Title:Sulfaphenazole and α-Naphthoflavone Attenuate the Metabolism of the Synthetic Cannabinoids JWH-018 and AM2201 Found in K2/Spice
VOLUME: 7 ISSUE: 1
Author(s):Krishna C. Chimalakonda, Laura P. James, Anna Radominska-Pandya and Jeffery H. Moran
Affiliation:Arkansas Department of Health, Public Health Laboratory, 201 S. Monroe Street, Little Rock, AR, 72205, USA.
Keywords:AM2201, Cytochrome P450, JWH-018, K2/Spice, Synthetic cannabinoids.
Abstract:“K2” or “Spice” is an emerging drug of abuse that is laced with psychoactive synthetic cannabinoids JWH-018
and AM2201. Previous studies have identified hydroxylated (OH) and carboxylated (COOH) species as primary human
metabolites, and kinetic studies have implicated CYP2C9 and -1A2 as major hepatic P450s involved in JWH-018 and
AM2201 oxidation. The present study extends these findings by testing the hypothesis that CYP2C9- and 1A2-selective
chemical inhibitors, sulfaphenazole (SFZ) and -naphthoflavone (ANF), block oxidation of JWH-018 and AM2201 in
human liver microsomes (HLM). A concentration-dependent inhibition of JWH-018 and AM2201 oxidation was observed
in the presence of increasing concentration of SFZ (0.5 – 50 μM) and ANF (0.1 – 5.0 μM). No metabolic inhibition was
observed with omeprazole, quinidine, and ketoconazole. The results presented herein further demonstrate the importance
of CYP2C9- and 1A2-mediated oxidation of JWH-018 and AM2201 and the likelihood of adverse toxicity in populations
with polymorphic alleles of these enzymes.
