Neuroinflammation is an important contributor to HIV-associated neurocognitive disorders, in part because inflammatory monocytes can migrate into the brain and activate astrocytes. In this laboratory study, both THC and CBD reduced the production of several inflammatory mediators—including IL-6, IL-8, and MCP-1—during interactions between CD16+ monocytes and astrocytes. THC showed an additional effect not observed with CBD: it suppressed monocyte migration, including the heightened migration seen in cells from people with HIV. The findings suggest that THC, and to a lesser extent CBD, may influence multiple immune mechanisms involved in HIV-associated neuroinflammation and warrant further investigation as potential therapeutic targets.
“CD16+ monocytes are a minor subset of the total monocyte population that play a disproportionate role in contributing to neuroinflammation in human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND).
This has been evidenced by the enhanced transmigration of CD16+ monocytes into the brain compared to their CD16– counterpart. CD16+ monocytes can be activated by HIV ssRNAs through toll-like receptors (TLR) 7 and TLR8, and subsequently interact with brain-resident cells, including astrocytes. Previous studies from our laboratory identified monocyte-derived IL-1ß as an inducing cytokine for astrocyte-derived neuroinflammatory factors.
Despite cannabis use among the HIV community, the mechanisms by which immune-modulating cannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), alter human immune responses in the context of HAND-associated neuroinflammation remain elusive.
We hypothesized that THC and CBD suppress CD16+ monocyte-induced astrocyte secretion of inflammatory mediators and monocyte recruitment via chemotaxis in the context of HIV.
Results from this study show that THC and CBD impair CD16+ monocyte IL-1ß-mediated astrocyte production of IL-6, IL-8, and MCP-1 when these two cell types are cocultured in the presence of TLR7 or TLR8 stimulation. Additionally, monocytes from HIV+ subjects exhibited enhanced migration compared to monocytes from HIV- subjects, which was suppressed by THC treatment but not by CBD. The effects on migration were associated with reduced cellular expression of polymerized actin and high-affinity conformation integrin receptors.
Collectively, these findings suggest that THC, and to a lesser extent CBD, may have therapeutic potential for mitigating CD16+ monocyte-mediated neuroinflammation associated with HAND.”
https://pubmed.ncbi.nlm.nih.gov/42400870
“Taken together, this study provides evidence to support that THC, and to a lesser extent CBD, exert anti-inflammatory effects on CD16+ monocyte-mediated inflammatory and migratory responses that may be associated with HAND.”
https://link.springer.com/article/10.1007/s11481-026-10300-2