Study: CBD Reduces Neuroinflammation in Alzheimer’s Model by Targeting Key Immune Pathways

Researchers from Augusta University and the Georgia Institute of Cannabis Research tested CBD in male 5XFAD mice, a widely used Alzheimer’s model. The team focused on two key immune regulators—Indoleamine 2,3-dioxygenase (IDO) and cyclic GMP-AMP synthase (cGAS)—which play central roles in neuroinflammatory signaling. These pathways are increasingly recognized as important drivers of Alzheimer’s beyond the buildup of amyloid-β plaques. The mice received CBD through inhalation, and researchers measured immune responses using gene expression analysis, flow cytometry, and immunofluorescence. They found that CBD treatment led to significant reductions in IDO and cGAS activity. This was associated with lower levels of pro-inflammatory cytokines, including TNF-α, IL-1β, and IFN-γ.

Bioinformatics work further identified possible interactions between CBD and targets such as AKT1, TRPV1, and GPR55, all of which are linked to immune regulation and neuronal health. These findings suggest CBD influences multiple mechanisms tied to inflammation and cell survival.

The results support the growing “autoinflammatory hypothesis” of Alzheimer’s, which proposes that chronic immune dysfunction drives neuronal damage. By dampening upstream inflammatory pathways, CBD could provide a therapeutic option as either a stand-alone or an adjunct treatment. Researchers caution that more work is needed to confirm these effects and determine clinical applications, but the study highlights CBD’s potential to address immune dysfunction at the root of Alzheimer’s disease.

Several studies published in 2025 further reinforce the growing evidence that cannabinoids may help regulate neuroinflammation and neurodegeneration in Alzheimer’s disease. One study reported that CBD reversed over 75% of molecular changes linked to early Alzheimer’s onset—spanning synaptic, metabolic, and immune pathways—in mice. Another investigation using a rat Alzheimer’s model found that chronic CBD treatment improved memory and social behavior while reducing neuroinflammation, with evidence that CB1 receptor activity underlies much of the benefit.

A third study published this year examined the synthetic cannabinoid WIN 55,212-2 in Tg4-42 mice and observed improvements in both cognitive and motor function, along with reductions in microgliosis and enhanced brain glucose metabolism. Together, these works complement the present study by illuminating multiple cannabinoid-linked pathways (beyond amyloid or tau) that may be harnessed in Alzheimer’s therapy.