- Montreal researchers conducted a 12-week study of cannabis extracts with 10 people with HIV
- Cannabinoids appeared to reduce intestinal injury, inflammation and immune activation
- A larger and longer study is needed to better understand the long-term effect of cannabinoids
When taken as directed, HIV treatment (antiretroviral therapy; ART) can usually reduce the amount of HIV in the blood to very low levels. This is commonly called “undetectable” because the level of HIV in the blood is so low that routinely used tests cannot detect it. Continued adherence to ART helps to keep HIV suppressed. As a result, the immune system can repair much of the injury caused by HIV and the risk of AIDS-related complications decreases dramatically. The power of ART is so tremendous that researchers increasingly expect that many people with HIV will have near-normal life expectancy.
However, ART does not resolve all HIV-related issues. For instance, HIV causes excess inflammation and immune activation. Being on ART and having an undetectable viral load greatly reduce these issues, but inflammation and immune activation still remain elevated.
In people without HIV, chronic excess inflammation likely contributes to an increased risk for the following:
- cardiovascular disease
- type 2 diabetes
- degenerative conditions of the brain
- fat accumulation in the liver
- thinning of bones (osteopenia and osteoporosis)
- loss of muscle tissue
- premature aging of the immune system
- high levels of cholesterol
It is likely that excess inflammation and immune activation over the long term contribute to similar issues in people with HIV.
The precise cause of excess inflammation and immune activation in people with HIV despite the use of ART is not clear. However, some research suggests that early in the course of HIV infection the virus causes events that injure the lining of the gut and depletes cells of the immune system in the intestine. ART does not fully reverse these issues. Furthermore, bacteria and fungi in the intestine can leak proteins across the gut that then enter the blood. These microbial proteins stimulate the immune system and help keep it activated and inflamed.
There are more than 100 compounds in cannabis (marijuana)—collectively called cannabinoids. Researchers are studying cannabinoids for their anti-inflammatory activity and effect on the immune system. In lab experiments with cells and HIV, as well as in monkeys susceptible to simian immunodeficiency virus (SIV), researchers have found that cannabinoids can reduce inflammation and immune activation.
A pilot study in Montreal
A team of scientists at McGill University and the Université du Québec à Montréal conducted a small and relatively short study of cannabinoids taken in capsule formulation. Participants were given increasing doses of cannabinoids over 12 consecutive weeks.
The team found that cannabinoids reduced levels of proteins in the blood that indicate the following:
- intestinal injury
- immune activation
- immunological exhaustion
- premature aging of the immune system
Levels of CD4+ T-cells in the blood were unaffected, as was the overall burden of HIV-infected cells in the body (scientists refer to this as the viral reservoir).
The researchers stated that their results show promise. Their study builds a foundation on which a larger and longer trial of cannabinoids in people with HIV can be done.
An American study
The findings from the Montreal study are broadly supported by a recent U.S. study with 75 people with HIV—33 of whom used cannabis and 42 who did not. The study did not specify how the participants consumed cannabis, but it is likely that the main method of consumption was smoking. Researchers obtained blood samples and analysed them at only one point in time. They found that, in general, people who used cannabis had cells of the immune system that were less likely to be activated, inflamed and prematurely aged or exhausted.
As mentioned earlier, cannabis contains more than 100 compounds. A strength of the Montreal study was that it used specific extracts taken in pill form, as the researchers did not want to facilitate lung injury that accompanies smoking cannabis. Another strength of the Montreal study was that it monitored people over a period of time.
A previous report from the Montreal pilot study revealed that two participants had to stop taking cannabinoids prematurely; in one case because of anemia (with mild liver injury) and in the other case because of more severe liver injury. The researchers stated that people with pre-existing liver injury may be susceptible to CBD-induced liver injury. Details about these cases are available here. Based on the results of the present and other studies, the Quebec research team had advice for two groups—scientists who are planning to conduct research of CBD in people with HIV and physicians caring for people with HIV who want to use such compounds.
Prior to initiating study medicines, participants with risk factors for fatty liver could undergo a specialized ultrasound scan of the liver (Fibroscan). Once in a study, participants’ liver enzyme levels could be closely monitored “to detect any subtle rises […] which may suggest undiagnosed [fatty liver].” If a Fibroscan machine is unavailable, the researchers suggested that simple blood tests (called Fibrosis-4 or Fib-4) could be done prior to initiation of cannabinoid-containing medicines.
For physicians caring for people with HIV
Physicians are encouraged to speak to their patients with HIV who may use or want to use cannabinoid-containing oils about their potential toxicity. Such oils are available without a prescription in Canada.
For the present study, the Quebec researchers had hoped to recruit a total of 26 people with HIV for the study. However, due to manufacturing and other issues, they were only able to obtain sufficient cannabinoid capsules for 10 people, so they recruited eight males and two females. The capsules were supplied by Tilray Brands and contained the following cannabinoids:
- a combination of THC (delta-9-tetrahydrocannabinol) and CBD (cannabidiol) in a 1:1 ratio (2.5 mg THC and 2.5 mg CBD)
- CBD only – 200 mg
Some participants received the combination of cannabinoids while others received CBD only. Over the course of 12 weeks, participants gradually increased the number of capsules taken daily.
Participants were around 57 years old. All participants were taking ART and had an undetectable viral load (less than 40 copies/mL).
Cannabinoids were taken for 12 weeks. Participants were monitored for four weeks prior to initiating cannabinoids and for two weeks after they ceased taking them.
Researchers relied on the levels of certain proteins in the blood to indicate the degree of injury and inflammation to the lining of the gut. In future studies, it may be useful to perform biopsies (removal of a tiny sample of intestinal tissue) for analysis to confirm that gut injury and inflammation has been reduced with cannabinoids.
The Montreal pilot study was supported by the Canadian HIV Trials Network.
—Sean R. Hosein
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