Abstract Body

Background:

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

Methods:

This cross-sectional study was performed in 1896 PLHIV using antiretroviral treatment. Cannabis and tobacco use were assessed by self-questionnaire MATE-Q, and cannabis use was validated by metabolomic mass spectrometry. Systemic inflammation was assessed using targeted proteomics to assess a total of 2365 plasma proteins. Immune function was assessed by extensive phenotyping of circulating immune cells using flow cytometry, and assessing ex vivo cytokine production capacity of peripheral blood mononuclear upon bacterial, fungal and viral stimulation. The relation between these omics data and the use of cannabis was assessed correcting for age, sex, tobacco use and multiple hypothesis testing.

Results:

Cannabis use was associated with an upregulation of 15 and a downregulation of 50 proteins. Downregulated proteins in cannabis users were involved in leukocyte-mediated cytotoxicity and NK cell-mediated cytotoxicity. Regarding immune function, 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 IL1A. Extensive flow cytometry showed that cannabis use was associated with increased levels of CD27+CD21- B-cells only. In contrast, tobacco use was associated with an extensive upregulation of systemic immune-related proteins, increased ex vivo production of various cytokines, as well as extensive alternations in immune cell phenotypes.

Conclusions:

Our results suggest that cannabis has systemic anti-inflammatory effects, and little effect on immune function, even when used by inhalation. Based on our data, no conclusions can be drawn regarding local immunological effect of cannabis in the airways. Given the increasing legalization of cannabis use worldwide, future research on the health effects of cannabis inhalation is of crucial importance, especially for PLHIV.