment and prolonged survival in Delta(9)-THC treated mice when compared to vehicle controls. In addition, we present an improved method for the analysis of disease progression in the ALS mouse model. This logistic model provides an estimate of the age at which muscle endurance has declined by 50% with much greater accuracy than could be attained for any other measure of decline. In vitro, Delta(9)-THC was extremely effective at reducing oxidative damage in spinal cord cultures. Additionally, Delta(9)-THC is anti-excitotoxic in vitro. These cellular mechanisms may underlie the presumed neuroprotective effect in ALS. As Delta(9)-THC is well tolerated, it and other cannabinoids may prove to be novel therapeutic targets for the treatment of ALS.”

http://www.ncbi.nlm.nih.gov/pubmed/15204022

Survey of cannabis use in patients with amyotrophic lateral sclerosis.

Abstract

“Cannabis (marijuana) has been proposed as treatment for a widening spectrum of medical conditions and has many properties that may be applicable to the management of amyotrophic lateral sclerosis (ALS). This study is the first, anonymous survey of persons with ALS regarding the use of cannabis. There were 131 respondents, 13 of whom reported using cannabis in the last 12 months. Although the small number of people with ALS that reported using cannabis limits the interpretation of the survey findings, the results indicate that cannabis may be moderately effective at reducing symptoms of appetite loss, depression, pain, spasticity, and drooling. Cannabis was reported ineffective in reducing difficulties with speech and swallowing, and sexual dysfunction. The longest relief was reported for depression (approximately two to three hours).”

http://www.ncbi.nlm.nih.gov/pubmed/15055508

Cannabinol delays symptom onset in SOD1 (G93A) transgenic mice without affecting survival.

Abstract

“Therapeutic options for amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron disorder, remain limited. Emerging evidence from clinical studies and transgenic mouse models of ALS suggests that cannabinoids, the bioactive ingredients of marijuana (Cannabis sativa) might have some therapeutic benefit in this disease. However, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the predominant cannabinoid in marijuana, induces mind-altering effects and is partially addictive, compromising its clinical usefulness. We therefore tested whether cannabinol (CBN), a non-psychotropic cannabinoid, influences disease progression and survival in the SOD1 (G93A) mouse model of ALS. CBN was delivered via subcutaneously implanted osmotic mini-pumps (5 mg/kg/day) over a period of up to 12 weeks. We found that this treatment significantly delays disease onset by more than two weeks while survival was not affected. Further research is necessary to determine whether non-psychotropic cannabinoids might be useful in ameliorating symptoms in ALS.”

http://www.ncbi.nlm.nih.gov/pubmed/16183560