Category Archives: Huntington’s Disease

Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: relevance for Huntington’s disease.

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“Cannabinoid agonists might serve as neuroprotective agents in neurodegenerative disorders… Cannabinoids may also offer neuroprotection in Huntington’s disease (HD)…

Here, we examined this hypothesis in a rat model ofHuntington’s disease (HD)…

Our results showed that only compounds able to activate CB2 receptors were capable of protecting striatal projection neurons from malonate-induced death. That CB2 receptor agonists are neuroprotective was confirmed…

…neuroprotection was attained exclusively with antioxidant cannabinoids like Δ9-tetrahydrocannabinol (Δ9-THC; or cannabidiol (CBD)…

In summary, our results demonstrate that stimulation of CB2 receptors protect the striatum against malonate toxicity, likely through a mechanism involving glial cells, in particular reactive microglial cells in which CB2 receptors would be upregulated in response to the lesion. Activation of these receptors would reduce the generation of proinflammatory molecules like TNF-alpha.

Altogether, our results support the hypothesis that CB2 receptors could constitute a therapeutic target to slowdown neurodegeneration in HD.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2706932/

http://www.thctotalhealthcare.com/category/huntingtons/

Microglial CB2 cannabinoid receptors are neuroprotective in Huntington’s disease excitotoxicity.

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Brain

“Cannabinoid-derived drugs are promising agents for the development of novel neuroprotective strategies.

…in Huntington’s disease there is a very early downregulation of CB1 receptors in striatal neurons that, together with the undesirable psychoactive effects triggered by CB1 receptor activation, foster the search for alternative pharmacological treatments.

These findings support a pivotal role for CB2 receptors in attenuating microglial activation and preventing neurodegeneration that may pave the way to new therapeutic strategies for neuroprotection in Huntington’s disease as well as in other neurodegenerative disorders with a significant excitotoxic component.

Overall, the reduction of neuronal CB1 receptors and the upregulation of microglial CB2 receptors support a crucial role for the ECB system in the pathogenesis of Huntington’s disease.

The use of drugs targeting the ECB system via CB1 receptors aimed at restoring neurochemical alterations and palliating symptoms might constitute an interesting strategy for the management of Huntington’s disease and other neurodegenerative disorders with a significant excitotoxicity component.”

 http://brain.oxfordjournals.org/content/132/11/3152.long

http://www.thctotalhealthcare.com/category/huntingtons/

Cannabinoid receptor 2 signaling in peripheral immune cells modulates disease onset and severity in mouse models of Huntington’s disease.

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“Here, we show that the genetic deletion of CB2 receptors in a slowly progressing HD mouse model accelerates the onset of motor deficits and increases their severity.

Treatment of mice with a CB2 receptor agonist extends life span and suppresses motor deficits, synapse loss, and CNS inflammation…

CB2 receptor signaling in peripheral immune cells suppresses neurodegeneration in HD mouse models

The development of peripherally restricted CB2 receptor agonists holds promise for treating HD and other neurodegenerative diseases.

In summary, our results suggest CB2 receptor signaling in peripheral immune cells has an important role in HD and other neurodegeneration disorders. Further elucidation of the molecular mechanisms that underlie these effects may lead to novel therapeutic strategies to treat these disorders.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753072/

http://www.thctotalhealthcare.com/category/huntingtons/

THC for Huntington’s Disease? CB1 receptors important for more than drug use

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Psychology Today: Here to Help

“Smoking marijuana doesn’t have to be a bad thing – Especially if you have HD.

The idea that THC can be used to relieve disease symptoms isn’t a new thing – Glaucoma, HIV, and cancer patients have all benefited from the use of CB1 agonists whether in the form of marijuana leaves or a pharmacologically similar product (like dronabinol).

Nevertheless, the idea of using THC or other CB1 agonists for the treatment of HD is pretty new…

The results of this study suggest that THC and other CB1 compounds may not only be able to improve symptoms in already symptomatic HD patients, but also slow down the progression of such a devestating disease.

Good news all around and a great use of THC as far as I’m concerned (medical use and removal from schedule-1 anyone?!).”

http://www.psychologytoday.com/blog/all-about-addiction/201102/thc-huntingtons-disease-cb1-receptors-important-more-drug-use

http://www.thctotalhealthcare.com/category/huntingtons/

Chronic cannabinoid receptor stimulation selectively prevents motor impairments in a mouse model of Huntington’s disease.

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“Huntington’s disease (HD) is a devastating neurodegenerative disease…

The endocannabinoid system (ECS) is a relevant candidate to participate in the etiopathology of HD as it is a key modulator of brain function, especially in areas primarily affected by HD…

… improving ECS function may constitute a useful strategy to eliminate or at least delay the appearance of HD symptoms…

…chronic administration was able to prevent the appearance of motor deficits, to increase the number of striatal huntingtin inclusions and to prevent the loss of striatal medium-sized spiny neurons, without affecting the social or cognitive alterations.

These findings suggest that prolonged administration of cannabinoid receptor agonists could be an appropriate strategy for selectively improving motor symptoms and stimulating neuroprotective processes in HD patients.”

http://www.ncbi.nlm.nih.gov/pubmed/25123645

http://www.thctotalhealthcare.com/category/huntingtons/

The endocannabinoid system: a putative role in neurodegenerative diseases.

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“Scientific evidence shows that an hypofunction or a dysregulation of the endocannabinoid system may be responsible for some of the symptoms of diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s, Parkinson’s and Alzheimer’s diseases.

The aim of this review is to highlight the role of endocannabinoid system in neurodegenerative diseases

Scientific evidence shows that cannabis can provide symptomatic relief in several neurodegenerative diseases such as multiple sclerosis, Huntington’s, Parkinson’s and Alzheimer’s diseases, and amyotrophic lateral sclerosis. These findings imply that a hypofunction or a dysregulation of the endocannabinoid system may be responsible for some of the symptoms of these diseases. Moreover, given the abundance of CB1 receptors in areas associated with movement and executive thought, researchers’ interest has often focused on endocannabinoid levels in patients with motor degenerative disorders.

CONCLUSIONS:

The important role played by endocannabinoid system promises interesting developments, in particular to evaluate the effectiveness of new drugs in both psychiatry and neurology.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070159/

Cannabinoid receptor CB2 is expressed on vascular cells, but not astroglial cells in the post-mortem human Huntington’s disease brain.

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“Huntington’s disease (HD) is an inherited neurological disease with motor, cognitive and psychiatric symptoms. Characterised by neuronal degeneration, HD pathology is initially apparent in the striatum and cortex.

Considerable research has recently suggested that the neurological immune response apparent in brain injury and disease may provide a valuable therapeutic target.

Cannabinoid CB2 receptors are localised and up-regulated on a number of peripheral immune cell types following inflammation and injury.

…our observation that CB2 is present on blood vessel cells, with increased CD31 co-localisation in HD may represent a new context for CB2 therapeutic approaches to neurodegenerative diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/24978314

http://www.thctotalhealthcare.com/category/huntingtons/

The influence of cannabinoids on generic traits of neurodegeneration

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“In an increasingly ageing population, the incidence of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease are rising. While the aetiologies of these disorders are different, a number of common mechanisms that underlie their neurodegenerative components have been elucidated; namely neuroinflammation, excitotoxicity, mitochondrial dysfunction and reduced trophic support. Current therapies focus on treatment of the symptoms and attempt to delay the progression of these diseases but there is currently no cure.

Modulation of the endogenous cannabinoid system is emerging as a potentially viable option in the treatment of neurodegeneration. Endocannabinoid signalling has been found to be altered in many neurodegenerative disorders. To this end, pharmacological manipulation of the endogenous cannabinoid system, as well as application of phytocannabinoids and synthetic cannabinoids have been investigated. Signalling from the CB1 and CB2 receptors are known to be involved in the regulation of Ca2+ homeostasis, mitochondrial function, trophic support and inflammatory status, respectively, while other receptors gated by cannabinoids such as PPARγ, are gaining interest in their anti-inflammatory properties.

Through multiple lines of evidence, this evolutionarily conserved neurosignalling system has shown neuroprotective capabilities and is therefore a potential target for neurodegenerative disorders. This review details the mechanisms of neurodegeneration and highlights the beneficial effects of cannabinoid treatment.”

http://onlinelibrary.wiley.com/doi/10.1111/bph.12492/full

The cytokine and endocannabinoid systems are co-regulated by NF-κB p65/RelA in cell culture and transgenic mouse models of Huntington’s disease and in striatal tissue from Huntington’s disease patients.

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“Transcriptional dysregulation is a major pathological feature of Huntington’s disease (HD). The goal of this study was to understand how p65/RelA co-regulated genes, specifically those of the cytokine and endocannabinoid systems, were affected in HD. p65/RelA levels were lower in human HD tissue and R6/2 HD mice, as were the levels of the type 1 cannabinoid receptor (CB1), IL-1β, IL-8, CCL5, GM-CSF, MIP-1β, and TNFα, all of which may be regulated by p65/RelA. Activation of p65/RelA restored CB1 and CCL5 expression in STHdh cell models of HD. Therefore, p65/RelA activation may normalize the expression of some genes in HD.”

http://www.ncbi.nlm.nih.gov/pubmed/24360910

Therapeutic potential of cannabinoid medicines.

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Drug Testing and Analysis

“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.

The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.

In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24006213

http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract