Tag Archives: treatment

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 activation of cannabinoid CB2 receptors stimulates in situ and in vitro beta-amyloid removal by human macrophages.

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“The endocannabinoid system is a promising therapeutic target in a wide variety of diseases. However, the non-desirable psychotropic effects of natural and synthetic cannabinoids have largely counteracted their clinical usefulness. These effects are mostly mediated by cannabinoid receptors of the CB(1) type, that exhibit a wide distribution in neuronal elements of the CNS. Thus, the presence of other elements of this system in the CNS, such as CB(2) receptors, may open new possibilities for the development of cannabinoid-based therapies. These receptors are almost absent from the CNS in normal conditions but are up-regulated in glial cells under chronic neuroinflammatory stimuli, as has been described in Alzheimer’s disease. To understand the functional role of these receptors, we tested their role in the process of beta-amyloid removal, that is currently considered as one of the most promising experimental approaches for the treatment of this disease.

Our results show that a CB(2) agonist (JWH-015) is capable of inducing the removal of native beta-amyloid removal from human frozen tissue sections as well as of synthetic pathogenic peptide by a human macrophage cell line (THP-1). Remarkably, this effect was achieved at low doses and was specific for this type of cells, as U373MG astrocytoma cells did not respond to the treatment. The effect was CB(2)-mediated, at least partially, as the selective CB(2) antagonist SR144528 prevented the JWH-015-induced plaque removal in situ.

 These data corroborate the possible therapeutic interest of CB(2) cannabinoid specific chemicals in the treatment of Alzheimer’s disease.”

http://www.ncbi.nlm.nih.gov/pubmed/19505450

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

Role of CB2 receptors in neuroprotective effects of cannabinoids.

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“CB2 receptors, the so-called peripheral cannabinoid receptor type, were first described in the immune system, but they have been recently identified in the brain in healthy conditions and, in particular, after several types of cytotoxic stimuli. Specifically, CB2 receptors were identified in microglial cells, astrocytes and, to a lesser extent, in certain subpopulations of neurons.

Given the lack of psychoactivity demonstrated by selective CB2 receptor agonists, this receptor becomes an interesting target for the treatment of neurological diseases, in particular, the case of certain neurodegenerative disorders in which induction/up-regulation of CB2 receptors has been already demonstrated. These disorders include Alzheimer’s disease, Huntington’s chorea, amyotrophic lateral sclerosis and others. Interestingly, in experimental models of these disorders, the activation of CB2 receptors has been related to a delayed progression of neurodegenerative events, in particular, those related to the toxic influence of microglial cells on neuronal homeostasis.

 The present article will review the evidence supporting that CB2 receptors might represent a key element in the endogenous response against different types of cytotoxic events, and that this receptor type may be a clinically promising target for the control of brain damage in neurodegenerative disorders.”

 http://www.ncbi.nlm.nih.gov/pubmed/18291574

Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression.

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“Pharmacological inhibition of beta-amyloid (Aβ) induced reactive gliosis may represent a novel rationale to develop drugs able to blunt neuronal damage and slow the course of Alzheimer’s disease (AD). Cannabidiol (CBD), the main non-psychotropic natural cannabinoid, exerts in vitro a combination of neuroprotective effects in different models of Aβ neurotoxicity. The present study, performed in a mouse model of AD-related neuroinflammation, was aimed at confirming in vivo the previously reported antiinflammatory properties of CBD.

Cannabidiol (CBD), the main non-psychotropic component of the glandular hairs of Cannabis sativa, exhibits a plethora of actions including anti-convulsive, sedative, hypnotic, anti-psychotic, anti-nausea, anti-inflammatory and anti-hyperalgesic properties. CBD has been proved to exert in vitro a combination of neuroprotective effects in Aβ-induced neurotoxicity, including anti-oxidant and anti-apoptotic effects, tau protein hyperphosphorylation inhibition through the Wnt pathway, and marked decrease of inducible nitric oxide synthase (iNOS) protein expression and nitrite production in Aβ-challenged differentiated rat neuronal cells.

In spite of the large amount of data describing the significant neuroprotective and anti-inflammatory properties of CBD in vitro, to date no evidence has been provided showing similar effects in vivo. To achieve this, the present study investigated the potential anti-inflammatory effect of CBD in a mouse model of AD-related neuroinflammation induced by the intrahippocampal injection of the human Aβ (1–42) fragment.

The results of the present study confirm in vivo anti-inflammatory actions of CBD, emphasizing the importance of this compound as a novel promising pharmacological tool capable of attenuating Aβ evoked neuroinflammatory responses.

 …on the basis of the present results, CBD, a drug well tolerated in humans, may be regarded as an attractive medical alternative for the treatment of AD, because of its lack of psychoactive and cognitive effects.”

Read more: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2189818/

 

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

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

The role of phytochemicals in the treatment and prevention of dementia.

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Drugs & Aging

“Dementia pathologies such as Alzheimer’s disease (AD) are reaching epidemic proportions, yet they are not successfully managed by effective symptomatic treatments. Only five drugs have been developed to alleviate cognitive symptoms, and more effective and safe treatments are needed for both the cognitive symptoms and behavioural and psychological symptoms of dementia (BPSD). As two of these licensed drugs (cholinesterase inhibitors [ChEIs]) are naturally derived (galantamine and rivastigmine), the potential for plants to yield new therapeutic agents has stimulated extensive research to discover new ChEIs together with plant extracts, phytochemicals and their derivatives with other mechanistic effects relevant to dementia treatment. This review presents the potential and actual therapeutic strategies for dementia in relation to the known mechanisms of dementia pathology. Phytochemicals that have shown mechanistic effects relevant to the pathological targets in dementia are discussed, with an emphasis on those showing positive clinical trial evidence. Those phytochemicals discussed include the alkaloid physostigmine, a ChEI from the calabar bean (Physostigma venenosum), which has been used as a template for the development of synthetic derivatives that inhibit acetylcholinesterase, including the drug rivastigmine. Also discussed are other ChEI alkaloids including huperzine A, from Huperzia serrata, and galantamine, originally from the snowdrop (Galanthus woronowii); both alkaloids improve cognitive functions in AD patients.

Other phytochemicals discussed include cannabinoids (e.g. cannabidiol) from Cannabis sativa, which are emerging as potential therapeutic agents for BPSD, and resveratrol (occurs in various plants) and curcumin (from turmeric [Curcuma longa]), which have been investigated for their pharmacological activities relevant to dementia and their potential effects on delaying dementia progression. The review also discusses plant extracts, and their known constituents, that have shown relevant mechanistic effects for dementia and promising clinical data, but require more evidence for their clinical efficacy and safety. Such plants include Ginkgo biloba, which has been extensively studied in numerous clinical trials, with most outcomes showing positive effects on cognitive functions in dementia patients; however, more reliable and consistent clinical data are needed to confirm efficacy. Other plants and their extracts that have produced promising clinical data in dementia patients, with respect to cognition, include saffron (Crocus sativus), ginseng (Panax species), sage (Salvia species) and lemon balm (Melissa officinalis), although more extensive and reliable clinical data are required. Other plants that are used in traditional practices of medicine have been suggested to improve cognitive functions (e.g. Polygala tenuifolia) or have been associated with alleviation of BPSD (e.g. the traditional prescription yokukansan); such remedies are often prescribed as complex mixtures of different plants, which complicates interpretation of pharmacological and clinical data and introduces additional challenges for quality control. Evidence for the role of natural products in disease prevention, the primary but considerably challenging aim with respect to dementia, is limited, but the available epidemiological and clinical evidence is discussed, with most studies focused on ChEIs, nicotine (from Nicotiana species), curcumin, wine polyphenols such as resveratrol and G. biloba. Challenges for the development of phytochemicals as drugs and for quality control of standardized plant extracts are also considered.”

http://www.ncbi.nlm.nih.gov/pubmed/21639405

https://link.springer.com/article/10.2165%2F11591310-000000000-00000