Jump to main content
Jump to site search
PLANNED MAINTENANCE Close the message box

Scheduled maintenance upgrade on Thursday 4th of May 2017 from 8.00am to 9.00am (BST).

During this time our websites will be offline temporarily. If you have any questions please use the feedback button on this page. We apologise for any inconvenience this might cause and thank you for your patience.

Issue 6, 2016
Previous Article Next Article

Synthetic cannabinoid, JWH-030, induces QT prolongation through hERG channel inhibition

Author affiliations


The problem of new psychoactive substance (NPS) abuse, which includes synthetic cannabinoids, is emerging globally, and the cardiotoxicity of these synthetic cannabinoids has not yet been evaluated extensively. In the present study, we investigated the effects of synthetic cannabinoids on the cytotoxicity, human Ether-à-go-go-related gene (hERG) channel, action potential duration (APD), and QT interval. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that JWH-030 was more cytotoxic than JWH-210, JWH-250, and RCS4 in H9c2 cells at 0.1 μM. In addition, the cytotoxicity was associated with its pro-apoptotic effects as evidenced by the increase in caspase-3 levels. We demonstrated that a cannabinoid receptor type 2 (CB2) antagonist, AM630, inhibited JWH-030-induced cytotoxicity, whereas a CB1 antagonist, rimonabant, did not. Furthermore, fluorescence polarization assay showed JWH-030 to block the hERG channel (half-maximal inhibitory concentration, IC50 was 88.36 μM). JWH-030 significantly reduced the APD at 90% repolarization (APD90) in rabbit Purkinje fibers and decreased the left ventricular end diastolic pressure (LVEDP) in Langendorff-perfused Sprague-Dawley (SD) rat hearts at 30 μM. In addition, the electrocardiogram (ECG) measurement revealed that the intravenous injection of JWH-030 (0.5 mg kg−1) prolonged the QT interval in SD rats. These results suggest that JWH-030 is cytotoxic and its cytotoxicity is mediated by its action on the CB2 receptor; it prolongs the QT interval by regulating ion current channels and APD.

Graphical abstract: Synthetic cannabinoid, JWH-030, induces QT prolongation through hERG channel inhibition

Back to tab navigation
Please wait while Download options loads

Supplementary files

Publication details

The article was received on 13 Jun 2016, accepted on 05 Sep 2016 and first published on 07 Sep 2016

Article type: Paper
DOI: 10.1039/C6TX00259E
Citation: Toxicol. Res., 2016,5, 1663-1671
  •   Request permissions

    Synthetic cannabinoid, JWH-030, induces QT prolongation through hERG channel inhibition

    J. Yun, K. S. Yoon, T. Lee, H. Lee, S. M. Gu, Y. J. Song, H. J. Cha, K. M. Han, H. Seo, J. Shin, H. Park, H. S. Kim and Y. Kim, Toxicol. Res., 2016, 5, 1663
    DOI: 10.1039/C6TX00259E

Search articles by author