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Toxic by design? Formation of thermal degradants and cyanide from carboxamide-type synthetic cannabinoids CUMYL-PICA, 5F-CUMYL-PICA, AMB-FUBINACA, MDMB-FUBINACA, NNEI, and MN-18 during exposure to high temperatures



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 of 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.


Compounds were heated sequentially to 200, 400, 600 and 800 °C using a thermolysis probe, and the resultant thermolysis products were analysed via gas chromatography–mass spectrometry. A secondary analysis quantified thermolytically generated cyanide via liquid chromatography–tandem mass spectrometry.


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 general degradative pathways for carboxamide-type synthetic cannabinoids, which proceed via indole- or indazole-amide formation and subsequent dehydration to an indole- or indazole-carbonitrile. These degradative pathways culminated in the thermolytic liberation of cyanide, in amounts up to 27 µg per mg of starting material.


People who smoke carboxamide-type synthetic cannabinoids are likely to be exposed to a range of potentially toxic thermal degradants, including cyanide. These degradants could have significant health impacts in human users.

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This work was supported by research grant funding to BFT from the National Institute on Drug Abuse (1R01DA-040460), and to JLW from the National Institutes of Health (DA-03672). ISM was supported by a National Health and Medical Research Council Fellowship.

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Correspondence to Richard C. Kevin.

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Kevin, R.C., Kovach, A.L., Lefever, T.W. et al. Toxic by design? Formation of thermal degradants and cyanide from carboxamide-type synthetic cannabinoids CUMYL-PICA, 5F-CUMYL-PICA, AMB-FUBINACA, MDMB-FUBINACA, NNEI, and MN-18 during exposure to high temperatures. Forensic Toxicol 37, 17–26 (2019).

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  • Synthetic cannabinoids
  • Toxicity
  • Carboxamides
  • Thermolytic products
  • Cyanide
  • Degradants