Table 2.

Summary of main findings regarding the alterations of the ECS components in animals and human studies in Alcohol Use Disorders.

Alcohol Use Disorders
References	Type of Sample	Type of Evaluation	Outcomes
[428]	Humans	Neuroimaging (PET)	AUD showed ↑ CB1r binding in a circuit that included the AMY, HIPP, PT, insula, anterior and posterior cingulate cortices, and OFC.
[433]	Humans	Neuroimaging (PET)	AD subjects showed ↓ CB1r binding during early abstinence (3–7 days), which remained reduced during protracted abstinence (2–4 weeks).
[429]	Humans	Neuroimaging (PET)	Acute alcohol consumption resulted in a ↑ CB1r availability Chronic alcohol drinking resulted in a ↓ CB1r availability that remained unaltered after abstinence (1 month).
[437]	Humans	Post-mortem	Cloninger type 1 alcohol dependent subjects showed ↑ DHEA levels in the AMY and a negative correlation between AEA concentrations and mGlu1/5 receptor density in the HIPP compared to Cloninger type 2 alcohol-dependent subjects and controls.
[438]	Humans	Post-mortem	CB1r protein expression in the PFC of the suicidal alcohol-dependent group Alcohol-dependent subjects, regardless of the cause of death, ↓ MAGL activity, ↓ ERK, and ↓ CREB levels.
[154]	Humans	Post-mortem	Alcohol-dependent subjects presented hyper-functional CB1r in the caudate nucleus Non-suicidal alcohol-dependent subjects showed hypofunctional CB1r in the cerebellum.
[439]	Animals	CB1R KO vs WT mice	CB1r KO mice exhibited voluntary alcohol consumption and completely lacked alcohol-induced DA release in the NAcc compared to WT mice.
[440]	Animals	CB1R KO vs WT mice	CB1r KO mice displayed ↓ OH-induced CPP compared to WT mice. This ↓ OH-induced CPP exhibited by CB1r KO mice was correlated with an increase in striatum D2/D3 receptors.
[441]	Animals	CB1r KO vs WT mice	CB1r KO mice ↓OH consumption and preference, compared to WT mice CB1r KO mice were more sensitive to the acute alcohol effects than WT mice. The severity of alcohol withdrawal was also increased in CB1r KO mice
[139,436]	Animals	C57/BJ6 male mice	Mice with high-alcohol preference had a lower gene expression of CNR2 at the ventral midbrain
[442]	Animals	CB2r KO vs WT mice	CB2r KO mice presented ↑ a response to alcohol effects, OH-induced CPP, voluntary OH intake and preference, acquisition of alcohol self-administration, and motivation to drink alcohol compared to WT mice.
[443]	Animals	FAAH gene KO vs WT mice	FAAH KO mice showed a ↑ preference for alcohol and consumed more alcohol than WT mice There were no significant differences between FAAH KO and WT mice in the severity of alcohol induced acute withdrawal, CPP, or sensitivity to the hypnotic effect of alcohol. FAAH KO mice showed a shorter duration and a faster recovery from intoxicating effects induced by alcohol.
[444]	Animals	FAAH gene KO vs WT mice	Female FAAH KO mice had an ↑ alcohol intake and preference, were less sensitive to the effects of acute alcohol, and no CB1r levels and function down-regulation after voluntary alcohol consumption, compared to male FAAH KO, and male and female WT mice.
[445]	Animals	Male Wistar rats exposed to continuous OH access vs intermittent OH access	Alcohol withdrawal was associated with significant ↓ mRNA expression FAAH, MAGL, CB1r, CB2r, and GPR55r in the AMY. ↓ MAGL, CB1r, CB2r, and GPR55r were more pronounced following intermittent alcohol exposure.
[446]	Animals	Male Wistar rats exposed to intermittent OH access	Alcohol-exposed rats expressed ↑ mRNA levels of NAPE-PLD and DGL in the mPFC and the AMY, respectively, and ↓mRNA levels of CB1r, CB2r, and PPARα in the striatum.