Precision Nanomedicine · Published 2025-07-02 · DOI 10.33218/001c.141764
Liposomal synthetic cannabidiol (LPT-CBD) is an injectable drug designed for sustained CBD release into the bloodstream. While Epidiolex, an oral CBD drug, is FDA-approved for epilepsy, the safety of its major human metabolite, 7-carboxy-CBD (7-COOH-CBD), remains unclear. To further investigate the safety of this major metabolite, a suitable animal model is needed that ac-curately reflects human levels. This study investigated the pharmacokinetics (PK) and prelimi-nary safety of subcutaneous LPT-CBD injection in rabbits and minipigs, predicted to emulate CBD human metabolism by producing high 7-COOH-CBD levels. Rabbits received doses of 12, 24, and 30 mg/kg LPT-CBD, with PK monitoring at 24 mg/kg, demonstrating sustained CBD release over 10 days. Peak CBD plasma concentra-tions were observed within 2 days; however, 7-COOH-CBD levels did not accurately mimic hu-man metabolism. The brain distribution of CBD was evaluated in all rabbits, presenting a dose-proportional level. Minipigs, administered doses of 5, 7.5, and 10 mg/kg, exhibited prolonged CBD PK, with plasma concentrations peaking within a day, and a half-lives of 4.4–7.6 days. Im-portantly, 7-COOH-CBD plasma levels exceeded those of CBD at all doses, with area under the curve values 19-100 times higher than those of CBD, aligning with human data. Safety evalua-tions in minipigs, including clinical assessments and histopathology, confirmed good tolerability with minimal injection site reactions. This study supports the prolonged PK profile of CBD fol-lowing a single subcutaneous injection of LPT-CBD, accompanied by detectable levels in the brain. Minipigs exhibited similar CBD metabolism to 7-COOH-CBD as humans do, offering a promising translational model. These findings highlight the therapeutic potential of LPT-CBD and provide initial data on PK and safety profiles.
Abstract from DOAJ. Public domain (CC0 1.0).
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