Turned-off Cannabinoid Receptor Turns On Colorectal Tumor Growth – CB1 Suppresses Tumors, A New Potential Path For Treatment, Prevention

“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.

“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.medicalnewstoday.com/releases/117055.php

Cannabinoids inhibit energetic metabolism and induce AMPK-dependent autophagy in pancreatic cancer cells.

“The anti-tumoral effects of cannabinoids have been described in different tumor systems, including pancreatic adenocarcinoma, but their mechanism of action remains unclear.

We used cannabinoids specific for the CB1 (ACPA) and CB2 (GW) receptors and metabolomic analyses to unravel the potential pathways mediating cannabinoid-dependent inhibition of pancreatic cancer cell growth. Panc1 cells treated with cannabinoids show elevated AMPK activation induced by a ROS-dependent increase of AMP/ATP ratio. ROS promote nuclear translocation of GAPDH, which is further amplified by AMPK, thereby attenuating glycolysis. Furthermore, ROS determine the accumulation of NADH, suggestive of a blockage in the respiratory chain, which in turn inhibits the Krebs cycle. Concomitantly, inhibition of Akt/c-Myc pathway leads to decreased activity of both the pyruvate kinase isoform M2 (PKM2), further downregulating glycolysis, and glutamine uptake.

Altogether, these alterations of pancreatic cancer cell metabolism mediated by cannabinoids result in a strong induction of autophagy and in the inhibition of cell growth.”

http://www.ncbi.nlm.nih.gov/pubmed/23764845

Marijuana Rivals Mainstream Drugs For HIV/AIDS Symptoms – MedicalNewsToday

“Those in the United States living with HIV/AIDS are more likely to use marijuana than those in Kenya, South Africa or Puerto Rica to alleviate their symptoms, according to a new study published in Clinical Nursing Research, published by SAGE. Those who did use marijuana rate it as effective as prescribed or over the counter (OTC) medicines for the majority of common symptoms, once again raising the issue that therapeutic marijuana use merits further study and consideration among policy makers.”

More: http://www.medicalnewstoday.com/releases/151972.php

Compounds That Stimulate The Cannabinoid Type 2 Receptor In White Blood Cells Can Weaken HIV-1 Infection – MedicalNewsToday

“A new use for compounds related in composition to the active ingredient in marijuana may be on the horizon: a new research report published in the Journal of Leukocyte Biology shows that compounds that stimulate the cannabinoid type 2 (CB2) receptor in white blood cells, specifically macrophages, appear to weaken HIV-1 infection. The CB2 receptor is the molecular link through which the pharmaceutical properties of cannabis are manifested. Diminishing HIV-1 infection in this manner might make current anti-viral therapies more effective and provide some protection against certain HIV-1 complications.”

More:  http://www.medicalnewstoday.com/releases/259885.php

Marijuana-Like Compounds Fight AIDS, Study Finds

“Marijuana-like drugs can do more for AIDS patients than simply help them with their nausea or loss of appetite, according to a new study.

Doctor Tipster found new research published in the medical journal PLoS One that suggests marijuana-like compounds actually fight the HIV virus in late-stage AIDS patients.

Researchers told Doctor Tipster that they already know “cannabinoid drugs” like marijuana can have a therapeutic effect in AIDS patients. But they wanted to further understand how they “influence the spread of the virus itself.”

The study found that “cannabinoid receptors” are triggered by marijuana-like compounds and can actually block the spread of the HIV virus throughout the body.”

More: http://www.huffingtonpost.com/2012/03/22/marijuana-fights-aids_n_1373224.html

Human Immunodeficiency Virus In Late-Stage AIDS Inhibited By Marijuana-Like Chemicals – MedicalNewsToday

“Mount Sinai School of Medicine researchers have discovered that marijuana-like chemicals trigger receptors on human immune cells that can directly inhibit a type of human immunodeficiency virus (HIV) found in late-stage AIDS, according to new findings published online in the journal PLoS ONE.

Medical marijuana is prescribed to treat pain, debilitating weight loss and appetite suppression, side effects that are common in advanced AIDS. This is the first study to reveal how the marijuana receptors found on immune cells – called cannabinoid receptors CB1 and CB2 – can influence the spread of the virus. Understanding the effect of these receptors on the virus could help scientists develop new drugs to slow the progression of AIDS.

“We knew that cannabinoid drugs like marijuana can have a therapeutic effect in AIDS patients, but did not understand how they influence the spread of the virus itself,” said study author Cristina Costantino, PhD, Postdoctoral Fellow in the Department of Pharmacology and Systems Therapeutics at Mount Sinai School of Medicine. “We wanted to explore cannabinoid receptors as a target for pharmaceutical interventions that treat the symptoms of late-stage AIDS and prevent further progression of the disease without the undesirable side effects of medical marijuana.”

HIV infects active immune cells that carry the viral receptor CD4, which makes these cells unable to fight off the infection. In order to spread, the virus requires that “resting” immune cells be activated. In advanced AIDS, HIV mutates so it can infect these resting cells, gaining entry into the cell by using a signaling receptor called CXCR4. By treating the cells with a cannabinoid agonist that triggers CB2, Dr. Costantino and the Mount Sinai team found that CB2 blocked the signaling process, and suppressed infection in resting immune cells.

Triggering CB1 causes the drug high associated with marijuana, making it undesirable for physicians to prescribe. The researchers wanted to explore therapies that would target CB2 only. The Mount Sinai team infected healthy immune cells with HIV, then treated them with a chemical that triggers CB2 called an agonist. They found that the drug reduced the infection of the remaining cells.

“Developing a drug that triggers only CB2 as an adjunctive treatment to standard antiviral medication may help alleviate the symptoms of late-stage AIDS and prevent the virus from spreading,” said Dr. Costantino. Because HIV does not use CXCR4 to enhance immune cell infection in the early stages of infection, CB2 agonists appear to be an effective antiviral drug only in late-stage disease.

As a result of this discovery, the research team led by Benjamin Chen, MD, PhD, Associate Professor of Infectious Diseases, and Lakshmi Devi, PhD, Professor of Pharmacology and Systems Therapeutics at Mount Sinai School of Medicine, plans to develop a mouse model of late-stage AIDS in order to test the efficacy of a drug that triggers CB2 in vivo. In 2009 Dr. Chen was part of a team that captured on video for the first time the transfer of HIV from infected T-cells to uninfected T-cells.”

http://www.medicalnewstoday.com/releases/243183.php

Medical Marijuana Might Reduce Nerve Pain Among People Living With HIV/AIDS, Study Says – MedicalNewsToday

“Medical marijuana might reduce the pain of peripheral neuropathy, a type of nerve damage, among people living with HIV/AIDS, according to a study published in the Feb. 13 issue of the journal Neurology, the Washington Post reports (Weiss, Washington Post, 2/13). Donald Abrams of the University of California-San Francisco and colleagues examined the effects of smoking medicinal marijuana among people living with HIV/AIDS during a two-year period beginning in May 2003, the San Francisco Chronicle reports.

The results are “evidence, using the gold standard for clinical research, that cannabis has some medical benefits for a condition that can be severely debilitating,” Abrams said.”

More:  http://www.medicalnewstoday.com/releases/62955.php

Synthetic Agents Related To Active Ingredient In Marijuana Weaken HIV Infection – MedicalNewsToday

“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.”

More: http://www.medicalnewstoday.com/releases/259980.php

Synthetic derivatives of THC may weaken HIV-1 infection to enhance antiviral therapies – MedicalXpress

“A new use for compounds related in composition to the active ingredient in marijuana may be on the horizon: a new research report published in the Journal of Leukocyte Biology shows that compounds that stimulate the cannabinoid type 2 (CB2) receptor in white blood cells, specifically macrophages, appear to weaken HIV-1 infection. The CB2 receptor is the molecular link through which the pharmaceutical properties of cannabis are manifested. Diminishing HIV-1 infection in this manner might make current anti-viral therapies more effective and provide some protection against certain HIV-1 complications.

“The synthetic compounds we used in our study may show promise in helping the body fight HIV-1 infection,'” said Yuri Persidsky, M.D., Ph.D., a researcher involved in the work from the Department of Pathology and Laboratory Medicine at Temple University School of Medicine in Philadelphia, PA. “As compounds like these are improved further and made widely available, we will continue to explore their potential to fight other viral diseases that are notoriously difficult to treat.”

To make this discovery, scientists used a cell culture model to infect human macrophages with HIV-1 and added synthetic compounds similar to the active ingredient in marijuana to activate the CB2 receptor. At different times during the infection, samples from the culture were taken to see if the replication of the HIV virus was decreased. The researchers observed diminished HIV growth and a possible protective effect from some HIV-1 complications.

“HIV/AIDS has posed one of the most significant health challenges in modern medicine,” said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology. “Recent high profile vaccine failures mean that all options need to be on the table to prevent or treat this devastating infection. Research on the role of cannabinoid type 2 receptors and viral infection may one day allow targeting these receptors to be part of combination therapies that use exploit multiple weaknesses of the virus simultaneously.””

http://medicalxpress.com/news/2013-04-synthetic-derivatives-thc-weaken-hiv-.html

Outlawing drugs like marijuana censors science, researchers say – FOX

“The outlawing of drugs such as cannabis, magic mushrooms and other psychoactive substances amounts to scientific censorship and is hampering research into potentially important medicinal uses, leading scientists argued on Wednesday.”

New-Pot.jpg
 

“Laws and international conventions dating back to the 1960s have set back research in key areas such as consciousness by decades, they argued in the journal Nature Reviews Neuroscience.

“The decision to outlaw these drugs was based on their perceived dangers, but in many cases the harms have been overstated,” said David Nutt, a professor of neuropsychopharmacology at Imperial College London.

In a statement accompanying the Nature Reviews paper, he said the laws amounted “to the worst case of scientific censorship since the Catholic Church banned the works of Copernicus and Galileo”.

“The laws have never been updated despite scientific advances and growing evidence that many of these drugs are relatively safe. And there appears to be no way for the international community to make such changes,” he said.

“This hindering of research and therapy is motivated by politics, not science.”

Nutt and Leslie King, both former British government drugs advisers, and co-author David Nichols of the University of North Carolina, called for the use of psychoactive drugs in research to be exempted from severe restrictions.

“If we adopted a more rational approach to drug regulation, it would empower researchers to make advances in the study of consciousness and brain mechanisms of psychosis, and could lead to major treatment innovations in areas such as depression and PTSD,” Nutt said.

Nutt was sacked as a government adviser in 2009 after publicly criticizing the government for ignoring scientific advice on cannabis and ecstasy. He has conducted a small human trial using psilocybin, the psychedelic ingredient in magic mushrooms.

His study, using volunteers, suggested the drug had the potential to alleviate severe forms of depression in people who did not respond to other treatments.

But in April, Nutt said his plans to conduct the first full clinical trial to explore psilocybin as a treatment had stalled because of stringent rules on the use of illegal drugs in research.

The scientists said their call for reform had been endorsed by the British Neuroscience Association and the British Association for Psychopharmacology.”

http://www.foxnews.com/health/2013/06/12/outlawing-drugs-like-marijuana-censors-science-researchers-say/