Marijuana-like chemicals inhibit human immunodeficiency virus (HIV) in late-state AIDS
March 20, 2012
Science Daily/Mount Sinai Medical Center
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.
Funding for this study was provided to Drs. Chen and Devi by the National Institutes of Health in Bethesda, Maryland. Dr. Costantino is supported by a National Institutes of Health Clinical and Translational Science Award grant awarded to Mount Sinai School of Medicine.
https://www.sciencedaily.com/releases/2012/03/120320195252.htm
Marijuana may help HIV patients keep mental stamina longer
December 12, 2017
Science Daily/Michigan State University
A chemical found in marijuana, known as tetrahydrocannabinol, or THC, has been found to potentially slow the process in which mental decline can occur in up to 50 percent of HIV patients, says a new Michigan State University study.
"It's believed that cognitive function decreases in many of those with HIV partly due to chronic inflammation that occurs in the brain," said Norbert Kaminski, lead author of the study, now published in the journal AIDS. "This happens because the immune system is constantly being stimulated to fight off disease."
Kaminski and his co-author, Mike Rizzo, a graduate student in toxicology, discovered that the compounds in marijuana were able to act as anti-inflammatory agents, reducing the number of inflammatory white blood cells, called monocytes, and decreasing the proteins they release in the body.
"This decrease of cells could slow down, or maybe even stop, the inflammatory process, potentially helping patients maintain their cognitive function longer," Rizzo said.
The two researchers took blood samples from 40 HIV patients who reported whether or not they used marijuana. Then, they isolated the white blood cells from each donor and studied inflammatory cell levels and the effect marijuana had on the cells.
"The patients who didn't smoke marijuana had a very high level of inflammatory cells compared to those who did use," Kaminski said. "In fact, those who used marijuana had levels pretty close to a healthy person not infected with HIV."
Kaminski, director of MSU's Institute for Integrative Toxicology, has studied the effects of marijuana on the immune system since 1990. His lab was the first to identify the proteins that can bind marijuana compounds on the surface of immune cells. Up until then, it was unclear how these compounds, also known as cannabinoids, affected the immune system.
HIV, which stands for human immunodeficiency virus, infects and can destroy or change the functions of immune cells that defend the body. With antiretroviral therapy -- a standard form of treatment that includes a cocktail of drugs to ward off the virus -- these cells have a better chance of staying intact.
Yet, even with this therapy, certain white blood cells can still be overly stimulated and eventually become inflammatory.
"We'll continue investigating these cells and how they interact and cause inflammation specifically in the brain," Rizzo said. "What we learn from this could also have implications to other brain-related diseases like Alzheimer's and Parkinson's since the same inflammatory cells have been found to be involved."
Knowing more about this interaction could ultimately lead to new therapeutic agents that could help HIV patients specifically maintain their mental function.
"It might not be people smoking marijuana," Kaminski said. "It might be people taking a pill that has some of the key compounds found in the marijuana plant that could help."
https://www.sciencedaily.com/releases/2017/12/171212092100.htm