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Heavy marijuana use associated with a reduction in immune activation

Marijuana is a widely used substance, particularly among some HIV-positive people who use it to reduce chronic pain, nausea and anxiety/depression and to improve appetite.

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As mentioned in TreatmentUpdate 223, excess inflammation and immune activation in HIV-positive people is only partially reduced with treatment (ART). Therefore, researchers are studying additional options to try to reduce these consequences of HIV infection.

Lab research suggests that marijuana or its extracts can reduce inflammation and immune activation, and there is interest in finding out if marijuana can have the same effect in people.

A team of researchers in San Francisco analysed stored blood samples from 185 HIV-positive ART users, some of whom disclosed that they used marijuana. The researchers found that participants had decreased levels of activated cells of the immune system, specifically T-cells, in their blood. They also found that there were decreased levels of other cells of the immune system that could incite and maintain inflammation.

These findings should be considered preliminary because the present study was not able to prove that marijuana use resulted in the decreased immune activation. However, the present study was necessary and provides a foundation for designing robust studies to find out if heavy or light use of marijuana can lead to a reduction in inflammatory conditions and better health.

Study details

As part of an ongoing study with more than 1,500 HIV-positive people, researchers analysed blood samples from 198 participants. Among this latter group, 65 participants disclosed daily marijuana use (which the researchers classified as “heavy”). Researchers subjected the blood samples to extensive analysis, including testing for the presence of several cannabinoids—the compounds in marijuana responsible for its effects.

The average profile of participants upon entering the study was as follows:

  • 87% men, 13% women
  • age – 53 years
  • CD4+ count – 533 cells/mm3
  • CD8+ count – 972 cells/mm3
  • viral load – less than 75 copies/mL (the lower limit of quantification used in this study)
  • duration of viral suppression – four years
  • length of time since HIV diagnosis – 17 years

Results—Verifying marijuana exposure

As mentioned earlier, researchers subjected the blood samples of participants to extensive testing, including analysing the blood for the presence of cannabinoids.

Among five people who reported not using marijuana, researchers found the presence of two or more cannabinoids in their blood. Among eight other people who reported daily marijuana use, researchers did not find significant levels of cannabinoids in their blood. Therefore, they decided to exclude these 13 people from further analysis, leaving 185 people’s samples to be used for the study.

Results—Inflammation and immune activation

  • Researchers found that heavy marijuana users had significantly reduced levels of activated CD4+ and CD8+ cells (written as CD4+ HLA-DR+ CD38+ and CD8+ HLA-DR+ CD38+) compared to non-users.
  • Levels of another group of cells (monocytes) of the immune system that displayed the proteins CD14+ and CD16+ on their surface were decreased among moderate and heavy marijuana users compared to non-users.
  • Another group of cells of the immune system are called dendritic cells. Researchers found that a subset of these called myeloid dendritic cells were “significantly lower in the moderate and heavy cannabis-using groups as compared to non-users.”
  • Another group of cells of the immune system called APCs (antigen-presenting cells), which produce chemical signals of inflammation, were significantly reduced in heavy cannabis users vs. other participants.

Bear in mind

Taken together, the findings from the present study are highly suggestive of marijuana’s ability to reduce immune activation and to some extent inflammation. The study was strengthened by the researchers’ ability to assess the blood samples of participants for the presence of key compounds found in marijuana. The reduction in immune activation and inflammation occurred because certain compounds in marijuana were able to interfere with the functioning of the immune system. There was no signal from the present study that this interference with the immune system was harmful (though the researchers did not appear to assess that). Studies are needed to assess the short-term and long-term safety of marijuana.

However, as the present study was observational in design, it does not prove that the use of marijuana caused the reduction in immune activation and inflammation. The present study does provide a foundation for designing a more robust future study. Such a study needs to examine at least the following:

  • Which strains of marijuana were used?
  • What was the relative mix of cannabinoids in such strains?
  • How was marijuana used—smoked, ingested (edibles) or vapourized?
  • How much marijuana was used and how often?
  • Did marijuana interact with ART and/or other medicines commonly used by co-infected people?
  • Are there differences in the effect of marijuana by gender?

—Sean R. Hosein

REFERENCE:

Manuzak JA, Gott TM, Kirkwood JS, et al. Heavy cannabis use associated with reduction in activated and inflammatory immune cell frequencies in antiretroviral therapy-treated human immunodeficiency virus-infected individuals. Clinical Infectious Diseases. 2018; in press.