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Chem Res Toxicol. 2012 Apr 16;25(4):825-7. doi: 10.1021/tx3000472. Epub 2012 Mar 15.

A major glucuronidated metabolite of JWH-018 is a neutral antagonist at CB1 receptors.

Author information

1
Public Health Laboratory, Arkansas Department of Health , Little Rock, Arkansas 72205, USA. katie.seely@arkansas.gov

Abstract

Recently, hydroxylated metabolites of JWH-018, a synthetic cannabinoid found in many K2/Spice preparations, have been shown to retain affinity and activity for cannabinoid type 1 receptors (CB1Rs). The activity of glucuronidated metabolites of JWH-018 is not known; hence, this study investigated the affinity and activity of a major metabolite, JWH-018-N-(5-hydroxypentyl) β-D-glucuronide (018-gluc), for CB1Rs. The 018-gluc binds CB1Rs (K(i) = 922 nM), has no effect on G-protein activity, but antagonizes JWH-018 activity at CB1Rs. The data suggests that hydroxylation by cytochrome P450s and subsequent glucuronidation by UDP-glucuronosyltransferases produces a metabolite, 018-gluc, which possesses antagonistic activity at CB1Rs.

PMID:
22404317
PMCID:
PMC3921679
DOI:
10.1021/tx3000472
[Indexed for MEDLINE]
Free PMC Article

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