Faculty and Student Publications
Document Type
Article
Publication Date
1-1-2019
Abstract
© 2019 by the authors. The goal of this study was to investigate the potential for a cannabidiol-rich cannabis extract (CRCE) to interact with the most common over-the-counter drug and the major known cause of drug-induced liver injury–acetaminophen (APAP)–in aged female 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 three consecutive days followed by intraperitoneally (i.p.) acetaminophen (APAP) administration (400 mg/kg) on day 4 resulted in overt toxicity with 37.5% mortality. No mortality was observed in mice treated 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 degree of alterations in physiological and clinical biochemistry end points. Mechanistically, glutathione depletion and oxidative stress were observed between the APAP-only and co-administration groups, but co-administration resulted in much greater activation of c-Jun N-terminal kinase (JNK). Strikingly, these effects were not observed in mice gavaged with 290 mg/kg CBD in CRCE followed by APAP administration. These findings highlight the potential for CBD/drug interactions, and reveal an interesting paradoxical effect of CBD/APAP-induced hepatotoxicity.
Relational Format
journal article
Recommended Citation
Hamerly, T., Tweedell, R. E., Hritzo, B., Nyasembe, V. O., Tekwani, B. L., Nanayakkara, N. P. D., Walker, L. A., & Dinglasan, R. R. (2019). NPC1161B, an 8-Aminoquinoline Analog, Is Metabolized in the Mosquito and Inhibits Plasmodium falciparum Oocyst Maturation. Frontiers in Pharmacology, 10, 1265. https://doi.org/10.3389/fphar.2019.01265
DOI
10.3389/fphar.2019.01265