Category Archives: Endocannabinoid System

CB(2) receptor and amyloid pathology in frontal cortex of Alzheimer’s disease patients.

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“The cannabinoid system seems to play an important role in various neurodegenerative diseases including Alzheimer’s disease (AD). The relationship of cannabinoid receptors (CB(1)R and CB(2)R) to cognitive function and neuropathological markers in AD remains unclear. In the present study, postmortem cortical brain tissues (Brodmann area 10) from a cohort of neuropathologically confirmed AD patients and age-matched controls were used to measure CB(1)R and CB(2)R by immunoblotting. Correlational analyses were performed for the neurochemical and cognitive data. CB(1)R expression was significantly decreased in AD. Levels of CB(1)R correlated with hypophagia, but not with any AD molecular marker or cognitive status (Mini Mental State Examination score). The level of CB(2)R was significantly higher (40%) in AD. Increases in the expression of the glial marker glial fibrillar acidic protein were also found. CB(2)R expression did not correlate with cognitive status. Interestingly, expression levels of CB(2)R correlated with two relevant AD molecular markers, Aβ(42) levels and senile plaque score.

These results may constitute the basis of CB(2)R-based therapies and/or diagnostic approaches.”

http://www.ncbi.nlm.nih.gov/pubmed/22763024

Stimulation of cannabinoid receptor 2 (CB2) suppresses microglial activation

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“Activated microglial cells have been implicated in a number of neurodegenerative disorders, including Alzheimer’s disease (AD), multiple sclerosis (MS), and HIV dementia. Many data reveal that cannabinoids mediate suppression of inflammation in vitro and in vivo through stimulation of cannabinoid receptor 2 (CB2).

Taken together, these results provide mechanistic insight into beneficial effects provided by cannabinoid receptor CB2 modulation in neurodegenerative diseases, particularly AD.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1352348/

A molecular link between the active component of marijuana and Alzheimer’s disease pathology.

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“A link between the endocannabinoid system and Alzheimer’s disease has been discovered which has provided a new therapeutic target for the treatment of patients suffering from Alzheimer’s disease. These studies have demonstrated the ability of cannabinoids to provide neuroprotection against β-amyloid peptide (Aβ) toxicity.

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. 

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

Since the characterization of the Cannabis sativa-produced cannabinoid, Δ9-tetrahydrocannabinol (THC), in the 1960’s,1 this natural product has been widely explored as an anti-emetic, anti-convulsive, anti-inflammatory, and analgesic.”

Read more: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562334/

 

The endocannabinoid system in targeting inflammatory neurodegenerative diseases.

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“The classical divide between degenerative and inflammatory disorders of the CNS is vanishing as accumulating evidence shows that inflammatory processes are important in the pathophysiology of primarily degenerative disorders, and neurodegeneration complicates primarily inflammatory diseases of the brain and spinal cord. Here, we review the contribution of degenerative and inflammatory processes to CNS disorders such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis and HIV-associated dementia.

An early combination of neuroprotective and anti-inflammatory approaches to these disorders seems particularly desirable because isolated treatment of one pathological process might worsen another.

We also discuss the apparently unique opportunity to modify neurodegeneration and neuroinflammation simultaneously by pharmacological manipulation of the endocannabinoid system in the CNS and in peripheral immune cells. Current knowledge of this system and its involvement in the above CNS disorders are also reviewed.”

http://www.ncbi.nlm.nih.gov/pubmed/17350694

Endocannabinoid system: emerging role from neurodevelopment to neurodegeneration.

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“The endocannabinoid system, including endogenous ligands (‘endocannabinoids’ ECs), their receptors, synthesizing and degrading enzymes, as well as transporter molecules, has been detected from the earliest stages of embryonic development and throughout pre- and postnatal development. ECs are bioactive lipids, which comprise amides, esters and ethers of long chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol (2-AG) are the best studied ECs, and act as agonists of cannabinoid receptors.

Thus, AEA and 2-AG mimic several pharmacological effects of the exogenous cannabinoid delta9-tetrahydrocannabinol (Delta(9)-THC), the psychoactive principle of cannabis sativa preparations like hashish and marijuana. Recently, however, several lines of evidence have suggested that the EC system may play an important role in early neuronal development as well as a widespread role in neurodegeneration disorders. Many of the effects of cannabinoids and ECs are mediated by two G protein-coupled receptors (GPCRs), CB1 and CB2, although additional receptors may be implicated. Both CB1 and CB2 couple primarily to inhibitory G proteins and are subject to the same pharmacological influences as other GPCRs. This new system is briefly presented in this review, in order to put in a better perspective the role of the EC pathway from neurodevelopment to neurodegenerative disorders, like Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis.

In addition, the potential exploitation of antagonists of CB1 receptors, or of inhibitors of EC metabolism, as next-generation therapeutics is discussed.”

http://www.ncbi.nlm.nih.gov/pubmed/19356123

Regulation of cannabinoid CB1 receptors in the central nervous system by chronic cannabinoids.

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“The potential therapeutic benefits of certain cannabinoid-mediated effects, as well as the use of marijuana for its psychoactive properties, has raised interest in understanding the cellular adaptations produced by chronic administration of this class of drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/14977366

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

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“The present in vivo and in vitro findings clearly indicate that the CB1 receptor possesses anti-inflammatory properties and inhibits microglia-mediated oxidative stress.

 Our results collectively suggest that the cannabinoid system is beneficial for the treatment of Parkinson’s disease and other disorders associated with neuroinflammation and microglia-derived oxidative damage.

CB1 receptor is a useful pharmacological target for treating PD and other disorders associated with neuroinflammation and microglia-derived oxidative damage. ”

http://www.jimmunol.org/content/187/12/6508.long

Intact cannabinoid CB1 receptors in the Alzheimer’s disease cortex.

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“The cannabinoid CB1 receptor has gained much attention as a potential pharmacotherapeutic target in various neurodegenerative diseases including Alzheimer’s disease (AD). Our study suggests that CB1 receptors are intact in AD and may play a role in preserving cognitive function.

 Therefore, CB1 receptors should be further assessed as a potential therapeutic target in AD.”

http://www.ncbi.nlm.nih.gov/pubmed/21034788

Molecular reorganization of endocannabinoid signalling in Alzheimer’s disease

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“CB1 cannabinoid receptor expression is unchanged in Alzheimer’s disease

Therefore, endocannabinoid signalling networks may represent novel targets to reinstate the precision of synaptic communication under neurodegenerative conditions associated with cognitive deficit.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069704/

Cannabinoid system in neurodegeneration: new perspectives in Alzheimer’s disease.

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“Alzheimer’s disease is a chronic and progressive neurodegenerative disorder. The presence of functional cannabinoid CB2 receptors in central nervous system (CNS) has provoked that this receptor and its agonist ligands are now considered as promising pharmacological targets for neurological diseases. Herein, we review the evidences supporting the potential role of the ECS as a therapeutic target, focused on CB2 receptor and its ligands, for the treatment of Alzheimer’s disease.”

http://www.ncbi.nlm.nih.gov/pubmed/19456285