Category Archives: Parkinson’s Disease

Cannabis could provide relief for Parkinson’s pain

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Woman smokes a marijuana cigarette [illustrative]

“As many as eight out of every 10 of those with Parkinson’s disease suffer from inexplicable pains that until now have been left untreated because they were thought to be an inevitable part of the progressive and eventually fatal neurological disease. Parkinson’s, a brain disorder that leads to tremors and difficulty with walking, coordination and movement, usually develops after age 50 and is one of the most common nervous system disorders of the elderly.But new research at the Rabin Medical Center- Beilinson Campus has found that genetic factors explain such Parkinson’s pain, and that the new understanding will make unique treatments possible. Eight genes known to be involved in pain were examined in 237 Parkinson’s patients, according to a research paper published recently in the European Journal of Pain, and the observed variations were connected to functions of cannabis-like substances (cannabinoids) in the brain.

Research project head Prof. Ruth Djaldetti, a senior physician in the neurology department and head of the movement disorders clinic, said that the results support the treatment of Parkinson’s patients with medical marijuana.

Djaldetti encourages more research into the use of cannabis for pain relief.

There are some 20,000 people with Parkinson’s in Israel, and about 50 percent to 80% of them suffer from this previously unexplained and untreated pain. Djaldetti expects that in the future, gene mapping will make it possible to suit personalized medication to these patients.”

 

Cannabis compound can help cells

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“Cannabis has been used recreationally and for medicinal purposes for centuries, yet its 60 plus active components are only partly understood. Now scientists have discovered how a compound in cannabis can help cells to function in our bodies, and aid recovery after a damaging event.

In a paper published in the Journal of Neuroscience, the researchers report on their studies into cannabidiol – a naturally occurring molecule found in cannabis.

Also known as CBD, it is not the constituent that gives the high – that compound is called tetrahydrocannabinol or THC – and so may be more acceptable as a drug treatment.

Both compounds are currently used in a pharmaceutical medicine to help patients relieve pain and other symptoms of Multiple Sclerosis.

Now researchers have discovered how CBD actually works within brain cells.

By interacting with mitochondria – which are the power generators of all cells – it can help maintain normal levels of calcium allowing cells to function properly and providing a greater resistance to damage.

Disturbance of calcium levels has long been associated with a number of brain disorders. So the finding could have implications for the development of new treatments for disorders related to malfunctioning mitochondria.

Dr Bettina Platt, from the University’s School of Medical Sciences, said: “Scientists have known for a long time that cannabidiol can help with pain relief but we never really knew how it worked.

“However we have discovered what it actually does at the cellular level.

“We are hoping that our findings can instruct the development of cannabidiol based treatments for disorders related to mitochondrial dysfunction such as Parkinson’s disease or Huntington’s disease.”

More: http://phys.org/news154280470.html

Cannabidiol: a promising drug for neurodegenerative disorders?

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“Neurodegenerative diseases represent, nowadays, one of the main causes of death in the industrialized country. They are characterized by a loss of neurons in particular regions of the nervous system. It is believed that this nerve cell loss underlies the subsequent decline in cognitive and motor function that patients experience in these diseases. A range of mutant genes and environmental toxins have been implicated in the cause of neurodegenerative disorders but the mechanism remains largely unknown. At present, inflammation, a common denominator among the diverse list of neurodegenerative diseases, has been implicated as a critical mechanism that is responsible for the progressive nature of neurodegeneration.

Since, at present, there are few therapies for the wide range of neurodegenerative diseases, scientists are still in search of new therapeutic approaches to the problem. An early contribution of neuroprotective and antiinflammatory strategies for these disorders seems particularly desirable because isolated treatments cannot be effective.

 In this contest, marijuana derivatives have attracted special interest, although these compounds have always raised several practical and ethical problems for their potential abuse. Nevertheless, among Cannabis compounds, cannabidiol (CBD), which lacks any unwanted psychotropic effect, may represent a very promising agent with the highest prospect for therapeutic use.”

http://www.ncbi.nlm.nih.gov/pubmed/19228180

Cannabidiol Reduces Aβ-Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPARγ Involvement

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“CBD blunted neuroinflammation sustained by astrocytes through PPARγ selective activation in vitro and in vivo.

Results from the present study prove the selective involvement of PPARγ in the anti-inflammatory and neuroprotective effects of CBD here observed either in vitro and in vivo. In addition, CBD significantly promoted neurogenesis in Aβ injured rat hippocampi, much expanding its already wide spectrum of beneficial actions exerted in AD models, a non negligible effect, due to its capability to activate PPARγ.

In conclusion, results of the present research demonstrate that CBD may exert protective functions through a PPARγ dependent activation, which leads to a reduction in reactive gliosis and consequently in neurodegeneration. Moreover, in the current experimental conditions this phytocannabinoid appears to stimulate neurogenesis since it increases DCX immunopositive cell proliferation rate in rat DG.

Innovative therapeutic approaches which could significantly improve AD course require new molecules that will be able to have an impact on different pathological pathways, which converge at the progressive neurological decline. CBD has shown a capability to profoundly reduce reactive astrogliosis and to guarantee both direct and indirect neuronal protection in Aβ induced neuroinflammation/neurodegeration. So far, the lack of understanding of the precise molecular mechanism involved in CBD pharmacological actions, has had limited interest and has puzzled investigators.

Currently, findings of the present study throw some light on the issue, and frame CBD as a new PPARγ activator.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230631/

The development of cannabinoid CBII receptor agonists for the treatment of central neuropathies.

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“Cannabinoids have been used in the treatment of nausea and emesis, anorexia and cachexia, tremor and pain associated with multiple sclerosis. These treatments are limited by the psychoactive side-effects of CBI activation. Recently CBII has been described within the CNS, both in microglia and neuronal progenitor cells (NPCs), but with few exceptions, not by neurons within the CNS.

This has suggested that CBII agonists could have potential to treat various conditions without psycho-activity.

This article reviews the potential for CBII agonists as treatments for neurological conditions, with a focus on microglia and NPCs as drug targets. We first discuss the role of microglia in the healthy brain, and then the role of microglia in chronic neuroinflammatory disorders, including Alzheimer’s disease and Parkinson’s disease, as well as in neuroinflammation following acute brain injury such as stroke and global hypoxia. As activation of CBII receptor on microglia results in suppression of the proliferation and activation of microglia, there is potential for the anti-inflammatory properties of CBII agonist to treat neuropathologies that involve heightened microglia activity. In addition, activating CBII receptors may result in an increase in proliferation and affect migration of NPCs.Therefore, it is possible that CBII agonists may assist in the treatment of neuropathologies by increasing neurogenesis…”

http://www.ncbi.nlm.nih.gov/pubmed/20236042

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

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

Cannabinoids Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Inhibit the Lipopolysaccharide-activated NF-κB and Interferon-β/STAT Proinflammatory Pathways in BV-2 Microglial Cells

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“Cannabinoids have been shown to exert anti-inflammatory activities in various in vivo and in vitro experimental models as well as ameliorate various inflammatory degenerative diseases. Δ9-Tetrahydrocannabinol (THC)is a major constituent of Cannabis and serves as an agonist of the cannabinoid receptors CB1 and CB2.

The second major constituent of Cannabis extract is cannabidiol (CBD). CBD lacks the psychoactive effects that accompany the use of THC. Moreover, CBD was demonstrated to antagonize some undesirable effects of THC, including intoxication, sedation, and tachycardia, while sharing neuroprotective, anti-oxidative, anti-emetic, and anti-carcinogenic properties. Both THC and CBD have been shown to exert anti-inflammatory properties and to modulate the function of immune cells…

In summary, our results show that although both THC and CBD exert anti-inflammatory effects, the two compounds engage different, although to some extent overlapping, intracellular pathways. Both THC and CBD decrease the activation of proinflammatory signaling…

 The cannabinoids by moderating or disrupting these signaling networks may show promise as anti-inflammatory agents.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804319/

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