The objective of this examine was to research the potential for a cannabidiol-rich cannabis extract (CRCE) to work together with the most typical over-the-counter drug and the key recognized explanation for drug-induced liver injury-acetaminophen (APAP)-in aged feminine CD-1 mice. Gavaging mice with 116 mg/kg of cannabidiol (CBD) [mouse equivalent dose (MED) of 10 mg/kg of CBD] in CRCE delivered with sesame oil for 3 consecutive days adopted by intraperitoneally (i.p.) acetaminophen (APAP) administration (400 mg/kg) on day four resulted in overt toxicity with 37.5% mortality. No mortality was noticed in mice handled with 290 mg/kg of CBD+APAP (MED of 25 mg/kg of CBD) or APAP alone. Following CRCE/APAP co-administration, microscopic examination revealed a sinusoidal obstruction syndrome-like liver injury-the severity of which correlated with the diploma of alterations in physiological and medical biochemistry finish factors. Mechanistically, glutathione depletion and oxidative stress had been noticed between the APAP-only and co-administration teams, however co-administration resulted in a lot better activation of c-Jun N-terminal kinase (JNK). Strikingly, these results weren’t noticed in mice gavaged with 290 mg/kg CBD in CRCE adopted by APAP administration. These findings spotlight the potential for CBD/drug interactions, and reveal an attention-grabbing paradoxical impact of CBD/APAP-induced hepatotoxicity.