Study Finds CBDA May Reduce Neuroinflammation and Improve Brain Insulin Signaling

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Cannabidiolic acid (CBDA), a naturally occurring cannabinoid found in cannabis, reduced several markers of brain inflammation and improved insulin signaling in rats fed a high-fat diet, according to a new study published in Inflammopharmacology.

Researchers from the Medical University of Bialystok and Medical University of Gdańsk used 40 male Wistar rats divided into four groups: a standard-diet control group, a standard-diet group receiving CBDA, a high-fat-diet group and a high-fat-diet group receiving CBDA. The cannabinoid was administered at 0.1 milligrams per kilogram once daily during the final 14 days of the eight-week experiment.

Among rats receiving the high-fat diet, CBDA was associated with reductions in lipid inflammatory mediators and arachidonic acid, along with lower expression of pro-inflammatory cytokines and markers of microglial activation. Researchers also observed improvements in proteins involved in insulin signaling, particularly in the posterior cortex, and increased expression of enzymes involved in glucose metabolism.

“The results suggest an anti-inflammatory role for this cannabinoid,” researchers said, adding that CBDA was “able to exert anti-neuroinflammatory properties” under conditions involving high availability of fatty acids.

CBDA treatment also reduced expression of BACE1, a protein involved in the production of amyloid-beta, in both cortical regions. Levels of brain-derived neurotrophic factor (BDNF) increased in cerebrospinal fluid, while amyloid-beta 42 deposition declined in the frontal cortex.

The study concludes by stating:

Our study demonstrated a preliminary analysis of the impact of CBDA on the inflammatory profile of the brain under conditions of excess calories from fat. The results suggest an anti-inflammatory role for this cannabinoid, particularly in inhibiting the synthesis of lipid inflammatory mediators. Changes in the total content of deposited TAG and DAG lipid fractions and decreased arachidonic acid content in them were concomitant with diminished cyclooxygenase expression and PGE2 and LTB4 content in both frontal and posterior parts of the brain cortex. CBDA also significantly decreased the expression of pro-inflammatory cytokines, which also affected the attenuation of microglial activation markers. Thus, it indicates that CBDA under high availability of fatty acids is able to exert anti-neuroinflammatory properties. Moreover, in addition to changes in lipid deposition and attenuated inflammation, CBDA improved the phosphorylation profile of insulin signaling proteins, especially in the posterior brain cortex, and enhanced expression of enzymes responsible for glucose metabolism in both tissues. The present study also showed decreased BACE1 expression in both brain regions and increased BDNF levels in CSF after CBDA usage. Although the decrease in Aβ42 deposition was observed in the frontal cortex, the CBDA effect on neurodegeneration in our study is only partial and needs further investigation with memory, cognitive, or behavioral testing. Although creatinine, phenylalanine, and sarcosine levels were not affected by HFD, the diminishment in its deposition exerted by CBDA treatment may be both advantageous and disadvantageous in the treatment of some neurological disorders, suggesting a new direction for future studies. However, in our study, the precise mechanism through which CBDA is able to exert the described changes was revealed only partially. We suspect that the observed changes may result from COX-2 inhibition. In future studies, it is necessary to conduct research with specific COX-2 inhibitors to confirm our findings. Moreover, identifying more specific receptors responsible for the observed results is important. The present study sheds light on the need to deepen the knowledge about CBDA as a new therapeutic option.