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 Rivals Mainstream Drugs for Alleviating HIV/AIDS Symptoms

May 29, 2009

Science Daily/SAGE Publications

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.

A significant percentage of those with HIV/AIDS use marijuana as a symptom management approach for anxiety, depression, fatigue, diarrhoea, nausea, and peripheral neuropathy. Members of the University of California, San Francisco (UCSF) International HIV/AIDS Nursing Research Network examined symptom management and quality of life experiences among those with HIV/AIDS in the US, Africa, and Puerto Rico, to gain a fuller picture of marijuana’s effectiveness and use in this population.

With data from a longitudinal, multi-country, multi-site, randomised control clinical trial, the researchers used four different evaluation tools to survey demographics, self-care management strategies for six common symptoms experienced by those living with HIV/AIDS, quality of life instrument and reasons for non-adherence to medications.

Either marijuana use for symptom management is vastly higher in the US, or participants elsewhere chose not to disclose that they use it: nine tenths of study participants who said they used marijuana live in the US. No African participants said they used it, and the remaining ten percent were from Puerto Rico.

The researchers found no differences between marijuana users and nonusers in age, race, and education level, income adequacy, having an AIDS diagnosis, taking ARV medications, or years on ARV medications. But the two groups did differ in that marijuana users had been HIV positive longer, and were more likely to have other medical conditions. Transgender participants were also more likely to use marijuana.

Participants using marijuana as a management strategy were spread fairly consistent across all six symptoms, ranging from a low of 20% for fatigue to a high of 27% for nausea. Prescribed medications were used by 45% of those with fatigue, ranging down to almost 18% of those with neuropathy.

The findings contained nuances when comparing marijuana to other medications. Those who used marijuana rated their anxiety significantly lower than those who did not, and women who used marijuana had more intense nausea symptoms. For those who use both marijuana and medications for symptom management, antidepressants were considered more effective than marijuana for anxiety and depression, but marijuana was rated more highly than anti-anxiety medications. Immodium was better for diarrhoea than marijuana, as were prescribed medications for fatigue. However, marijuana was perceived to be more effective than either prescribed or OTC medications for nausea and neuropathy. However, the differenced in perceived efficacy in all these results were slight.

As found in previous studies, those who used marijuana were less likely to comply with their regime of ARV medications. But perhaps counter-intuitively of the many reasons given for skipping pills, ‘forgetfulness’ was no different in this group than among those who did not use marijuana. Marijuana use is known to contribute to patients’ lack of compliance with ARV drugs, however those who use marijuana to target a particular symptom are actually more likely to stick closely to their ARV regimen too. The researchers point out that of those who used marijuana for their symptoms, it is not known whether they also used the drug for recreation. Patterns of how marijuana use interferes with patients’ adherence to medication regimens, along with other drugs, warrant further study.

The 775 participants were recruited from Kenya, South Africa, two sites in Puerto Rico, and ten sites in the United States. They had on average been diagnosed for a decade - the majority (70%) were taking anti-retroviral (ARV) medications and more than half had other medical conditions alongside HIV/AIDS. It is hard to pinpoint the marijuana use targeted to alleviate symptoms of those other illnesses as distinct from those relating solely to HIV/AIDS.

Data suggest that marijuana is a trigger among those susceptible to psychosis, and is also associated with the risk of suicidal thoughts. However it is not linked to an increased risk of lung cancer (over and above risks associated with smoking it along with tobacco).

The question of the use of marijuana for symptom management when legal drugs are available remains a practice and policy issue.

“Given that marijuana may have other pleasant side effects and may be less costly than prescribed or OTC drugs, is there a reason to make it available?” asks study leader Inge Corless.  “These are the political ramifications of our findings. Our data indicate that the use of marijuana merits further inquiry.”

https://www.sciencedaily.com/releases/2009/05/090529081627.htm