Immunomodulatory effects of cannabis use: a multi-omics study in people living with HIV

Cannabis is one of the most commonly used substances worldwide. Cannabinoids are known to have anti-inflammatory effects. However, cannabis is mainly smoked, resulting in exposure to reactive particles, toxins and oxidants, inducing pro-inflammatory effects. Because the net immunological effect of cannabis use on systemic inflammation and immune function has barely been studied in humans, we assessed this in a large cohort of people living with HIV (PLHIV), while taking into account the effects of tobacco use.

This cross-sectional study was performed in 1895 PLHIV on antiretroviral therapy. Cannabis use was assessed by self-report (MATE-Q) and validated by plasma mass spectrometry. Systemic inflammation was assessed using by measuring 2365 plasma proteins. Immune function was assessed by measuring ex vivo cytokine production capacity of peripheral blood mononuclear cells upon stimulation, and by extensive phenotyping of circulating immune cells.

Cannabis use was associated with 15 upregulated and 50 downregulated plasma proteins. These downregulated proteins were involved in leukocyte-mediated cytotoxicity, NK cell-mediated cytotoxicity and the transcriptional regulation of white adipocyte differentiation, amongst other pathways. On the other hand, the production of monocyte- and lymphocyte derived cytokines did not differ between cannabis users and non-users, apart from increased MCP-1 production upon stimulation with IL-1α. Finally, with regards to circulating immune cell phenotypes, cannabis use was only associated with increased numbers of CD27⁺CD21^- B-cells.

Cannabis use was mainly associated with reduced levels of systemic inflammation-related proteins, but showed limited effect on the function and phenotypes of circulating immune cells. Future studies should further explore the clinical consequences of these anti-inflammatory effects.