Tag Archives: treatment

Biological effects of THC and a lipophilic cannabis extract on normal and insulin resistant 3T3-L1 adipocytes.

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“Type 2 diabetes, a chronic disease, affects about 150 million people world wide.

It is characterized by insulin resistance of peripheral tissues such as liver, skeletal muscle, and fat. Insulin resistance is associated with elevated levels of tumor necrosis factor alpha (TNF-alpha), which in turn inhibits insulin receptor tyrosine kinase autophosphorylation.

It has been reported that cannabis is used in the treatment of diabetes.

A few reports indicate that smoking cannabis can lower blood glucose in diabetics.

Delta(9)-tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis.”

http://www.ncbi.nlm.nih.gov/pubmed/19345076

Abnormal cannabidiol attenuates experimental colitis in mice, promotes wound healing and inhibits neutrophil recruitment.

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“Non-psychotropic atypical cannabinoids have therapeutic potential in a variety of inflammatory conditions including those of the gastrointestinal tract.

Here we examined the effects of the atypical cannabinoid abnormal cannabidiol (Abn-CBD) on wound healing, inflammatory cell recruitment and colitis in mice.

TNBS-induced colitis was attenuated by treatment with Abn-CBD.

Abn-CBD is protective against TNBS-induced colitis, promotes wound healing of endothelial and epithelial cells and inhibits neutrophil accumulation on HUVEC monolayers.

Thus, the atypical cannabinoid Abn-CBD represents a novel potential therapeutic in the treatment of intestinal inflammatory diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/27418880

Potential therapeutic targets and the role of technology in developing novel cannabinoid drugs from cyanobacteria.

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“Cyanobacteria find several applications in pharmacology as potential candidates for drug design. The need for new compounds that can be used as drugs has always been on the rise in therapeutics. Cyanobacteria have been identified as promising targets of research in the quest for new pharmaceutical compounds as they can produce secondary metabolites with novel chemical structures. Cyanobacteria is now recognized as a vital source of bioactive molecules like Curacin A, Largazole and Apratoxin which have succeeded in reaching Phase II and Phase III into clinical trials.

The discovery of several new clinical cannabinoid drugs in the past decade from diverse marine life should translate into a number of new drugs for cannabinoid in the years to come. Conventional cannabinoid drugs have high toxicity and as a result, they affect the efficacy of chemotherapy and patients’ life very much. The present review focuses on how potential, safe and affordable drugs used for cannabinoid treatment could be developed from cyanobacteria.”

http://www.ncbi.nlm.nih.gov/pubmed/27416557

Cannabinoids inhibit HIV-1 Gp120-mediated insults in brain microvascular endothelial cells.

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“HIV-1 infection has significant effect on the immune system as well as on the nervous system.

Breakdown of the blood-brain barrier (BBB) is frequently observed in patients with HIV-associated dementia (HAD) despite lack of productive infection of human brain microvascular endothelial cells (HBMEC).

Cellular products and viral proteins secreted by HIV-1 infected cells, such as the HIV-1 Gp120 envelope glycoprotein, play important roles in BBB impairment and HIV-associated dementia development.

HBMEC are a major component of the BBB.

Using cocultures of HBMEC and human astrocytes as a model system for human BBB as well as in vivo model, we show for the first time that cannabinoid agonists inhibited HIV-1 Gp120-induced calcium influx mediated by substance P and significantly decreased the permeability of HBMEC as well as prevented tight junction protein down-regulation of ZO-1, claudin-5, and JAM-1 in HBMEC.

Furthermore, cannabinoid agonists inhibited the transmigration of human monocytes across the BBB and blocked the BBB permeability in vivo.

These results demonstrate that cannabinoid agonists are able to restore the integrity of HBMEC and the BBB following insults by HIV-1 Gp120.

These studies may lead to better strategies for treatment modalities targeted to the BBB following HIV-1 infection of the brain based on cannabinoid pharmacotherapies.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735224/

The CB2 receptor and its role as a regulator of inflammation.

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“The CB2 receptor is the peripheral receptor for cannabinoids.

It is mainly expressed in immune tissues, highlighting the possibility that the endocannabinoid system has an immunomodulatory role.

In this respect, the CB2 receptor was shown to modulate immune cell functions, both in cellulo and in animal models of inflammatory diseases.

In this regard, numerous studies have reported that mice lacking the CB2 receptor have an exacerbated inflammatory phenotype.

This suggests that therapeutic strategies aiming at modulating CB2 signaling could be promising for the treatment of various inflammatory conditions.

Herein, we review the pharmacology of the CB2 receptor, its expression pattern, and the signaling pathways induced by its activation. We next examine the regulation of immune cell functions by the CB2 receptor and the evidence obtained from primary human cells, immortalized cell lines, and animal models of inflammation.

Finally, we discuss the possible therapies targeting the CB2receptor and the questions that remain to be addressed to determine whether this receptor could be a potential target to treat inflammatory disease.”

http://www.ncbi.nlm.nih.gov/pubmed/27402121

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