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Cytotoxicity of the synthetic cannabinoids 5C-AKB48, 5F-MDMB-PINACA, ADB-CHMINACA, MDMB-CHMICA and NM-2201 in A549 and TR146 cell lines

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Abstract

Purpose

The aim of the present study was to evaluate the cytotoxicity of five synthetic cannabinoids in two cell lines, for which both reference standards and herbal blends were available.

Methods

An in-house smoking device was developed to produce smoke condensates. The cell viability of reference standards, herbal blend extracts and smoke condensates was measured using an MTT assay in the A549 lung carcinoma cell line and the TR146 buccal carcinoma cell line. Damiana extracts and damiana smoke condensates were also tested for cytotoxicity.

Results

For the reference standards of 5F-MDMB-PINACA, ADB-CHMINACA and MDMB-CHMICA, a significant concentration-dependent decrease in cell viability was observed. ADB-CHMINACA and MDMB-CHMICA extracts were more potent than the damiana extract, whereas the NM-2201 blend extract abrogated the effects of the damiana leaves. Compared with damiana smoke condensate, MDMB-CHMICA smoke condensate had higher sensitivity, while ADB-CHMINACA smoke condensate was less potent.

Conclusions

This is the first study to investigate the comparative cytotoxicity of reference standards, herbal blend extracts and smoke condensates of synthetic cannabinoids. The data showed that the presence of damiana plant contributed to enhancing the cytotoxicity of 5C-AKB48, 5F-MDMB-PINACA, and MDMB-CHMICA. The plant effects were generally more marked for smoke condensates. MDMB-CHMICA was the most potent substance. The NM-2201 reference standard and extract led to an increase in cell viability as compared to the control. This is of special interest, because the NM-2201 herbal blend extract seemed to abrogate the effects of the damiana leaf extracts. Further studies would be necessary to assess potential procarcinogenic or tumorigenic effects of NM-2201.

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Acknowledgements

The authors would like to thank Christian Bissig of the Forensic Institute Zurich for providing all herbal blend samples and the Institute of Forensic Medicine Freiburg for providing the synthetic cannabinoid reference standards and the damiana, and Dr. Patrick Juchli for fruitful discussion. Further, we would like to acknowledge Severine Krönert, Beatrice Grossen, Tim Gelmi, Andrea Salm, Matthias Bärtschi and Ines Reynoso for their support in the laboratory.

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Authors and Affiliations

  1. Institute of Forensic Medicine, Forensic Toxicology and Chemistry, University of Bern, Bühlstrasse 20, 3012, Bern, Switzerland

    Katharina Elisabeth Grafinger, Alain Broillet & Wolfgang Weinmann

  2. Graduate School for Cellular and Biomedical Sciences, University of Bern, Freiestrasse 1, 3012, Bern, Switzerland

    Katharina Elisabeth Grafinger

  3. Institute of Biochemistry and Molecular Medicine, National Centre of Competence in Research TransCure, University of Bern, Muesmattstrasse 27, 3012, Bern, Switzerland

    Harpreet Kaur Mandhair & Jürg Gertsch

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  1. Katharina Elisabeth Grafinger
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Correspondence to Katharina Elisabeth Grafinger.

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Grafinger, K.E., Mandhair, H.K., Broillet, A. et al. Cytotoxicity of the synthetic cannabinoids 5C-AKB48, 5F-MDMB-PINACA, ADB-CHMINACA, MDMB-CHMICA and NM-2201 in A549 and TR146 cell lines. Forensic Toxicol 37, 398–411 (2019). https://doi.org/10.1007/s11419-019-00474-1

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