Stimulation of ALK by the growth factor midkine renders glioma cells resistant to autophagy-mediated cell death

“Δ9-tetrahydrocannabinol (THC), the main active component of marijuana, promotes cancer cell death via autophagy stimulation.

We find that activation of the tyrosine kinase receptor ALK by its ligand midkine interferes with the signaling mechanism by which THC promotes autophagy-mediated glioma cell death.”

 http://www.ncbi.nlm.nih.gov/pubmed/21593591

Marijuana Chemical May Fight Brain Cancer – CBSNews

“The active chemical in marijuana promotes the death of brain cancer cells by essentially helping them feed upon themselves, researchers in Spain report.

Guillermo Velasco and colleagues at Complutense University in Spain have found that the active ingredient in marijuana, THC, causes brain cancer cells to undergo a process called autophagy. Autophagy is the breakdown of a cell that occurs when the cell essentially self-digests.

The team discovered that cannabinoids such as THC had anticancer effects in mice with human brain cancer cells and people with brain tumors . When mice with the human brain cancer cells received the THC, the tumor growth shrank.

Two patients enrolled in a clinical trial received THC directly to the brain as an experimental treatment for recurrent glioblastoma multiforme , a highly aggressive brain tumor. Biopsies taken before and after treatment helped track their progress. After receiving the THC, there was evidence of increased autophagy activity.

The findings appear in the April 1 issue of the Journal of Clinical Investigation.

The patients did not have any toxic effects from the treatment. Previous studies of THC for the treatment of cancer have also found the therapy to be well tolerated, according to background information in journal article.

Study authors say their findings could lead to new strategies for preventing tumor growth.”

http://www.cbsnews.com/2100-500368_162-4913095.html

“Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells…These findings describe a mechanism by which THC can promote the autophagic death of human and mouse cancer cells and provide evidence that cannabinoid administration may be an effective therapeutic strategy for targeting human cancers.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673842/

 

Biochemical and immunohistochemical changes in delta-9-tetrahydrocannabinol-treated type 2 diabetic rats.

“The regulation of glucose, lipid metabolism and immunoreactivities of insulin and glucagon peptides by delta-9-tetrahydrocannabinol (Δ9-THC) in diabetes were examined in an experimental rat model… 

These results indicate that Δ9-THC may serve a protective role against hyperlipidemia and hyperglycemia in diabetic rats.”

http://www.ncbi.nlm.nih.gov/pubmed/23845579

Researchers Have Discovered Synthetic Agents Used To Treat HIV Inflammation – Medical News Today

“HIV can cause serious inflammation, regardless of drug therapy, as it develops slowly in immune cells called macrophages. However, new research conducted at the Temple University School of Medicine’s Department of Pathology and Laboratory Medicine and Center for Substance Abuse Research (CSAR) has just found that there are synthetic agents with anti-inflammatory properties, related to the active ingredient in cannabis, THC (tetrahydrocannabinol) which could limit and treat the chronic inflammation.

These findings suggest that CB2 agonists could be used along with antiretroviral drugs which could lead to a new form of therapy for HIV/AIDS.

It also suggests that the human immune system itself could be used to fight off the HIV infection.

According to Persidsky: “Our study suggests that the body’s own natural defenses can be made more powerful to fight some of the worst symptoms of HIV.”

Stimulating CB2 receptors could also be applied for treating other infections.”

More: http://www.medicalnewstoday.com/articles/260152.php

TEMPLE SCIENTISTS WEAKEN HIV INFECTION IN IMMUNE CELLS USING SYNTHETIC AGENTS RELATED TO ACTIVE INGREDIENT IN MARIJUANA

“HIV, the virus that causes AIDS, is notorious for hiding within certain types of cells, where it reproduces at a slowed rate and eventually gives rise to chronic inflammation, despite drug therapy. But researchers at Temple University School of Medicine’s Department of Pathology and Laboratory Medicine and Center for Substance Abuse Research (CSAR) recently discovered that synthetic anti-inflammatory substances distantly related to the active ingredient of marijuana may be able to take the punch out of HIV while inside one of its major hideouts – immune cells known as macrophages. 

The breakthrough comes at a crucial time in the HIV/AIDS pandemic…

To better understand the connection between inflammation and neurocognitive conditions linked to long-term exposure to HIV, Ramirez and colleagues looked specifically at the CB2 receptor, a protein located on the surface of macrophages. CB2 is a binding site for substances called cannabinoids, the primary active compounds of cannabis (marijuana), and it may play a role in blocking inflammation in the CNS. Unlike its counterpart, the CB1 receptor, which is found primarily on neurons in the brain, CB2 does not mediate the psychoactive effects for which cannabis is popularly known.

Ramirez explained that there has been much pharmacological interest in developing agents that selectively target CB2. Ideally, these compounds would help limit chronic inflammatory responses and would not bind to CB1. The most promising compounds are those derived from THC (tetrahydrocannabinol), the main active substance in cannabis. 

The scientists landed on their discovery by conducting a series of experiments in a well-established, non-clinical HIV macrophage cell model. They began by treating the HIV-infected cells with one of three different synthetic CB2-activating compounds. The cells were then sampled periodically to measure the activity of an enzyme called reverse transcriptase, which is essential for HIV replication. After seven days, the team found that all three compounds had successfully attenuated HIV replication. The experiments and findings are detailed in the May issue of the Journal of Leukocyte Biology. 

The results suggest that selective CB2 agonists could potentially be used in tandem with existing antiretroviral drugs, opening the door to the generation of new drug therapies for HIV/AIDS. The data also support the idea that the human immune system could be leveraged to fight HIV infection. 

“Our study suggests that the body’s own natural defenses can be made more powerful to fight some of the worst symptoms of HIV,” Persidsky explained. He also noted that stimulating CB2 receptors in white blood cells could produce similar benefits against other viral infections.”

More: http://www.temple.edu/medicine/hiv_immune_cells.htm

Antibacterial activity of delta9-tetrahydrocannabinol and cannabidiol.

Image result for Antonie Van Leeuwenhoek. journal

“The minimum inhibiting concentrations (MIC) of delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) for staphylococci and streptococci in broth are in the range of 1-5 mug/ml.

In the same range, both compounds are also bactericidal.

In media containing 4% serum or 5% blood the antibacterial activity is strongly reduced (MIC 50 mug/ml). Gram-negative bacteria are resistant to THC and CBD.”

http://www.ncbi.nlm.nih.gov/pubmed/1085130

Large Study Finds No Link between Marijuana and Lung Cancer – Scientific American

“…Scientists were therefore surprised to learn that a study of more than 2,000 people found no increase in the risk of developing lung cancer for marijuana smokers.

“We expected that we would find that a history of heavy marijuana use–more than 500 to 1,000 uses–would increase the risk of cancer from several years to decades after exposure to marijuana,” explains physician Donald Tashkin of the University of California, Los Angeles, and lead researcher on the project. But looking at residents of Los Angeles County, the scientists found that even those who smoked more than 20,000 joints in their life did not have an increased risk of lung cancer.

The study does not reveal how marijuana avoids causing cancer. Tashkin speculates that perhaps the THC chemical in marijuana smoke prompts aging cells to die before becoming cancerous. Tashkin and his colleagues presented the findings yesterday at a meeting of the American Thoracic Society in San Diego.”

More: http://www.scientificamerican.com/article.cfm?id=large-study-finds-no-link

Preparation and characterization of Δ9-tetrahydrocannabinol-loaded biodegradable polymeric microparticles and their antitumoral efficacy on cancer cell lines.

“Cannabinoids present an interesting therapeutic potential as antiemetics, appetite stimulants in debilitating diseases (cancer, AIDS and multiple sclerosis), analgesics, and in the treatment of multiple sclerosis and cancer, among other conditions.

However, despite their high clinical potential, only few dosage forms are available to date. In this paper, the development of Δ9-tetrahydrocannabinol (THC) biodegradable microspheres as an alternative delivery system for cannabinoid parenteral administration is proposed. Tetrahydrocannabinol was encapsulated into biodegradable microspheres by the oil-in-water (o/w) emulsion solvent evaporation method. Several formulations were prepared using different drug:polymer ratios. The influence of antioxidant (α-tocopherol acetate) concentration on the release of THC from the microparticles was studied. Elevated process yield and entrapment efficiencies were achieved.The in vitro drug release studies showed that the encapsulated drug was released over a two week period.

 As THC has shown therapeutic potential as anticancer drug, the efficacy of the microspheres was tested on different cancer cell lines.

 Interestingly, the microspheres were able to inhibit cancer cell proliferation during the nine-day study period.

 All the above results suggest that the use of biodegradable microspheres would be a suitable alternative delivery system for THC administration.”

http://www.ncbi.nlm.nih.gov/pubmed/23773072

Acute Δ9-tetrahydrocannabinol blocks gastric hemorrhages induced by the nonsteroidal anti-inflammatory drug diclofenac sodium in mice.

“Nonsteroidal anti-inflammatory drugs (NSAIDs), which are among the most widely used analgesics in the world, cause gastrointestinal inflammation that is potentially life-threatening.

Although inhibitors of endocannabinoid catabolic enzymes protect against gastropathy in fasted NSAID-treated mice, the gastroprotective effects of Δ9-tetrahydrocannabinol (THC), the primary psychoactive component of marijuana, have yet to be investigated…

 These data indicate that the phytocannabinoid Δ9-THC protects against diclofenac-induced gastric inflammatory tissue damage at doses insufficient to cause common cannabinoid side effects.”

http://www.ncbi.nlm.nih.gov/pubmed/23769745

Synthetic Compounds From Marijuana Appear to Fight HIV

“Synthetic anti-inflammatory compounds derived from the active ingredient of marijuana appear to show potential as anti-HIV agents, Wired.co.uk reports. Publishing their findings in the Journal of Leukocyte Biology, researchers from Temple University School of Medicine’s Department of Pathology and Laboratory Medicine and Center for Substance Abuse Research (CSAR) studied synthetic derivations of THC, or tetrahydrocannabinol, a key chemical compound in marijuana, in cultures of HIV-infected cells.

Cannabinoids, which are the primary active compounds in marijuana, bind to proteins called CB2 receptors on the surface of macrophage immune cells. The CB2 site may play a role in reducing inflammation in the central nervous system, which is a major concern for people living with HIV, even those whose virus is fully suppressed thanks to antiretrovirals (ARVs). It is the CB1 receptors, mostly found in neurons in the brain, however, that cause marijuana’s psychoactive effects. So synthetic THC that has been developed to bind only to CB2 receptors should not make people stoned.

It is believed that macrophage cells, which are found throughout the body, are a major component of the HIV reservoir and are probably the first cells infected after sexual transmission of the virus.

Using a non-clinical cell model, the investigators treated HIV-infected macrophages with one of three different synthetic compounds that bind to CB2. By periodically measuring the activity of the enzyme reverse transcriptase, which HIV needs to replicate itself, the investigators concluded after a seven-day period that all three compounds fought HIV replication.

The findings suggest that these “CB2 agonists” could be a potential addition to ARV therapy, and also that the human immune system could be prompted to fight the virus using similar mechanisms.”

http://www.aidsmeds.com/articles/pot_CB2_1667_23905.shtml