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@ARTICLE{Esdar:1021216,
      author       = {Esdar, Nicole and Pawlik, Evelyn and Eickhoff, Simon B. and
                      Raupach, Annika and Ritz-Timme, Stefanie and Mayer, Felix},
      title        = {{C}ardiac effects of 5{F}-{C}umyl-{PEGACLONE}},
      journal      = {International journal of legal medicine},
      volume       = {138},
      issn         = {0367-0031},
      address      = {Getzville, NY},
      publisher    = {HeinOnline},
      reportid     = {FZJ-2024-00657},
      pages        = {823-831},
      year         = {2024},
      abstract     = {Synthetic cannabinoids become increasingly popular as a
                      supposedly safe and legal alternative to cannabis. In order
                      to circumvent the German New Psychoactive Substances Law,
                      producers of so-called herbal mixtures rapidly design new
                      substances with structural alterations that are not covered
                      by the law. Acting as full agonists not only at the
                      cannabinoid receptors 1 and 2, synthetic cannabinoids might
                      have not only desired mental but also serious physical
                      adverse effects. However, knowledge of adverse effects of
                      specific substances is sparse and incomplete. This also
                      accounts for 5F-Cumyl-PEGACLONE, a synthetic cannabinoid,
                      which has been detected regularly in Germany in recent
                      years. By using an animal model, the isolated perfused
                      Langendorff heart, the study at hand aimed on finding out
                      more about possible cardiovascular adverse effects of
                      5F-Cumyl-PEGACLONE. Hearts of male Wistar rats, which were
                      excised postmortem, were exposed to two different
                      concentrations of 5F-Cumyl-PEGACLONE: 13 hearts were exposed
                      to 50 ng/ml and 12 hearts were exposed to 100 ng/ml.
                      Thirteen control hearts were merely exposed to an additional
                      amount of buffer solution. Functional parameters heart rate,
                      minimal and maximum left ventricular pressure and coronary
                      flow were documented at pre-defined time points during and
                      after the administration of 5F-Cumyl-PEGACLONE/additional
                      buffer solution. Electrocardiograms (ECGs) were documented
                      throughout the experiments and evaluated afterwards.
                      Kruskal–Wallis analysis was performed for each functional
                      parameter as well as for the duration of the QRS complexes
                      and the duration of RR intervals as derived from the ECGs.
                      Furthermore, a multivariate analysis, comprising all
                      functional and ECG parameters, was performed.
                      Kruskal–Wallis analysis revealed only single significant
                      p-values for QRS duration and minimum left ventricular
                      pressure that did not pass a Bonferroni test. The results of
                      the multivariate approach were also comparably homogeneous,
                      but still the model correctly recognized hearts exposed to
                      100 ng/ml of 5F-Cumyl-PEGACLONE more often than hearts
                      exposed to the low concentration of 5F-Cumyl-PEGACLONE or
                      additional buffer solution. Evaluation of the ECGs presented
                      single cases of ST depression and QT prolongation. Though
                      certainly not unambiguous, these findings support the
                      assumption that 5F-Cumyl-PEGACLONE can cause severe, if not
                      lethal, cardiac adverse effects like arrhythmias or
                      myocardial infarctions especially if it is consumed in
                      combination with other drugs like alcohol or if the consumer
                      suffers from pre-existing heart diseases.},
      cin          = {INM-7},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-7-20090406},
      pnm          = {5251 - Multilevel Brain Organization and Variability
                      (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5251},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {38214738},
      UT           = {WOS:001141933800001},
      doi          = {10.1007/s00414-023-03146-3},
      url          = {https://juser.fz-juelich.de/record/1021216},
}