Cannabis use frequency and its impact on monocyte-mediated inflammation in HIV patients

This study examines the relationship between cannabis use and peripheral monocyte-mediated inflammation in people living with HIV. The investigators compared circulating CD16+ monocyte numbers and plasma levels of IFN-γ-inducible protein 10 (IP-10) between HIV-infected cannabis users (HIV+MJ+) and HIV-infected nonusers (HIV+MJ-), and also tested the effects of in-vitro Δ-9-tetrahydrocannabinol (THC), a major cannabis constituent, on monocyte CD16 expression and monocyte-derived IP-10 production. The rationale derives from the role of chronic immune activation and elevated activated monocytes (CD16+) in HIV-associated neuroinflammation; understanding how cannabis exposure influences these peripheral immune parameters could inform mechanisms linking cannabis use to altered inflammatory states in HIV.

Using flow cytometry, the team quantified numbers of CD16+ monocytes and measured plasma IP-10 in whole blood and serum collected from HIV-MJ-, HIV+MJ-, and HIV+MJ+ donors. Peripheral blood mononuclear cells (PBMCs) and purified monocytes from these donor groups were used for in-vitro experiments. PBMCs and monocytes were treated with IFNα to stimulate CD16 induction and IP-10 production, and separate experiments pretreated cells with graded concentrations of THC (0.5–10 μM) before IFNα stimulation to evaluate direct effects of THC on monocyte phenotype and chemokine output.

Key findings reported include a lower level of circulating CD16+ monocytes and reduced plasma IP-10 in HIV+MJ+ donors compared with HIV+MJ- donors, indicating an association between cannabis use and decreased peripheral markers linked to monocyte activation and chemokine-mediated inflammatory signaling. Functionally, monocytes from HIV+MJ+ donors demonstrated an impaired ability to upregulate CD16 in response to IFNα stimulation in vitro, whereas monocytes from HIV-MJ- and HIV+MJ- donors showed pronounced CD16 induction under the same conditions. This differential responsiveness suggests that prior cannabis exposure or ongoing use may alter monocyte responsiveness to interferon-mediated stimuli.

In vitro application of THC corroborated these observational findings: THC treatment reduced the transition of monocytes to CD16+ phenotype and diminished monocyte-derived IP-10 in IFNα-stimulated cultures. Dose-dependent decreases in percentages of CD16+, CD163+, and CD16+CD163+ monocyte subsets were observed with THC pretreatment, and THC—but not cannabidiol (CBD) in tested conditions—decreased these monocyte activation markers and IP-10 production. These results collectively point to anti-inflammatory effects of cannabis constituents, particularly THC, on peripheral monocyte processes implicated in HIV-associated neuroinflammation.

The study concludes that components of cannabis, including THC, may decelerate peripheral monocyte activation and chemokine production processes that contribute to neuroinflammatory pathology in HIV. By combining clinical donor comparisons with mechanistic in-vitro experiments, the work by Kaminski and colleagues provides evidence that cannabis use is associated with reduced circulating activated monocytes and lower IP-10, and that THC can directly impair monocyte activation responses. These findings support further research into how cannabis exposure modulates immune activation in HIV and the potential implications for neuroinflammation and clinical outcomes.