Tag Archives: cannabinoid

The endocannabinoid system and Alzheimer’s disease.

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“The importance of the role of the endocannabinoid system (ECS) in neurodegenerative diseases has grown during the past few years. Mostly because of the high density and wide distribution of cannabinoid receptors of the CB(1) type in the central nervous system (CNS), much research focused on the function(s) that these receptors might play in pathophysiological conditions.

Our current understanding, however, points to much diverse roles for this system. In particular, other elements of the ECS, such as the fatty acid amide hydrolase (FAAH) or the CB(2) cannabinoid receptor are now considered as promising pharmacological targets for some diseases and new cannabinoids have been incorporated as therapeutic tools.

 Although still preliminary, recent reports suggest that the modulation of the ECS may constitute a novel approach for the treatment of Alzheimer’s disease (AD). Data obtained in vitro, as well as in animal models for this disease and in human samples seem to corroborate the notion that the activation of the ECS, through the use of agonists or by enhancing the endogenous cannabinoid tone, may induce beneficial effects on the evolution of this disease.”

http://www.ncbi.nlm.nih.gov/pubmed/17952652

Medical Marijuana as Effective Treatment for Alzheimer’s Disease

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“Regular low dose cannabis smoking 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 cannabinoid, 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.”

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“Alzheimer’s is a disease unique to humans…, but rat brains are similar enough to human brains to serve as partial models for humans, Wenk said.

… marijuana is the first substance that has worked on older brains in experiments.”

 

Read more: http://alzheimers-review.blogspot.com/2009/11/medical-marijuana-as-effective.html

 

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

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“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

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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/

Israeli Research Shows Cannabidiol May Slow Alzheimer’s Disease

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“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

Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer’s disease brains.

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.”We have studied the status of some of the components of the endocannabinoid system, fatty acid amide hydrolase and cannabinoid CB1 and CB2 receptors, in postmortem brains from patients with Alzheimer’s disease. Our results show that both fatty acid amide hydrolase and cannabinoid CB2 receptors are abundantly and selectively expressed in neuritic plaque-associated astrocytes and microglia, respectively, whereas the expression of CB1 receptors remains unchanged. In addition, the hydrolase activity seems to be elevated in the plaques and surrounding areas.

Thus, some elements of the endocannabinoid system may be postulated as possible modulators of the inflammatory response associated with this neurodegenerative process and as possible targets for new therapeutic approaches.

To our knowledge, this report is the first evidence for the presence of CB2 receptors in the human CNS. Furthermore, these receptors have recently been reported to play an important role in microglial migration. It is important to note that we detected CB2 receptors only in microglial cells, which is in agreement with the well known immunomodulatory effects of CB2 activation. Thus, many studies have shown that CB2 receptor activation leads to a myriad of changes in the production of inflammation-related substances, although with results that vary depending on the experimental model used and the concentration of cannabinoids used.

 In any case, the selective presence of CB2 receptors in microglial cells opens new perspectives on the role of CB2 receptors in the human CNS and suggests that the modulation of their activity may have therapeutic implications.”

http://www.jneurosci.org/content/23/35/11136.long

Activation of the CB(2) receptor system reverses amyloid-induced memory deficiency.

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“Cannabinoid type 2 (CB(2)) agonists are neuroprotective and appear to play modulatory roles in neurodegenerative processes in Alzheimer’s disease. We have studied the effect of 1-((3-benzyl-3-methyl-2,3-dihydro-1-benzofuran-6-yl) carbonyl) piperidine (MDA7)-a novel selective CB(2) agonist that lacks psychoactivity-on ameliorating the neuroinflammatory process, synaptic dysfunction, and cognitive impairment 

 Our findings suggest that MDA7 is an innovative therapeutic approach for the treatment of Alzheimer’s disease.”

http://www.ncbi.nlm.nih.gov/pubmed/22795792

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

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“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.

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“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/

Marijuana linked to preventing and treating Alzheimer’s disease

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“Alzheimer’s disease is the leading cause of dementia among the elderly, and with the ever-increasing size of this population, cases of Alzheimer’s disease are expected to triple over the next 50 years. Consequently, the development of treatments that slow or halt the disease progression have become imperative to both improve the quality of life for patients as well as reduce the health care costs attributable to Alzheimer’s disease.

Here, we demonstrate that the active component of marijuana, Δ9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid β-peptide (Aβ) aggregation, the key pathological marker of Alzheimer’s disease. Computational modeling of the THC-AChE interaction revealed that THC binds in the peripheral anionic site of AChE, the critical region involved in amyloidgenesis.

Compared to currently approved drugs prescribed for the treatment of Alzheimer’s disease, THC is a considerably superior inhibitor of Aβaggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.”

http://www.agoracosmopolitan.com/news/health/2011/11/26/1936.html