Chronic cannabidiol (CBD) treatment reduced excessive brain inflammation and partially restored impaired immune-cell function in a model of Gulf War Illness, according to a new study from researchers at the University of California.
The study examined how Gulf War Illness affects microglia, the brain’s resident immune cells, as animals age. Gulf War Illness is a chronic condition associated with fatigue, pain, cognitive problems and mood disturbances among veterans of the 1990–1991 Persian Gulf War.
Researchers used an established mouse model in which animals were exposed to pyridostigmine bromide and permethrin, two chemicals associated with Gulf War deployment. The mice were aged to 19 months before their brain tissue and microglia were analyzed through several forms of RNA sequencing.
The researchers identified what they described as a “dual” neuroimmune condition in the mice. The brain as a whole was primed to produce an exaggerated inflammatory response, while microglia showed signs of exhaustion and responded abnormally weakly when challenged.
When mice were given lipopolysaccharide, or LPS, to trigger an immune response, the brains of Gulf War Illness mice produced 143 significantly altered genes, compared with 59 among control mice. The Gulf War Illness group also showed 620 enriched biological pathways, more than five times the 116 observed in controls.
Despite the heightened brain-wide response, microglia taken from the same animals were comparatively unresponsive. Control microglia produced 2,768 significantly altered genes following the immune challenge, while Gulf War Illness microglia produced 1,427.
The Gulf War Illness microglia also showed reduced antigen presentation, impaired oxidative phosphorylation and other signs that they were unable to meet the energy demands required for a normal immune response.
Researchers then treated Gulf War Illness mice with 30 milligrams of CBD per kilogram of body weight for 28 consecutive days, followed by maintenance doses every other day for two weeks.
At baseline, CBD reduced biological pathways associated with chronic immune priming. Following the LPS challenge, CBD suppressed the exaggerated inflammatory response throughout the brain, including pathways involved in leukocyte-mediated and lymphocyte-mediated immunity.
CBD also partially restored microglial antigen presentation and increased pathways involved in oxidative phosphorylation and ATP production, suggesting improved cellular energy metabolism. However, it did not fully reverse all aspects of microglial exhaustion.
“Our results indicate that chronic CBD treatment normalizes both arms of the dual phenotype,” the researchers said.
The authors said CBD may work by reducing chronic microglial sensitization while restoring some of the cells’ metabolic and immune capabilities during inflammatory stress.
They cautioned that the findings were based entirely on gene-expression data from male mice. Additional studies will be needed to confirm the effects through functional immune tests and determine whether the results translate to people with Gulf War Illness.
