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

By January 14, 2019 No Comments
2019;37(1):207-214. doi: 10.1007/s11419-018-0457-2. Epub 2018 Nov 24.



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.


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 CB1ligand, [3H]CP55940.


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.


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 CB1receptor.


CB1 receptor; Cannabidiol; Cannabinoid; Pentobarbital-induced sleep; ∆9-Tetrahydrocannabinol

PMID: 30636988
PMCID: PMC6314990
DOI: 10.1007/s11419-018-0457-2

Conflict of interest statement

There are no financial or other relations that could lead to a conflict of interest.All animal experiments were performed in accordance with the institutional guidelines for the care and use of animals. The Ethics Review Committee for Animal Experimentation of Hokuriku University, Kanazawa, Japan, approved the experimental protocol and carried out welfare-related assessment prior to experiments.
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