March 21, 2012
Marijuana and its CD4 Receptors: A New HIV Treatment Strategy?
by Tim Horn
Drugs that target one of the two cellular receptors stimulated by the active ingredient in marijuana may prove to be effective at blocking a form of HIV that has been linked to faster disease progression during late stages of the infection. Though the PLoS One research report highlighting these findings—published March 20 by a team of scientists at Mt. Sinai School of Medicine in New York—stops short of concluding that marijuana is one of nature’s best antiretrovirals, the authors suggest that further study of cannabinoids is needed to ultimately discover drugs with both antiviral and symptom-reducing properties.
Marijuana—purchased legally or illegally and either smoked or ingested—along with its synthetic counterpart Marinol (dronabinol) are used by many people living with HIV to manage various symptoms of illness, including pain, depression and weight loss.
The numerous effects of marijuana are the result of chemical interactions between the drug’s active ingredient, tetrahydrocannabinol (THC), and two receptors on a variety of cells in the body: cannabinoid receptor 1 (CR1) and cannabinoid receptor 2 (CR2).
CR1 receptors are densely populated in the brain and, when stimulated by chemicals like THC, can have a variety of neurological effects. It is THC’s interaction with CR1 in the brain and central nervous system that contributes to marijuana’s “high”-like effects.
THC also interacts with CR2, which is not only found on some cells in the brain, but also on cells of the immune system, gastrointestinal tract and peripheral nervous system. It is THC’s stimulation of CR2 in the latter two compartments that may account for the drug’s positive therapeutic effects on nausea and neuropathic pain, to name a few important symptoms.
CR2 has also been found on a variety of immune system cells and is present on CD4 cells in abundance. While some studies have classified CR2 as a suppressor of CD4 cells and early trials indicated that marijuana use was associated with progression to AIDS, more recent analyses suggest that the drug isn’t associated with significant immune suppression. In fact, both smoked marijuana and Marinol have been associated with increases in CD4 cell counts—along with a decrease in viral load—in at least one short-term study and laboratory experiments.
In effect, the mechanisms by which the interactions between THC and the cannabinoid receptors alter CD4 cell function remain unclear. One particular area of interest, though, is the connection between CR2 and CXCR4, another receptor on immune system cells. For example, CR2 activation blocks CXCR4 from directing the movement of certain cells in the body (chemotaxis). CR2 also plays a role in moving white blood cells out of bone marrow (egress), a role previously attributed largely to CXCR4.
The apparent “cross talk” between CR2 and CXCR4, therefore, led the Mt. Sinai researchers—under the direction of Cristina Maria Costantino, PhD—to explore whether stimulation of CR2 can block the way CXCR4 interacts with a particular form of HIV: CXCR4-tropic virus.
During the early years of untreated HIV infection, HIV primarily targets—or is tropic for—cells with the CCR5 receptor. As HIV disease progresses, however, approximately 50 percent of people living with HIV see their virus develop preference for the CXCR4 receptor on CD4 cells. This particular form of the virus, research has shown, is associated with rapid disease progression, though it is unclear if the emergence of CXCR4-tropic virus is a cause or an effect of immune suppression.
Costantino’s test tube experiments proved encouraging. Using a cannabinoid receptor agonist—a THC-like compound—her team found that activation of CR2 inhibited CXCR4-tropic HIV infection. It did this, not by altering the number of CXCR4 receptors on CD4 cells—this is a therapeutic approach being explored by others—but rather by blocking the receptor’s “signaling process” and interaction with HIV.
According to the PLoS One report, activation of CR2 blocked the ability of CXCR4-tropic virus to infect other cells by 30 to 60 percent. “This inhibition is pronounced in resting cells,” the researchers explain, “which are a target of CXCR4-tropic HIV.”
“Developing a drug that triggers only [CR2] 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 in an accompanying news announcement.
As a result of this discovery, additional research at Mt. Sinai is being planned. Specifically, researchers there will be developing a mouse model of late-stage HIV infection in order to test the efficacy of a drug that triggers CR2, not in test tubes, but in living organisms.
Search: marijuana, thc, cannabinoids, receptors, cd4 cells, cxcr4, hiv, mt. sinai, costantino, plos one
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comments 1 - 15 (of 50 total) next
Jen, Sacramento, 2015-03-09 14:36:54
I noticed a lot of high numbers. I'm still new to diagnosis. In July 2014, my CD4 921, VL 225. Then test again in February CD4 837 VL818. I've been unmedicated, but I am being monitored. I have never been a drug user, and have been in a monogamous relationship since 2006. I am a heavy medical marijuana smoker and constantly use edibles thru out the day. A lot of unanswered questions about how I was infected. Coupled with odd reactions I've gotten from doctors who see my labs.Needanswers
smokeout, fort wayne, 2014-10-11 04:19:04
I was diagnosed with HIV about a year ago I have had such improvements with my counts that I only need to see my doctor twice a yr instead of every six months I will be sure to mention this study to him!!! He approved of my smoking of marijuana. I didn't think it effected my amazing results I seen every 3 months!! Hopefully they can use these results and maybe one day find a cure!!!
lebogang, mbombela, 2014-02-05 11:32:45
I am living hiv just discovered my CD4 cound is 419 and I smoke marijuana so should I stop or not
dee niro, cape town, 2013-07-16 19:41:34
I have been smoking weed for 4years naw believe it or not since then.am never sick.not evin flue.I can evin go for 3 days with no food.love marijuana
jose ilarraza,jr, new york., 2013-04-25 18:22:34
I've smoked pot and ,I know pot helps patient with nausea and appetite. So in my opinion pot is very medicinal and has good properties. In all honesty,I would love to find a marijuana study, this is long do. We spend lots of money buying pot. I think the time has come.
AdamTalbert, Aurora ,Co, 2013-04-10 15:09:35
This is Adam Talbert I was just reading on this article about marijuana and living with HIV. I was diagnosed With HIV in 2008 and I have been smoking Marijuana for since I was 14 years old . My best friend Passed away 3 days before Christmas. He was a survivor Of 30 years of having HIV/AIDS. He was diagnosed in 1980 and started the cocktail of the regimen in 1982.
Thank you for letting me speak about my best friend .
Spring, Texas, 2013-04-03 16:01:19
Where do I sign of for the research study..... illegal here in Texas to smoke. Texas has always been under times and money controled... Cant regulate something you make it illegal...bunch of selfish pharma's that care nothing about us just their pocket books.
Theresa, Northbend, 2013-01-23 09:50:45
I have lived with hiv for 17 years now I have been undetectable and cd4 count of 1300, I believe my meds which are only 2 and daily smoking has kept me at 1300 cd4 count and undetectable
Gals fewer, Tampa, 2012-12-31 00:27:38
HIV+, newly diagnosed 2011. Started Stribild had VL of 714000 and CD4 of 312...nearly undetectable now after 1 1/2 months. Expensive though and have difficulty eating. Law Officer so I can't use MJ but know from professional exp that I've never had a violent encounter from an MJ user! Ever! Wish I could say the same for alcohol, which is a daily issue for us. Personally quitting my career and moving to a friendly state so maybe I can gain some weight. Down to 138 lbs and feel MJ will help.
AndroTrop, Springfield, MO, 2012-12-28 03:07:56
I have proof that when I smoke pot my T-Cells increase, and when I don't they decrease. AND I am in a city that denies me treatment IF they find THC in my system and I am forced to take random urine drug screenings in order to receive treatment/meds w/a primary care physician. HELP ME!
30 year survivor here! HELP ME!
storm, london, 2012-10-20 16:44:53
I am from the uk been living with hiv since 1989, i have smoked cannabis since diagnosis and im still going strong, im on meds, my viral load undectable and cd4 count 1800..when im mentioned about medicle marijuana to hiv doctor at the hospital they dais they wasnt able to help. this drug i believe is the reason im so well as well as the hiv meds are taking..i hate going to buy of dealers but its my only choice..i would like to grow my own just 2 plants containing high THC
nathan, Long Beach, 2012-10-12 18:38:19
I went on meds when my viral load hit 140000 and my cd4s were in the 300s. After being undectable for several years, I lost my medical coverage. I stopped therapy (not advised!!) and continued to smoke marijuana daily. I have been off meds for over 4 years now, have a viral load of just over 2000 and cd4s in the 400s. I feel better than I have in many years so I believe there is a connection that needs to be explored more.
Barbara, Smithfield, 2012-10-11 04:41:38
I can testify to the affect of THC with HIV. With out it I stay sick with it I want to be a part of every day living. I feel much better and stronger on THC. I now have AIDS but my cd4 is 1266 and undetectable. I have always known that the THC has helped with pain, nausea, stiffness. Life in general is much easier on THC. The government is afraid they don't know how to charge for it. Call some thing a disease make a pill and profit. Just sayin!
Scott, Texarkana, 2012-09-19 23:38:03
I have been living with HIV/HCV for almost 15 yrs. I have used marijuana, not on a daily basis, but throughout all these yrs. I do not take other meds and my CD4 averages around 550, and my viral load at last check was only 17,000 for HIV.
Kelvin, Chicago, 2012-09-14 02:09:05
comments 1 - 15 (of 50 total) next
Manny, You don.t DIE from AIDS, You DIE from an AIDS related problem for instance not being able to recover from a case of Phneumonia. Secondly, smoking should not be as if a chain use but casual use and this is with taking Meds. Please in the future DON'T TELL OR SAY SOMEONE DIE OF AIDS...PLEASE SAY IF YOU DON'T know the cause They die of an AIDS related deasase. Meaning they had no cellular ability to fight the illness.
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