CNR1 and Alzheimer disease: The individual contributions of CB1r and CB2r in the context of AD neuropathology have also been extensively studied in AD transgenic mice (see Table 4), or conditions of Aβ42-induced pathology in vitro and in vivo (Esposito et al., 2006a,2007a,b; Haghani et al., 2012; Wang et al., 2018; Zhang R. et al., 2020; see Table 5), but the synergism of CB1r and CB2r activation (via THC) in the presence of a negative allostatic modulator (CBD) appears to demonstrate the most favorable therapeutic profile (Aso et al., 2015; Aso and Ferrer, 2016; Schubert et al., 2019).