Major findings supporting the involvement of CB2R in anxiety disorders

Animal studies
Genetic studiesGenetic manipulationAnimal specieExperimental testBehavioral changesReferences
CB2xPMouse, ICRLDB↓ vulnerability
(↓ time in the lighted box and open arms)
[39]
EPM
CB2–/–Mouse, ICRLDB↑ vulnerability
(↑ time in the lighted box and open arms)
[44]
EPM
Cnr2 KOMouse, C57BL/6JSD↑ aggressive behavior[49]
Pharmacological studiesAcute treatmentDrugAnimal specieExperimental testDosisBehavioral changesReferences
CB2R messenger RNA antisense probeMouse, DBA/2, C57BL/6J, BALB/cEPM4 µg/µL per 12 h (3 days)↓ anxiogenic response[45]
JWH015 (CB2R agonist)Mouse, DBA/2, C57BL/6J, BALB/cEPM1–20 mg/kg↑ anxiogenic response[38]
JWH133 (CB2R agonist)Mouse, ICRLDB, EPM0.5, 1, 2 mg/kgNo effect[47]
Mouse, C57BL/6JSD1, 2 mg/kg↓ aggressive behavior[49]
GW405833 (CB2R agonist)Mouse, C57BL/6JMB10, 30, 100 mg/kg↓ anxiogenic response[46]
Rat, Sprague-DawleyRotarod100 mg/kg
AM630 (CB2R antagonist)Mouse, ICRLDB1, 2, 3 mg/kg↑ anxiogenic response[47]
Chronic treatmentDrugAnimal specieExperimental testDosisBehavioral changesReferences
AM630 (CB2R antagonist)Mouse, ICRLDB
EPM
1, 2, 3 mg/kg per 12 h (7 days)↓ anxiogenic response[47]
JWH133 (CB2R agonist)Mouse, ICRLDB
EPM
0.5, 1, 2 mg/kg per 12 h (7 days)↑ anxiogenic response[47]
Human studies
VariablePopulationResultsReferences
rs2070956 polymorphismCaucasian (infant)↓ response to the treatment[50]

Cnr2 KO: mouse lacking CB2R gene in the CNS with C57BL/6J background; LDB: light-dark box test; EPM: elevated plus-maze test; SD: experimental paradigm of social defeat; MB: marble-burying behavioral test. ↑: increases; ↓: decreases