Impact of a synthetic cannabinoid CP47497C8 o

Authors: Andrea Bileck Franziska Ferk Halh AlSerori Verena J Koller Besnik Muqaku Alexander Haslberger Volker Auwärter Christopher Gerner Siegfried Knasmüller

Publish Date: 2015/07/21

Volume: 90, Issue: 6, Pages: 1369-1382

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Abstract

Synthetic cannabinoids SCs are marketed worldwide as legal surrogates for marihuana In order to predict potential health effects in consumers and to elucidate the underlying mechanisms of action we investigated the impact of a representative of the cyclohexylphenols CP47497C8 which binds to both cannabinoid receptors on protein expression patterns genomic stability and on induction of inflammatory cytokines in human lymphocytes After treatment of the cells with the drug we found pronounced upregulation of a variety of enzymes in nuclear extracts which are involved in lipid metabolism and inflammatory signaling some of the identified proteins are also involved in the endogenous synthesis of endocannabinoids The assumption that the drug causes inflammation is further supported by results obtained in additional experiments with cytosols of LPSstimulated lymphocytes which showed that the SC induces proinflammatory cytokines IL12p40 and IL6 as well as TNFα Furthermore the proteome analyses revealed that the drug causes downregulation of proteins which are involved in DNA repair This observation provides an explanation for the formation of comets which was seen in singlecell gel electrophoresis assays and for the induction of micronuclei which reflect structural and numerical chromosomal aberrations by the drug These effects were seen in experiments with human lymphocytes which were conducted under identical conditions as the proteome analysis Taken together the present findings indicate that the drug and possibly other structurally related SCs may cause DNA damage and inflammation in directly exposed cells of consumers

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