Table 1.

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

Nicotine Use Disorder
Authors	Type of Sample	Type of Evaluation	Outcomes
[417]	Humans	Neuroimaging (fMRI)	↓ reward anticipation activity in the NAcc after THC administration in NUDs
[418]	Humans	Neuroimaging (PET)	↓ CB1r in all brain areas in NUDs
[422]	Animals	CB1r KO vs WT mice	Nicotine rewarding effects in WT mice but not in CB1r KO mice No significant differences in the severity of nicotine withdrawal between WT and CB1r KO mice
[423]	Animals	CB1r KO vs FAAH KO vs WT mice	CB1r KO mice blocked nicotine reward FAAH KO mice had an enhanced expression of nicotine reward Nicotine withdrawal was unaffected in CB1r KO mice, FAAH KO mice displayed increased nicotine withdrawal
[424]	Animals	MAGL KO vs WT mice	MAGL KO mice failed to develop a nicotine CPP compared to WT mice
[425]	Animals	CB2r KO vs WT mice	CB2r KO mice did not show nicotine-induced PCC and hardly self-administered nicotine compared to WT mice Somatic signs of nicotine withdrawal ↑ in WT but were absent in CB2r KO mice
[426]	Animals	CB2r KO vs WT mice	Nicotine-induced CPP was absent in CB2r KO WT, and CB2r KO nicotine-dependent mice showed a similar response during nicotine withdrawal
[427]	Animals	DAT-CNR2 KO vs WT mice	Compared to WT, DAT-CNR2 KO mice showed the absence of nicotine-induced CPP.