Cannabidiol (CBD) is a phytocannabinoid from Cannabis sativa L., in which there is currently growing interest for medicinal use. Here, we focused on the safety and pharmacokinetics of a CBD-rich (77 %, w/w) full-spectrum hemp extract in male and female rats. A 90-day sub-chronic toxicity assay was conducted with doses of 0.5, 5, 10, and 35 mg CBD extract/kg/day administered orogastrically. No adverse effects or disruption in organ or body weight, behaviour, locomotion, food intake, or impact on morbidity/mortality were observed. Pathomorphological examination showed no gastrointestinal or liver changes. Blood cell analysis showed a significant (p < 0.05) decrease in the number of leukocytes for both sexes, and a significant difference (p < 0.01 or 0.05) between the control and treated animals for mean corpuscular haemoglobin concentration, mean corpuscular volume of erythrocytes, and number of neutrophils and monocytes. However, blood cell analysis revealed significant (p < 0.05) sex-dependent differences, such as haematocrit and erythrocyte count. The levels of ions (Ca2+, Na+, K+ and Cl-), alkaline phosphatase, and creatinine in treated animals were also observed for both sexes. Males exhibited decreased alanine transaminase levels, and females exhibited hyperalbuminemia (p < 0.01). CBD was quantified in treated animals in a dose-dependent manner, with statistical significance varying from p < 0.05 to 0.0001. The accumulation of CBD in the individual tissues increased in the order: brain < serum < liver < heart << kidney <<< muscle and skin. The results indicated sex-dependent latent disruption of kidney and liver homeostasis, most likely reversible in nature.
Keywords: Biodistribution; CBD hemp extract; Cross-gender study; Organ accumulation; Safety; Sub-chronic toxicity; cannabis.
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