PSIX-2 The long-term effect of cannabidiol on the circulating metabolome of healthy adult dogs.

Abstract The therapeutic potential of Cannabidiol (CBD), a prominent phytocannabinoid derived from Cannabis sativa, has gained considerable attention in veterinary medicine. This study investigated the long-term effects of a broad-spectrum hemp extract containing >94.60% CBD on the serum metabolome of healthy adult dogs. Eighteen healthy, adult dogs (n=6) on the same commercial food 28 days prior, were randomly assigned to a placebo, 5 mg/kg or 10 mg/kg CBD once daily, for 36 weeks and remaining on the same food. Blood was collected at the start of the study and then every four weeks, just before feeding and administering the oil. Serum samples were analyzed as mixed models with repeated measures; wherein, treatment oil (placebo, 5 and 10 mg/kg) and collection time point (every 4 weeks) were the fixed effects. The interaction term was non-significant in all metabolites, and thus removed from the model and log-fold change (from baseline) was analyzed. Dog was added as the subject and month as the repeated effect. Pairwise comparisons were protected against type I error using Tukey-Kramer adjustment, significance noted at P(FDR) < 0.05. Long-term supplementation of the broad-spectrum CBD significantly shifted 584 metabolites in total. Of which, cannabidiol significantly altered major lipid classes (291/584) including fatty acid synthesis and metabolism in dogs by upregulating molecules in the acyl carnitine pathway (16/584) and various fatty acids (74/584), while down-regulating lysophospholipids (45/584). Additionally, the 5 mg/kg CBD group showed relative reductions s of lysoplasmalogens (9/584), plasmalogens (17/584), sphingomyelins (29/584), eicosanoids 12-HTE, thromboxane B2 and 12-HHTrE, alongside reductions in cortisol, corticosterone, and increases in omega-3 fatty acids, indicating an ability to possibly better control inflammation. Additionally, markers of reduced gut inflammation, such as gamma glutamyl peptides and beneficial indoles, were elevated in both CBD groups. Cannabidiol appeared to have an antioxidant effect, as evidenced by increases in glutathione degradation products and vitamin E derivatives, although vitamin C metabolites decreased. Furthermore, both groups showed increased bile acids and bilirubin degradation products, with dose-dependent elevation of taurine-derived endocannabinoids and reduction of endocannabinoid linoleoyl ethanolamide. Further studies (including those using either a purified CBD formula or a broad-spectrum extract with diverse cannabinoids and terpenes) are needed to explore these findings more deeply, as different formula profiles may produce different changes than the CBD-enriched broad-spectrum hemp extract tested here. The findings of this study provide a global metabolome perspective and indicate that CBD administration impacts various metabolic pathways, suggesting potential therapeutic benefits including anti-inflammatory and neuroprotective effects.