Distinct circulating monocyte profiles in chronic cannabis users compared to cocaine users without changes in plasma levels of proinflammatory cytokines and LPS.

Abstract

Objectives: Chronic cannabis use is linked to anti-inflammatory effects, and cocaine exhibits context-dependent immunomodulation; their distinct impacts on monocyte subsets and systemic inflammation are not fully understood. Systemic microbial translocation contributes to monocyte differentiation, but the levels in chronic cocaine and cannabis users in humans in vivo are lacking.

Methods: Peripheral blood mononuclear cells (PBMCs) and plasma samples were collected from chronic cocaine users, cannabis users, and non-drug users. The route of drug administration was via smoking or snorting. Monocyte subsets were analyzed using flow cytometry; plasma levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) and lipopolysaccharide (LPS, a marker of microbial translocation) were measured using a Meso Scale immunoassay and Limulus amoebocyte lysate assay, respectively.

Results: Cannabis use was associated with increased total monocyte counts, increased percentages of a classical subset (CD14++CD16-), and decreased percentages of a non-classical subset (CD14+CD16++) in CD14+ monocytes compared to cocaine users and/or healthy controls. Similar levels were observed in the percentages of intermediate monocytes (CD14++CD16+) and plasma levels of six cytokines and LPS among the three study groups. Cocaine users exhibited similar frequencies of monocyte subsets, cytokine levels, and LPS levels compared to controls.

Conclusions: Chronic use of cannabis, but not cocaine, is associated with shifts in non-activated monocyte subset distribution, characterized by increased classical and decreased non-classical monocyte subsets, without concurrent systemic cytokine dysregulation or LPS translocation. These findings highlight substance-specific immune effects, potentially affecting long-term immune function.