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MDMB-CHMICA induces thrashing behavior, bradycardia, and slow pressor response in a CB1- and CB2-receptor-dependent manner in conscious rats

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Abstract

Purpose

MDMB-CHMICA, a new synthetic cannabinoid (SC), has become prevalent since 2014 as an ingredient of recreational drugs. Reports on intoxication due to the drug have been increasing, which show diverse cardiovascular, psychiatric, and neuronal symptoms. Reports on sudden death and accidental death related to psychiatric disorders in MDMB-CHMICA intoxication have also increased, but the underlying mechanisms are largely unknown.

Methods

As there has been no experimental study on the drug, we investigated the effects of peripheral injection of MDMB-CHMICA in conscious rats.

Results

MDMB-CHMICA induced rapid bradycardia and a slow pressor response. Cardiovascular responses to other SCs have been shown to be inhibited only by cannabinoid receptor-1 (CB1)-antagonists. However, the MDMB-CHMICA-induced bradycardia was inhibited not only by a CB1-antagonist, AM281, but also by a CB2-antagonist, AM630. Unlike other SCs, MDMB-CHMICA induced a gradual increase in mean blood pressure, which was marginally enhanced by the CB1- and CB2- antagonists. For the first time, we demonstrated that MDMB-CHMICA induces a thrashing hypermobile behavior in a CB1- and CB2-receptor-dependent manner, following catalepsy-like hypomobile behavior.

Conclusions

This unexpected response to MDMB-CHMICA may help explain the mechanisms underlying the sudden deaths and accidents associated with its use.

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Acknowledgements

This study is supported by a grant-in-aid of the Ministry of Education, Culture, Sports and Technology of Japan (No. 16K09218). We would like to thank Editage (www.editage.jp) for English language editing.

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Authors and Affiliations

  1. Department of Forensic Medicine, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan

    Hideyuki Maeda, Erika Nagashima & Ken-ichi Yoshida

  2. Department of Pathological Physiology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan

    Yukiko K. Hayashi

  3. Division of Pharmacognosy, Phytochemistry and Narcotics, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan

    Ruri Kikura-Hanajiri

Authors
  1. Hideyuki Maeda
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  2. Erika Nagashima
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  5. Ken-ichi Yoshida
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Correspondence to Ken-ichi Yoshida.

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There are no financial or other relations that could lead to a conflict of interest.

Ethical approval

The use of animals for this study was approved by the Experimental Animal Committee of Tokyo Medical University (approval number: S28066). This article does not contain any studies with human participants.

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Maeda, H., Nagashima, E., Hayashi, Y.K. et al. MDMB-CHMICA induces thrashing behavior, bradycardia, and slow pressor response in a CB1- and CB2-receptor-dependent manner in conscious rats. Forensic Toxicol 36, 313–319 (2018). https://doi.org/10.1007/s11419-018-0405-1

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  • DOI: https://doi.org/10.1007/s11419-018-0405-1

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