Tag Archives: cannabinoid

Anandamide, Cannabinoid Type 1 Receptor, and NMDA Receptor Activation Mediate Non-Hebbian Presynaptically Expressed Long-Term Depression at the First Central Synapse for Visceral Afferent Fibers.

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“Presynaptic long-term depression (LTD) of synapse efficacy generally requires coordinated activity between presynaptic and postsynaptic neurons and a retrograde signal synthesized by the postsynaptic cell in an activity-dependent manner.

In this study, we examined LTD in the rat nucleus tractus solitarii (NTS), a brainstem nucleus that relays homeostatic information from the internal body to the brain.

We found that coactivation of N-methyl-D-aspartate receptors (NMDARs) and type 1 cannabinoid receptors (CB1Rs) induces LTD at the first central excitatory synapse between visceral fibers and NTS neurons. This LTD is presynaptically expressed. However, neither postsynaptic activation of NMDARs nor postsynaptic calcium influx are required for its induction. Direct activation of NMDARs triggers cannabinoid-dependent LTD.  In addition, LTD is unaffected by blocking 2-arachidonyl-glycerol synthesis, but its induction threshold is lowered by preventing fatty acid degradation.

Altogether, our data suggest that LTD in NTS neurons may be entirely expressed at the presynaptic level by local anandamide synthesis.”

http://www.ncbi.nlm.nih.gov/pubmed/23904599

Active Ingredient in Marijuana Kills Brain Cancer Cells – ABCNews

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ABC News

 

 

“New research out of Spain suggests that THC — the active ingredient in marijuana — appears to prompt the death of brain cancer cells.

The finding is based on work with mice designed to carry human cancer tumors, as well as from an analysis of THC’s impact on tumor cells extracted from two patients coping with a highly aggressive form of brain cancer.

Explaining that the introduction of THC into the brain triggers a cellular self-digestion process known as “autophagy,” study co-author Guillermo Velasco said his team has isolated the specific pathway by which this process unfolds, and noted that it appears “to kill cancer cells, while it does not affect normal cells…”

 The findings were published in the April issue of The Journal of Clinical Investigation.”: http://www.jci.org/articles/view/37948

More: http://abcnews.go.com/Health/Healthday/story?id=7235037&page=1

“Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells” Full Text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673842/

Cannabidiol enhances the inhibitory effects of Δ9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival

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Molecular Cancer Therapeutics

“Δ9-THC and other cannabinoids can act as direct anticancer agents in multiple types of cancer in culture and in vivo. 

Individually, Δ9-THC and CBD can activate distinct pathways in glioblastoma cells that ultimately culminate in inhibition of cancer cell growth and invasion as well as induction of cell death.

We hypothesized that, if the individual agents were combined, a convergence on shared pathways may ensue leading to an enhanced ability of the combination treatment to inhibit certain cancer cell phenotypes.

We found this to be true in this investigation.

CBD enhances the inhibitory effects of Δ9-THC on glioblastoma cell growth.

Cannabidiol significantly improved the inhibitory effects of Δ9-tetrahydrocannabinol on glioblastoma cell proliferation and survival.

The Combination Treatment of Δ9-THC and Cannabidiol Inhibits Cell Cycle and Induces Apoptosis.

Our results suggest that the addition of CBD to Δ9-THC may improve the overall effectiveness of Δ9-THC in the treatment of glioblastoma in cancer patients.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806496/

http://mct.aacrjournals.org/content/9/1/180.full

“CBD Enhances the Anticancer Effects of THC”  https://www.scribd.com/document/50154001/CBD-Enhances-the-Anticancer-Effects-of-THC-Journal-MCT-Marcu

Cannabis-Linked Cell Receptor Might Help Prevent Colon Cancer

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“A cannabinoid receptor lying on the surface of cells may help suppress colorectal cancer, say U.S. researchers. When the receptor is turned off, tumor growth is switched on. Cannabinoids are compounds related to the tetrahydrocannabinol (THC) found in the cannabis plant.”

Photo of colon composite

“It’s already known that the receptor, CB1, plays a role in relieving pain and nausea, elevating mood and stimulating appetite by serving as a docking station for the cannabinoid group of signaling molecules. This study suggests that CB1 may offer a new path for cancer prevention or treatment.”

More: http://www.medicinenet.com/script/main/art.asp?articlekey=91511

Cannabinoid cell surface receptor plays a tumor-suppressing role in human colorectal cancer

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“New preclinical research shows that cannabinoid cell surface receptor CB1 plays a tumor-suppressing role in human colorectal cancer, scientists report in the Aug. 1 edition of the journal Cancer Research.

CB1 is well-established for relieving pain and nausea, elevating mood and stimulating appetite by serving as a docking station for the cannabinoid group of signaling molecules. It now may serve as a new path for cancer prevention or treatment.

“We’ve found that CB1 expression is lost in most colorectal cancers, and when that happens a cancer-promoting protein is free to inhibit cell death,” said senior author Raymond DuBois, M.D., Ph.D., provost and executive vice president of The University of Texas M. D. Anderson Cancer Center.

DuBois and collaborators from Vanderbilt-Ingram Cancer Center also show that CB1 expression can be restored with an existing drug, decitabine. They found that mice prone to developing intestinal tumors that also have functioning CB1 receptors develop fewer and smaller tumors when treated with a drug that mimics a cannabinoid receptor ligand. Ligands are molecules that function by binding to specific receptors. Agonists are synthetic molecules that mimic the action of a natural molecule.

“Potential application of cannabinoids as anti-tumor drugs is an exciting prospect, because cannabinoid agonists are being evaluated now to treat the side-effects of chemotherapy and radiation therapy,” DuBois said. “Turning CB1 back on and then treating with a cannabinoid agonist could provide a new approach to colorectal cancer treatment or prevention.”

Cannabinoids are a group of ligands that serve a variety of cell-signaling roles. Some are produced by the body internally (endocannabinoids). External cannabinoids include manmade versions and those present in plants, most famously the active ingredient in marijuana (THC).”

More: http://www.news-medical.net/news/2008/08/03/40485.aspx

Marijuana Ingredient Inhibits VEGF Pathway Required For Brain Tumor Blood Vessels

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“Cannabinoids, the active ingredients in marijuana, restrict the sprouting of blood vessels to brain tumors by inhibiting the expression of genes needed for the production of vascular endothelial growth factor (VEGF).

“Blockade of the VEGF pathway constitutes one of the most promising antitumoral approaches currently available,” said Manuel Guzmán, professor of biochemistry and molecular biology, with the Complutense University in Madrid, Spain, and the study’s principal investigator.

“The present findings provide a novel pharmacological target for cannabinoid-based therapies.””

More: http://www.sciencedaily.com/releases/2004/08/040816085401.htm

“Cannabinoids inhibit the vascular endothelial growth factor pathway in gliomas.” http://cancerres.aacrjournals.org/content/64/16/5617.long

Inhibition of tumor angiogenesis by cannabinoids

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“Cannabinoids, the active components of marijuana and their derivatives, inhibit tumor growth in animal models… Because the generation of a new vascular supply (angiogenesis) is causally involved in the progression of the majority of solid tumors, the aim of this study was to test whether cannabinoids inhibit tumor angiogenesis.”

Figure 1.

“PRINCIPAL FINDINGS

1. Cannabinoid administration inhibits tumor angiogenesis

2. Cannabinoid administration inhibits vascular endothelial cell migration and survival

3. Cannabinoid administration inhibits tumor expression of proangiogenic factors and improves other markers of tumor malignancy

 

 …In the context of the renaissance in the study of the therapeutic effects of cannabinoids, our findings show that these compounds may be considered promising anti-tumoral agents as they inhibit tumor angiogenesis and growth in vivo with no significant side effects.

 This report provides a mechanistic basis for the anti-tumoral action of cannabinoids and a novel pharmacological target for cannabinoid-based anti-tumoral therapies…”

Full text:  http://www.fasebj.org/content/17/3/529.full

Cannabinoids Decrease the Th17 Inflammatory Autoimmune Phenotype.

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“Cannabinoids, the Cannabis constituents, are known to possess anti-inflammatory properties but the mechanisms involved are not understood. Here we show that the main psychoactive cannabinoid, Δ-9-tetrahydrocannabinol (THC), and the main nonpsychoactive cannabinoid, cannabidiol (CBD), markedly reduce the Th17 phenotype which is known to be increased in inflammatory autoimmune pathologies such as Multiple Sclerosis…

Pretreatment with CBD also resulted in increased levels of the anti-inflammatory cytokine IL-10. Interestingly, CBD and THC did not affect the levels of TNFα and IFNγ. The downregulation of IL-17 secretion by these cannabinoids does not seem to involve the CB1, CB2, PPARγ, 5-HT1A or TRPV1 receptors…

In conclusion, the results show a unique cannabinoid modulation of the autoimmune cytokine milieu combining suppression of the pathogenic IL-17 and IL-6 cytokines along with boosting the expression of the anti-inflammatory cytokine IL-10.”

http://www.ncbi.nlm.nih.gov/pubmed/23892791

The use of cannabinoids in chronic pain.

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“We present the case of a 56-year-old man who developed chronic pain following the excision of a facial cancer that was poorly controlled despite multiple analgesic medications. Following the starting of nabilone (a synthetic cannabinoid) his pain control was greatly improved and this had a huge impact on his quality of life.

We also managed to significantly reduce his doses of opioid analgesia and ketamine.

We review the current literature regarding the medicinal use of cannabinoids, with an emphasis on chronic pain, in an attempt to clarify their role and how to select patients who may benefit from this treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/23893276

Activation of spinal cannabinoid cb2 receptors inhibits neuropathic pain in streptozotocin-induced diabetic mice.

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“The role of spinal cannabinoid systems in neuropathic pain of streptozotocin-induced diabetic mice was studied…

 … A low dose of WIN-55,212-2  significantly recovered the tail-flick latency in streptozotocin-induced diabetic mice… The selective cannabinoid CB2 receptor agonist L-759,656 also dose-dependently recovered the tail-flick latency in streptozotocin-induced diabetic mice…

 These results indicate that spinal cannabinoid systems are changed in diabetic mice and suggest that cannabinoid CB2 receptor agonists might have an ability to recover diabetic neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/23892011