Four-Week Oral Pseudocannabinoid, H2CBD, Improved Redox Imbalance in a Rat Model of Metabolic Syndrome

Cardiovascular disease (CVD) remains the number one cause of death in the world, with an increasing prevalence in the United States. Metabolic Syndrome (MetS) is a precursor of CVD with its 6 cluster risk factors individually associated with redox imbalance. There is developing knowledge that cannabidiol analogs and pseudocannabinoids such as H2CBD have similar antioxidant properties like those in phytocannabinoids (CBD). Nonetheless, there is little understanding of the impact of CBD or its analogs on MetS related cardiac damage. To better comprehend these effects during early metabolic dysfunction, 15-weeks-old animals were assigned into three groups, (n=8/group): (1) lean-strain control, Long Evans Tokushima Otsuka (LETO) rats, (2) untreated, Otsuka Long Evans Tokushima Fatty (OLETF) rats, and (3) OLETF + H2CBD (200 mg/kg/day x 4 weeks). Our hypothesis is that continuous treatment with H2CBD during MetS reduces indicators of cardiac oxidation (NOX2 and NOX4) and injury (4-hydroxynonenal;4HNE and 3-nitrotyrosine; 3NT). After four-weeks, H2CBD decreased cardiac 4HNE and 3NT expression by 56% (p<0.05) compared to untreated OLETF, indicating that H2CBD reduced cardiac lipid peroxidation and tyrosine oxidation. Continued research on NOX2 and NOX4 will provide additional insight to the mechanisms by which CBD and its analogs modifies redox regulatory pathways. These findings highlight the potential of CBD and its analytes as an emerging therapeutic to mitigate MetS associated CVD. Center Medical Cannabis Research pilot Grant A21-0086 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.