Drug Metabolism Letters

Zhiyang Zhao
Cambridge, MA


Sulfaphenazole and α-Naphthoflavone Attenuate the Metabolism of the Synthetic Cannabinoids JWH-018 and AM2201 Found in K2/Spice

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.


“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.

Keywords: AM2201, Cytochrome P450, JWH-018, K2/Spice, Synthetic cannabinoids.

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Article Details

Page: [34 - 38]
Pages: 5
DOI: 10.2174/187231280701131211151523