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Forensic Toxicology
Published in: Forensic Toxicology 1/2019

Open Access 01-01-2019 | Original Article

∆9-Tetrahydrocannabinol, a major marijuana component, enhances the anesthetic effect of pentobarbital through the CB1 receptor

Authors: Toshiyuki Kimura, Makiko Takaya, Noriyuki Usami, Kazuhito Watanabe, Ikuo Yamamoto

Published in: Forensic Toxicology | Issue 1/2019

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Abstract

Purpose

∆9-Tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD), major psychoactive constituents of marijuana, induce potentiation of pentobarbital-induced sleep in mice. We have elucidated the mechanism of enhancement of the anesthetic effect of pentobarbital by cannabinoids.

Methods

We carried out pharmacological experiment and cannabinoid1 (CB1) receptor binding assay using CB1 antagonists to clarify whether the CB1 receptor is involved in the synergism or not. The affinities of cannabinoids for the CB1 receptor in the mouse brain synaptic membrane were evaluated using a specific CB1 ligand, [3H]CP55940.

Results

Although the potentiating effect of ∆9-THC on pentobarbital-induced sleep was attenuated by co-administration of CB1 receptor antagonists, such as SR141716A and AM251, at a dose of 2 mg/kg, intravenously (i.v.) to mice, the CBD-enhanced pentobarbital-induced sleep was not inhibited by SR141716A. The inhibitory constant (Ki) values of ∆9-THC and CBD were 6.62 and 2010 nM, respectively, showing a high affinity of ∆9-THC and a low affinity of CBD for the CB1 receptor, respectively. A high concentration of pentobarbital (1 mM) did not affect specific [3H]CP55940 binding on the mouse brain synaptic membrane.

Conclusions

These results suggest that binding of ∆9-THC to the CB1 receptor is involved in the synergism with pentobarbital, and that potentiating effect of CBD with pentobarbital may differ from that of ∆9-THC. We successfully demonstrated that ∆9-THC enhanced the anesthetic effect of pentobarbital through the CB1 receptor.
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Metadata
Title
∆9-Tetrahydrocannabinol, a major marijuana component, enhances the anesthetic effect of pentobarbital through the CB1 receptor
Authors
Toshiyuki Kimura
Makiko Takaya
Noriyuki Usami
Kazuhito Watanabe
Ikuo Yamamoto
Publication date
01-01-2019
Publisher
Springer Singapore
Published in
Forensic Toxicology / Issue 1/2019
Print ISSN: 1860-8965
Electronic ISSN: 1860-8973
DOI
https://doi.org/10.1007/s11419-018-0457-2

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