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Rapid CommunicationMinireview

CB2 Cannabinoid Receptors as a Therapeutic Target—What Does the Future Hold?

Amey Dhopeshwarkar and Ken Mackie
Molecular Pharmacology October 2014, 86 (4) 430-437; DOI: https://doi.org/10.1124/mol.114.094649
Amey Dhopeshwarkar
Department of Psychological and Brain Sciences and Gill Center, Indiana University, Bloomington, Indiana
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Ken Mackie
Department of Psychological and Brain Sciences and Gill Center, Indiana University, Bloomington, Indiana
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Abstract

The past decades have seen an exponential rise in our understanding of the endocannabinoid system, comprising CB1 and CB2 cannabinoid receptors, endogenous cannabinoids (endocannabinoids), and the enzymes that synthesize and degrade endocannabinoids. The primary focus of this review is the CB2 receptor. CB2 receptors have been the subject of considerable attention, primarily due to their promising therapeutic potential for treating various pathologies while avoiding the adverse psychotropic effects that can accompany CB1 receptor–based therapies. With the appreciation that CB2-selective ligands show marked functional selectivity, there is a renewed opportunity to explore this promising area of research from both a mechanistic as well as a therapeutic perspective. In this review, we summarize our present knowledge of CB2 receptor signaling, localization, and regulation. We discuss the availability of genetic tools (and their limitations) to study CB2 receptors and also provide an update on preclinical data on CB2 agonists in pain models. Finally, we suggest possible reasons for the failure of CB2 ligands in clinical pain trials and offer possible ways to move the field forward in a way that can help reconcile the inconsistencies between preclinical and clinical data.

Footnotes

    • Received July 7, 2014.
    • Accepted August 8, 2014.
  • This work was supported by the National Institutes of Health National Institute on Drug Abuse [Grants R01-DA011322, K05-DA021696, and R21-DA035068].

  • dx.doi.org/10.1124/mol.114.094649.

  • Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 86 (4)
Molecular Pharmacology
Vol. 86, Issue 4
1 Oct 2014
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Rapid CommunicationMinireview

CB2 as a Therapeutic Target

Amey Dhopeshwarkar and Ken Mackie
Molecular Pharmacology October 1, 2014, 86 (4) 430-437; DOI: https://doi.org/10.1124/mol.114.094649

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Rapid CommunicationMinireview

CB2 as a Therapeutic Target

Amey Dhopeshwarkar and Ken Mackie
Molecular Pharmacology October 1, 2014, 86 (4) 430-437; DOI: https://doi.org/10.1124/mol.114.094649
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  • Article
    • Abstract
    • Introduction
    • CB2 Receptors
    • Adenylyl Cyclase
    • MAPK
    • Ion Channels
    • Internalization
    • β-Arrestin Signaling
    • CB2 Receptor Dimerization
    • Functional Selectivity of CB2 Signaling
    • Regulation of CB2 Receptor Expression and CB2 Receptor Localization
    • CB2 Ligands
    • Genetic Tools To Study CB2 Receptor Signaling
    • Preclinical Studies of CB2 Agonists in Pain
    • Reconciling Preclinical and Clinical Studies
    • Concluding Comments
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