title: Cytotoxicity of synthetic cannabinoids found in "Spice" products: the role of cannabinoid receptors and the caspase cascade in the NG 108-15 cell line.
abstract: The worldwide distribution of "Spice" that contains synthetic cannabinoids with a pharmacological activity similar to Δ⁹-tetrahydrocannabinol has been reported. In the current study, we evaluated the cytotoxicity of the synthetic cannabinoids, CP-55,940, CP-47,497 and CP-47,497-C8 towards NG 108-15 cells and investigated their mechanism of cytotoxicity. CP-55,940, CP-47,497 and CP-47,497-C8 were all cytotoxic for NG 108-15 cells in a concentration-dependent manner. The cytotoxicity of these synthetic cannabinoids was suppressed by preincubation with the selective CB₁ receptor antagonist AM251, but not with the selective CB₂ receptor antagonist AM630. Preincubation with a caspase-3 inhibitor significantly suppressed the cytotoxicity of these synthetic cannabinoids for NG 108-15 cells. Induction of apoptosis by these cannabinoids was also confirmed by staining of the cells with annexin V. Our results indicate that the cytotoxicity of synthetic cannabinoids towards NG 108-15 cells is mediated by the CB₁ receptor, but not by the CB₂ receptor, and further suggest that caspase-cascades may play an important role in the apoptosis induced by these synthetic cannabinoids.
authors: Department of Drug Dependence Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, Japan.
authors: Kenichi
authors: K
authors: Tomiyama
authors: Masahiko
authors: M
authors: Funada
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D002186:Cannabinoids / Q000037:antagonists & inhibitors / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism*; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003511:Cyclohexanols / Q000037:antagonists & inhibitors / Q000633:toxicity*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism*
chemical_list: D002186:Cannabinoids; D061945:Caspase Inhibitors; D003511:Cyclohexanols; D015853:Cysteine Proteinase Inhibitors; D007211:Indoles; D009842:Oligopeptides; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C103505:AM 251; C036088:CP 47497; D053148:Caspase 3; C094023:iodopravadoline