Category Archives: Endocannabinoid System

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

Cannabinoids and neurodegenerative diseases.

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“Although significant advances have taken place in recent years on our understanding of the molecular mechanisms of different neurodegenerative diseases, its translation into effective therapeutic treatments has not been as successful as could be expected. There is still a dramatic lack of curative treatments for the most frequent disorders and only symptomatic relief for many others. Under this perspective, the search for novel therapeutic approaches is demanding and significant attention and efforts have been directed to studying additional neurotransmission systems including the endocannabinoid system (ECS).

The neuroprotective properties of exogenous as well as endogenous cannabinoids have been known for years and the underlying molecular mechanisms have been recently unveiled. As discussed later, antioxidative, antiglutamatergic and antiinflammatory effects are now recognized as derived from cannabinoid action and are known to be of common interest for many neurodegenerative processes.

 Thus, these characteristics make cannabinoids attractive candidates for the development of novel therapeutic strategies.

 The present review will focus on the existing data regarding the possible usefulness of cannabinoid agents for the treatment of relevant neurological pathologies for our society such as Alzheimer’s disease, multiple sclerosis, Huntington’s disease and amyotrophic lateral sclerosis.”

http://www.ncbi.nlm.nih.gov/pubmed/19839933

New pathways in drug discovery for Alzheimer’s disease.

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Abstract

“Specific treatments for Alzheimer’s disease (AD) were first introduced in the 1990s using the acetyl-cholinesterase inhibitors. More recently, the N-methyl-D-aspartate (NMDA) antagonist memantine has become available. Although these treatments do provide a modest improvement in the cognitive abnormalities present in AD, their pharmacology is based on manipulation of neurotransmitter systems, and there is no compelling evidence that they interfere with the underlying pathogenic process. Pathologic and genetic data have led to the hypothesis that a peptide called amyloid ss(Abeta) plays a primary role in the pathophysiology of AD. Several investigational therapies targeting Abeta are now undergoing clinical trials. This paper reviews the available data regarding Abeta-directed therapies that are in the clinic and summarizes the approach to biomarkers and clinical trial designs that can provide evidence of modification of the underlying disease process.”

http://www.ncbi.nlm.nih.gov/pubmed/16928346