PURPOSE: The use of novel synthetic cannabinoids as intoxicants continues in spite of associated health risks. These compounds are typically smoked or vaporized, but many synthetic cannabinoids contain thermally labile chemical moieties. This study investigated the thermal stability six carboxamide-type synthetic cannabinoids (CUMYL-PICA, 5F-CUMYL-PICA, AMB-FUBINACA, MDMB-FUBINACA, NNEI, and MN-18) in order to characterise potential user exposure to thermolysis products. METHODS: Compounds were heated sequentially to 200, 400, 600 and 800 °C using a thermolysis probe, and the resultant thermolysis products were analysed via GC-MS. A secondary analysis quantified thermolytically generated cyanide via LC-MS/MS. RESULTS: All six synthetic cannabinoids underwent thermal degradation when heated above 400 °C, and released a variety of potentially toxic products, including toluene, naphthalene, and 1-naphthalamine. Compound-specific degradants were tentatively identified together with a general degradative pathway for carboxamide-type synthetic cannabinoids, which proceeds via indole- or indazole-amide formation and subsequent dehydration to an indole- or indazole-carbonitrile. This degradative pathway culminated in the thermolytic liberation of cyanide, in amounts up to 27 μg per mg of starting material. CONCLUSIONS: People who smoke carboxamide-type synthetic cannabinoids are likely to be exposed to range of potentially toxic thermal degradants, including cyanide. These degradants could have significant health impacts in human users.
PURPOSE: The use of novel synthetic cannabinoids as intoxicants continues in spite of associated health risks. These compounds are typically smoked or vaporized, but many synthetic cannabinoids contain thermally labile chemical moieties. This study investigated the thermal stability six carboxamide-type synthetic cannabinoids (CUMYL-PICA, 5F-CUMYL-PICA, AMB-FUBINACA, MDMB-FUBINACA, NNEI, and MN-18) in order to characterise potential user exposure to thermolysis products. METHODS: Compounds were heated sequentially to 200, 400, 600 and 800 °C using a thermolysis probe, and the resultant thermolysis products were analysed via GC-MS. A secondary analysis quantified thermolytically generated cyanide via LC-MS/MS. RESULTS: All six synthetic cannabinoids underwent thermal degradation when heated above 400 °C, and released a variety of potentially toxic products, including toluene, naphthalene, and 1-naphthalamine. Compound-specific degradants were tentatively identified together with a general degradative pathway for carboxamide-type synthetic cannabinoids, which proceeds via indole- or indazole-amide formation and subsequent dehydration to an indole- or indazole-carbonitrile. This degradative pathway culminated in the thermolytic liberation of cyanide, in amounts up to 27 μg per mg of starting material. CONCLUSIONS: People who smoke carboxamide-type synthetic cannabinoids are likely to be exposed to range of potentially toxic thermal degradants, including cyanide. These degradants could have significant health impacts in human users.
Authors: John W Huffman; Gulay Zengin; Ming-Jung Wu; Jianzhong Lu; George Hynd; Kristen Bushell; Alicia L S Thompson; Simon Bushell; Cindy Tartal; Dow P Hurst; Patricia H Reggio; Dana E Selley; Michael P Cassidy; Jenny L Wiley; Billy R Martin Journal: Bioorg Med Chem Date: 2005-01-03 Impact factor: 3.641
Authors: Thomas F Gamage; Charlotte E Farquhar; Ryan J McKinnie; Richard C Kevin; Iain S McGregor; Mark L Trudell; Jenny L Wiley; Brian F Thomas Journal: J Pharmacol Exp Ther Date: 2018-12-14 Impact factor: 4.030