Major findings supporting the involvement of CB2R in anxiety disorders

Animal studies
Genetic studies Genetic manipulation Animal specie Experimental test Behavioral changes References
CB2xP Mouse, ICR LDB ↓ vulnerability
(↓ time in the lighted box and open arms)
[39]
EPM
CB2–/– Mouse, ICR LDB ↑ vulnerability
(↑ time in the lighted box and open arms)
[44]
EPM
Cnr2 KO Mouse, C57BL/6J SD ↑ aggressive behavior [49]
Pharmacological studies Acute treatment Drug Animal specie Experimental test Dosis Behavioral changes References
CB2R messenger RNA antisense probe Mouse, DBA/2, C57BL/6J, BALB/c EPM 4 µg/µL per 12 h (3 days) ↓ anxiogenic response [45]
JWH015 (CB2R agonist) Mouse, DBA/2, C57BL/6J, BALB/c EPM 1–20 mg/kg ↑ anxiogenic response [38]
JWH133 (CB2R agonist) Mouse, ICR LDB, EPM 0.5, 1, 2 mg/kg No effect [47]
Mouse, C57BL/6J SD 1, 2 mg/kg ↓ aggressive behavior [49]
GW405833 (CB2R agonist) Mouse, C57BL/6J MB 10, 30, 100 mg/kg ↓ anxiogenic response [46]
Rat, Sprague-Dawley Rotarod 100 mg/kg
AM630 (CB2R antagonist) Mouse, ICR LDB 1, 2, 3 mg/kg ↑ anxiogenic response [47]
Chronic treatment Drug Animal specie Experimental test Dosis Behavioral changes References
AM630 (CB2R antagonist) Mouse, ICR LDB
EPM
1, 2, 3 mg/kg per 12 h (7 days) ↓ anxiogenic response [47]
JWH133 (CB2R agonist) Mouse, ICR LDB
EPM
0.5, 1, 2 mg/kg per 12 h (7 days) ↑ anxiogenic response [47]
Human studies
Variable Population Results References
rs2070956 polymorphism Caucasian (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