Tag Archives: treatment

Cannabinoid signalling in glioma cells

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“Cannabinoids, originally derived from Cannabis sativa, as well as their endogenous and synthetic counterparts, were shown to induce apoptosis of glioma cells in vitro and tumour regression in vivo via their specific receptors, cannabinoid receptors CB1 and/or CB2.

CB2 are abnormally expressed in human gliomas and glioma cell lines. Most of the analysed gliomas expressed significant levels of CB2 receptor and the extent of CB2 expression in the tumour specimens was related to tumour malignancy.

A synthetic cannabinoid, WIN 55,212-2, down-regulated the Akt and Erk signalling pathways in C6 glioma cells that resulted in reduction of phosphorylated Bad levels, mitochondrial depolarization and activation of caspase cascade leading to apoptosis.

We examined whether synthetic cannabinoids with different receptor specificity: WIN55,212-2 (a non-selective CB1/CB2 agonist) and JWH133 (a CB2-selective agonist) affect survival of four human glioma cell lines and three primary human glioma cell lines.

WIN-55,212-2 decreased cell viability in all examined cell lines and induced cell death. Susceptibility of the cells to JWH133 treatment correlated with the CB2 expression. Cannabinoids triggered a decrease of mitochondrial membrane potential, cleavage of caspase-9 and effector caspases.

Induction of cell death by cannabinoid treatment led to the generation of a pro-apoptotic sphingolipid ceramide and disruption of signalling pathways crucial for regulation of proliferation and survival. Increased ceramide levels induced ER-stress and autophagy in drug-treated glioblastoma cells.

We conclude that cannabinoids are efficient inhibitors of human glioma cells growth, once the cells express specific type of cannabinoid receptor.”

http://springerplus.springeropen.com/articles/10.1186/2193-1801-4-S1-L11

Does cannabidiol have a role in the treatment of schizophrenia?

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“Schizophrenia is a debilitating psychiatric disorder which places a significant emotional and economic strain on the individual and society-at-large. Unfortunately, currently available therapeutic strategies do not provide adequate relief and some patients are treatment-resistant.

In this regard, cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa, has shown significant promise as a potential antipsychotic for the treatment of schizophrenia.

However, there is still considerable uncertainty about the mechanism of action of CBD as well as the brain regions which are thought to mediate its putative antipsychotic effects. We argue that further research on CBD is required to fast-track its progress to the clinic and in doing so, we may generate novel insights into the neurobiology of schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/27374322

The endocannabinoid system – a target for the treatment of LUTS?

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“Lower urinary tract symptoms (LUTS) are common in all age groups and both sexes, resulting in tremendous personal suffering and a substantial burden to society.

Antimuscarinic drugs are the mainstay of symptom management in patients with LUTS, although their clinical utility is limited by the high prevalence of adverse effects, which often limit patients’ long-term adherence to these agents.

Data from controversial studies in the 1990s revealed the positive effects of marijuana-based compounds on LUTS, and sparked an interest in the possibility of treating bladder disorders with cannabis.

Increased understanding of cannabinoid receptor pharmacology and the discovery of endogenous ligands of these receptors has prompted debate and further research into the clinical utility of exogenous cannabinoid receptor agonists relative to the unwanted psychotropic effects of these agents.

Currently, the endocannabinoid system is considered as a potential drug target for pharmacological management of LUTS, with a more favourable adverse event profile than antimuscarinic agents.”

http://www.ncbi.nlm.nih.gov/pubmed/27377161

Researcher explores effects of cannabinoids on blood pressure

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Andrei Derbenev, associate professor of physiology, Tulane School of Medicine

“Hypertension — or high blood pressure — is a long-term, high-risk condition for millions of people worldwide.

At the moment, synthetic beta-blockers are one of the most common drugs prescribed to treat hypertension.

But what if a natural drug, marijuana, which has been known for 5,000 years, could be used in the treatment of high blood pressure?

Andrei Derbenev, associate professor of physiology in the Tulane University School of Medicine, recently received a four-year, $1.5 million research grant from the National Institutes of Health to study how cannabinoids — the compounds of cannabis (another name for marijuana) — affect a brain stem area involved in blood pressure control.

His research may have important clinical applications for the treatment of hypertension.

He is identifying the cells in the sympathetic nervous system linked to the kidneys, a key organ in hypertension. (The sympathetic nervous system is the part of the autonomic nervous system that stimulates the body’s “fight or flight” response. Overactivity of the sympathetic nervous system is a cause of high blood pressure.)

He and his research team are studying the effect of exogenous cannabinoids — from the marijuana plant — and endogenous cannabinoids —those naturally produced within the body.

Cannabis “has lots of different chemicals inside. Some of them are painkillers. Some of them, we don’t know what they are doing.”

People ask Derbenev all the time: Is marijuana good? Is it bad? But the debate, he says, should be, instead, “Which works? Which does not work?”

About a decade ago, Derbenev led a study about the effect of cannabinoids on the parasympathetic nervous system, the part of the autonomic nervous system that stimulates the body to “rest and digest.” In that investigation, his team showed the mechanism by which cannabis can reduce digestive spasms and thus decrease vomiting. It’s a finding of great interest to cancer patients experiencing nausea while undergoing chemotherapy.”

https://news.tulane.edu/news/researcher-explores-effects-cannabinoids-blood-pressure

Medical Marijuana for Epilepsy?

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“Treatment-refractory epilepsy remains an important clinical problem. There is considerable recent interest by the public and physicians in using medical marijuana or its derivatives to treat seizures. The endocannabinoid system has a role in neuronal balance and ictal control. There is clinical evidence of success in diminishing seizure frequencies with cannabis derivatives, but also documentation about exacerbating epilepsy or of no discernible effect. There are lay indications and anecdotal reports of success in attenuating the severity of epilepsy, but without solid investigational corroboration. Marijuana remains largely illegal, and may induce adverse consequences. Clinical applications are not approved, thus are restricted and only recommended in selected treatment unresponsive cases, with appropriate monitoring.”

http://www.ncbi.nlm.nih.gov/pubmed/27354925

Delta-9-tetrahydrocannabinol protects against MPP+ toxicity in SH-SY5Y cells by restoring proteins involved in mitochondrial biogenesis.

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“Proliferator-activated receptor γ (PPARγ) activation can result in transcription of proteins involved in oxidative stress defence and mitochondrial biogenesis which could rescue mitochondrial dysfunction in Parkinson’s disease (PD). The PPARγ agonist pioglitazone is protective in models of PD; however side effects have limited its clinical use.

The cannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) may have PPARγ dependent anti-oxidant properties. Here we investigate the effects of Δ9-THC and pioglitazone on mitochondrial biogenesis and oxidative stress.

We found that only Δ9-THC was able to restore mitochondrial content in MPP+ treated SH-SY5Y cells in a PPARγ dependent manner by increasing expression of the PPARγ co-activator 1α (PGC-1α), the mitochondrial transcription factor (TFAM) as well as mitochondrial DNA content.

… unlike pioglitazone, Δ9-THC resulted in a PPARγ dependent reduction of MPP+ induced oxidative stress.

We therefore suggest that, in contrast to pioglitazone, Δ9-THC mediates neuroprotection via PPARγ-dependent restoration of mitochondrial content which may be beneficial for PD treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/27366949

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=10314&path[]=32486

Endocannabionoid System in Neurological Disorders.

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“Several studies support the evidence that the endocannabinoid system and cannabimimetic drugs might have therapeutic potential in numerous pathologies. These pathologies range from neurological disorders, atherosclerosis, stroke, cancer to obesity/metabolic syndrome and others.

In this paper we review the endocannabinoid system signaling and its alteration in neurodegenerative disorders like multiple sclerosis, Alzheimer’s disease, Parkinson’s disease and Huntington’s disease and discuss the main findings about the use of cannabinoids in the therapy of these pathologies.

Despite different etiologies, neurodegenerative disorders exhibit similar mechanisms like neuro-inflammation, excitotoxicity, deregulation of intercellular communication, mitochondrial dysfunction and disruption of brain tissue homeostasis.

Current treatments ameliorate the symptoms but are not curative.

Interfering with the endocannabinoid signaling might be a valid therapeutic option in neuro-degeneration.

To this aim, pharmacological intervention to modulate the endocannabinoid system and the use of natural and synthetic cannabimimetic drugs have been assessed. CB1 and CB2 receptor signaling contributes to the control of Ca2+ homeostasis, trophic support, mitochondrial activity, and inflammatory conditions.

Several studies and patents suggest that the endocannabinoid system has neuro-protective properties and might be a target in neurodegenerative diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/27364363

Marijuana fights Alzheimer’s disease, Salk Institute scientists discover

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Cannabinoids remove plaque-forming Alzheimer's proteins from brain cells

“Salk Institute scientists have discovered that a main compound found in marijuana can fight a toxic protein associated with Alzheimer’s disease. According to the scientists, at this time, there are no drugs that significantly inhibit cell death associated with Alzheimer’s disease (AD), Parkinson’s or Huntington’s diseases. However, the most recent data about Alzheimer’s and marijuana suggests that there is a therapeutic potential of cannabinoids (the chemical compounds secreted by cannabis flowers) for the treatment of AD. Cannabinoids are able to remove plaque-forming Alzheimer’s proteins from brain cells, reports the Medical Express on June 29.”  http://www.examiner.com/article/marijuana-fights-alzheimer-s-disease-salk-institute-scientists-discover

“Cannabinoids remove plaque-forming Alzheimer’s proteins from brain cells”  http://medicalxpress.com/news/2016-06-cannabinoids-plaque-forming-alzheimer-proteins-brain.html

“Cannabinoids remove toxic proteins associated with Alzheimer’s disease from the brain” http://www.irishexaminer.com/examviral/science-world/cannabinoids-remove-toxic-proteins-associated-with-alzheimers-disease-from-the-brain-407788.html

“Marijuana Compound Helps Remove Alzheimer’s Disease Protein From Brain” -brain.” http://www.scienceworldreport.com/articles/42990/20160630/marijuana-compound-helps-remove-alzheimers-disease-protein-from-brain.htm

“Marijuana compound removes toxic Alzheimer’s protein from the brain”  http://www.sciencealert.com/marijuana-compound-removes-toxic-alzheimer-s-protein-from-the-brain

“Cannabinoids remove plaque-forming Alzheimer’s proteins from brain cells”  https://www.sciencedaily.com/releases/2016/06/160629095609.htm

“Cannabinoids Remove Plaque-forming Alzheimer’s Proteins from Brain Cells”  https://www.laboratoryequipment.com/news/2016/06/cannabinoids-remove-plaque-forming-alzheimers-proteins-brain-cells

“MARIJUANA COMPOUND REMOVES ALZHEIMER’S PLAQUE FROM BRAIN CELLS, STUDY FINDS” http://www.popsci.com/marijuana-compound-removes-alzheimers-plaque-from-brain-cells-study

“Cannabinoids remove plaque-forming Alzheimer’s proteins from brain cells. Preliminary lab studies at the Salk Institute find THC reduces beta amyloid proteins in human neurons.” http://www.salk.edu/news-release/cannabinoids-remove-plaque-forming-alzheimers-proteins-from-brain-cells/

 

Expression of the endocannabinoid receptors in human fascial tissue.

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“Cannabinoid receptors have been localized in the central and peripheral nervous system as well as on cells of the immune system, but recent studies on animal tissue gave evidence for the presence of cannabinoid receptors in different types of tissues.

Their presence was supposed also in myofascial tissue, suggesting that the endocannabinoid system may help resolve myofascial trigger points and relieve symptoms of fibromyalgia.

However, until now the expression of CB1 (cannabinoid receptor 1) and CB2 (cannabinoid receptor 2) in fasciae has not yet been established.

Small samples of fascia were collected from volunteers patients during orthopedic surgery. For each sample were done a cell isolation, immunohistochemical investigation (CB1 and CB2 antibodies) and real time RT-PCR to detect the expression of CB1 and CB2.

Both cannabinoid receptors are expressed in human fascia and in human fascial fibroblasts culture cells, although to a lesser extent than the control gene. We can assume that the expression of mRNA and protein of CB1 and CB2 receptors in fascial tissue are concentrated into the fibroblasts.

This is the first demonstration that the fibroblasts of the muscular fasciae express CB1 and CB2. The presence of these receptors could help to provide a description of cannabinoid receptors distribution and to better explain the role of fasciae as pain generator and the efficacy of some fascial treatments.

Indeed the endocannabinoid receptors of fascial fibroblasts can contribute to modulate the fascial fibrosis and inflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/27349320

Fatty Acid Amide Hydrolase Binding in Brain of Cannabis Users: Imaging With the Novel Radiotracer [11C]CURB.

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“One of the major mechanisms for terminating the actions of the endocannabinoid anandamide is hydrolysis by fatty acid amide hydrolase (FAAH), and inhibitors of the enzyme were suggested as potential treatment for human cannabis dependence.

In cannabis users, FAAH binding was significantly lower by 14%-20% across the brain regions examined than in matched control subjects.

Lower FAAH binding levels in the brain may be a consequence of chronic and recent cannabis exposure and could contribute to cannabis withdrawal. This effect should be considered in the development of novel treatment strategies for cannabis use disorder that target FAAH and endocannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/27345297