Table 1.

Main findings supporting the involvement of CB2r in the regulation of the reinforcing and motivational effects of alcohol.

CB2r & Alcohol-ANIMAL STUDIES
Genetic Manipulation CB2r
Genetic manipulation	Specie	Experimental paradigm	Results	References
CB2r deletion, knock-out (CB2-/- and CNR2 KO)	Swiss ICR and C57BL/6J mice	CPP	↑ Conditioned place preference	[50]
		VC	↑ Voluntary ethanol consumption and preference
		OESA	↑ Motivation to drink ethanol
CB2r deletion, knock-out (CNR2 KO)	C57BL/6J mice	FD IFD	No differences	[72]
		VC	↑ Alcohol drinking in group-housing conditions
CB2r deletion, knock-out (CNR2 KO)	C57BL/6J mice	CPP	↑ Conditioned place preference	[73]
CB2r deletion, in dopaminergic neurons, knock out condicional (DAT-Cnr2-/-)	C57BL/6J mice	CPP	↓ Conditioned place preference	[77]
		VC
Pharmacological manipulation of CB2r
Doses	Specie	Experimental paradigm	Results	References
β-caryophyllene, CB2r agonist (25, 50 and 100 mg/kg)	C57BL/6J mice	CPP	↓ Conditioned place preference	[74]
		VC	↓ Voluntary ethanol consumption and preference
JWH133, CB2r agonist (10 y 20 mg/kg)	HS/Ibg mice	CPP	No differences	[73]
		VC	No differences
JWH133, CB2r agonist (5 mg/kg)	C57BL/6J mice	CPP	↓ Conditioned place preference	[28]
JWH133, CB2r agonist (1 mg/kg)	C57BL/6J mice	OESA	↓ Motivation to drink ethanol	[75]
CB2r & Alcohol-Human Studies
Diagnosis	Population	Variable	Results	References
SUD	Japanese	Q63R (CB2r) polymorphism association-SUD	↑ Incidence	[51,68]
SUD	Caucasian	Relative gene expression (CB2r)	↓ DLPFCx y NAcc	[71]

↑: increase, ↓: decrease, CPP: Conditioned Place Preference, VC: Voluntary Consumption, ESA: Oral Ethanol Self-Administration, FD: Forced Drinking, IFD: Intermittent Forced Drinking, SUD: Substance Use Disorder, DLPFCx: Dorsolateral Prefrontal Cortex, NAcc: Nucleus Accumbens.