9-Tetrahydrocannabinol, a major marijuana component, enhances the anesthetic effect of pentobarbital through the CB1 receptor
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...
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Published in | Forensic toxicology Vol. 37; no. 1; pp. 207 - 214 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Singapore
Springer Singapore
01.01.2019
Springer Japan |
Subjects | |
Online Access | Get full text |
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Summary: | 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 cannabinoid
1
(CB
1
) receptor binding assay using CB
1
antagonists to clarify whether the CB
1
receptor is involved in the synergism or not. The affinities of cannabinoids for the CB
1
receptor in the mouse brain synaptic membrane were evaluated using a specific CB
1
ligand, [
3
H]CP55940.
Results
Although the potentiating effect of ∆
9
-THC on pentobarbital-induced sleep was attenuated by co-administration of CB
1
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 CB
1
receptor, respectively. A high concentration of pentobarbital (1 mM) did not affect specific [
3
H]CP55940 binding on the mouse brain synaptic membrane.
Conclusions
These results suggest that binding of ∆
9
-THC to the CB
1
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 CB
1
receptor. |
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ISSN: | 1860-8965 1860-8973 |
DOI: | 10.1007/s11419-018-0457-2 |