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Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro.
Br J Pharmacol. 2007 Mar; 150(5):613-23.BJ

Abstract

BACKGROUND AND PURPOSE

A nonpsychoactive constituent of the cannabis plant, cannabidiol has been demonstrated to have low affinity for both cannabinoid CB1 and CB2 receptors. We have shown previously that cannabidiol can enhance electrically evoked contractions of the mouse vas deferens, suggestive of inverse agonism. We have also shown that cannabidiol can antagonize cannabinoid receptor agonists in this tissue with a greater potency than we would expect from its poor affinity for cannabinoid receptors. This study aimed to investigate whether these properties of cannabidiol extend to CB1 receptors expressed in mouse brain and to human CB2 receptors that have been transfected into CHO cells.

EXPERIMENTAL APPROACH

The [35S]GTPS binding assay was used to determine both the efficacy of cannabidiol and the ability of cannabidiol to antagonize cannabinoid receptor agonists (CP55940 and R-(+)-WIN55212) at the mouse CB1 and the human CB2 receptor.

KEY RESULTS

This paper reports firstly that cannabidiol displays inverse agonism at the human CB2 receptor. Secondly, we demonstrate that cannabidiol is a high potency antagonist of cannabinoid receptor agonists in mouse brain and in membranes from CHO cells transfected with human CB2 receptors.

CONCLUSIONS AND IMPLICATIONS

This study has provided the first evidence that cannabidiol can display CB2 receptor inverse agonism, an action that appears to be responsible for its antagonism of CP55940 at the human CB2 receptor. The ability of cannabidiol to behave as a CB2 receptor inverse agonist may contribute to its documented anti-inflammatory properties.

Authors+Show Affiliations

School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK. a.thomas@ed.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17245363

Citation

Thomas, A, et al. "Cannabidiol Displays Unexpectedly High Potency as an Antagonist of CB1 and CB2 Receptor Agonists in Vitro." British Journal of Pharmacology, vol. 150, no. 5, 2007, pp. 613-23.
Thomas A, Baillie GL, Phillips AM, et al. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br J Pharmacol. 2007;150(5):613-23.
Thomas, A., Baillie, G. L., Phillips, A. M., Razdan, R. K., Ross, R. A., & Pertwee, R. G. (2007). Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. British Journal of Pharmacology, 150(5), 613-23.
Thomas A, et al. Cannabidiol Displays Unexpectedly High Potency as an Antagonist of CB1 and CB2 Receptor Agonists in Vitro. Br J Pharmacol. 2007;150(5):613-23. PubMed PMID: 17245363.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. AU - Thomas,A, AU - Baillie,G L, AU - Phillips,A M, AU - Razdan,R K, AU - Ross,R A, AU - Pertwee,R G, Y1 - 2007/01/22/ PY - 2007/1/25/pubmed PY - 2007/5/11/medline PY - 2007/1/25/entrez SP - 613 EP - 23 JF - British journal of pharmacology JO - Br J Pharmacol VL - 150 IS - 5 N2 - BACKGROUND AND PURPOSE: A nonpsychoactive constituent of the cannabis plant, cannabidiol has been demonstrated to have low affinity for both cannabinoid CB1 and CB2 receptors. We have shown previously that cannabidiol can enhance electrically evoked contractions of the mouse vas deferens, suggestive of inverse agonism. We have also shown that cannabidiol can antagonize cannabinoid receptor agonists in this tissue with a greater potency than we would expect from its poor affinity for cannabinoid receptors. This study aimed to investigate whether these properties of cannabidiol extend to CB1 receptors expressed in mouse brain and to human CB2 receptors that have been transfected into CHO cells. EXPERIMENTAL APPROACH: The [35S]GTPS binding assay was used to determine both the efficacy of cannabidiol and the ability of cannabidiol to antagonize cannabinoid receptor agonists (CP55940 and R-(+)-WIN55212) at the mouse CB1 and the human CB2 receptor. KEY RESULTS: This paper reports firstly that cannabidiol displays inverse agonism at the human CB2 receptor. Secondly, we demonstrate that cannabidiol is a high potency antagonist of cannabinoid receptor agonists in mouse brain and in membranes from CHO cells transfected with human CB2 receptors. CONCLUSIONS AND IMPLICATIONS: This study has provided the first evidence that cannabidiol can display CB2 receptor inverse agonism, an action that appears to be responsible for its antagonism of CP55940 at the human CB2 receptor. The ability of cannabidiol to behave as a CB2 receptor inverse agonist may contribute to its documented anti-inflammatory properties. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/17245363/Cannabidiol_displays_unexpectedly_high_potency_as_an_antagonist_of_CB1_and_CB2_receptor_agonists_in_vitro_ L2 - https://doi.org/10.1038/sj.bjp.0707133 DB - PRIME DP - Unbound Medicine ER -