treatsGlaucoma

R(+)-Methanandamide and Other Cannabinoids Induce the Expression of Cyclooxygenase-2 and Matrix Metalloproteinases in Human Nonpigmented Ciliary Epithelial Cells

Susanne Rösch, Robert Ramer, Kay Brune, and Burkhard Hinz

Department of Experimental and Clinical Pharmacology and Toxicology, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany

how?: Prostaglandins (PGs) and matrix metalloproteinases (MMP) have been implicated in lowering intraocular pressure (IOP) by facilitating aqueous humor outflow. A possible role of cyclooxygenase-2 (COX-2) in this process was emphasized by findings showing an impaired COX-2 expression in the nonpigmented ciliary epithelium (NPE) of patients with primary open-angle glaucoma. Using human NPE cells, the present study therefore investigated the effect of the IOP-lowering cannabinoid R(+)-methanandamide [R(+)-MA] on the expression of COX-2 and different MMPs and tissue inhibitors of MMPs (TIMPs). R(+)-MA led to a concentration- and time-dependent increase of COX-2 mRNA expression. R(+)-MA-induced COX-2 expression was accompanied by time-dependent phosphorylations of p38 mitogen-activated protein kinase (MAPK) and p42/44 MAPK and was abrogated by inhibitors of both pathways. Moreover, R(+)-MA increased the mRNA and protein expression of MMP-1, MMP-3, MMP-9, and TIMP-1 but not that of MMP-2 and TIMP-2. Inhibition of COX-2 activity with NS-398 [N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide] was associated with a virtually complete suppression of R(+)-MA-induced MMP-9 and TIMP-1 expression. Consistent with these data, MMP-9 and TIMP-1 expression was also induced by PGE₂, a major COX-2 product. Two other COX-2-inducing cannabinoids, anandamide and ⁹-tetrahydrocannabinol, caused the same pattern of MMP and TIMP expression as R(+)-MA both in the absence and presence of NS-398. Altogether, cannabinoids induce the production of several outflow-facilitating mediators in the human NPE. Our results further imply an involvement of COX-2-dependent PGs in MMP-9 and TIMP-1 expression. In conclusion, stimulation of intraocular COX-2 and MMP expression may represent a potential mechanism contributing to the IOP-lowering action of different cannabinoids. ...click the title to reference the abstract at it's source.

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medicalMarijuana cancerTreatment

Breakthrough Discovered in Medical Marijuana Cancer Treatment - Salem-News.Com: "...Cancer cells that were treated with combinations of cannabinoids, antagonists of cannabinoid receptors, and small interfering ribo nucleic acid or 'siRNA' to tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) were assessed for invasiveness, protein expression, and activation of signal transduction pathways.

The biggest contribution of this breakthrough discovery, is that the expression of TIMP-1 was shown to be stimulated by cannabinoid receptor activation and to mediate the anti-invasive effect of cannabinoids.

In other words, they learned that treatment with cannabinoids, one of the active ingredients of the medicinal side of marijuana, has been shown to reduce the invasiveness of cancer cells. Prior to now the cellular mechanisms underlying this effect were unclear and the relevance of the findings to the behavior of tumor cells in vivo remains to be determined.

It is already known that marijuana can stimulate the appetite of patients, but researchers have learned that cannabinoids, in addition to having palliative benefits in cancer therapy, have been associated with anti-carcinogenic effects, which are responsible in preventing or delaying the development of cancer.

'Although the anti-proliferative activities of cannabinoids have been intensively investigated, little is known about their effects on tumor invasion,' the article stated...." ...Click the title for the rest in context

psychiatricEffects!

Medical News: Psychiatric Side Effects Cloud Another Promising Obesity Drug - in Primary Care, Weight Management from MedPage Today: "Mechanism-of-action studies suggested that engagement of the cannabinoid-1 receptor inverse agonist by taranabant leads to weight loss by reducing food intake and increasing energy expenditure and fat oxidation.

Taranabant targets the cannabinoid-1 receptor, as does rimonabant (Zimulti, Acomplia), developed by sanofi-aventis. The latter's application to the FDA for approval has been held up because of clinical reports of severe depression and suicidal ideation among some users. Rimonabant is available in some 40 other markets, including the European Union.

A Merck executive told stock analysts last month that psychiatric adverse effects had been seen in taranabant-treated patients, but details had not been disclosed until today's journal publication.

A Merck spokesperson said it now appears that psychiatric effects are intrinsic to drugs targeting the cannabinoid-1 receptor." ...emphasis mine (duH!),
click title to read full article.

mindReading

Misreading the mind - Los Angeles Times: "Our sensations have been reduced to a set of specific circuits. The mind has been imaged as it thinks about itself, with every thought traced back to its cortical source. The most ineffable of emotions have been translated into the terms of chemistry, so that the feeling of love is just a little too much dopamine. Fear is an excited amygdala. Even our sense of consciousness is explained away with references to some obscure property of the frontal cortex. It turns out that there is nothing inherently mysterious about those 3 pounds of wrinkled flesh inside the skull. There is no ghost in the machine." ...click the title for the rest of the story.