CB<sub>2</sub> receptor | Cannabinoid receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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CB2 receptor

Target id: 57

Nomenclature: CB2 receptor

Family: Cannabinoid receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     CB2 receptor has curated data in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 360 1p35-p36 CNR2 cannabinoid receptor 2 30,41
Mouse 7 347 4 D3 Cnr2 cannabinoid receptor 2 (macrophage) 43
Rat 7 410 5q36 Cnr2 cannabinoid receptor 2 7
Previous and Unofficial Names
rCB2 | cannabinoid receptor 2 (spleen) | CB2-R | Peripheral cannabinoid receptor | cannabinoid receptor 2 (macrophage)
Database Links
Specialist databases
GPCRDB cnr2_human (Hs), cnr2_mouse (Mm), cnr2_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Natural/Endogenous Ligands
Comments: Endogenous ligands include other endocannabinoids

Download all structure-activity data for this target as a CSV file

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]HU-243 Hs Full agonist 10.2 pKd 2
pKd 10.2 [2]
[3H]CP55940 Hs Full agonist 8.1 – 9.7 pKd 6,14,30,42-44
pKd 8.1 – 9.7 [6,14,30,42-44]
[3H]WIN55212-2 Hs Full agonist 8.4 – 8.7 pKd 30,45
pKd 8.4 – 8.7 [30,45]
AM7499 Mm Agonist 10.0 pKi 24
pKi 10.0 (Ki 1x10-10 M) [24]
HU-210 Hs Full agonist 9.3 – 9.8 pKi 14,37,44
pKi 9.3 – 9.8 [14,37,44]
Sch.336 Hs Inverse agonist 8.7 – 9.4 pKi 26-27
pKi 9.4 (Ki 4x10-10 M) [26]
pKi 8.7 (Ki 1.8x10-9 M) [27]
Description: Measuring competitin binding with [3H]CP55,940 for binding to human CB2 on Sf9 cell membranes.
WIN55212-2 Hs Full agonist 8.4 – 9.6 pKi 14,43-44
pKi 8.4 – 9.6 [14,43-44]
CP55940 Hs Full agonist 8.6 – 9.2 pKi 14,40,44
pKi 8.6 – 9.2 [14,40,44]
AM2201 Mm Agonist 8.6 pKi 28
pKi 8.6 (Ki 2.6x10-9 M) [28]
Description: Binding affinity vs. mouse spleen membranes.
AM7499 Hs Agonist 8.5 pKi 24
pKi 8.5 (Ki 3.1x10-9 M) [24]
JWH-133 Hs Full agonist 8.5 pKi 22,34
pKi 8.5 (Ki 3.16x10-9 M) [22,34]
JWH-018 Hs Full agonist 8.5 pKi 10
pKi 8.5 [10]
nabilone Hs Agonist 8.2 pKi 5
pKi 8.2 (Ki 6.31x10-9 M) [5]
AM1241 Hs Agonist 8.1 pKi 46
pKi 8.1 (Ki 7.94x10-9 M) [46]
L-759,633 Hs Full agonist 7.7 – 8.2 pKi 17,40
pKi 7.7 – 8.2 (Ki 1.99x10-8 – 6.31x10-9 M) [17,40]
L-759,656 Hs Full agonist 7.7 – 7.9 pKi 17,40
pKi 7.7 – 7.9 (Ki 1.99x10-8 – 1.26x10-8 M) [17,40]
HU-308 Hs Full agonist 7.6 pKi 20
pKi 7.6 (Ki 2.51x10-8 M) [20]
Δ9-tetrahydrocannabinol Hs Partial agonist 7.1 – 7.5 pKi 3,14,37,44
pKi 7.1 – 7.5 [3,14,37,44]
ajulemic acid Hs Agonist 6.8 pKi 18,36
pKi 6.8 (Ki 1.7x10-7 M) [18,36]
VCE-004.3 Hs Agonist 6.7 pKi 12
pKi 6.7 (Ki 2.04x10-7 M) [12]
taranabant Hs - 6.5 pKi 15
pKi 6.5 (Ki 2.9x10-7 M) [15]
2-arachidonoylglycerol Hs Partial agonist 5.8 – 6.8 pKi 4,29
pKi 5.8 – 6.8 [4,29]
anandamide Hs Partial agonist 5.7 – 6.4 pKi 14,29,44
pKi 5.7 – 6.4 [14,29,44]
APD371 Hs Full agonist 8.2 pEC50 19
pEC50 8.2 (EC50 6.2x10-9 M) [19]
Description: In a DiscoverX PathHunter β-arrestin recruitment assay.
APD371 Rn Full agonist 8.1 pEC50 19
pEC50 8.1 (EC50 7.6x10-9 M) [19]
Description: In a DiscoverX PathHunter β-arrestin recruitment assay.
AM2201 Hs Agonist 7.2 pEC50 1
pEC50 7.2 (EC50 5.88x10-8 M) [1]
BMS-202 Hs Agonist 6.9 pEC50 1
pEC50 6.9 (EC50 1.31x10-7 M) [1]
View species-specific agonist tables
Agonist Comments
The higher pKi value for anandamide (6.43) was determined in the presence of phenylmethylsulfonyl fluoride to prevent enzymic hydrolysis. For reviews, see references [21,32-33]
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
SR144528 Hs Antagonist 8.3 – 9.2 pKi 39-40
pKi 8.3 – 9.2 (Ki 5.01x10-9 – 6.3x10-10 M) [39-40]
AM-630 Hs Antagonist 7.5 pKi 40
pKi 7.5 (Ki 3.16x10-8 M) [40]
surinabant Hs Full agonist 6.3 pKi 38
pKi 6.3 (Ki 4.42x10-7 M) [38]
Description: Inhbition of [3H]-CP 55,940 binding to human CB2 receptors expressed in CHO cells
ibipinabant Hs Antagonist 5.1 pKi 25
pKi 5.1 (Ki 7.943x10-6 M) [25]
Description: Displacement of specific CP-55,940 binding in CHO cells stably transfected with human CB2 receptor
TM-38837 Hs Antagonist 6.2 pIC50 23
pIC50 6.2 (IC50 6.05x10-7 M) [23]
Immunopharmacology Comments
CB2 receptor on eosinophils mainly mediates anti-inflammatory and immunomodulatory actions e.g. downregulation of pro-inflammatory mediator release. Pharmacological targeting with the CB2 receptor selective antagonist SR144528 attenuates the recruitment of eosinophils and ear swelling in a murine chronic contact dermatitis model [31].
Cell Type Associations
Immuno Cell Type:  Mast cells
Cell Ontology Term:   mast cell (CL:0000097)
Comment:  Mast cells express both cannabinoid receptors.
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   eosinophil (CL:0000771)
Comment:  Eosinophils do not express CB1 receptor.
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 4 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0006954 inflammatory response IEA
GO:0030595 leukocyte chemotaxis IEA
GO:0033004 negative regulation of mast cell activation IEA
GO:0050728 negative regulation of inflammatory response IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0033004 negative regulation of mast cell activation IEA
GO:0050728 negative regulation of inflammatory response IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0030595 leukocyte chemotaxis IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0033004 negative regulation of mast cell activation IEA
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Other - See Comments
Comments:  Activation of MAP kinase leading to immediate early gene expression[21,42].
References:  6-7,14,21,43-45
Secondary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
References:  21,35
Tissue Distribution
Spleen, tonsils, bone marrow and peripheral blood leukocytes
Species:  Human
Technique:  RT-PCR
References:  16,21,30,32
Monocytes, macrophages, and microglial cells,
Species:  Rat
Technique:  RT-PCR
References:  9,11,13,21,30
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Physiological Consequences of Altering Gene Expression
This has been little investigated. There is one report that cannabinoid-induced inhibition of helper T cell activation is lost in macrophages obtained from CB2 knockout mice.
Species:  Mouse
Technique:  Induced mutation.
References:  8
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Cnr2tm1Zim Cnr2tm1Zim/Cnr2tm1Zim
involves: 129 * C57BL/6
MGI:104650  MP:0002451 abnormal macrophage physiology PMID: 10822068 
Cnr2tm1Dgen Cnr2tm1Dgen/Cnr2tm1Dgen
involves: 129P2/OlaHsd * C57BL/6
MGI:104650  MP:0000414 alopecia
General Comments
Techniques used include Northern blot, in situ hybridization and receptor autoradiography[21,32]


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23. Hung MS, Chang CP, Li TC, Yeh TK, Song JS, Lin Y, Wu CH, Kuo PC, Amancha PK, Wong YC et al.. (2010) Discovery of 1-(2,4-dichlorophenyl)-4-ethyl-5-(5-(2-(4-(trifluoromethyl)phenyl)ethynyl)thiophen-2-yl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide as a potential peripheral cannabinoid-1 receptor inverse agonist. ChemMedChem, 5 (9): 1439-43. [PMID:20652930]

24. Kulkarni S, Nikas SP, Sharma R, Jiang S, Paronis CA, Leonard MZ, Zhang B, Honrao C, Mallipeddi S, Raghav JG et al.. (2016) Novel C-Ring-Hydroxy-Substituted Controlled Deactivation Cannabinergic Analogues. J. Med. Chem., 59 (14): 6903-19. [PMID:27367336]

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How to cite this page

Mary Abood, Francis Barth, Tom I. Bonner, Guy Cabral, Pierre Casellas, Ben F. Cravatt, William A. Devane, Maurice R. Elphick, Christian C. Felder, Miles Herkenham, Allyn C. Howlett, George Kunos, Ken Mackie, Raphael Mechoulam, Roger G. Pertwee.
Cannabinoid receptors: CB2 receptor. Last modified on 22/08/2018. Accessed on 21/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=57.