Alzheimer’s: Marijuana as Effective Medicine

“Cannabis is getting much positive publicity and seems to be regaining its popularity of one hundred years ago when it was the most widely used drug for about 100 different diseases. There is a big toodoo nowadays about Alzheimers which has turned into almost an epidemic for old folks with some even in their 50’s. So far nobody seems to have put a handle on it and I won’t either.The latest information seems to be that there are senile plaques in the cerebral cortex and subcortical grey matter but whether these plaques are a cause or effect seems to be up for grabs.

I don’t know either. My Merck manual says that four million Americans have it, mostly those over 60 years old. It is a very expensive disease for nursing homes and nursing care probably at least 100 billion dollars per year.

As a Medical Marijuana doctor, I jumped into this fracas when I heard that a lady spouse of an Alzheimers patient went to a Medical Marijuana Advisory Committee meeting of The Oregon Medical Marijuana Program (OMMP) and demanded that her husband be given a permit. She was successful and the medical statistics from OMMP indicate that somewhat less than 50 people have Marijuana permits for this disease. It is called Alzheimers Rage.

The above really didn’t surprise me because there are several Central Nervous System (CNS) diseases for which Cannabis/Marijuana (C/MJ) works very well. These include ALS, Epilepsy, Multiple Sclerosis, Parkinsonism, PTSD and Traumatic Brain Injuries (TBIs). I don’t know if anyone has figured out why C/MJ works for these conditions but why ask if those suffering say that C/MJ works.

Tod Mikiyuria, the foremost scholar in this area, says that C/MJ works as a modulator which is a term of general meaning which possibly just means that it works.

The standard drugs are almost worthless, many seem to be Cholinergics related to Acetyl Choline, the standard Neuro transmitter nerve cell to cell and nerve cell to muscle. At any rate C/MJ seems to work better than any of the heavily advertised drugs.

Cannabis/Marijuana is simultaneously getting much positive publicity and seems to be regaining its popularity of one hundred years ago when it was the most widely used drug for about 100 different diseases.

Those of us advocates for Medical Marijuana who have suffered scorn and derision for DEVIL WEED causing REEFER MADNESS can finally say

WE TOLD YOU SO!!!” –
 
Dr. Phil Leveque 
 

Marijuana and Alzheimer’s – How Marijuana Outperforms Drugs for Alzheimer’s Disease

“Marijuana and Alzheimer’s – Alzheimer’s Help without Nasty Drug-Induced Side Effects.”

marijuanaplants 235x147 Marijuana and Alzheimers   How Marijuana Outperforms Drugs for Alzheimer’s Disease

“The war on drugs has most people believing there is no legitimate argument for marijuana, causing it to be highly looked down upon and illegal under federal law throughout the United States. But there is an exceptionally large body of research pointing to the positive impact marijuana can have on various health ailments, with recent research revealing a link between marijuana and Alzheimer’s – showing that THC, the psychoactive component of marijuana, may be beneficial for Alzheimer’s patients.

As published in the journal Molecular Pharmacology, a Skaggs Institute for Chemical Biology study shows that Δ9-tetrahydrocannabinol (THC) both “competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid β-peptide (Aβ) aggregation.” In other words, cannabinoid molecules found in cannabis could halt the progression of Alzheimer’s disease.”

Read more by  : http://naturalsociety.com/marijuana-and-alzheimers-outperforms-harmful-drugs/

“A Molecular Link Between the Active Component of Marijuana and Alzheimer’s Disease Pathology” – Free full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562334/

Cannabidiol affects the expression of genes involved in zinc homeostasis in BV-2 microglial cells.

“Cannabidiol (CBD) has been shown to exhibit anti-inflammatory, antioxidant and neuroprotective properties. Unlike Δ(9)-tetrahydrocannabinol (THC), CBD is devoid of psychotropic effects and has very low affinity for both cannabinoid receptors, CB(1) and CB(2). We have previously reported that CBD and THC have different effects on anti-inflammatory pathways in lipopolysaccharide-stimulated BV-2 microglial cells, in a CB(1)/CB(2) independent manner. Moreover, CBD treatment of BV-2 cells, was found to induce a robust change in the expression of genes related to oxidative stress, glutathione deprivation and inflammation. Many of these genes were shown to be controlled by Nrf2 and ATF4 transcription factors. Using the Illumina MouseRef-8 BeadChip platform, DAVID Bioinformatics and Ingenuity Pathway Analysis, we identified functional sets of genes and networks affected by CBD. A subset of genes was found to be regulated by the metal responsive element (MRE)-binding transcription factor-1 (MTF-1) and is shown to be related to zinc homeostasis. We found that CBD upregulates the expression of the mRNAs for metallothionein 2 (Mt2), N-myc-downstream regulated gene 1 and matrix metalloproteinase 23 as well as of the zinc transporters ZnT1/Slc30a1 and Zip4/Slc39a4 but downregulates the expression of the mRNA for the zinc transporter Zip10/Slc39a10 as well as for the zinc finger protein 472. Among these genes, ZnT1, Mt2 and the zinc transporters ZIPs are known to function together to control the intracellular zinc concentration. These results show that CBD, but much less so THC, affects the expression of genes involved in zinc homeostasis and suggest that the regulation of zinc levels could have an important role through which CBD may exert its antioxidant and anti-inflammatory effects.”

http://www.ncbi.nlm.nih.gov/pubmed/22178458

Cannabidiol as an Emergent Therapeutic Strategy for Lessening the Impact of Inflammation on Oxidative Stress

Figure 1

“Growing evidence suggests that the endocannabinoid system, which includes the CB1 and CB2 G protein-coupled receptors and their endogenous lipid ligands, may be an area that is ripe for therapeutic exploitation. In this context, the related nonpsychotropic cannabinoid cannabidiol, which may interact with the endocannabinoid system, but has actions that are distinct, offers promise as a prototype for anti-inflammatory drug development.

This review discusses recent studies suggesting that cannabidiol may have utility in treating a number of human diseases and disorders now known to involve activation of the immune system and associated oxidative stress, as a contributor to their etiology and progression. These include rheumatoid arthritis, types I and II diabetes, atherosclerosis, Alzheimer’s disease, hypertension, the metabolic syndrome, ischemia-reperfusion injury, depression, and neuropathic pain.

Cannabidiol (CBD) is the major nonpsychotropic cannabinoid compound derived from the plant Cannabis sativa, commonly known as marijuana…

Conclusions

Inflammation and oxidative stress are intimately involved in the genesis of many human diseases. Unraveling that relationship therapeutically has proven challenging, in part because inflammation and oxidative stress “feed off” each other. However, CBD would seem to be a promising starting point for further drug development given its anti-oxidant (although relatively modest) and anti-inflammatory actions on immune cells, such as macrophages and microglia. CBD also has the advantage of not having psychotropic side effects. Studies on models of human diseases support the idea that CBD attenuates inflammation far beyond its antioxidant properties, for example, by targeting inflammation-related intracellular signaling events. The details on how CBD targets inflammatory signaling remain to be defined.

The therapeutic utility of CBD is a relatively new area of investigation that portends new discoveries on the interplay between inflammation and oxidative stress, a relationship that underlies tissue and organ damage in many human diseases.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085542/

Cannabidiol: a promising drug for neurodegenerative disorders?

“Neurodegenerative diseases represent, nowadays, one of the main causes of death in the industrialized country. They are characterized by a loss of neurons in particular regions of the nervous system. It is believed that this nerve cell loss underlies the subsequent decline in cognitive and motor function that patients experience in these diseases. A range of mutant genes and environmental toxins have been implicated in the cause of neurodegenerative disorders but the mechanism remains largely unknown. At present, inflammation, a common denominator among the diverse list of neurodegenerative diseases, has been implicated as a critical mechanism that is responsible for the progressive nature of neurodegeneration.

Since, at present, there are few therapies for the wide range of neurodegenerative diseases, scientists are still in search of new therapeutic approaches to the problem. An early contribution of neuroprotective and antiinflammatory strategies for these disorders seems particularly desirable because isolated treatments cannot be effective.

 In this contest, marijuana derivatives have attracted special interest, although these compounds have always raised several practical and ethical problems for their potential abuse. Nevertheless, among Cannabis compounds, cannabidiol (CBD), which lacks any unwanted psychotropic effect, may represent a very promising agent with the highest prospect for therapeutic use.”

http://www.ncbi.nlm.nih.gov/pubmed/19228180

Israeli Research Shows Cannabidiol May Slow Alzheimer’s Disease

“An Israeli researcher has found that a non-psychoactive component of cannabis may help slow the progression of Alzheimer’s disease. The initial findings of a study at the Hebrew University of Jerusalem show that a non-psychoactive component of cannabis, marijuana, may hold out hope for slowing down the progression of Alzheimer’s disease.The research, still at an early stage, indicates that memory loss, the first and primary symptom of Alzheimer’s disease, can be slowed down significantly in mice by cannabidiol. Alzheimer’s disease, the most common form of dementia, affects some 24.3 million people worldwide.”

Read more: http://www.israelnationalnews.com/News/News.aspx/125564

Cannabidiol Reduces Aβ-Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPARγ Involvement

“CBD blunted neuroinflammation sustained by astrocytes through PPARγ selective activation in vitro and in vivo.

Results from the present study prove the selective involvement of PPARγ in the anti-inflammatory and neuroprotective effects of CBD here observed either in vitro and in vivo. In addition, CBD significantly promoted neurogenesis in Aβ injured rat hippocampi, much expanding its already wide spectrum of beneficial actions exerted in AD models, a non negligible effect, due to its capability to activate PPARγ.

In conclusion, results of the present research demonstrate that CBD may exert protective functions through a PPARγ dependent activation, which leads to a reduction in reactive gliosis and consequently in neurodegeneration. Moreover, in the current experimental conditions this phytocannabinoid appears to stimulate neurogenesis since it increases DCX immunopositive cell proliferation rate in rat DG.

Innovative therapeutic approaches which could significantly improve AD course require new molecules that will be able to have an impact on different pathological pathways, which converge at the progressive neurological decline. CBD has shown a capability to profoundly reduce reactive astrogliosis and to guarantee both direct and indirect neuronal protection in Aβ induced neuroinflammation/neurodegeration. So far, the lack of understanding of the precise molecular mechanism involved in CBD pharmacological actions, has had limited interest and has puzzled investigators.

Currently, findings of the present study throw some light on the issue, and frame CBD as a new PPARγ activator.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230631/

The Cannabinoid CB2 Receptor as a Target for Inflammation-Dependent Neurodegeneration

“THE CANNABINOID CB2 RECEPTOR AS A BIORATIONAL TARGET FOR THE TREATMENT OF NEURODEGENERATION. The presence of CB2 receptors in microglia in the human Alzheimer’s diseased brain suggests that CB2 may provide a novel target for a range of neuropathologies.

 The first approved cannabinoid drugs were analogues of Δ9-tetrahydrocannabinol (Δ9-THC). Dronabinol is a natural isomer of THC that is found in the cannabis plant, and Marinol contains synthetic dronabinol. Marinol, and another analogue nabilone (Cesamet ) are used to prevent nausea and vomiting after treatment with anti-cancer medicines. More recently, GW-100 (Sativex) which combines nearly equal amounts of Δ9-THC and cannabidiol in a whole plant extract from cultivated cannabis, has been approved in Canada…

We conclude that the administration of CB2 agonists and antagonists may differentially alter microglia-dependent neuroinflammation. CB2 specific compounds have considerable therapeutic appeal over CB1 compounds, as the exclusive expression of CB2 on immune cells within the brain provides a highly specialised target, without the psychoactivity that plagues CB1 directed therapies.

In addition, CB2 activation appears to prevent or decrease microglial activation.

In a rodent model of Alzheimer’s disease microglial activation was completely prevented by administration of a selective CB2 agonist.”

http://www.ncbi.nlm.nih.gov/pubmed/18615177

Cannabinoid CB2 receptors in human brain inflammation.

“CB2 receptors in neuroinflammatory conditions of the human brain.

“CB2 receptors have been found to be present in the CNS, thus offering new opportunities for the pharmacological use of cannabinoid agents. Furthermore, the fact that their expression is increased by inflammatory stimuli suggests that they may be involved in the pathogenesis and/or in the endogenous response to injury. Data obtained in vitro and in animal models show that CB2 receptors may be part of the general neuroprotective action of the ECS…

The anti-inflammatory effects triggered by the activation of the CB2 receptor make it an attractive target for the development of novel anti-inflammatory therapies.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219537/

Pot joins the fight against Alzheimer’s, memory loss

“The researchers ducked the obvious question of whether it might be simpler, faster and cheaper to simply light up a joint. “Could people smoke marijuana to prevent Alzheimer’s disease if the disease is in their family?” Wenk said in a statement. “We’re not saying that, but it might actually work.””

http://www.scientificamerican.com/blog/post.cfm?id=pot-joins-the-fight-against-alzheim-2008-11-19