THC blocked immune cell development by eliminating oxidative stress through a novel mechanism | Research

The takeaway

THC prevented bone marrow cells from developing into macrophages by reducing reactive oxygen species through two pathways: activating antioxidant genes and chemically blocking the Fenton Reaction, independent of known cannabinoid receptors.

People interested in how cannabis affects the immune system at a cellular level.

THC effect was independent of all 5 tested cannabinoid receptors

What the researchers found

THC blocked M-CSF-induced macrophage differentiation from bone marrow cells through a receptor-independent mechanism. RNA-seq showed upregulation of NRF2-ARE antioxidant genes. THC also directly prevented ROS formation via the Fenton Reaction. The effect was independent of CB1, CB2, GPR18, GPR55, and adenosine A2A receptors.

Why it matters

This study reveals a previously unknown way THC affects the immune system: by blocking the development of macrophages through antioxidant mechanisms independent of traditional cannabinoid receptors. This has implications for understanding how cannabis affects immune defense.

The numbers in context

THC blocked differentiation of CD45+CD11b+F4/80+ macrophages. Effect was independent of 5 known receptors (CB1, CB2, GPR18, GPR55, A2A). KEGG pathway analysis linked to ferroptosis and glutathione metabolism. THC-treated cells showed increased iron but decreased ROS.

How the study worked

Bone marrow-derived cells were cultured with M-CSF and THC. Flow cytometry tracked macrophage differentiation markers. RNA sequencing identified affected pathways. Receptor knockout and antagonist studies tested known cannabinoid receptors. Fluorescence assays measured intracellular iron and ROS levels.

What this study cannot tell us

In vitro study using mouse bone marrow cells. The concentrations of THC used may not reflect physiological levels after cannabis use. Blocking macrophage development in a dish does not necessarily translate to impaired immunity in a living organism.

How to read the evidence

Preliminary in vitro study with rigorous mechanistic investigation. While the receptor-independent finding is novel, translation to whole-organism immunity requires further research.

When this study was published

Published in 2024 in Antioxidants.

The bigger picture

Most research on THC and immunity focuses on cannabinoid receptor signaling. This finding that THC can block immune cell development through a completely receptor-independent antioxidant mechanism opens up new questions about how cannabis use might compromise immune surveillance.

Questions still open

Does chronic cannabis use impair macrophage populations in humans? Could this mechanism explain some of the immunosuppressive effects reported with heavy cannabis use? Is the Fenton Reaction-blocking property unique to THC or shared by other cannabinoids?

Common questions

How does THC affect immune cells?

This study found THC prevents bone marrow cells from developing into macrophages (key immune defenders) by eliminating reactive oxygen species, which are normally needed for the differentiation process.

Does this mean cannabis weakens the immune system?

The study shows THC can block immune cell development in laboratory conditions, but whether this translates to meaningful immune impairment in cannabis users requires further research in living organisms.

Read the original research

Delta-9-Tetrahydrocannabinol Blocks Bone Marrow-Derived Macrophage Differentiation through Elimination of Reactive Oxygen Species.

Antioxidants (Basel, Switzerland), 13(8)

View on PubMed ↗Publisher’s paper ↗

Citation

Carter, Taylor H; Weyer-Nichols, Chloe E; Garcia-Sanchez, Jeffrey I; Wilson, Kiesha; Nagarkatti, Prakash; Nagarkatti, Mitzi. (2024). Delta-9-Tetrahydrocannabinol Blocks Bone Marrow-Derived Macrophage Differentiation through Elimination of Reactive Oxygen Species.. Antioxidants (Basel, Switzerland), 13(8). https://doi.org/10.3390/antiox13080887