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Forensic Toxicology

, Volume 36, Issue 2, pp 313–319 | Cite as

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

  • Hideyuki Maeda
  • Erika Nagashima
  • Yukiko K. Hayashi
  • Ruri Kikura-Hanajiri
  • Ken-ichi Yoshida
Original Article

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.

Keywords

MDMB-CHMICA Synthetic cannabinoid CB1-and CB2-receptors Bradycardia Thrashing hypermobile behavior In vivo pharmacology 

Notes

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.

Compliance with ethical standards

Conflict of interest

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.

Supplementary material

SV. 1 Temporal change in video recordings of MDMB-CHMICA-treated rats (upper panel), and the graph on the mobility parameters analyzed from the digital image using EthoVision (lower panel): immobile (green), mobile (red), and hypermobile (blue). Tap the time-scale panel in the bottom to see the temporal changes.

11419_2018_405_MOESM1_ESM.mp4 (21.5 mb)
Supplementary material 1 (MP4 22019 kb)

SV. 2 Effects of the CB1-antagonist, AM281, on the temporal changes in the behaviors of MDMB-CHMICA-treated rats, as shown in SV. 1.

11419_2018_405_MOESM2_ESM.mp4 (2.7 mb)
Supplementary material 2 (MP4 2765 kb)

SV. 3 Effects of the CB2-antagonist, AM630, on the temporal changes in the behaviors of MDMB-CHMICA-treated rats, as shown in SV. 1.

11419_2018_405_MOESM3_ESM.mp4 (3.6 mb)
Supplementary material 3 (MP4 3695 kb)

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Copyright information

© Japanese Association of Forensic Toxicology and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  • Hideyuki Maeda
    • 1
  • Erika Nagashima
    • 1
  • Yukiko K. Hayashi
    • 2
  • Ruri Kikura-Hanajiri
    • 3
  • Ken-ichi Yoshida
    • 1
  1. 1.Department of Forensic MedicineTokyo Medical UniversityTokyoJapan
  2. 2.Department of Pathological PhysiologyTokyo Medical UniversityTokyoJapan
  3. 3.Division of Pharmacognosy, Phytochemistry and NarcoticsNational Institute of Health SciencesTokyoJapan

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